Ann Intern Med Research Articles

Promoting speaking-up behaviours among nurses working in the care for older people: A scoping review.

To explore interventions employed to foster speaking-up behaviours of registered nurses (RNs) working in the care of older people. Scoping review. The updated Joann Briggs Institute scoping review methodological guidelines were followed. CINAHL, PubMed, PsycINFO, and Scopus were searched. A total of 1691 titles and abstracts were screened, resulting in 11 articles that met the inclusion criteria. Analysis focused upon intervention types, methodologies, speaking up strategies, barriers and effectiveness. Education was the most used intervention. There is a lack of published research on successful interventions to promote speaking-up behaviours in the care of older people, particularly relating to poor care practices. Evidence of speaking-up interventions in the residential aged care setting is absent. This highlights the need to develop strategies to support the RN to lead and enable others to raise care concerns. Developing strategies that enable staff, care recipients and their families to speak up about care concerns is a vital future area for nursing practice development. Nursing leadership of such strategies is central to improving the quality of care for older people, particularly those living in residential aged care. Older people receiving care should feel respected and be treated humanely. Evidence suggests this is often not the case. This review found a paucity of interventions to promote speaking-up about poor care practices among RNs working in the care of older people. Future research needs to address this, to empower RNs and improve the care afforded to older people. The PRISMA-ScR (Tricco etal., Annals of Internal Medicine, 169, 467-473, 2018) were adhered to throughout this scoping review. No patient or public contribution in this review.

Palliative care needs of people and/or their families with serious and/or chronic health conditions in low- or middle-income country (LMIC) humanitarian settings—a systematic scoping review protocol

BackgroundPalliative care in low- or middle-income country (LMIC) humanitarian settings is a new area, experiencing a degree of increased momentum over recent years. The review contributes to this growing body of knowledge, in addition to identifying gaps for future research. The overall aim is to systematically explore the evidence on palliative care needs of patients and/or their families in LMIC humanitarian settings.MethodsArksey and O’Malley’s (Int J Soc Res Methodol. 8:19-32, 2005) scoping review framework forms the basis of the study design, following further guidance from Levac et al. (Implement Sci 5:1-9, 2010), the Joanna Briggs Institute (JBI) Peters et al. (JBI Reviewer’s Manual JBI: 406-452, 2020), and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) from Tricco et al. (Ann Intern Med 169:467-73, 2018). This incorporates a five-step approach and the population, concept, and context (PCC) framework. Using already identified key words/terms, searches for both published research and gray literature from January 2012 to October 2022 will be undertaken using databases (likely to include Cumulative Index of Nursing and Allied Health (CINAHL), MEDLINE, Embase, Global Health, Scopus, Applied Social Science Index and s (ASSIA), Web of Science, Policy Commons, JSTOR, Library Network International Monetary Fund and World Bank, Google Advanced Search, and Google Scholar) in addition to selected pre-print sites and websites. Data selection will be undertaken based on the inclusion and exclusion criteria and will be reviewed at each stage by two reviewers, with a third to resolve any differences. Extracted data will be charted in a table. Ethical approval is not required for this review.DiscussionFindings will be presented in tables and diagrams/charts, followed by a narrative description. The review will run from late October 2022 to early 2023. This is the first systematic scoping review specifically exploring the palliative care needs of patients and/or their family, in LMIC humanitarian settings. The paper from the review findings will be submitted for publication in 2023.

Cardiac Arrest During Delivery Hospitalization: A Cohort Study

(Ann Intern Med. 2023;176:472–479) Cardiac arrest is a rare but serious complication in the parturient and is associated with very poor outcomes. The objective of this study was to assess the incidence of cardiac arrest from 2017 to 2019 in the United States by patient demographics, co-morbidity, and type and size of hospital. This analysis can aid in identifying strategies to reduce pregnancy-related maternal morbidity and mortality.

Risk for Congenital Anomalies in Children Conceived With Medically Assisted Fertility Treatment

(Abstracted from Ann Intern Med 2023;176:1308–1320) In the United States, more than 2% of all infants are conceived by assisted reproductive technology (ART). Children born from ART have been shown to have up to 50% increased risk for congenital anomalies (CAs) compared with naturally conceived children.

Clinical trials of pharmacological interventions for SARS-CoV-2 published in leading medical journals report adherence but not how it was assessed.

Adherence to pharmacological interventions in clinical trials is crucial for accurate identification of beneficial and adverse outcomes. The ways in which adherence to interventions should be reported in trial publications are described in the Template for Intervention Description and Replication (TIDieR), a 12-item extension of the Consolidated Standards of Reporting Trials reporting guidelines. The objective of this study was to assess compliance with TIDieR Items 11 and 12 of randomized controlled trials (RCTs) of interventions in SARS-CoV-2 infection published in 5 selected journals during 2021. We assessed pharmacological interventions for SARS-CoV-2 infection reported in RCTs published in 2021 in the Annals of Internal Medicine, The BMJ, JAMA, The Lancet and The New England Journal for Medicine for compliance with TIDieR items addressing intervention adherence (Items 11 and 12). We calculated proportional adherence for pharmacological and comparator interventions where available. We found 75 eligible RCTs. Twenty-eight (37%) reported results of SARS-CoV-2 vaccinations. Compliance with Items 11 and 12 could be assessed in 71 of these 75. Of the 71 RCTs, 37 (52%) reported how adherence was assessed (Item 11), and 70 reported adherence rates (Item 12). Only 1 of the 71 RCTs (1.4%, 0-7.6%) fully complied with TIDieR Items 11 and 12. Half of RCTs of SARS-CoV-2 pharmacological interventions published in leading medical journals in 2021 complied with reporting of how adherence assessments were made and almost none complied with both TIDieR Items 11 and 12. The implications for interpretation, application and replication of findings based on these publications warrant consideration.

In older adults, postoperative oral haloperidol vs. antipsychotics was linked to similar risk for in-hospital adverse events.

Kim DH, Lee SB, Park CM, et al. Comparative safety analysis of oral antipsychotics for in-hospital adverse clinical events in older adults after major surgery: a nationwide cohort study. Ann Intern Med. 2023;176:1153-1162. 37665998.

In Phase 2 and Phase 3 Trials, Broadening the Definition of Acute Vaso-Occlusive Pain to Include at Least One Episode of Pain Requiring Nsaids, Opioids, or Both Treatments at Home within 30 Days of a Physician Visit

Introduction:Despite the high incidence of acute painful events in children and adults with SCD, there is a lack of consensus on the acute pain definition in controlled clinical trials. To address this limitation, we elected to have three definitions of acute vaso-occlusive pain based on the setting for the pain location: inpatient, outpatient, ED, or at home. Based on the results of the SPRING Trial, the primary stroke prevention trial in children with SCD conducted in Nigeria (The Lancet Haematol. 2022 Jan 1;9(1):e26-37), and the PISCES study (Annals of internal medicine. 2008 Jan 15;148(2):94-101), most acute pain events in low-middle and high-income countries occur at home. We tested the hypothesis that the majority of negative phase 2 and phase 3-controlled trials for SCD failed to consider acute pain events in all four settings. Methods: To identify the relevant Phase II and III trials with acute pain as an outcome, we conducted a literature review using the website clinicaltrials.gov with the following key terms: “Sickle Cell Disease,” and “Vaso-occlusive.”. Studies that were not Phase II or Phase III were excluded from our search. We identified Phase 2 or 3 SCD pain trials published between 2015 and 2023. Inclusion criteria: definitions in the clinicaltrials.gov trial page, protocol, or method section. An inclusive, consensus definition for vaso-occlusive pain was chosen from the SPRING Trial. This definition was compared to the acute vaso-occlusive pain definitions of both SCD Phase 2 and 3 trials, with vaso-occlusive pain as a primary or secondary outcome. Based on the SPRING Trial and the results of the PISCES study, we elected to have three definitions of acute vaso-occlusive pain: 1. inpatient uncomplicated pain that excludes a concomitant diagnosis of acute chest syndrome; 2. Pain that required either an inpatient or outpatient visit and opioid treatment; and 3. An acute pain event at home requiring NSAIDs, opioids, or both. Only uncomplicated pain events were included to avoid double counting participants who developed acute chest syndrome or strokes that may have preceded the vaso-occlusive pain event. Results: We identified 35 articles based on our criteria. Our study sample included 3 clinical trials that led to the FDA approval for therapy to prevent acute vaso-occlusive pain events (FDA-approved therapy trials). Among these 35 trials, 32 clinical trials did not provide any evidence of the therapeutic benefits of the experimental agent (negative controlled trials). The three randomized controlled trials that led to FDA approval for therapy to prevent acute pain were: Hydroxyurea, L-Glutamine, and Crizanlizumab. Hospitalization for pain was included in all three FDA-approved therapy trials and 34.4% (11/32) of negative controlled trials. The ED visits in the pain definition were included in all 3 FDA-approved therapy trials and 28.1% (9/32) of negative controlled trials. Outpatient visits in the pain definition were included in all 3 FDA-approved therapy trials and 21.9% (7/32) of negative controlled trials. Home pain episodes were included in none of the FDA-approved therapy trials and 9.4% (3/32) of negative controlled trials. Finally, 43.8% (14/32) negative controlled trials were excluded as they failed to define vaso-occlusive pain in their methods or definition section and 15.6% (5/32) negative controlled trials did not have a publication. Conclusion: Most controlled trials designed to evaluate the efficacy of new treatment did not include the setting where pain occurs most frequently, at home. For future therapeutic trials designed to address whether a new therapy decreases the incidence rate of acute pain, we recommend an assessment of pain in all 4 four settings (Hospitalization, ED, Outpatient, and Home).

Extended Thromboprophylaxis in Patients Hospitalized with COVID-19 at Time of Discharge from the Hospital Is Not Associated with an Improvement in Quality of Life: Results from the Activ 4c Clinical Trial

Introduction. Post-acute sequelae of SARS-CoV2 infection, or PASC, is defined as the presence of persistent symptoms for at least two months after an acute infection with COVID-19. A potential pathophysiologic mechanism for PASC is microvascular thrombosis. Using EQ-5D-5L index scores, we previously reported that extended thromboprophylaxis for 30 days with apixaban did not impact quality of life (QoL) at 30 or 90 days after discharge (Wang et al, Ann Intern Med 2023; 176:515-523). The purpose of this investigation was to determine whether anticoagulation had a variable impact on the individual domains measured by EQ-5D-5L. Methods. ACTIV 4c was a prospective, randomized, placebo-controlled, double-blind clinical trial comparing post-discharge thromboprophylaxis with apixaban 2.5 mg twice daily to placebo for 30 days in patients hospitalized with COVID-19. Participants were enrolled at 107 hospitals in the US between February 2021 and June 2022. We ascertained symptoms and QoL by EQ-5D-5L at 2 days, 30 days, and 90 days after hospital discharge by electronic or telephone follow-up. The five domains of EQ-5D-5L are: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each domain has 5 levels of response, ranging from “no problems/none” to “unable to perform/extreme”, which are used to determine individual scores. We analyzed the impact of treatment (placebo vs. apixaban), antiplatelet therapy (yes vs. no), and highest WHO severity score during hospitalization (score <5 vs. score ≥5) on degree of impairment at 2, 30, and 90 days post-discharge using a chi-square test for those participants who completed the survey at each timepoint. We also used a proportional odds model to test for at least moderate impairment in each EQ-5D-5L domain, also at 30 and 90 days, using odds ratios adjusted for age (restricted cubic spline with 3 knots), sex, D-dimer (normal or abnormal), BMI (restricted cubic spline with 3 knots), antiplatelet usage (yes/no - at enrollment), WHO severity score (<=5 vs. > 5), and the randomized treatment. Results. We randomized 1217 participants hospitalized with acute COVID-19 onto ACTIV 4c, with 610 participants assigned to apixaban and 607 participants to placebo. A total of 208 participants taking apixaban (43.5%) and 219 participants taking placebo (45.0%) reported moderate or greater impairment in one or more of the EQ-5D-5L domains by 2 days after hospital discharge. The individual domain most frequently reported as impaired was usual activities (33.0% of all study participants). By 30 days after discharge, 151 participants taking apixaban (30.8%) and 165 taking placebo (33.4%) reported moderate or greater impairment in one or more domains. The individual domain with the largest improvement was usual activities, affecting 17.4% of all study participants. By 90 days, 152 participants taking apixaban (31.5%) and 142 participants taking placebo (28.5%) reported moderate or greater impairment in one or more domains. Extended thromboprophylaxis with apixaban was not associated with improved scores for any of the individual EQ-5D-5L domains at 30 days or 90 days (Table 1). Stratification by WHO severity score during hospitalization revealed a significant improvement in the domain for usual activities for participants with score <5 compared to those with a score ≥5 (p=0.015) by 30 days, but this difference was not present by 90 days. Stratification by anti-platelet use did not identify any domains with improvement associated with antiplatelet therapy at 30 or 90 days. Using adjusted odds ratios, we did not find a benefit for apixaban at 30 days (Figure 1) or at 90 days (data not shown). Conclusion. Almost half of patients hospitalized with COVID-19 have decreased QoL at time of discharge, with the greatest impact on performance of usual activities. Impaired QoL persists for up to 90 days after hospital discharge in one-third of patients. Extended thromboprophylaxis with apixaban for 30 days at the time of hospital discharge in participants with acute COVID-19 was not associated with improvements in QoL as assessed by EQ-5D-5L.

Allogeneic Hematopoietic Cell Transplantation in the 7 th Decade of Life and Beyond

Background The upper age limit for patients undergoing allogeneic hematopoietic cell transplantation (HCT) has increased over the past several years due to continued improvements in supportive care and increased expertise in management of older recipients of allogeneic HCT. This change is particularly important for hematologic malignancies such as acute myeloid leukemia (AML) where the median age at diagnosis is in the late 60s and HCT provides, in many instances, the only potential chance of cure. While some previous analyses have suggested favorable post-HCT outcomes for older AML patients in general, information is limited about allogeneic HCT for patients aged 70 years or older. Here, we set out to retrospectively analyze post-HCT outcomes for those aged 70+ and compare these outcomes to those aged 60-69 in a large single-center observational study. Methods Eligible patients were identified using our Fred Hutchinson Cancer Center database of transplant outcomes. All patients signed consents at time of HCT. Severity of disease was categorized as previously described (McDonald GB et al Ann Intern Med 2020). Kaplan-Meier estimates were used to evaluate overall survival (OS) and relapse-free survival (RFS); cumulative incidence estimates were used to summarize relapse and non-relapse mortality (NRM). Multivariable Cox regression models were fit to compare outcomes across age groups after adjusting for potential imbalances in various factors between groups. In addition, we used a multivariable model for overall mortality (OM) to identify risk factors for death in this population. Results We identified 1237 patients given allogeneic HCT between 2000-2022 aged at least 60 years old, 229 (18.5%) of whom were of age 70+. Baseline characteristics included severity of disease, donor type, patient CMV serostatus, conditioning intensity (Table 1). The median OS among patients 60-69 was 2.8 years (95% confidence interval, 2.4-3.6 years) and among those 70+, 1.8 years (1.3-2.9 years). Point estimates of OS at 3, 5, and 7 years were 49% (46-52%), 46% (43-49%), and 37% (34-40%), respectively for patients aged 60-69, and 43% (36-49%), 38% (31-45%), and 28% (21-36%), respectively, for patients age 70+. In the subgroup of patients age 75+ (n=29), the 3- and 5-year point estimates of OS were each 41% (22-59%). The unadjusted hazard ratio (HR, 70+ vs. 60-69) for death was 1.24 (1.04-1.49, p=0.02). However, after adjusting for various factors (Table 2), the adjusted HR for death was 1.02 (0.76-1.36, p=0.90), suggesting the apparent reduction in OS for the 70+ group relative to the 60-69 group was largely due to a higher proportion of adverse risk factors in the 70+ group. Median RFS for the two groups were 1.9 years (1.4-2.3 years) and 1.3 years (0.9-1.8 years), respectively. Similar to the HR for death, the unadjusted HR for RFS failure was significant at 1.23 (1.03-1.46, p=0.02), but the adjusted HR for was no longer significant at 0.96 (0.72-1.26, p=0.74). The unadjusted and adjusted HRs for relapse were 1.10 (0.84-1.44, p=0.51) and 0.77 (0.50-1.17, p=0.22), respectively, and for NRM 1.33 (1.06-1.67, p=.02) and 1.12 (0.77-1.61, p=0.56), respectively. Factors that were demonstrably associated with increased mortality included severity of disease, patient/donor CMV serostatus, conditioning intensity, and type of donor (Table 2). Conclusions We report here on one of the largest groups of patients aged 70+ receiving allogeneic HCT in a single center. Our results suggest that allogeneic HCT is feasible and potentially safe in this age group as compared to the group aged 60-69. These results should be encouraging for consideration of patients 70+ for allogeneic HCT. We are in process of complementing our analyses with information on comorbidities. On the other hand, 7-year OS for all older pts (60-80.9 years old) ranged from 28-37%, highlighting the need for dedicated HCT trials targeting this group of older patients to further improve outcomes.

Development and Validation of the Early-Stage Hodgkin Lymphoma (HL) International Prognostication Index (E-HIPI): A Report from the Hodgkin Lymphoma International Study for Individual Care (HoLISTIC) Consortium

Background: There are a lack of clinical prediction tools in early-stage Hodgkin lymphoma (E-HL). We developed and validated a modern-day model, known as E-HIPI, to predict progression-free survival (PFS) within the first 5 years (y) incorporating detailed individual patient (pt) data from international clinical trials and prospective registry data that were standardized, normalized & harmonized as part of the HoLISTIC Consortium (www.hodgkinconsortium.org). Methods: Model development utilized Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines (Moons, Ann Intern Med 2015) on a cohort of 3,080 newly-diagnosed E-HL pts treated on 4 seminal phase 3 clinical trials (NCIC: Meyer, NEJM 2012; RAPID: Radford, NEJM 2015; EORTC-GELA H9U: Ferme, E ur J Cancer 2017; EORTC/LYSA/FIL H10: Andre, JCO 2017). External validation was done in an independent cohort of 462 E-HL pts from a large registry (Princess Margaret, Toronto). Pts with classic HL, stage I or II disease, and ages 18-65 y were included. The primary outcome was PFS. Cox models were utilized with follow-up truncated at 5 years. Baseline predictors were: sex, stage, B symptoms, histology, number & location of nodal sites, and continuous data values of age, maximum tumor diameter (MTD), white blood cell count (WBC), lymphocyte count, hemoglobin, albumin & erythrocyte sedimentation rate (ESR). Multiple imputation was used for missing data. To consider possible non-linear relationships for continuous variables we examined plots & cubic splines. We used backward elimination ( P<0.1) to develop the models & internal validation with 200 bootstrap samples was conducted to estimate optimism & correct for overfitting. The final prediction equations applied optimism corrections to beta coefficients & hazard ratios (HR). Sensitivity analyses included model results stratified by PET staging (vs CT) and each HL trial. The models were evaluated in the external validation cohort & compared using c-statistics. Model scores were also grouped by tertiles for visualization in Kaplan-Meier (KM) curves. Results: Median age in the development cohort was 35y; 51% were female; 81% had nodular sclerosis & 77% stage II disease; 26% had B symptoms; 32% had mediastinal bulk (≥10cm or >1/3 diameter) and the mean MTD was 6.4 cm (interquartile range (IQR), 3.9-8.2). Median follow-up was 60 months (IQR 45-75). KM estimates at 5y was 90.7% (264 events) for PFS, and 97.1% (78 events) for overall survival (OS). After backward elimination, significant variables retained were age, sex, nodal location (cervical region), MTD & albumin. Stage, ESR, or the number of nodal sites were not significant. Age was modeled with piecewise linear splines due to its non-linear relationship. See the Table for the final prediction model and optimism-corrected HRs. Optimism-corrected c-statistics in the development model was 0.63. Sensitivity analyses of stratification by type of imaging at staging or by each clinical trial demonstrated no change in model parameters or c-statistics. Most baseline characteristics and outcomes of the external validation cohort were similar besides median follow-up time (74 months, IQR 37-129). C-statistics for the E-HIPI model in external validation was 0.63. In addition, observed 5y outcomes stratified by tertile of predicted risk in the external cohort separated pts into a low & higher-risk group, which comprised 1/3 & 2/3 of pts, respectively ( Figure). Finally, model diagnostics revealed the potential for time dependency in the retained covariates. Further assessment of differential prediction between early (<2y) vs. later (2-5y) PFS events is ongoing. Conclusion: Following TRIPOD methodology, we rigorously developed and externally validated the E-HIPI among >3,500 E-HL pts.Discrete risk groups were delineated, and we identified several novel factors, including nodal location, sex & key continuous variables that predict 5y PFS. Additional model refinement is underway, including formal calibration & external validation via other HL registries (Stanford, Mayo/Iowa SPORE). A web-based calculator to simplify application of the E-HIPI will also be presented at ASH. Future planned modeling includes integration of differing treatments & response-adapted imaging via multistate modeling to enrich individualized survival estimates and simulation modeling to predict late consequences.

Exploring communication apprehension in nursing and healthcare education: A scoping review

AbstractCommunication among healthcare professionals is critical to optimizing patient outcomes, and communication education is incorporated into the educational programs of healthcare professions students. Communication can be a source of stress for new healthcare professionals, however, there is a lack of research on communication apprehension (CA) in healthcare students, especially in nursing education. This scoping review sought to explore CA and factors associated with CA among healthcare professions students. This scoping review report was guided by the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses extension for Scoping Reviews (Tricco et al., Annals of Internal Medicine, 2018, 169, 467–473). Twenty studies of healthcare professions students were included for analysis. The percentage of health professions students with high CA ranged from 0.7% to 27%. Five out of seven intervention studies demonstrated a significant decrease in CA after the intervention. This review identified inconsistent associations between CA and various individual and educational factors. More research is needed utilizing rigorous research designs, designs employing qualitative methodology, and studies to investigate the impact of language on CA in health professions students who speak English as a second language.

Double-Negative Results Matter: A Reevaluation of Sensitivities for Detecting SARS-CoV-2 Infection Using Saliva Versus Nasopharyngeal Swabs.

In a recent systematic review, Bastos et al. (Ann Intern Med. 2021;174(4):501-510) compared the sensitivities of saliva sampling and nasopharyngeal swabs in the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by assuming a composite reference standard defined as positive if either test is positive and negative if both tests are negative (double negative). Even under a perfect specificity assumption, this approach ignores the double-negative results and risks overestimating the sensitivities due to residual misclassification. In this article, we first illustrate the impact of double-negative results in the estimation of the sensitivities in a single study, and then propose a 2-step latent class meta-analysis method for reevaluating both sensitivities using the same published data set as that used in Bastos et al. by properly including the observed double-negative results. We also conduct extensive simulation studies to compare the performance of the proposed method with Bastos et al.'s method for varied levels of prevalence and between-study heterogeneity. The results demonstrate that the sensitivities are overestimated noticeably using Bastos et al.'s method, and the proposed method provides a more accurate evaluation with nearly no bias and close-to-nominal coverage probability. In conclusion, double-negative results can significantly impact the estimated sensitivities when a gold standard is absent, and thus they should be properly incorporated.

In healthy older adults, low-dose aspirin increased incident anemia at a median 4.7 y.

McQuilten ZK, Thao LT, Pasricha SR, et al. Effect of low-dose aspirin versus placebo on incidence of anemia in the elderly: a secondary analysis of the Aspirin in Reducing Events in the Elderly trial. Ann Intern Med. 2023;176:913-921. 37335992.

Chronic or recurrent Campylobacter enteritis in primary immunodeficiency: a UK national case-series and review of the literature.

Clinical ImplicationsCampylobacter infection is an important diagnosis to consider in primary immunodeficiency patients with chronic or recurrent diarrhea, particularly in those with very low diagnostic immunoglobulin levels. Macrolides, aminoglycosides, and/or carbapenems are promising treatment options for this potentially debilitating condition. Campylobacter infection is an important diagnosis to consider in primary immunodeficiency patients with chronic or recurrent diarrhea, particularly in those with very low diagnostic immunoglobulin levels. Macrolides, aminoglycosides, and/or carbapenems are promising treatment options for this potentially debilitating condition. Campylobacter infection, usually by Campylobacter jejuni, is the most common cause of bacterial enteritis in the world. In healthy individuals, the infection is self-limiting, but in patients with immunodeficiency, recurrent or persistent symptomatic infection may occur. In this case series, we present a cohort of primary immunodeficiency patients with chronic or recurrent Campylobacter enteritis from the United Kingdom and review the previously published literature. To identify relevant cases, a request was circulated via the UK Clinical Immunology mailing list, which includes 41 centers. Primary immunodeficiency (PID) cases with confirmed Campylobacter in stool or colonic tissue, by culture or PCR, and symptoms of longer than 3-month duration or 3 or more symptomatic flares, were included. Successful clearance of the infection was defined as resolution of symptoms and no recurrence for at least 3 months. In parallel, a literature review was performed to identify previously published cases in PubMed, using the terms “chronic,” “recurrent,” “Campylobacter,” “enteritis,” “diarrhoea,” “immune deficiency,” “immunodeficiency,” and “hypogammaglobulinemia.” Six centers replied, reporting 13 cases of chronic or recurrent Campylobacter enteritis in total: 4 from Queen Elizabeth Hospital (Glasgow), 3 from Southmead Hospital (Bristol), 2 from Royal London Hospital (London), 1 from Frimley Park Hospital (Surrey), 1 from Derriford Hospital (Plymouth), 1 from Northern Care National Health Service Foundation Trust (Greater Manchester), and 1 from Gloucester Royal Hospital (Gloucester). Patients were all adults, aged 21 to 71 years, with the vast majority (n = 12) having common variable immunodeficiency (CVID, Table I). Laboratory investigations at diagnosis revealed undetectable (<0.1 g/L) serum IgA in 85% (11 of 13) of cases and IgM in 62% (8 of 13). Where data were available, very low (<1 g/L) pretreatment serum IgG was seen in 67% (6 of 9) of cases. Low circulating B cells (<0.1 × 109 cells/L), natural killer cells (<0.1 × 109 cells/L), and T cells (<0.67 × 109 cells/L) were seen in 58% (7 of 12), 33% (4 of 12), and 17% (2 of 12) of cases, respectively. In patients with normal B cells and where B-cell immunophenotyping was performed, 67% (2 of 3) had low (<2%) class-switched memory B cells (Table I).Table IUK cohort with PID and recurrent or persistent Campylobacter enteritis: Immunologic profileCaseImmune deficiencyComorbiditiesDiagnostic serum immunoglobulin levels (g/L) & postvaccination responses (where data are available)Diagnostic lymphocyte subsets (×109 cells/L)Immunoglobulin replacement (at Campylobacter diagnosis)Trough immunoglobulin level (at Campylobacter diagnosis)1CVIDBronchiectasis, proliferative bronchiolitis, asthma, obesity, raised alcohol intakeUndetectable IgA & IgMB cells 0.05, normal T & NK cellsIVIg 25 g every 3 wk8 g/L2CVIDExcised brain tumor with residual learning difficulties, previous B-cell lymphoma, pulmonary nodules, splenomegalyIgG 0.8, undetectable IgA & IgMB cells <0.01, T cells 0.15, NK cells <0.01IVIg 70 g every 2 wk13.1 g/L3CVIDIntermittent low-level CMV and EBV viremiaIgG 19 (units /mL), undetectable IgA, IgM 0.11B cells 0.02 T cells 0.14, NK cells 0.01 (class- switch memory B cells 0.9%, CD21 low B cells 6%)IVIg 30 g every 3 wk6.2 g/L4CVIDNoneUndetectable IgG, IgA, & IgM with poor response to Pneumococcal polysaccharide vaccineB cells <0.01, normal T cells, NK cells 0.03SCIg 20 g every week12.1 g/L5CVID (NFKB2 mutation)Asthma, chronic rhinosinusitisIgG 3.6, undetectable IgA, IgM 0.16 with poor response to Pneumococcal polysaccharide vaccineB cells 0.01, normal T & NK cellsIVIg 40 g every 3 wk10.9 g/L6CVIDBronchiectasis, hypersplenism, ulcerative colitisUndetectable IgA & IgMNASCIg 14 g every week11 g/L7XLA (btk mutation confirmed)BronchiectasisIgG 0.73, undetectable IgA, IgM 0.29B cells <0.01, normal T & NK cellsIVIg 40 g every 3 wk10.4 g/L8CVIDNoneIgG 0.7, undetectable IgA & IgM with poor response to Pneumococcal polysaccharide vaccineNormal B, T, & NK cells (class- switch memory B cells 1%)IVIg 35 g every 3 wk7.5 g/L9CVIDBronchiectasisIgG 3.8, IgA 0.53, IgM 0.61 with poor response to Pneumococcal polysaccharide vaccineNormal B, T, & NK cellsNo (patient declined)3.8 g/L10CVIDNoneUndetectable IgA & IgMB cells 0.03, normal T cells, NK cells 0.05IVIG 30 g every 3 wkNA11CVIDInterstitial lung disease, ischemic heart diseaseUndetectable IgG, IgM, & IgA with poor response to Pneumococcal polysaccharide vaccineNormal B, T, & NK cells (class- switch memory B cells 0.6%)No (began after Campylobacter diagnosis)<1.1 g/L12CVIDBronchiectasis, chronic sinusitisIgG 0.69, undetectable IgA & IgM with poor response to Pneumococcal polysaccharide vaccineNormal B, T, & NK cellsSCIg 12 g every week11.7 g/L13CVIDLiver nodular regenerative hyperplasia, monoclonal gammopathy of undetermined significanceIgG 3.37, IgA 0.38, IgM 0.25 with poor response to Pneumococcal polysaccharide vaccineNormal B, T, & NK cells (class-switch memory B cells 6.3%)No (patient declined)3.4 g/LCMV, Cytomegalovirus; EBV, Epstein Barr virus; IVIg, intravenous immunoglobulin; NA, not available; NK, natural killer; SCIg, subcutaneous immunoglobulin.Undetectable = <0.1 g/L for IgA & IgM, <1 g/L for IgG. Open table in a new tab CMV, Cytomegalovirus; EBV, Epstein Barr virus; IVIg, intravenous immunoglobulin; NA, not available; NK, natural killer; SCIg, subcutaneous immunoglobulin. Undetectable = <0.1 g/L for IgA & IgM, <1 g/L for IgG. The total duration of gastrointestinal symptoms varied from 10 months to 17 years, and symptoms were intermittent in 6 patients (Table II). Three patients also exhibited malabsorption and/or weight loss, and 4 had systemic symptoms and/or bacteremia. In all cases, Campylobacter jejuni was isolated, with 3 patients harboring strains that were resistant to multiple antibiotics. Detection was by stool culture in most (n = 11), but 2 patients were positive only by colonic tissue culture or PCR analysis. In certain patients, other potential causes of chronic diarrhea were detected, for example, colon inflammation, duodenal villous atrophy, and chronic norovirus infection (Table II). Clinically however, Campylobacter remained the most likely cause for their symptoms, with onset and resolution of the diarrhea coinciding with Campylobacter detection (Table II).Table IIUK cohort with PID and recurrent or persistent Campylobacter enteritis: Clinical features, microbiology, and antimicrobial therapyCaseAge at symptoms onset (y), sexGastrointestinal symptoms/ malabsorption, and durationNo. of Campylobacter- positive samplesOther GI investigationsSystemic symptomsUnsuccessful antibiotic courses (temporary or no clinical improvement)Successful antibiotic course (symptoms resolution & no recurrence for >3 mo)142, MChronic diarrhea for 10 mo10× Campylobacter jejuni (MCS stool, multiresistant)Stool: calprotectin normal; negative for other bacteria, parasites, Norovirus, Enterovirus;GI endoscopy: chronic active pancolitisNoneMultiple PO clarithromycin,IV ertapenem,IV meropenemIV 1 g once a day ertapenem for 4 wk with PO neomycin for 7 d255, MIntermittent diarrhea with malabsorption and weight loss for 8 y13× C jejuni (MCS stool, multiresistant)Stool: calprotectin >600 μg/g; Norovirus+, negative for other bacteria, parasites, Enterovirus;GI endoscopies: chronic villous atrophy in duodenum, widespread focal active colitisEpisodes of arthralgia, headache and fever but negative blood MCS for Clostridium difficilePO doxycycline, clarithromycin, azithromycin, ciprofloxacin,cotrimoxazoleIV 1 g once a day ertapenem for 4 wk with PO neomycin for 7 d353, MIntermittent diarrhea for 17 y3× C jejuni (MCS stool)Stool: Norovirus+ negative for other bacteria, parasites;GI endoscopies: antral gastritis, increased intraepithelial lymphocytes and substantial villous atrophy in duodenum, mild active chronic inflammation without granulomata in colonNone (blood MCS not tested)PO coamoxiclav, neomycin, rifaximin, immunoglobulin; IV meropenem, ertapenem(spontaneous resolution)460, MChronic diarrhea with malabsorption and weight /protein loss3× C jejuni (PCR & MCS stool, multiresistant)Stool: negative for other bacteria, parasites, Norovirus, Enterovirus, Adenovirus, Astrovirus, Rotavirus, Sapovirus;GI endoscopies: nil significantSeveral episodes of bacteremia (MCS confirmed)PO azithromycin; IV carbapenem, aminoglycoside, chloramphenicolIV meropenem & aminoglycoside, PO ciprofloxacin532, FChronic diarrhea for 2 y4× C jejuni (PCR & MCS stool)Stool: calprotectin 116 μg/g; Norovirus+, Helicobacter pylori+Negative for other bacteria, parasites, Enterovirus, Adenovirus, Astrovirus, Rotavirus, SapovirusNone (blood MCS not tested)NonePO azithromycin 500 mg once a day with ciprofloxacin 500 mg twice a day for 3 wk654, MChronic diarrhea for 10 mo3× C jejuni (2× MCS & 1× PCR stool)Stool: negative for other bacteria, parasitesNonePO erythromycin, azithromycin, coamoxiclav(ongoing infection)724, MIntermittent diarrhea for 3 y>10× C jejuni (MCS stool)Stool: H pylori+, calprotectin 500 μg/g; negative for other bacteria, parasites, Norovirus, Adenovirus, Astrovirus, Rotavirus, Sapovirus;GI endoscopy: colon cryptitis with crypt abscessesEpisode of suspected bacteremia (blood MCS not tested)PO ciprofloxacin, azithromycinIV meropenem for 10 d829, MIntermittent diarrhea for 12 y2× C jejuni (MCS stool)NoneNone (blood MCS not tested)NonePO clarithromycin926, FChronic diarrhea for 6 mo with weight loss1× C jejuni (MCS colonic tissue)Stool: calprotectin 907 μg/g; negative for other bacteria, parasites;GI endoscopy: severe inflammation in lamina propria with cryptitis, crypt abscess formation and prominent lymphoid follicles in right & transverse colon, mild chronic inflammatory infiltrate in left colon, negative CMV stainsFevers but negative blood MCS for C difficilePO ciprofloxacinPO azithromycin 500 mg once a day for 2 wk1060, MIntermittent diarrhea for 15 y with weight loss5× C jejuni (MCS stool)NoneNone (blood MCS not tested)NonePO erythromycin 500 mg 4 times a day for 2 wk1171, MIntermittent diarrhea for 8 y3× C jejuni (MCS stool)Stool: negative for other bacteria, parasites, Norovirus, Adenovirus, Astrovirus, Rotavirus, Sapovirus;GI endoscopy: normal colonNone (blood MCS not tested)PO clarithromycin 500 mg twice a day for 2 wk(patient passed away)1248, FIntermittent diarrhea for 4 y4× C jejuni (MCS stool)Stool: calprotectin >600 μg/g; negative for other bacteria, parasites, Norovirus, Adenovirus, Astrovirus, Rotavirus, SapovirusNone (blood MCS not tested)PO ciprofloxacin 500 mg twice a day for 2 wk, clarithromycin 3 d (not tolerated)PO ciprofloxacin 500 mg twice a day for 2 wk1355, FIntermittent diarrhea for 8 y2× C jejuni (MCS stool)Stool: negative for other bacteria, parasites, Norovirus, Adenovirus, Astrovirus, Rotavirus, Sapovirus;GI endoscopy: focal mild acute inflammation in cecumNone (blood MCS not tested)NonePO clarithromycin 500 mg twice a day for 1 wkF, female; GI, gastrointestinal; IV, intravenous; M, male; MCS, microscopy, culture & sensitivities, includes screen for Salmonella, Shigella, Giardia, Escherichia coli O157, Cryptosporidium, Giardia; PO, per os (by mouth); PCR, polymerase chain reaction. Open table in a new tab F, female; GI, gastrointestinal; IV, intravenous; M, male; MCS, microscopy, culture & sensitivities, includes screen for Salmonella, Shigella, Giardia, Escherichia coli O157, Cryptosporidium, Giardia; PO, per os (by mouth); PCR, polymerase chain reaction. Fifty-eight percent (7 of 12) of patients were on adequate immunoglobulin replacement (serum IgG trough ≥ 8 g/L) when they developed enteritis (Table I). In patients who successfully cleared the infection and had no relapse, oral macrolides (n = 5, azithromycin, clarithromycin, or erythromycin) and intravenous carbapenems (n = 4, meropenem or ertapenem) were most commonly used, followed by aminoglycosides (n = 3, eg, neomycin), oral ciprofloxacin (n = 3), and coamoxiclav (n = 1), either alone or in combination. A literature review identified 32 published cases of recurrent or persistent Campylobacter enteritis or multiple Campylobacter spp. stool isolation in PID (see Table E1 in this article’s Online Repository at www.jaci-inpractice.org). Most were in X-linked agammaglobulinemia (XLA, n = 17), whereas 5 were in CVID and 3 in Good syndrome. Based on their diagnosis, very low or absent circulating B cells were expected to be present in at least 69% (22 of 32) of these cases, 18 with agammaglobulinemia and 3 with Good syndrome. The total duration of symptoms varied from 3 months to 15 years and resulted in weight loss in 7 of 32 (22%) cases. Sixty-six percent (21 of 32) also developed Campylobacter bacteremia, in some cases recurrent. Most stool cultures revealed C jejuni (n = 25), with Campylobacter coli being isolated in 6 cases and 1 patient harboring both. At least 20 of 32 (63%) patients were on immunoglobulin replacement when they developed enteritis, and these cases were more likely to clear the infection (80% vs 58% those who were not). The institution of immunoglobulin therapy alone led to resolution of the infection in 3 of 32 (9%) patients.1Schønheyder H.C. Søgaard P. Frederiksen W. A survey of Campylobacter bacteremia in three Danish counties, 1989 to 1994.Scand J Infect Dis. 1995; 27: 145-148Crossref PubMed Scopus (0) Google Scholar,2Borleffs J.C.C. Schellekens J.F. Brouwer E. Rozenberg-Arska M. Use of an immunoglobulin M containing preparation for treatment of two hypogammaglobulinemic patients with persistent Campylobacter jejuni infection.Eur J Clin Microbiol Infect Dis. 1993; 12: 772-775Crossref PubMed Scopus (0) Google Scholar In those patients who successfully cleared the infection, oral macrolides were most commonly used (n = 10; erythromycin, clarithromycin, or azithromycin), followed by aminoglycosides (n = 5; neomycin, gentamicin, netilmicin, or kanamycin), carbapenems (n = 5; meropenem, biapenem, or imipenem), tetracyclines (n = 4; doxycycline or minocycline), metronidazole (n = 3), fosfomycin (n = 2), ciprofloxacin (n = 1), and piperacillin (n = 1). Antibiotics were administered for a duration of 4 or more weeks in 7 of 32 (22%) cases. Overall, recurrent or persistent Campylobacter enteritis may contribute to significant morbidity in patients with PID, including debilitating diarrhea, malabsorption, weight loss, electrolyte disturbances, and bacteremia. A high index of suspicion for Campylobacter infection should be kept in these patients, particularly in those who have previously tested positive. Campylobacter can persist in the intestinal tract only giving intermittent symptoms and reinfection is commonly by the same microorganism.3Okada H. Kitazawa T. Harada S. Itoyama S. Hatakeyama S. Ota Y. et al.Combined treatment with oral kanamycin and parenteral antibiotics for a case of persistent bacteremia and intestinal carriage with Campylobacter coli.Intern Med. 2008; 47: 1363-1366Crossref Scopus (16) Google Scholar Furthermore, Campylobacter is difficult to grow even in specific culture media, and there are no validated consensus mechanisms to measure the bioburden in the gut flora, let alone eradication.4Buss J.E. Cresse M. Doyle S. Buchan B.W. Craft D.W. Young S. Campylobacter culture fails to correctly detect Campylobacter in 30% of positive patient stool specimens compared to non-cultural methods.Eur J Clin Microbiol Infect Dis. 2019; 38: 1087Crossref Scopus (25) Google Scholar Colonic tissue culture or stool PCR may thus be necessary in patients with ongoing symptoms.4Buss J.E. Cresse M. Doyle S. Buchan B.W. Craft D.W. Young S. Campylobacter culture fails to correctly detect Campylobacter in 30% of positive patient stool specimens compared to non-cultural methods.Eur J Clin Microbiol Infect Dis. 2019; 38: 1087Crossref Scopus (25) Google Scholar Other causes of chronic diarrhea should also be considered in these patients, particularly in those who remain symptomatic despite Campylobacter eradication. Most cases in our series were patients with CVID (12 of 13), in contrast to previously published cases where XLA was the most frequent diagnosis (17 of 32). This may echo improvements in patient management, with more patients being treated with adequate immunoglobulin replacement in recent years. The fact that fewer patients were suspected to be bacteremic in our cohort compared with previously published literature (31% vs 66%) also suggests the latter. The cases described above highlight the importance of humoral immunity in the prevention of chronicity or reinfection from Campylobacter spp. Previously published case reports suggest that patients who are on immunoglobulin therapy are more likely to clear the infection and immunoglobulin therapy alone led to eradication in a few cases. Most patients in our case series also had undetectable or very low diagnostic immunoglobulin levels. It is well established that most patients with CVID and XLA lack plasma cells in the lamina propria of their small and/or large intestine and this is important because the intestinal mucosa normally harbors the largest population of antibody-secreting plasma cells in the body.5Khan F. Person H. Dekio F. Ogawa M. Ho Hen Dunkin D. et al.Crohn’s-like enteritis in X-linked agammaglobulinemia: a case series and systematic review.J Allergy Clin Immunol Pract. 2021; 9: 3466-3478Abstract Full Text Full Text PDF Scopus (0) Google Scholar Interestingly, 58% of patients in our case series also had low or absent circulating B cells. This contrasts with what is known for CVID, where only 10% to 20% are expected to have low B cells.6Selenius J.S. Martelius T. Pikkarainen S. Siitonen S. Mattila E. Pietikäinen R. et al.Unexpectedly high prevalence of common variable immunodeficiency in Finland.Front Immunol. 2017; 8: 1190Crossref PubMed Scopus (39) Google Scholar This finding was echoed by the literature review, where 69% of patients were expected to have very low or absent circulating B cells based on their diagnosis. Low circulating B cells also seem to play an important role in the predisposition to other chronic gastrointestinal infections, like norovirus.7Grammatikos A. Moghaddas F. Reeve H. Johnston S. Gompels M. Albur M. Low circulating B cells in immunocompromised individuals are linked to poorer antibody responses to vaccines and a predisposition to viral infections.J Allergy Clin Immunol Global. 2023; 2: 111-113Abstract Full Text Full Text PDF Google Scholar Finally, 42% of patients in our case series had inadequate serum immunoglobulin trough levels when diagnosed with Campylobacter enteritis. These observations suggest that patients with CVID who are not maintained on adequate immunoglobulin replacement are at a higher risk of infection. In patients with CVID and low B cells in particular, higher IgG therapeutic targets may need to be considered. HIV-infected patients can also develop chronic or recurrent Campylobacter enteritis,8Molina J.M. Casin I. Hausfater P. Giretti E. Welker Y. Decazes J.M. et al.Campylobacter infections in HIV-infected patients: clinical and bacteriological features.AIDS. 1995; 9: 881-885Crossref PubMed Google Scholar but even in these patients, humoral immunity seems to play a key role: HIV patients who fail to clear the infection have poor Campylobacter-specific antibody responses while low CD4 T-cell levels do not seem to correlate with a worse outcome.9Perlman D.M. Ampel N.M. Schifman R.B. Cohn D.L. Patton C.M. Aguirre M.L. et al.Persistent Campylobacter jejuni infections in patients infected with the human immunodeficiency virus (HIV).Ann Intern Med. 1988; 108: 540-546Crossref PubMed Google Scholar In conclusion, Campylobacter enteritis is an important diagnosis to consider in patients with PID with chronic or recurrent diarrhea, particularly in those with very low diagnostic immunoglobulin levels. Diarrhea in CVID can be highly multifaceted and other potential causes should always be considered. We thank the patients for their collaboration and participation and the respective departments of the authors for supporting this study. Table E1Previously published cases of chronic/recurrent Campylobacter enteritis or Campylobacter spp. stool isolation in PIDLead author, year of publicationAge of onset (y), sexImmune deficiencyImmunoglobulin replacementSymptomsNo. of Campylobacter+ stool samplesFailed treatments (temporary or no clinical improvement)Definitive treatment (resulting in symptom resolution)Aguilar-Company et al,E1Aguilar-Company J. Los-Arcos I. Pigrau C. Rodríguez-Pardo D. Larrosa M.N. Rodríguez-Garrido V. et al.Potential use of fosfomycin-tromethamine for treatment of recurrent campylobacter species enteritis.Antimicrob Agents Chemother. 2016; 60: 4398-4400Crossref PubMed Scopus (9) Google Scholar 201664, FCVIDIVIg every 3 wkDiarrhea and hypovolemic shock1× Campylobacter jejuni, 1× Campylobacter coliNRPO fosfomycin 3 g every 48 h for 6 wkBarker et al,E2Barker C.R. Painset A. Swift C. Jenkins C. Godbole G. Maiden M.C.J. et al.Microevolution of Campylobacter jejuni during long-term infection in an immunocompromised host.Sci Rep. 2020; 1010109Crossref Scopus (11) Google Scholar 2020NRCVIDNRIntermittent diarrhea for 15 y25× C jejuniNRNRMerrick et al,E3Merrick B. Tamilarasan A.G. Luber R. Yong P.F.K. Cheent K. Irving P.M. et al.Recurrent Campylobacter jejuni infection in an immunodeficient patient treated with repeated faecal microbiota transplant (FMT)-A case report.Infect Dis Rep. 2022; 14: 56-62Crossref Scopus (0) Google Scholar 202270, FCVIDIVIg 20 g every 2 wkIntermittent diarrhea for 6 y, episode of bacteremia6× C jejuniPO clarithromycin, erythromycin, fosfomycin;IV meropenem; fecal microbiota transplantNRWard et al,E4Ward T.T. Klein K. Borthistle B.K. Jejunal infection with Campylobacter.Arch Intern Med. 1984; 144: 1072-1074Crossref PubMed Google Scholar 198442, MCVIDNRIntermittent diarrhea, malabsorption, weight loss for 7 mo3× C jejuniPO chloramphenicol, erythromycinIV metronidazole 2 g/d and neomycin 1 g/dLebar et al,E5Le Bar W.D. Menard R.R. Check F.E. Hypogammaglobulinemia and recurrent Campylobacter jejuni infection.J Infect Dis. 1985; 152: 1099-1100Crossref Scopus (18) Google Scholar 198539, FCVIDNoneIntermittent diarrhea, vomiting, and 2 episodes of bacteremia for 8 mo2× C jejuniNRIV gentamicin 70 mg for a week;PO erythromycin 500 mg 4 times a day for 2 wkLebar et al,E5Le Bar W.D. Menard R.R. Check F.E. Hypogammaglobulinemia and recurrent Campylobacter jejuni infection.J Infect Dis. 1985; 152: 1099-1100Crossref Scopus (18) Google Scholar 198524, MXLANoneIntermittent diarrhea, vomiting, and 4 episodes of bacteremia for 8 mo4× C jejuniIV tobramycinNRVan de Bruele et al,E6Van den Bruele T. Mourad-Baars P.E.C. Claas E.C.J. van der Plas R.N. Kuijper E.J. Bredius R.G.M. Campylobacter jejuni bacteremia and Helicobacter pylori in a patient with X-linked agammaglobulinemia.Eur J Clin Microbiol Infect Dis. 2010; 29: 1315-1319Crossref PubMed Scopus (0) Google Scholar 201015, MXLAIVIg every 4 wkDiarrhea, weight loss, and 2 episodes of bacteremia for 18 mo2× C jejuniPO erythromycin;IV meropenemPO doxycycline for 4 wk and azithromycin for 2 wkVan der Meer et al,E7Van der Meer J.W.M. Mouton R.P. Daha M.R. Schuurman R.K.B. Campylobacter jejuni bacteraemia as a cause of recurrent fever in a patient with hypogammaglobulinaemia.J Infect. 1986; 12: 235-239Abstract Full Text PDF PubMed Google Scholar 198624, MXLANRDiarrhea, fever4× C jejuniPO cotrimoxazole, neomycin, doxycycline;IV gentamicinNRSchonheyder et al,E8Schønheyder H.C. Søgaard P. Frederiksen W. A survey of Campylobacter bacteremia in three Danish counties, 1989 to 1994.Scand J Infect Dis. 1995; 27: 145-148Crossref PubMed Scopus (0) Google Scholar 199523, MXLANRWeight loss and 2 episodes of bacteremia for 4 wk1× C coliPenicillinIV netilmicin for 10 d and IVIgTokuda et al,E9Tokuda K. Nishi J. Miyanohara H. Sarantuya J. Iwashita M. Kamenosono A. et al.Relapsing cellulitis associated with Campylobacter coli bacteremia in an agammaglobulinemic patient.Pediatr Infect Dis J. 2004; 23: 577-579Crossref PubMed Scopus (23) Google Scholar 200422, MXLAIVIg every 3 wk2 episodes of bacteremia in 5 mo2× C coliPO clarithromycin;IV ceftazidime, cefazolin, amikacin, panipenem/ betamipronPO kanamycin 750 mg 4 times a dayChusid et al,E10Chusid M.J. Coleman C.M. Dunne W.M. Chronic asymptomatic Campylobacter bacteremia in a boy with X-linked hypogammaglobulinemia.Pediatr Infect Dis J. 1987; 6: 943-944Crossref PubMed Google Scholar 198711, MXLAIVIg every 4 wkBacteremia for 6 wk>3× C coliNRPO erythromycin; IV erythromycin, gentamicin, piperacillinHagiya et al,E11Hagiya H. Kimura K. Nishi I. Yoshida H. Yamamoto N. Akeda Y. et al.Emergence of carbapenem non-susceptible campylobacter coli after long-term treatment against recurrent bacteremia in a patient with X-linked agammaglobulinemia.Intern Med. 2018; 57: 2077-2080Crossref Scopus (12) Google Scholar 201837, MXLAIVIg every 3 wk3 episodes of bacteremia in 12 mo1× C coliPO tebipenem;IV cefazolin, meropenemIV biapenem 600 mg twice a day;PO minocycline 100 mg twice a day for 2 wk, metronidazole 250 mg 4 times a day for 4 wkAriganello et al,E12Ariganello P. Angelino G. Scarselli A. Salfa I. della Corte M. de Matteis A. et al.Relapsing Campylobacter jejuni systemic infections in a child with X-Linked agammaglobulinemia.Case Rep Pediatr. 2013; 2013: 1-3Crossref Google Scholar 201311, MXLAIVIg every 4 wkIntermittent diarrhea, and 2 episodes of bacteremia for 12 mo1× C jejuniPO ciprofloxacin;IV ceftriaxone, vancomycinIV meropenem, clarithromycinRafi et al,E13Rafi A. Matz J. An unusual case of Campylobacter jejuni pericarditis in a patient with X-linked agammaglobulinemia.Ann Allergy Asthma Immunol. 2002; 89: 362-367Abstract Full Text PDF PubMed Google Scholar2002NRXLAIVIg every 4 wk2 episodes of bacteremia in 2 y1× C jejuniIV erythromycin, ceftazidimeNRBorleffs et al,E14Borleffs J.C.C. Schellekens J.F. Brouwer E. Rozenberg-Arska M. Use of an immunoglobulin M containing preparation for treatment of two hypogammaglobulinemic patients with persistent Campylobacter jejuni infection.Eur J Clin Microbiol Infect Dis. 1993; 12: 772-775Crossref PubMed Scopus (0) Google Scholar 199323, MXLAIVIg every 3 wk2 episodes of bacteremia in 6 mo2× C jejuniPO ciprofloxacin;IV imipenemIV pentaglobin 500 mL every 3 wkBorleffs et al,E14Borleffs J.C.C. Schellekens J.F. Brouwer E. Rozenberg-Arska M. Use of an immunoglobulin M containing preparation for treatment of two hypogammaglobulinemic patients with persistent Campylobacter jejuni infection.Eur J Clin Microbiol Infect Dis. 1993; 12: 772-775Crossref PubMed Scopus (0) Google Scholar 199325, MXLAIVIg every 3 wk3 episodes of bacteremia in 6 mo3× C jejuniPO ciprofloxacin;IV imipenem, erythromycinIV pentaglobin 500 mL every 3 wkKim et al,E15Kim Y. Shin J.A. Han S.B. Cho B. Jeong D.C. Kang J.H. et al.Recurrent Campylobacter jejuni bacteremia in a patient with hypogammaglobulinemia: A case report.Medicine. 2017; 96e7238Google Scholar 201718, MXLA (suspected)IVIg every 3 wkIntermittent diarrhea, and 4 episodes of bacteremia for 18 mo2× C jejuniPO amoxicillin/ clavulanate, roxithromycin, clarithromycin, doxycycline;IV cefazolin, meropenem, amikacinNRAutenrieth et al,E16Autenrieth I.B. Schuster V. Ewald J. Harmsen D. Kreth H.W. An unusual case of refractory Campylobacter jejuni infection in a patient with X-linked agammaglobulinemia: successful combined therapy with maternal plasma and ciprofloxacin.Clin Infect Dis. 1996; 23: 526-531Crossref PubMed Google Scholar 19967, MXLAIVIg every 4 wkIntermittent diarrhea, and 4 episodes of bacteremia for 18 moSeveral C jejuniIV amoxicillin, doxycycline, imipenem, pentaglobin;PO bovine colostrumPO ciprofloxacin 250 mg twice a day for 3 wk;IV maternal plasma for 5 wkArai et al,E17Arai A. Kitano A. Sawabe E. Kanegane H. Miyawaki T. Miura O. Relapsing Campylobacter coli bacteremia with reactive arthritis in a patient with X-linked agammaglobulinemia.Intern Med. 2007; 46: 605-609Crossref Scopus (22) Google Scholar 200735, MXLAIVIg every 4 wk4 episodes of bacteremia in 18 mo2× C coliIV cefepimeIV meropenem;PO minocyclineVan der Meer et al,E7Van der Meer J.W.M. Mouton R.P. Daha M.R. Schuurman R.K.B. Campylobacter jejuni bacteraemia as a cause of recurrent fever in a patient with hypogammaglobulinaemia.J Infect. 1986; 12: 235-239Abstract Full Text PDF PubMed Google Scholar 198624, MXLAIVIgIntermittent diarrhea, and 5 episodes of bacteremia for >1 y2× C jejuniPO cotrimoxazole, neomycin, doxycycline;IM gentamicinNRKerstens et al,E18Kerstens P.J.S.M. Endtz H.P. Meis J.F.G.M. Oyen W.J.G. Koopman R.J.I. van den Broek P.J. et al.Erysipelas-like skin lesions associated with Campylobacter jejuni septicemia in patients with hypogammaglobulinemia.Eur J Clin Microbiol Infect Dis. 1992; 11: 842-847Crossref PubMed Scopus (0) Google Scholar 199224, MXLASCIgIntermittent diarrhea, and 3 episodes of bacteremia for 5 y3× C jejuniPO erythromycin, amoxicillin, flucloxacillinIV imipenem 500 mg 4 times a day for 6 wkKerstens et al,E18Kerstens P.J.S.M. Endtz H.P. Meis J.F.G.M. Oyen W.J.G. Koopman R.J.I. van den Broek P.J. et al.Erysipelas-like skin lesions associated with Campylobacter jejuni septicemia in patients with hypogammaglobulinemia.Eur J Clin Microbiol Infect Dis. 1992; 11: 842-847Crossref PubMed Scopus (0) Google Scholar 199226, MXLASCIg2 episodes of bacteremia in 2 wk2× C jejuniPO erythromycin;IV amoxicillin, flucloxacillin, gentamicinIV imipenem 500 mg 4 times a day for 2 wkPines et al,E19Pines A. Goldhammer E. Bregman J. Kaplinsky N. Frankl O. Campylobacter enteritis associated with recurrent abortions in agammaglobulinemia.Acta Obstet Gynecol Scand. 1983; 62: 279-280Crossref PubMed Google Scholar 198328, FAgammaglobulinemiaIVIgDiarrhea, weight loss, for 3 mo2× C jejuniPO cotrimoxazolePO erythromycin 1 g thrice a day and metronidazole 500 mg 4 times a dayAguilar-Company et al,E1Aguilar-Company J. Los-Arcos I. Pigrau C. Rodríguez-Pardo D. Larrosa M.N. Rodríguez-Garrido V. et al.Potential use of fosfomycin-tromethamine for treatment of recurrent campylobacter species enteritis.Antimicrob Agents Chemother. 2016; 60: 4398-4400Crossref PubMed Scopus (9) Google Scholar 201683, FGood syndromeIVIg every 2 wkIntermittent diarrhea for 6 mo1× C coliPO amoxicillin /clavulanatePO fosfomycin 3 g every 48 h for 4 wkTarr et al,E20Tarr P.E. Sneller M.C. Mechanic L.J. Economides A. Eger C.M. Strober W. et al.Infections in patients with immunodeficiency with thymoma (Good syndrome). Report of 5 cases and review of the literature.Medicine. 2001; 80: 123-133Crossref PubMed Scopus (0) Google Scholar 200157, MGood syndromeIVIg every 4 wkIntermittent diarrhea with episodes of bacteremia for 7 mo3× C jejuniNRAntibiotics (not specified)Green et al,E21Green E.S. Parker N.E. Gellert A.R. Beck E.R. Campylobacter infection mimicking Crohn’s disease in an immuno-deficient patient.Br Med J (Clin Res Ed). 1984; 289: 159Crossref PubMed Google Scholar 198451, MGood syndromeNRChronic diarrhea and weight loss for 4 mo1× C jejuniNRPO erythromycin 500 mg twice a day for a weekLever et al,E22Lever A.M.L. Dolby J.M. Webster A.D.B. Chronic campylobacter colitis and uveitis in patient with hypogammaglobulinaemia.Br Med J (Clin Res Ed). 1984; 288: 531Crossref PubMed Google Scholar 198436, FHypogammaglobulinemiaIVIg every 2 wkIntermittent diarrhea with weight loss for 6 y5× C jejuniPO erythromycin, tetracyclineIV erythromycin 600 mg thrice a day for 2 wk followed by PO 500 mg 4 times a day for 2 wkJohnson et al,E23Johnson R.J. Nolan C. Wang S.P. Shelton W.R. Blaser M.J. Persistent Campylobacter jejuni infection in an immunocompromised patient.Ann Intern Med. 1984; 100: 832-834Crossref PubMed Google Scholar 198426, FHypogammaglobulinemiaNoneIntermittent diarrhea and 4 episodes of bacteremia for 12 mo6× C jejuniPO amoxicillin, gentamicin, erythromycin;IV amoxicillin, gentamicin, tobramycin, amikacinPO doxycycline 100 mg once a day for monthsMoore et al,E24Moore J. Curran M. Wareing D. Fox A. Boyd N. Glynn G. et al.Investigation of infection with Campylobacter jejuni in a man with hypogammaglobulinaemia using PCR-single-strandedconformational polymorphism (PCR-SSCP) typing.Int J Med Microbiol. 2001; 291: 21-25Crossref Scopus (6) Google Scholar 2001NR, MHypogammaglobulinemiaNRIntermittent diarrhea and 4 episodes of bacteremia for 2 y2× C jejuniNRNRAhnen et al,E25Ahnen D.J. Brown W.R. Campylobacter enteritis in immune-deficient patients.Ann Intern Med. 1982; 96: 187-188Crossref PubMed Google Scholar 198263, MHypogammaglobulinemiaNRIntermittent diarrhea for 2 y4× C jejuniPO erythromycinPO erythromycinAhnen et al,E25Ahnen D.J. Brown W.R. Campylobacter enteritis in immune-deficient patients.Ann Intern Med. 1982; 96: 187-188Crossref PubMed Google Scholar 198239, FHypogammaglobulinemiaNRIntermittent diarrhea for 25 y2× C jejuniPO erythromycinNRPonka et al,E26Pönkä A. Tilvis R. Kosunen T.U. Prolonged campylobacter gastroenteritis in a patient with hypogammaglobulinaemia.Acta Med Scand. 1983; 213: 159-160Crossref PubMed Google Scholar 198367, FHypogammaglobulinemiaNRDiarrhea and weight loss for 4 mo2× C jejuniPO erythromycinPO erythromycin 250 mg 4 times a day for 3 wkF, female; IM, intramuscular; IV, intravenous; IVIg, intravenous immunoglobulin; M, male; NR, not reported; PO, per os (by mouth); SCIg, subcutaneous immunoglobulin. Open table in a new tab F, female; IM, intramuscular; IV, intravenous; IVIg, intravenous immunoglobulin; M, male; NR, not reported; PO, per os (by mouth); SCIg, subcutaneous immunoglobulin.

A scoping review examining the association of housing quality and psychosocial well-being following homelessness: an ecological systems perspective

ABSTRACT Housing quality (HQ) has been previously associated with health and quality of life. Although HQ is an important factor in preventing homelessness, little is known about the range and breadth of this body of literature. To identify existing studies, we conducted a scoping review guided by the question: “in what ways has housing quality been associated with psychosocial well-being following homelessness in existing peer-reviewed literature?” using the framework proposed by Arksey & O'Malley and PRISMA-ScR guidelines. Our search was deployed in eight databases. A total of 713 titles and abstracts were screened following the removal of duplicates, and 32 articles were included in narrative synthesis. Six themes emerged from our data analysis of included articles: 1) quality of housing affecting well-being; 2) feeling forced to live in unsafe and poor-quality housing due to no other options; 3) HQ mediated by housing first; 4) determinants of HQ; 5) standardized measures of HQ; and 6) HQ is de-emphasized in research and practice following homelessness. Our findings demonstrate that HQ is associated with psychosocial well-being at micro, meso, exo, and macro systems levels for persons experiencing homelessness. We argue addressing HQ following homelessness is a key homelessness prevention strategy.

The Case Files

Figure 1.: ECG from the patient's first ED visit.FigureFigureOne ECG was normal; another showed a short PR interval and delta waves A 17-year-old girl with a history of mitral valve prolapse presented following an episode of palpitations and lightheadedness. The episode began during exercise but persisted while at rest. She had no fever, cough, congestion, or upper respiratory symptoms. She used oral contraceptives, but had no other known risk factors for venous thromboembolism. Her family had no history of sudden cardiac death. The patient had had an echocardiogram two months earlier that demonstrated mitral valve prolapse with mild mitral valve regurgitation. She had visited a pediatric cardiologist a month before for dyspnea on exertion and received an albuterol inhaler for presumed reactive airway disease. The patient's initial vitals were stable, and she had a regular rate and rhythm. Her initial ECG showed normal sinus rhythm without abnormal ST segments, T-waves, intervals, or conduction. (Figure 1.) Troponin, D-dimer, CBC, bedside ultrasound, and chest x-ray were all normal. She was discharged with a plan for outpatient cardiac monitoring. She returned to the ED five days later with similar symptoms that began during a basketball game. She had acute onset palpitations and felt she was about to faint. Her mother said it looked like she was turning blue, and she pulled her daughter from the game and brought her to the ED. The patient reported feeling somewhat better en route and nearly normal on arrival. Her vitals were again stable, and she had a regular rate and rhythm. Troponin and bedside ultrasound were again reassuring. A new ECG showed a change in the QRS morphology, a short PR interval, and delta waves concerning for Wolff-Parkinson-White (WPW) syndrome. (Figure 2.) This caused confusion because the previous ECG was unremarkable. Another ECG was ordered (the third overall and the second for the visit). It appeared similar to the first ECG from the original ED visit, though with a flipped T-wave in V3. (Figure 3.) The short PR interval and the delta waves had disappeared as well. This led to further diagnostic confusion.Figure 2.: Initial ECG from the patient's second ED visit.A pediatric cardiologist presumptively diagnosed intermittent WPW syndrome. The patient was cautioned against exertion and sports until seen by cardiology, and she was discharged with plans for expedited Holter monitoring and cardiology clinic follow-up. Her Holter monitor study demonstrated SVT with intermittent pre-excitation findings consistent with WPW syndrome, a pre-excitation condition where the bundle of Kent directly connects the atria and ventricles, bypassing AV nodal and His-Purkinje conduction regulation. This unregulated electrical impulse can lead to potentially lethal arrhythmias. The ECG of WPW syndrome classically includes a shortened PR interval less than 120 milliseconds, a slurred upstroke of the QRS complex (delta wave), and a QRS greater than 100 milliseconds. (Life in the Fast Lane. Feb. 2, 2022; https://bit.ly/3Pd5vvH.)Figure 3.: Second ECG from the patient's second ED visit.Common in Children WPW is one of the most common causes of tachyarrhythmias and symptomatic tachycardia in children. The diagnosis can be made when cardiac arrhythmias secondary to the accessory pathway are demonstrated on an ECG. (Heart. 2000;84[6]:625; https://bit.ly/3oX3bOr.) It is one of the most common pre-excitation disorder ECG findings with an incidence of 0.1 to 0.3 percent. (Ann Intern Med. 1992;116[6]:456.) One study of 432,166 children showed the prevalence of WPW syndrome was 0.07 percent. (J Pediatr. 2008;152[1]:85.) Atrioventricular reentrant tachycardia (AVRT) comprises the majority of tachyarrhythmias in WPW syndrome. Orthodromic AVRT accounts for up to 95 percent of reentrant tachycardias in WPW patients. (J Med Cases. 2018;9[2]54; https://bit.ly/3qCQbxZ; Clinical Cardiac Electrophysiology: Techniques and Interpretations. 4th ed., Philadelphia: Lippincott Williams & Wilkins; 2008; p. 339.) The incidence of sudden cardiac death in WPW patients is low, however. One meta-analysis of 20 studies including 1869 patients estimated its risk at 0.13 percent per year. (Circulation. 2012;125[19]:2308; https://bit.ly/45Vwj9r.) The WPW pattern on ECG can be intermittent and even disappear permanently over time. Multiple cohort studies illustrate the frequency of intermittent pre-excitation ranges between 10 and 40 percent. (Circulation. 1993;87[3]:866; https://bit.ly/3Nq9kfG; Pacing Clin Electrophysiol. 2013;36[9]:1117; https://bit.ly/3J8uT1y; Pacing Clin Electrophysiol. 2016;39[1]:14; https://bit.ly/3NpmXeQ.) One study of children with a confirmed WPW pattern showed 13 percent were noted to have intermittent pre-excitation. Another study illustrated that 39 percent of children with a documented WPW pattern had intermittent pre-excitation, and another 10 percent lost pre-excitation on ambulatory monitoring or exercise testing. It's important to be aware that the WPW ECG pattern can come and go. A patient may have a reassuring workup and normal-appearing ECG and still have it. Referral for outpatient cardiac monitoring is key. EPs should ensure close follow-up and consult cardiology when the history is suggestive of WPW. The patient in this case was taken to the electrophysiology suite the following month for a successful ablation of her accessory pathway. She has remained asymptomatic since and has returned to sports.

Pregnant Prisoners in Shackles

Photo by niu niu on Unsplash ABSTRACT Shackling prisoners has been implemented as standard procedure when transporting prisoners in labor and during childbirth. This procedure ensures the protection of both the public and healthcare workers. However, the act of shackling pregnant prisoners violates the principles of ethics that physicians are supposed to uphold. This paper will explore how shackling pregnant prisoners violates the principle of justice and beneficence, making the practice unethical. INTRODUCTION Some states allow shackling of incarcerated pregnant women during transport and while in the hospital for labor and delivery. Currently, only 22 states have legislation prohibiting the shackling of pregnant women.[1] Although many states have anti-shackling laws prohibiting restraints, these laws also contain an “extraordinary circumstances” loophole.[2] Under this exception, officers shackle prisoners if they pose a flight risk, have any history of violence, and are a threat to themselves or others.[3] Determining as to whether a prisoner is shackled is left solely to the correctional officer.[4] Yet even state restrictions on shackling are often disregarded. In shackling pregnant prisoners during childbirth, officers and institutions are interfering with the ability of incarcerated women to have safe childbirth experiences and fair treatment. Moreover, physicians cannot exercise various ethical duties as the law constrains them. In this article, I will discuss the physical and mental harms that result from the use of restraints under the backdrop of slavery and discrimination against women of color particularly. I argue that stereotypes feed into the phenomenon of shackling pregnant women, especially pregnant women of color. I further assert that shackling makes it difficult for medical professionals to be beneficent and promote justice. BACKGROUND Female incarceration rates in the United States have been fast growing since the 1980s.[5] With a 498 percent increase in the female incarceration population between 1981  and 2021, the rates of pregnancy and childbirth by incarcerated people have also climbed.[6],[7] In 2021, over 1.2 million women were incarcerated in the United States.[8] An estimated 55,000 pregnant women are admitted to jails each year.[9],[10] Many remain incarcerated throughout pregnancy and are transported to a hospital for labor and delivery. Although the exact number of restrained pregnant inmates is unclear, a study found that 83 percent of hospital prenatal nurses reported that their incarcerated patients were shackled.[11] I.     Harms Caused by Shackling Shackling has caused many instances of physical and psychological harm. In the period before childbirth, shackled pregnant women are at high risk for falling.[12] The restraints shift pregnant women’s center of gravity, and wrist restraints prevent them from breaking a fall, increasing the risk of falling on their stomach and harming the fetus.[13] Another aspect inhibited by using restraints is testing and treating pregnancy complications. Delays in identifying and treating conditions such as hypertension, pre-eclampsia, appendicitis, kidney infection, preterm labor, and especially vaginal bleeding can threaten the lives of the mother and the fetus.[14] During labor and delivery, shackling prevents methods of alleviating severe labor pains and giving birth.[15] Usually, physicians recommend that women in labor walk or assume various positions to relieve labor pains and accelerate labor.[16] However, shackling prevents both solutions.[17] Shackling these women limits their mobility during labor, which may compromise the health of both the mother and the fetus.[18] Tracy Edwards, a former prisoner who filed a lawsuit for unlawful use of restraints during her pregnancy, was in labor for twelve hours. She was unable to move or adjust her position to lessen the pain and discomfort of labor.[19] The shackles also left the skin on her ankles red and bruised. Continued use of restraints also increases the risk of potentially life-threatening health issues associated with childbirth, such as blood clots.[20] It is imperative that pregnant women get treated rapidly, especially with the unpredictability of labor. Epidural administration can also become difficult, and in some cases, be denied due to the shackled woman’s inability to assume the proper position.[21] Time-sensitive medical care, including C-sections, could be delayed if permission from an officer is required, risking major health complications for both the fetus and the mother.[22] After childbirth, shackling impedes the recovery process. Shackling can result in post-delivery complications such as deep vein thrombosis.[23]  Walking prevents such complications but is not an option for mothers shackled to their hospital beds.[24] Restraints also prevent bonding with the baby post-delivery and the safe handling of the baby while breast feeding.[25] The use of restraints can also result in psychological harm. Many prisoners feel as though care workers treat them like “animals,” with some women having multiple restraints at once— including ankles, wrists, and even waist restraints.[26] Benidalys Rivera describes the feeling of embarrassment as she was walking while handcuffed, with nurses and patients looking on, “Being in shackles, that make you be in stress…I about to have this baby, and I’m going to go back to jail. So it’s too much.”[27] Depression among pregnant prisoners is highly prevalent. The stress of imprisonment and the anticipation of being separated from their child is often overwhelming for these mothers.[28] The inhumane action has the potential to add more stress, anxiety, and sadness to the already emotionally demanding process of giving birth. Shackling pregnant prisoners displays indifference to the medical needs of the prisoner.[29] II.     Safety as a Pretense While public safety is an argument for using shackles, several factors make escape or violence extremely unlikely and even impossible.[30] For example, administering epidural anesthesia causes numbness and eliminates flight risk.[31] Although cited as the main reason for using shackles, public safety is likely just an excuse and not the main motivator for shackling prisoners. I argue that underlying the shackling exemplifies the idea that these women should not have become pregnant. The shackling reflects a distinct discrimination: the lawmakers allowing it perhaps thought that people guilty of crimes would make bad mothers.  Public safety is just a pretense. The language used to justify the use of restraint of Shawanna Nelson, the plaintiff in Nelson v. Correctional Medical Services, discussed below, included the word “aggressive.”[32] In her case, there was no evidence that she posed any danger or was objectively aggressive. Officer Turnesky, who supervised Nelson, testified that she never felt threatened by Nelson.[33] The lack of documented attempts of escape and violence from pregnant prisoners suggests that shackling for flight risk is a false pretense and perhaps merely based on stereotypes.[34]  In 2011, an Amnesty International report noted that “Around the USA, it is common for restraints to be used on sick and pregnant incarcerated women when they are transported to and kept in hospital, regardless of whether they have a history of violence (which only a minority have) and regardless of whether they have ever absconded or attempted to escape (which few women have).”[35] In a 2020 survey of correctional officers in select midwestern prisons, 76 percent disagreed or strongly disagreed with restraining pregnant women during labor and delivery.[36] If a correctional officer shackles a pregnant prisoner, it is not because they pose a risk but because of a perception that they do. This mindset is attributed to select law enforcement, who have authority to use restraints.[37] In 2022, the Tennessee legislature passed a bill prohibiting the use of restraints on pregnant inmates. However, legislators amended the bill due to the Tennessee Sherriff Association’s belief that even pregnant inmates could pose a “threat.”[38] Subjecting all prisoners to the same “precautions” because a small percentage of individuals may pose such risks could reflect stereotyping or the assumption that all incarcerated people pose danger and flight risk. To quell the (unjustified) public safety concern, there are other options that do not cause physical or mental harm to pregnant women. For example, San Francisco General Hospital does not use shackles but has deputy sheriffs outside the pregnant women’s doors.[39]  III.     Historical Context and Race           A.     Slavery and Post-Civil War The treatment of female prisoners has striking similarities to that of enslaved women. Originally, shackling of female slaves was a mechanism of control and dehumanization.[40] This enabled physical and sexual abuses. During the process of intentionally dehumanizing slaves to facilitate subordination, slave owners stripped slave women of their feminine identity.[41] Slave women were unable to exhibit the Victorian model of “good mothering” and people thought they lacked maternal feelings for their children.[42] In turn, societal perception defeminized slave women, and barred them from utilizing the protections of womanhood and motherhood. During the post-Civil War era, black women were reversely depicted as sexually promiscuous and were arrested for prostitution more often than white women.[43] In turn, society excluded black women; they were seen as lacking what the “acceptable and good” women had.[44] Some argue that the historical act of labeling black women sexually deviant influences today’s perception of black women and may lead to labeling them bad mothers.[45] Over two-thirds of incarcerated women are women of color.[46] Many reports document sexual violence and misconduct against prisoners over the years.[47] Male guards have raped, sexually assaulted, and inappropriately touched female prisoners. Some attribute the physical abuse of black female prisoners to their being depicted or stereotyped as “aggressive, deviant, and domineering.”[48] Some expect black women to express stoicism and if they do not, people label them as dangerous, irresponsible, and aggressive.[49] The treatment of these prisoners mirrors the historical oppression endured by black women during and following the era of slavery.  The act of shackling incarcerated pregnant women extends the inhumane treatment of these women from the prison setting into the hospital. One prisoner stated that during her thirty-hour labor, while being shackled, she “felt like a farm animal.”[50] Another pregnant prisoner describes her treatment by a guard stating: “a female guard grabbed me by the hair and was making me get up. She was screaming: ‘B***h, get up.’ Then she said, ‘That is what happens when you are a f***ing junkie. You shouldn’t be using drugs, or you wouldn’t be in here.”[51] Shackling goes beyond punishing by isolation from society – it is an additional punishment that is not justified.           B.     Reproductive Rights and “Bad Mothers” As with slaves not being seen as maternal, prisoners are not viewed as “real mothers.” A female prison guard said the following: “I’m a mother of two and I know what that impulse, that instinct, that mothering instinct feels like. It just takes over, you would never put your kids in harm’s way. . . . Women in here lack that. Something in their nature is not right, you know?”[52] This comment implies that incarcerated women lack maternal instinct. They are not in line with the standards of what society accepts as a “woman” and “mother” and are thought to have abandoned their roles as caretakers in pursuit of deviant behaviors. Without consideration of racial discrimination, poverty issues, trauma, and restricted access to the child right after delivery, these women are stereotyped as bad mothers simply because they are in prison. Reminiscent of the treatment of female black bodies post-civil war and the use of reproductive interventions (for example, Norplant and forced sterilization) in exchange for shorter sentences, I argue that shackles are a form of reproductive control. Justification for the use of shackles even includes their use as a “punitive instrument to remind the prisoner of their punishment.”[53] However, a prisoner’s pregnancy should have no relevance to their sentence.[54] Using shackles demonstrates to prisoners that society tolerates childbirth but does not support it.[55] The shackling is evidence that women are being punished “for bearing children, not for breaking the law.”[56]  Physicians and healthcare workers, as a result, are responsible for providing care for the delivery and rectifying any physical problems associated with the restraints. The issues that arise from the use of restraints place physicians in a position more complex than they experience with regular healthy pregnancies.           C.     Discrimination In the case of Ferguson v. City of Charleston, a medical university subjected black woman to involuntary drug testing during pregnancy. In doing so, medical professionals collaborated with law enforcement to penalize black women for their use of drugs during pregnancy.[57] The Court held the drug tests were an unreasonable search and violated the Fourth Amendment. Ferguson v. City of Charleston further reveals an unjustified assumption: the medical and legal community seemed suspicious of black women and had perhaps predetermined them more likely to use drugs while pregnant. Their fitness to become mothers needed to be proven, while wealthy, white women were presumed fit.[58] The correctional community similarly denies pregnant prisoners’ medical attention. In the case of Staten v. Lackawanna County, an African American woman whose serious medical needs were treated indifferently by jail staff was forced to give birth in her cell.[59] This woman was punished for being pregnant in prison through the withholding of medical attention and empathy. IV.     Failure to Follow Anti-Shackling Laws Despite 22 states having laws against shackling pregnant prisoners, officers do not always follow these laws. In 2015, the Correctional Association of New York reported that of the 27 women who gave birth under state custody, officers shackled 23 women in violation of the anti-shackling laws.[60] The lawyer of Tracy Edwards, an inmate who officers shackled unlawfully during her twelve-hour labor stated, “I don’t think we can assume that just because there’s a law passed, that’s automatically going to trickle down to the prison.”[61] Even with more restrictions on shackling, it may still occur, partly due to the stereotype that incarcerated women are aggressive and dangerous. V.     Constitutionality The Eighth Amendment protects people from cruel and unusual punishment. In Brown vs. Plata, the court stated, “Prisoners retain the essence of human dignity inherent in all persons.”[62] In several cases, the legal community has held shackling to be unconstitutional as it violates the Eighth Amendment unless specifically justified. In the case of Nelson v. Correctional Medical Services, a pregnant woman was shackled for 12 hours of labor with a brief respite while she pushed, then re-shackled. The shackling caused her physical and emotional pain, including intense cramping that could not be relieved due to positioning and her inability to get up to use a toilet.[63] The court held that a clear security concern must justify shackling. The court cited a similar DC case and various precedents for using the Eighth Amendment to hold correctional facilities and hospitals accountable.[64] An Arkansas law similarly states that shackling must be justified by safety or risk of escape.[65] If the Thirteenth Amendment applied to those convicted of crimes, shackling pregnant incarcerated people would be unconstitutional under that amendment as well as the Eighth. In the Civil Rights Cases, Congress upheld the right “to enact all necessary and proper laws for the obliteration and prevention of slavery with all its badges and incidents.”[66] Section two of the Thirteenth Amendment condemns any trace or acts comparable to that of slavery. Shackling pregnant prisoners, stripping them of their dignity, and justification based on stereotypes all have origins in the treatment of black female slaves. Viewed through the lens of the Thirteenth Amendment, the act of shackling would be unconstitutional. Nonetheless, the Thirteenth Amendment explicitly excludes people convicted of a crime. VI.     Justice As a result of the unconstitutional nature of shackling, physicians should have a legal obligation, in addition to their ethical duty, to protect their patients. The principle of justice requires physicians to take a stand against the discriminatory treatment of their patients, even under the eye of law enforcement.[67],[68] However, “badge and gun intimidation,” threats of noncompliance, and the fear of losing one’s license can impede a physician’s willingness to advocate for their patients. The American College of Obstetricians and Gynecologists (ACOG) finds the use of physical restraints interferes with the ability of clinicians to practice medicine safely.[69] ACOG, The American Medical Association, the National Commission on Correctional Health Care, and other organizations oppose using restraints on pregnant incarcerated people.[70] Yet, legislators can adopt shackling laws without consultation with physicians. The ACOG argues that “State legislators are taking it upon themselves to define complex medical concepts without reference to medical evidence. Some of the penalties [faced by OBGYNs] for violating these vague, unscientific laws include criminal sentences.”[71] Legislation that does not consider medical implications or discourages physicians’ input altogether is unjust. In nullifying the voice of a physician in matters pertaining to the patient’s treatment, physicians are prevented from fulfilling the principle of justice, making the act of shackling patients unethical. VII.     Principle of Beneficence The principle of beneficence requires the prevention of harm, the removal of harm, and the promotion of good.[72] Beneficence demands the physician not only avoid harm but benefit patients and promote their welfare.[73]  The American Board of Internal Medicine Foundation states that physicians must work with other professionals to increase patient safety and improve the quality of care.[74] In doing so, physicians can adequately treat patients with the goal of prevention and healing. It is difficult to do good when law enforcement imposes on doctors to work around shackles during labor and delivery. Law enforcement leaves physicians and healthcare workers responsible not only to provide care for the delivery, but also rectify any ailments associated with the restraints. The issues arising from using restraints place physicians in a position more complex than they experience with other pregnancies. Doctors cannot prevent the application of the shackles and can only request officers to take them off the patient.[75] Physicians who simply go along with shackling are arguably violating the principle of beneficence. However, for most, rather than violating the principle of beneficence overtly, physicians may simply have to compromise. Given the intricate nature of the situation, physicians are tasked with minimizing potential harm to the best of their abilities while adhering to legal obligations.[76] It is difficult to pin an ethics violation on the ones who do not like the shackles but are powerless to remove them. Some do argue that this inability causes physicians to violate the principle of beneficence.[77] However, promoting the well-being of their patients within the boundaries of the law limits their ability to exercise beneficence. For physicians to fulfill the principle of beneficence to the fullest capacity, they must have an influence on law. Protocols and assessments on flight risks made solely by the officers and law enforcement currently undermine the physician’s expertise. These decisions do not consider the health and well-being of the pregnant woman. As a result, law supersedes the influence of medicine and health care. CONCLUSION People expect physicians to uphold the four major principles of bioethics. However, their inability to override restraints compromises their ability to exercise beneficence. Although pledging to enforce these ethical principles, physicians have little opportunity to influence anti-shackling legislation. Instead of being included in conversations regarding medical complexities, legislation silences their voices. Policies must include the physician's voice as they affect their ability to treat patients. Officers should not dismiss a physician's request to remove shackles from a woman if they are causing health complications. A woman's labor should not harm her or her fetus because the officer will not remove her shackles.[78] A federal law could end shackling pregnant incarcerated people. Because other options are available to ensure the safety of the public and the prisoner, there is no ethical justification for shackling pregnant prisoners. An incarcerated person is a human being and must be treated with dignity and respect. To safeguard the well-being of incarcerated women and the public, it is essential for advocates of individual rights to join forces with medical professionals to establish an all-encompassing solution.   - [1] Ferszt, G. G., Palmer, M., &amp; McGrane, C. (2018). Where does your state stand on shackling of Pregnant Incarcerated Women? Nursing for Women’s Health, 22(1), 17–23. https://doi.org/10.1016/j.nwh.2017.12.005 [2] S983A, 2015-2016 Regular Sessions (N.Y. 2015). https://legislation.nysenate.gov/pdf/bills/2015/S983A [3] Chris DiNardo, Pregnancy in Confinement, Anti-Shackling Laws and the “Extraordinary Circumstances” Loophole, 25 Duke Journal of Gender Law &amp; Policy 271-295 (2018) https://scholarship.law.duke.edu/djglp/vol25/iss2/5 [4] Chris DiNardo (2018) [5] U.S. Bureau of Justice Statistics. 1980. " Prisoners in 1980 – Statistical Tables”. Retrieved April 20, 2023 (https://bjs.ojp.gov/content/pub/pdf/p80.pdf). [6] U.S. Bureau of Justice Statistics. 2022. " Prisoners in 2021 – Statistical Tables”. Retrieved April 20, 2023 (https://bjs.ojp.gov/sites/g/files/xyckuh236/files/media/document/p21st.pdf). [7] U.S. Bureau of Justice Statistics (1980) [8] Sufrin C, Jones RK, Mosher WD, Beal L. Pregnancy Prevalence and Outcomes in U.S. Jails. Obstet Gynecol. 2020;135(5):1177-1183. doi:10.1097/AOG.0000000000003834 [9] Kramer, C., Thomas, K., Patil, A., Hayes, C. M., &amp; Sufrin, C. B. (2022). Shackling and pregnancy care policies in US prisons and jails. Maternal and Child Health Journal, 27(1), 186–196. https://doi.org/10.1007/s10995-022-03526-y [10] House, K. T., Kelley, S., Sontag, D. N., &amp; King, L. P. (2021). Ending restraint of incarcerated individuals giving birth. AMA Journal of Ethics, 23(4). https://doi.org/10.1001/amajethics.2021.364 [11] Goshin, L. S., Sissoko, D. R., Neumann, G., Sufrin, C., &amp; Byrnes, L. (2019). Perinatal nurses’ experiences with and knowledge of the care of incarcerated women during pregnancy and the postpartum period. Journal of Obstetric, Gynecologic &amp;amp; Neonatal Nursing, 48(1), 27–36. https://doi.org/10.1016/j.jogn.2018.11.002 [12] Shackling and separation: Motherhood in prison. (2013). AMA Journal of Ethics, 15(9), 779–785. https://doi.org/10.1001/virtualmentor.2013.15.9.pfor2-1309 [13] King, L. (2018). Labor in chains: The shackling of pregnant inmates. Policy Perspectives, 25, 55–68. https://doi.org/10.4079/pp.v25i0.18348 [14] King, L. (2018). [15] AMA Journal of Ethics (2013) [16] Lawrence, A., Lewis, L., Hofmeyr, G. J., &amp; Styles, C. (2013). Maternal positions and mobility during first stage labour. Cochrane database of systematic reviews, (8). [17] Association of Women’s Health, Obstetric and Neonatal Nurses. (2011). AWHONN position statement: Shackling incarcerated pregnant women. Journal of Obstetric, Gynecologic, &amp; Neonatal Nursing, 40(6), 817–818. doi:10.1111/j.1552-6909.2011.01300.x [18] Ferszt, G. G., Palmer, M., &amp; McGrane, C. (2018). Where does your state stand on shackling of Pregnant Incarcerated Women? Nursing for Women’s Health, 22(1), 17–23. https://doi.org/10.1016/j.nwh.2017.12.005 [19] Thompson, E. (2022, August 30). Woman sues NC state prison system for mistreatment while pregnant. North Carolina Health News. Retrieved March 12, 2023, from https://www.northcarolinahealthnews.org/2022/05/25/woman-sues-nc-state-prison-system-for-mistreatment-while-pregnant/ [20] CBS Interactive. (2019, March 13). Shackling pregnant inmates is still a practice in many states. CBS News. Retrieved March 12, 2023, from https://www.cbsnews.com/news/shackling-pregnant-inmates-is-still-a-practice-in-many-states/ [21] Griggs, Claire Louise. "Birthing Barbarism: The Unconstitutionality of Shackling Pregnant Prisoners." American University Journal of Gender Social Policy and Law 20, no. 1 (2011): 247-271. [22] American Civil Liberties Union. (2012, October 12). ACLU briefing paper: The shackling of pregnant women &amp; girls in U.S ... American Civil Liberties Union (ACLU). https://www.aclu.org/wp-content/uploads/legal-documents/anti-shackling_briefing_paper_stand_alone.pdf [23] King.L (2018) [24] Griggs, Claire Louise (2011) [25] American Civil Liberties Union. (2012) [26] Clarke, J. G., &amp; Simon, R. E. (2013). Shackling and separation: Motherhood in prison. AMA Journal of Ethics, 15(9), 779–785. https://doi.org/10.1001/virtualmentor.2013.15.9.pfor2-1309 [27]  Berg, M. D. (2014, April 18). Pregnant prisoners are losing their shackles - The Boston Globe. BostonGlobe.com. Retrieved March 12, 2023, from https://www.bostonglobe.com/magazine/2014/04/18/taking-shackles-off-pregnant-prisoners/7t7r8yNBcegB8eEy1GqJwN/story.html [28] Levi, R., Kinakemakorn, N., Zohrabi, A., Afanasieff, E., &amp; Edwards-Masuda, N. (2010). Creating the bad mother: How the U.S. approach to pregnancy in prisons violates the right to be a mother. UCLA Women's Law Journal, 18(1). https://doi.org/10.5070/l3181017816 [29] Chris DiNardo (2018) [30] Griggs, Claire Louise (2011). [31] Allen, J. E. (2010, October 21). Shackled: Women Behind Bars Deliver in Chains. ABC News. https://abcnews.go.com/Health/WomensHealth/pregnant-shackled-women-bars-deliver-chains/story?id=11933376&amp;page=1 [32] Nelson v. Correctional, 533 F.3d 958 (8th Cir. 2009) [33] Nelson v. Correctional(2009) [34] House, K. T., Kelley, S., Sontag, D. N., &amp; King, L. P. (2021). Ending restraint of incarcerated individuals giving birth. AMA Journal of Ethics, 23(4). https://doi.org/10.1001/amajethics.2021.364 [35] Amnesty International USA. (1999, March). “Not part of my sentence” Violations of the Human Rights of Women in Custody. Amnesty International USA. Retrieved March 12, 2023, from https://www.amnestyusa.org/reports/usa-not-part-of-my-sentence-violations-of-the-human-rights-of-women-in-custody/ [36] Pendleton, V., Saunders, J. B., &amp; Shlafer, R. (2020). Corrections officers' knowledge and perspectives of maternal and child health policies and programs for pregnant women in prison. Health &amp; justice, 8(1), 1. https://doi.org/10.1186/s40352-019-0102-0 [37] Elizabeth Alexander, Unshackling Shawanna: The Battle Over Chaining Women Prisoners during Labor and Delivery, 32 U. ARK. LITTLE ROCK L. REV. 435 (2010). Available at: https://lawrepository.ualr.edu/lawreview/vol32/iss4/1 [38] Hernandez, J. (2022, April 22). More states are restricting the shackling of pregnant inmates, but it still occurs. NPR. Retrieved March 12, 2023, from https://www.npr.org/2022/04/22/1093836514/shackle-pregnant-inmates-tennessee [39] Sufrin, C. (2012, June 24). End practice of shackling pregnant inmates. SFGATE. Retrieved March 12, 2023, from https://www.sfgate.com/opinion/openforum/article/End-practice-of-shackling-pregnant-inmates-3176987.php [40] Mullings, L. (1997). On our own terms: Race, class, and gender in the lives of African American women. Routledge [41] Ocen, Priscilla A., (2011). [42] Ladd-Taylor, M. (1998). "Bad" mothers: The politics of blame in Twentieth-century America. New York Univ. Press. [43] Hine, D. C. (1998). Hine Sight: Black women and the re-construction of American history. Indiana University Press. [44] Baldwin, L. (2019). Excluded from good motherhood and the impact of prison: Motherhood and Social Exclusion, 129–144. https://doi.org/10.2307/j.ctvk12qxr.13 [45] Ocen, Priscilla A., Punishing Pregnancy: Race, Incarceration, and the Shackling of Pregnant Prisoners (October 3, 2011). California Law Review, Vol. 100, 2012, Available at SSRN: https://ssrn.com/abstract=1937872 [46] Johnson, P. C. (2004). Inner lives: Voices of african american women in prison. New York University Press. [47] Thomas, D. Q. (1996). All too familiar: Sexual abuse of women in U.S. state prisons. Human Rights Watch. [48] Ocen, Priscilla A., (2011). [49] Ashley W. The angry black woman: the impact of pejorative stereotypes on psychotherapy with black women. Soc Work Public Health. 2014;29(1):27-34. doi: 10.1080/19371918.2011.619449. PMID: 24188294. [50] CBS Interactive. (2019, March 13). Shackling pregnant inmates is still a practice in many states. CBS News. Retrieved March 12, 2023, from https://www.cbsnews.com/news/shackling-pregnant-inmates-is-still-a-practice-in-many-states/ [51] Guardian News and Media. (2020, January 24). Pregnant and shackled: Why inmates are still giving birth cuffed and bound. The Guardian. Retrieved March 25, 2023, from https://www.theguardian.com/us-news/2020/jan/24/shackled-pregnant-women-prisoners-birth [52] Oparah, J. C. (2015). Birthing justice: Black women, pregnancy, and childbirth. Routledge. [53] Chris DiNardo (2018) [54] Griggs, Claire Louise (2011). [55] Chris DiNardo (2018) [56] Griggs, Claire Louise (2011). [57] Song, Ji Seon, Policing the Emergency Room (June 10, 2021). 134 Harvard Law Review 2646 (2021), Available at SSRN: https://ssrn.com/abstract=3864225 [58] Ocen, Priscilla A., (2011). [59] Staten v. Lackawanna Cnty., No. 4:07-CV-1329, 2008 WL 249988, at *2 (M.D. Pa. Jan. 29, 2008) [60] Lovett, K. (2018, April 9). Pregnant inmates at New York prisons will no longer be shackled under new law. New York Daily News. Retrieved March 12, 2023, from https://www.nydailynews.com/new-york/new-york-pregnant-inmates-no-longer-shackled-article-1.2474021 [61] Thompson, E. (2022, August 30). Woman sues NC state prison system for mistreatment while pregnant. North Carolina Health News. Retrieved March 12, 2023, from https://www.northcarolinahealthnews.org/2022/05/25/woman-sues-nc-state-prison-system-for-mistreatment-while-pregnant/ [62] Brown v. Plata, 563 U.S. 493 (2011) [63] Nelson v. Correctional Medical Serices, et al., Nelson v. Correctional Med. Servs, 583 F.3d 522 (8th Cir. 2009) [64] Nelson citing Women Prisoners of D.C. Dep't of Corr. v. District of Columbia, 877 F.Supp. 634, 668-69 (D.D.C. 1994), modified in part on other grounds, 899 F.Supp. 659 (D.D.C. 1995). [65] Ark. Dep't of Corr. Admin. Reg. 403 § V (1992) [66] Civil Rights Cases, 109 U.S. 3 (1883) [67] Physician charter. ABIM Foundation. (2022, October 18). Retrieved March 10, 2023, from https://abimfoundation.org/what-we-do/physician-charter#:~:text=Principle%20of%20social%20justice.&amp;text=Physicians%20should%20work%20actively%20to,or%20any%20other%20social%20category. [68] Riddick FA Jr. The code of medical ethics of the american medical association. Ochsner J. 2003 Spring;5(2):6-10. PMID: 22826677; PMCID: PMC3399321. [69] American College of Obstetricians and Gynecologists’ Committee on Health Care for Underserved Women (2021). Reproductive Health Care for Incarcerated Pregnant, Postpartum, and Nonpregnant Individuals: ACOG Committee Opinion, Number 830. Obstetrics and gynecology, 138(1), e24–e34. https://doi.org/10.1097/AOG.0000000000004429 [70] American College of Obstetricians and Gynecologists’ Committee on Health Care for Underserved Women (2021). [71] American College of Obstetricians and Gynecologists’ Committee on Health Care for Underserved Women (2021). [72] Beauchamp, T. L., &amp; Childress, J. F. (2019). Principles of Biomedical Ethics. Oxford University Press. [73] Varkey, B. (2020). Principles of clinical ethics and their application to practice. Medical Principles and Practice, 30(1), 17–28. https://doi.org/10.1159/000509119 [74] Medical professionalism in the new millennium: A physician charter. (2002). Annals of Internal Medicine, 136(3), 243. https://doi.org/10.7326/0003-4819-136-3-200202050-00012 [75] Allen, J. E. (2010, October 21). Shackled: Women Behind Bars Deliver in Chains. ABC News. https://abcnews.go.com/Health/WomensHealth/pregnant-shackled-women-bars-deliver-chains/story?id=11933376&amp;page=1 [76] Jonsen, A. R. (2010). The Birth of Bioethics. Oxford University Press. [77] Beauchamp, T. L., &amp; Childress, J. F. (2019). [78] Amnesty International USA. (1999, March). “Not part of my sentence” Violations of the Human Rights of Women in Custody. Amnesty International USA. Retrieved March 12, 2023, from https://www.amnestyusa.org/reports/usa-not-part-of-my-sentence-violations-of-the-human-rights-of-women-in-custody/

Which trial do we need? Treatment of multiple erythema migrans with doxycycline for 7 days versus 14 days

Lyme borreliosis is the most prevalent vector-borne disease in Europe and North America [ 1 Mead P.S. Epidemiology of Lyme disease. Infect Dis Clin North Am. 2015; 29: 187-210https://doi.org/10.1016/j.idc.2015.02.010 Abstract Full Text Full Text PDF PubMed Scopus (268) Google Scholar ]; an estimated ≈232,000 cases in Western Europe [ 2 Sykes R.A. Makiello P. An estimate of Lyme borreliosis incidence in Western Europe. J Public Health. 2016; 39 (DOI: 0.1093/pubmed/fdw017): 74-81 Google Scholar ] and ≈476,000 cases in the US [ 3 Kugeler K.J. Schwartz A.M. Delorey M.J. Mead P.S. Hinckley A.F. Estimating the Frequency of Lyme Disease Diagnoses, United States, 2010–2018. Emerg Inf Dis. 2021; 27: 616-619https://doi.org/10.3201/eid2702.202731 Crossref PubMed Scopus (169) Google Scholar ] are diagnosed per year and erythema migrans is its most frequent clinical presentation, occurring in ≥80% of cases [ 1 Mead P.S. Epidemiology of Lyme disease. Infect Dis Clin North Am. 2015; 29: 187-210https://doi.org/10.1016/j.idc.2015.02.010 Abstract Full Text Full Text PDF PubMed Scopus (268) Google Scholar , 4 Stanek G. Strle F. Lyme borreliosis‒from tick bite to diagnosis and treatment. FEMS Microbiol Rev. 2018; 42: 233-258https://doi.org/10.1093/femsre/fux047 Crossref PubMed Scopus (96) Google Scholar ]. In solitary erythema migrans (SEM), the skin manifestation remains localised to the site of inoculation of borreliae, whereas multiple erythema migrans (MEM) represent hematogenous dissemination of borreliae, which may occur in 13.4% to 27% of US cases [ 5 Wormser G.P. McKenna D. Carlin J. et al. Brief communication: hematogenous dissemination in early Lyme disease. Ann Intern Med. 2005; 142: 751-755https://doi.org/10.7326/0003-4819-142-9k,-200505030-00011 Crossref PubMed Google Scholar , 6 Strle F. Nadelman R.B. Cimperman J. et al. Comparison of Culture-Confirmed Erythema Migrans Caused by Borrelia burgdorferi sensu stricto in New York State and by Borrelia afzelii in Slovenia. Ann Intern Med. 1999; 130: 32-36https://doi.org/10.7326/0003-4819-130-1-199901050-00006 Crossref PubMed Scopus (179) Google Scholar , 7 Nowakowski J. Nadelman R.B. Sell R. et al. Long-term follow-up of patients with culture-confirmed Lyme disease. Am J Med. 2003; 115: 91-96https://doi.org/10.1016/S0002-9343(03)00308-5 Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar ] and less frequently (up to 7%) in Europe [ 4 Stanek G. Strle F. Lyme borreliosis‒from tick bite to diagnosis and treatment. FEMS Microbiol Rev. 2018; 42: 233-258https://doi.org/10.1093/femsre/fux047 Crossref PubMed Scopus (96) Google Scholar , 6 Strle F. Nadelman R.B. Cimperman J. et al. Comparison of Culture-Confirmed Erythema Migrans Caused by Borrelia burgdorferi sensu stricto in New York State and by Borrelia afzelii in Slovenia. Ann Intern Med. 1999; 130: 32-36https://doi.org/10.7326/0003-4819-130-1-199901050-00006 Crossref PubMed Scopus (179) Google Scholar ]. The current Infectious Diseases Society of America treatment guidelines recommend doxycycline for 10 days or cefuroxime axetil or amoxicillin for 14 days as first line therapy for both SEM and MEM [ 8 Lantos P.M. Rumbaugh J. Bockenstedt L.K. et al. Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021; 72: e1-e48https://doi.org/10.1093/cid/ciaa1215 Crossref PubMed Scopus (0) Google Scholar ]. However, the clinical course and outcome of SEM and MEM may differ [ 7 Nowakowski J. Nadelman R.B. Sell R. et al. Long-term follow-up of patients with culture-confirmed Lyme disease. Am J Med. 2003; 115: 91-96https://doi.org/10.1016/S0002-9343(03)00308-5 Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar , 9 Dattwyler R.J. Volkman D.J. Conaty S.M. Platkin S.P. Luft B.J. Amoxycillin plus probenecid versus doxycycline for treatment of erythema migrans borreliosis. Lancet. 1990; 336: 1404-1406https://doi.org/10.1016/0140-6736(90)93103-V Abstract PubMed Scopus (154) Google Scholar , 10 Steere A.C. Hutchinson G.J. Rahn D.W. et al. Treatment of the early manifestations of Lyme disease. Ann Intern Med. 1983; 99: 22-26https://doi.org/10.7326/0003-4819-99-1-22 Crossref PubMed Scopus (321) Google Scholar , 11 Stupica D. Maraspin V. Bogovič P. et al. Comparison of Clinical Course and Treatment Outcome for Patients With Early Disseminated or Early Localized Lyme Borreliosis. JAMA Dermatol. 2018; 154: 1050-1056https://doi.org/10.1001/jamadermatol.2018.2306 Crossref PubMed Scopus (24) Google Scholar ] leading to concern that MEM requires a longer course of therapy than SEM. In Europe, 14-21 days of antibiotic therapy are recommended for treating early disseminated Lyme borreliosis, including MEM [ 4 Stanek G. Strle F. Lyme borreliosis‒from tick bite to diagnosis and treatment. FEMS Microbiol Rev. 2018; 42: 233-258https://doi.org/10.1093/femsre/fux047 Crossref PubMed Scopus (96) Google Scholar , 12 Hofmann H. Fingerle V. Hunfeld K.P. et al. Cutaneus Lyme borreliosis: guideline of the German Dermatology Society. Ger Med Sci. 2017; 15: 1-31https://doi.org/10.3205/000255.eCollection.2017 Crossref Google Scholar ], although a pathogenetic or pharmacodynamic rational for longer treatment is lacking. Results from our previous study showed that a 7-day course of doxycycline was non-inferior to a 14-day regimen for treating adult patients with SEM in Slovenia, where Lyme borreliosis is highly endemic [ 13 Stupica D. Collinet-Adler S. Blagus R. et al. Treatment of erythema migrans with doxycycline for 7 days versus 14 days in Slovenia: a randomised open-label non-inferiority trial. Lancet Infect Dis. 2023; 23: 371-379https://doi.org/10.1016/S1473-3099(22)00528-X Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar ]. The generalizability of these results to other regions or to patients with MEM is unclear. Multi-centre studies are preferable for optimal generalizability of conclusions, which may otherwise be limited due to the differential prevalence of various borrelial species throughout Europe and North America. Furthermore, the shortest effective treatment for MEM remains unknown. Shorter antibiotic treatment durations can reduce costs, side effects, and antimicrobial resistance [ 14 Sanchez G.V. Fleming-Dutra K.E. Roberts R.M. Hicks L.A. Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep. 2016; 65: 1-12https://doi.org/10.15585/mmwr.rr6506a1 Crossref PubMed Scopus (337) Google Scholar ].

Part I: Interactive case: Menopause

JACCP: JOURNAL OF THE AMERICAN COLLEGE OF CLINICAL PHARMACYVolume 6, Issue 6 p. 657-662 PSAP IN JACCP Part I: Interactive case: Menopause Nicole E. Cieri-Hutcherson Pharm.D., Nicole E. Cieri-Hutcherson Pharm.D. orcid.org/0000-0002-2861-3074 Search for more papers by this authorVeronica Vernon Pharm.D., Veronica Vernon Pharm.D. orcid.org/0000-0002-5638-3851 Search for more papers by this author Nicole E. Cieri-Hutcherson Pharm.D., Nicole E. Cieri-Hutcherson Pharm.D. orcid.org/0000-0002-2861-3074 Search for more papers by this authorVeronica Vernon Pharm.D., Veronica Vernon Pharm.D. orcid.org/0000-0002-5638-3851 Search for more papers by this author First published: 07 June 2023 https://doi.org/10.1002/jac5.1814Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL REFERENCES American College of Obstetricians and Gynecologists' Committee on Clinical Consensus – Gynecology (ACOG). Treatment of urogenital symptoms in individuals with a history of estrogen-dependent breast cancer: clinical consensus. Obstet Gynecol. 2021; 138: 950– 60. American College of Obstetricians and Gynecologists Committee on Gynecologic Practice, American Society for Reproductive Medicine Practice Committee (ACOG). Committee Opinion 532: compounded bioidentical menopausal hormone therapy. Obstet Gynecol. 2012; 120: 411– 5. Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004; 291: 1701– 12. Avis NE, Crawford SL, Greendale G, et al. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med. 2015; 175: 531– 9. Bassuk SS, Manson JE. Oral contraceptives and menopausal hormone therapy: relative and attributable risks of cardiovascular disease, cancer, and other health outcomes. Ann Epidemiol. 2015; 25: 193– 200. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists and American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract. 2020; 26(suppl 1): 1– 46. Clark K, Westberg SM. Benefits of levonorgestrel intrauterine device use vs. oral or transdermal progesterone for postmenopausal women using estrogen containing hormone therapy. Innov Pharm. 2019; 10: 7. https://doi.org/10.24926/iip.v10i3.200 Cobin RH, Goodman NF, AACE Reproductive Endocrinology Scientific Committee. American Association of Clinical Endocrinologists and American College of Endocrinology position statement on menopause – 2017 update. Endocr Pract. 2017; 23(23): 869– 80. Constantine GD, Goldstein SR, Archer DF. Endometrial safety of ospemifene: results of the phase 2/3 clinical development program. Menopause. 2015; 22: 36– 43. CJ Crandall, editor. Menopause practice: a clinician's guide. 6th ed. North American Menopause Society; 2019. Depypere H, Timmerman D, Donders G, et al. Treatment of menopausal vasomotor symptoms with fezolinetant, a neurokinin 3 receptor antagonist: a phase 2a trial. J Clin Endocrinol Metab. 2019; 104: 5893– 905. Eastell R, Rosen CJ, Black DM, et al. Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2019; 104: 1595– 622. Endocrine Society. Position statement: compounded bioidentical hormone. 2019. Ettinger B, Wang SM, Leslie RS, et al. Evolution of postmenopausal hormone therapy between 2002 and 2009. Menopause. 2018; 25: 1306– 12. Flores VA, Pal L, Manson JE. Hormone therapy in menopause: concepts, controversies, and approach to treatment. Endocr Rev. 2021; 42: 720– 52. Fraser GL, Lederman S, Waldbaum A, et al. A phase 2b, randomized, placebo-controlled, double-blind, dose-ranging study of the neurokinin 3 receptor antagonist fezolinetant for vasomotor symptoms associated with menopause. Menopause. 2020; 27: 389– 92. Hays J, Hunt JR, Hubbell FA, et al. The Women's Health Initiative recruitment methods and results. Ann Epidemiol. 2003; 13: S18– 77. LaCroix AZ, Chlebowski RT, Manson JE, et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA. 2011; 305: 1305– 14. LeBoff MS, Greenspan SL, Insogna KL, et al. The clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int. 2022; 33: 2049– 102. Manson JE, Aragaki AK, Bassuk SS, et al. Menopausal estrogen-alone therapy and health outcomes in women with and without bilateral oophorectomy: a randomized trial. Ann Intern Med. 2019; 171: 406– 14. Manson JE, Aragaki AK, Rossouw JE, et al. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women's Health Initiative randomized trials. JAMA. 2017; 318: 927– 38. Manson JE, Bassuk SS, Kaunitz AM, et al. The Women's Health Initiative trials of menopausal hormone therapy: lessons learned. Menopause. 2020; 27: 918– 28. Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA. 2013; 310: 1353– 68. Mehta J, Kling JM, Manson JE. Risks, benefits, and treatment modalities of menopausal hormone therapy: current concepts. Front Endocrinol (Lausanne). 2021; 12:564781. National Academies of Sciences, Engineering, and Medicine (NASEM). The clinical utility of compounded bioidentical hormone therapy: a review of safety, effectiveness, and use. National Academies Press; 2020. North American Menopause Society (NAMS). Isoflavones report. The role of soy isoflavones in menopausal health: report of the North American Menopause Society. Menopause. 2011; 18: 732– 53. North American Menopause Society (NAMS). Hormone Therapy Position Statement Advisory Panel. The 2020 genitourinary syndrome of menopause position statement of the North American Menopause Society. Menopause. 2020; 2020(27): 976– 92. North American Menopause Society (NAMS). Management of osteoporosis in postmenopausal women: the 2021 position statement of The North American Menopause Society. Menopause. 2021;(17): 25– 54. North American Menopause Society (NAMS). Hormone Therapy Position Statement Advisory Panel. The 2022 hormone therapy position statement of the North American Menopause Society. Menopause. 2022; 2022(29): 767– 94. North American Menopause Society-A (NAMSa). Use of compounded hormone therapy in the United States: report of The North American Menopause Society Survey. Menopause. 2015; 22: 1276– 84. North American Menopause Society-B (NAMSb). Nonhormonal management of menopause-associated vasomotor symptoms: 2015 position statement of The North American Menopause Society. Menopause. 2015; 28: 973– 97. Prague JK, Roberts RE, Comninos AN, et al. Neurokinin 3 receptor antagonism rapidly improves vasomotor symptoms with sustained duration of action. Menopause. 2018; 25: 862– 9. Qaseem A, Forciea MA, McLean RM, et al. Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians. Ann Intern Med. 2017; 166: 818– 39. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002; 288: 321– 33. Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007; 297: 1465– 77. Sahni S, Lobo-Romero A, Smith T. Contemporary non-hormonal therapies for the management of vasomotor symptoms associated with menopause: a literature review. TouchREV Endocrinol. 2021; 17: 133– 7. Shifren JL, Crandall CJ, Manson JE. Menopausal hormone therapy. JAMA. 2019; 321: 2458– 9. Shoback D, Rosen CJ, Black DM, et al. Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society guideline update. J Clin Endocrinol Metab. 2020; 105: 587– 94. Simon J, Anderson RA, Ballantyne E, et al. OR11-03 NT-814, a non-hormonal dual neurokinin 1,3 receptor antagonist markedly improves vasomotor symptoms in post-menopausal women; results of a randomised, double-blind, placebo- controlled, dose-finding study (SWITCH-1). J Endocr Soc. 2020; 4(suppl 1):OR11-03. Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015; 100: 3975– 4011. Szeliga A, Czyzyk A, Podfigurna A, et al. The role of kisspeptin/neurokinin B/dynorphin neurons in pathomechanism of vasomotor symptoms in postmenopausal women: from physiology to potential therapeutic applications. Gynecol Endocrinol. 2018; 34: 913– 9. Whiteley J, DiBonaventura MD, Wagner JS, et al. The impact of menopausal symptoms on quality of life, productivity, and economic outcomes. J Womens Health. 2013; 22: 983– 90. Wild RA, Hovey KM, Andrews C, et al. Cardiovascular disease (CVD) risk scores, age, or years since menopause to predict cardiovascular disease in the Women's Health Initiative. Menopause. 2021; 28: 610– 8. Zernig G, Lechner T, Kramer-Reinstadler K, et al. What the clinician still has to be reminded of. Ther Drug Monit. 2004; 26: 582. Zhang L, Brown SJ, Shan Y, et al. CYP2D6 genetic polymorphisms and risperidone pharmacokinetics: a systematic review and meta-analysis. Pharmacotherapy. 2020; 40: 632– 47. Zierhut HA, Campbell CA, Mitchell AG, et al. Collaborative counseling considerations for pharmacogenomic tests. Pharmacotherapy. 2017; 37: 990– 9. Volume6, Issue6June 2023Pages 657-662 ReferencesRelatedInformation

Annals On Call - Subclinical Coronary Atherosclerosis.

Web Exclusives6 June 2023Annals On Call - Subclinical Coronary AtherosclerosisFREERobert M. Centor, MD, and Klaus Fuglsang Kofoed, MD, PhD, DMScRobert M. Centor, MDHuntsville Regional Medical Campus, University of Alabama Birmingham School of Medicine, Birmingham, Alabama (R.M.C.)Search for more papers by this author, and Klaus Fuglsang Kofoed, MD, PhD, DMScDepartment of Cardiology and Department of Radiology, Copenhagen University Hospital–Rigshospitalet, and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (K.F.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/A22-0011 CME/MOC SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In this episode of Annals On Call, Dr. Centor discusses subclinical atherosclerosis and the risk for myocardial infarction with Dr. Klaus Fuglsang Kofoed.Annals articles discussed include...Subclinical Coronary Atherosclerosis and Risk for Myocardial Infarction in a Danish Cohort. A Prospective Observational Cohort Study: https://www.acpjournals.org/doi/10.7326/M22-3027About Annals On CallAnnals On Call focuses on a clinically influential article published in Annals of Internal Medicine. Dr. Robert Centor shares his own perspective on the material and interviews topic area experts to discuss, debate, and share diverse insights about patient care and health care delivery.For more information on Annals On Call and for more episodes, visit go.annals.org/OnCall. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Robert M. Centor, MD; Klaus Fuglsang Kofoed, MD, PhD, DMScAffiliations: Huntsville Regional Medical Campus, University of Alabama Birmingham School of Medicine, Birmingham, Alabama (R.M.C.)Department of Cardiology and Department of Radiology, Copenhagen University Hospital–Rigshospitalet, and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (K.F.K.)Disclosures: All relevant financial relationships have been mitigated. Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=A22-0011.Editors' Disclosures: The editors have no relevant financial relationships to disclose. Individual forms may be viewed at www.annals.org/editorsdisclosures.This article was published at Annals.org on 6 June 2023. Nextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoSubclinical Coronary Atherosclerosis and Risk for Myocardial Infarction in a Danish Cohort Andreas Fuchs , Jørgen Tobias Kühl , Per Ejlstrup Sigvardsen , Shoaib Afzal , Andreas Dehlbæk Knudsen , Mathias Bech Møller , Martina Chantal de Knegt , Mathias Holm Sørgaard , Børge Grønne Nordestgaard , Lars Valeur Køber , and Klaus Fuglsang Kofoed Metrics Latest ePublished: 6 June 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.Loading ...