Suboptimal Therapy Research Articles

EVOLOCUMAB USE IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS AND DYSLIPIDEMIA: PRIMARY RESULTS OF A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY (BEIJERINCK)

People living with human immunodeficiency virus (PLHIV) are at increased risk of cardiovascular disease due to metabolic abnormalities, chronic inflammation and immune dysregulation. PLHIV may receive suboptimal lipid-lowering therapy because of drug-drug interactions between high-intensity statins

Association of CYP2C19*2 polymorphism with clopidogrel resistance among patients with high cardiovascular risk in Northeastern Mexico.

Oral antiplatelet drugs are a key to modern pharmacotherapy in cardiovascular atherothrombotic diseases. Clopidogrel (CLO) constitutes the main preventive treatment of atherothrombosis. However, a considerable inter-individual variation in CLO response has been documented, resulting in suboptimal therapy and an increased risk of recurrent adverse effects in some patients. The enzyme CYP2C19 has been reported to be the CYP isoform that activates CLO to its active metabolite. Several single nucleotide polymorphisms in the CYP2C19 gene have been identified as strong predictors of CLO-impaired pharmacological response. At least 16 variants have been associated with changes in CYP2C19 activity. The following research was composed of a total of 102 subjects with high cardiovascular risk in the northeast of Mexico, with a maintenance dose of 75 mg of CLO per day. The platelet reactivity was measured with VerifyNow P2Y12 assay, while the presence of CYP2C19*2 was identified by real-time polymerase chain reaction. Patients were categorized by CYP2C19 metabolizer status based on *2 genotypes using the common consensus star allele nomenclature as normal metabolizer (G/G), intermediate metabolizer (G/A), and poor metabolizer (A/A), respectively. The phenotype frequency for CYP2C19*2 was 74.5% (G/G), 21.6% (G/A), and 3.9% (A/A). The subjects with the A allele presented ≥235 P2Y12 reaction unit levels, classifying them how poor metabolizer. The prevalence of reduced CLO effectiveness was associated with the presence of CYP2C19*2 polymorphism among Mexican patients. The presence of the CYP2C19*2 allele is related to resistance to the antiplatelet effect of CLO (p = 0.003).

Appropriateness of Antibiotic Prescribing in United States Children's Hospitals: A National Point Prevalence Survey.

Studies estimate that 30%-50% of antibiotics prescribed for hospitalized patients are inappropriate, but pediatric data are limited. Characterization of inappropriate prescribing practices for children is needed to guide pediatric antimicrobial stewardship. Cross-sectional analysis of antibiotic prescribing at 32 children's hospitals in the United States. Subjects included hospitalized children with ≥ 1 antibiotic order at 8:00 am on 1 day per calendar quarter, over 6 quarters (quarter 3 2016-quarter 4 2017). Antimicrobial stewardship program (ASP) physicians and/or pharmacists used a standardized survey to collect data on antibiotic orders and evaluate appropriateness. The primary outcome was the percentage of antibiotics prescribed for infectious use that were classified as suboptimal, defined as inappropriate or needing modification. Of 34 927 children hospitalized on survey days, 12 213 (35.0%) had ≥ 1 active antibiotic order. Among 11 784 patients receiving antibiotics for infectious use, 25.9% were prescribed ≥ 1 suboptimal antibiotic. Of the 17 110 antibiotic orders prescribed for infectious use, 21.0% were considered suboptimal. Most common reasons for inappropriate use were bug-drug mismatch (27.7%), surgical prophylaxis > 24 hours (17.7%), overly broad empiric therapy (11.2%), and unnecessary treatment (11.0%). The majority of recommended modifications were to stop (44.7%) or narrow (19.7%) the drug. ASPs would not have routinely reviewed 46.1% of suboptimal orders. Across 32 children's hospitals, approximately 1 in 3 hospitalized children are receiving 1 or more antibiotics at any given time. One-quarter of these children are receiving suboptimal therapy, and nearly half of suboptimal use is not captured by current ASP practices.

Potential drug-drug interactions associated with clinical and laboratory findings at hospital admission.

Background Drug-drug interactions represent one of the causes of adverse therapy outcomes through deteriorated efficacy or safety. However, the true extent of harm related to drug-drug interactions is not well established due to a lack of recognition and understanding. Objective The aim of this study was to investigate the association of potential drug-drug interactions with patients variables recorded at admission. Setting A cross-sectional correlation study was performed on the Cardiology ward of the University Clinical Hospital Center in Belgrade, Serbia. Method Data were retrospectively obtained from medical records and LexiInteract was used as the screening tool for potential drug-drug interactions. Main outcome measure Clinical and laboratory parameters recorded at the patients admission. Results A total of 351 patient records entered the analysis, with the mean age of 70 ± 10years. The prevalence of potentially relevant drug-drug interactions was 61% (N = 213). After controlling for patient characteristics, nine potential drug-drug interactions were significantly associated with laboratory values outside the range and five potential drug-drug interactions with inadequate clinical parameter values. Potential drug-drug interactions were associated with abnormalities in blood count, metabolic parameters, electrolyte imbalance and renal function parameters. Association with inadequate control of systolic, diastolic blood pressure, as well as heart rhythm was also shown. Conclusion Drug-drug interactions were associated with patients clinical and laboratory findings. Our findings may assist in the identification of patients with increased likelihood of suboptimal therapy outcomes. Generating evidence through post-marketing drug-drug interactions research would lead to improvement in clinical decision-support systems, increased effectiveness and utilization in everyday clinical practice.

Risk Factors for Suboptimal Medication Adherence in Persons With Multiple Sclerosis: Development of an Electronic Health Record-Based Explanatory Model for Disease-Modifying Therapy Use

ObjectiveTo determine which factors are associated with suboptimal disease-modifying therapy (DMT) adherence and to develop an explanatory model that could be used to identify individuals at risk and potentially inform interventions. DesignCross-sectional cohort study using electronic health records. SettingVeterans Health Administration (VA). ParticipantsVeterans with multiple sclerosis (MS) (N=2939; 79.69% men) who received care through the VA and were included in the VA MS Center of Excellence Data Repository. InterventionsNot applicable. Main Outcome MeasuresSuboptimal DMT adherence (<80%), demographics, co-occurring conditions, and health care use. ResultsNearly 31% of participants had suboptimal adherence. Flags for suboptimal adherence included >20% missed appointments (odds ratio [OR], 3.78; 95% CI, 2.45-2.82), traumatic brain injuries (OR, 1.55; 95% CI, 1.12-2.14), age younger than 59 years (OR, 1.47; 95% CI, 1.23-1.74), ≥1 emergency department visits (OR, 1.40; 95% CI, 1.18-1.67), mood disorders (ie, depressive and bipolar disorders) (OR, 1.40; 95% CI, 1.18-1.66), and service connection (OR, 1.22; 95% CI, 1.01-1.47). Hyperlipidemia (OR, 0.77; 95% CI, 0.65-0.92) and being issued a wheelchair (OR, 0.83; 95% CI, 0.70-1.00) were associated with lower risk. ConclusionsSuboptimal adherence to DMTs continues to be an issue. Interventions that focus on person-level barriers should be urgently explored to increase adherence and improve self-management abilities.

ICON: Diagnosis and management of allergic conjunctivitis

Ocular allergy (OA), interchangeably known as allergic conjunctivitis, is a common immunological hypersensitivity disorder affecting up to 40% of the population. Ocular allergy has been increasing in frequency, with symptoms of itching, redness, and swelling that significantly impacts an individual's quality of life (QOL). Ocular allergy is an often underdiagnosed and undertreated health problem, because only 10% of patients with OA symptoms seek medical attention, whereas most patients manage with over-the-counter medications and complementary nonpharmacological remedies. The clinical course, duration, severity, and co-morbidities are varied and depend, in part, on the specific ocular tissues that are affected and on immunologic mechanism(s) involved, both local and systemic. It is frequently associated with allergic rhinitis (commonly recognized as allergic rhino conjunctivitis), and with other allergic comorbidities. The predominance of self-management increases the risk of suboptimal therapy that leads to recurrent exacerbations and the potential for development of more chronic conditions that can lead to corneal complications and interference with the visual axis. Multiple, often co-existing causes are seen, and a broad differential diagnosis for OA, increasing the difficulty of arriving at the correct diagnosis(es). Ocular allergy commonly overlaps with other anterior ocular disease disorders, including infectious disorders and dry eye syndromes. Therefore, successful management includes overcoming the challenges of underdiagnosis and even misdiagnosis by a better understanding of the subtleties of an in-depth patient history, ophthalmologic examination techniques, and diagnostic procedures, which are of paramount importance in making an accurate diagnosis of OA. Appropriate cross-referral between specialists (allergists and eyecare specialists) would maximize patient care and outcomes. This would significantly improve OA management and overcome the unmet needs in global health.

Unequal Outcomes in Transplant Eligible Patients with Multiple Myeloma in Latin America: Differences between Public and Private Centers

Background Multiple myeloma (MM) is a frequent hematologic malignancy. The current gold standard frontline strategy includes a proteasome inhibitor (PI)-based induction, followed by autologous stem cell transplant (ASCT). Access to novel drugs in Latin America (LA) is limited. ASCT is available in most countries, but real access to it is highly heterogeneous. Data regarding patients´ outcomes in candidates to ASCT in the region is scarce. The aim of this study was to describe clinical characteristics and outcomes of MM transplant eligible patients in LA countries. Material and Methods Retrospective international multicenter cohort study. Consecutive MM transplant- eligible patients diagnosed between 2010 and 2018 from participating centers in Chile, Argentina, Ecuador, Mexico, Colombia, and Uruguay were included. Data were collected from clinical records in a standardized report form. We analyzed clinical characteristics at diagnosis and frontline therapy outcomes, including ASCT. Transplant-eligible patients were defined as fit patients younger than 66 years old. Active MM and response to treatment were defined according to current IMWG criteria. Inclusion criteria: 1.- Patients with newly diagnosed active MM between 2010 and 2018. 2.- Older than 18 years, and younger than 66 years. 3- Candidates for ASCT according to the evaluation of the attending physician Exclusion criteria: 1- Lack of minimum data in the clinical history 2- Plasma cell leukemia, AL amyloidosis or solitary plasmacytoma. 3- HIV infection 4-No consent and/or Ethics Committee approvals. Statistical analysis A descriptive statistic has been done. Comparisons of characteristics between groups was made usingT-student, Chi2 or ANOVA, as appropriate. Survival analysis was performed using Kaplan-Meier curves. Comparisons of survival between groups were made by the logarithmic recording method and the calculations of the risk relationships by Cox regression. Statistical analysis was performed by using STATA 13. Results We included 1293 patients in the study, 363 from Chile, 395 from Argentina, 209 from Colombia, 45 from Ecuador, 151 from Mexico, and 130 from Uruguay. The main characteristics at diagnosis and therapeutic strategies are shown in Table 1. Optimal response (sCR, CR and VGPR) was achieved in 38% of the patients in the cyclophosphamide, bortezomib, and dexamethasone (CyBorD) group, in 46% in the bortezomib, thalidomide, and dexamethasone (VTD) group, and in 36% in the cyclophosphamide, thalidomide, and dexamethasone (CTD) group, the 3 main induction regimens used. Only 53% of patients finally received ASCT. Significant differences were found between both groups, private and public institutions, regarding burden of symptoms, ISS staging, access to PI based induction, ASCT completion and adequate maintenance, with patients from the latter being more symptomatic, and receiving suboptimal therapy. FISH analysis was performed in less than 50% of patients, both in the public and private setting. With a median follow up of 34 months (range 1-113), median overall survival (OS) was 86 months. The 5-year progression free survival (PFS) was 38% and 5- year overall survival (OS) was 64%. When comparing public vs private settings, 5 year OS was 45% vs 80%, with a median OS of 56 months vs not reached, respectively (P&lt;0,0001). In the multivariable analysis renal failure (p=0.03), achieving less than VGPR response (p&lt;0.0001), not undergoing ASCT (p=0.001), and not receiving maintenance (p=0.005) were independent factors associated with worse outcome. Conclusion This is the largest report on transplant eligible patients with MM in LA. Great inequities are shown between public and private health systems. Survival in transplant-eligible patients is lower than that described in other regions. Only one third of patients had FISH performed. This means that very few patients are treated with a risk-based induction in LA. Patients in the public setting are diagnosed with a more symptomatic disease, probably due to a late diagnosis. OS is significantly worse in the public setting. This might be explained by the significant differences in access to PI-based induction, ASCT and maintenance between private and public institutions, with patients from the latter receiving suboptimal frontline therapy and maintenance. Reasons for 47% of potential candidates not being transplanted merit further analysis. Table 1 Disclosures Peña: Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Janssen: Other: Congress inscription and flights; Pfizer: Membership on an entity's Board of Directors or advisory committees. Rojas:Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfeizer: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Abello:Takeda: Other: Participation in advisory board meeting. Gomez-Almaguer:Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau.

1024. Evaluation of Atovaquone Prescribing for Pneumocystis jiroveci Pneumonia (PJP) Prophylaxis

BackgroundTrimethoprim-sulfamethoxazole (TMP-SMX) use for PJP prophylaxis has been associated with a variety of adverse reactions including myelosuppression, hypersensitivity reactions, acute kidney injury, and hyperkalemia. Atovaquone is used as an alternative drug, but it has several disadvantages, such as breakthrough PJP risk, dysgeusia, and higher cost compared with TMP-SMX. Indications for atovaquone prophylaxis at our institutions include severe cytopenias, hypersensitivity, renal impairment, or hyperkalemia. We evaluated atovaquone use and compliance with institutional PJP prophylaxis guidelines.MethodsThis was a retrospective study of inpatient atovaquone prescribing for PJP prophylaxis at Brigham and Women’s Hospital and Dana-Farber Cancer Institute from 7/1/18 to 9/30/18. We included adult patients who received ≥1 dose of atovaquone and ≥3 months of PJP prophylaxis with any agent. The primary endpoint of this study was the proportion of patients who could have been safely switched to TMP-SMX 3 months after atovaquone initiation. Other endpoints included the incidence of breakthrough PJP, reasons for TMP-SMX avoidance, and estimated cost savings.ResultsTwo-hundred and eighteen patients were evaluated and 164 were included. Most common indications for atovaquone prophylaxis were bone marrow transplant (44.5%), solid-organ transplant (30.5%) and use of immunosuppressive agents (21.9%). Atovaquone was started in 145 patients (88.4%) according to institutional guidance. Three months after initiation, 89 patients (45.7%) could have been safely switched to TMP-SMX. Failure to timely change to TMP-SMX was associated with 1,615 additional patient-days of atovaquone therapy and $103,683 in excess costs within 3 months of initiation. Major reasons for TMP-SMX avoidance were thrombocytopenia (51.3%), neutropenia (35.4%), renal impairment (31.7%), allergy history (26.8%), and hyperkalemia (19.5%). No breakthrough PJP infections were observed while patients were on atovaquone.ConclusionInstitutional-guideline compliance was high during atovaquone initiation. However, after 3 months, many patients who could have been safely transitioned to TMP-SMX continued to receive atovaquone. This resulted in excess costs and potentially sub-optimal therapy.Disclosures All authors: No reported disclosures.

1306. Evaluation and Predictors of Antiretroviral (ART)-Related Medication Errors in Hospitalized People Living with HIV (PWLH)

BackgroundAs HIV has become a chronic condition, management of the disease and preventing resistance is paramount to improving patient outcomes. Medication errors can lead to suboptimal therapy and potential development of resistance. The purpose of this study was to identify the rate of antiretroviral (ART)-related medication errors in hospitalized people living with HIV (PWLH).MethodsThis was a multi-center, retrospective cohort study of patients diagnosed with HIV and/or AIDS based on International Classification of Diseases codes. Patients were included if they were at least 18 years old and hospitalized between March 2016 and March 2018. Patients were excluded if they were pregnant and only received intravenous zidovudine during their hospitalization. Of the patients eligible for inclusion, 400 were randomly selected and included in this study. The primary objective was to determine the rate of inpatient ART-related medication errors. Secondary objectives included the type of errors and rate of error resolution prior to discharge.ResultsA total of 203 ART-related medication errors occurred during the study period (mean 0.9 ± 1.2 errors per patient). Incorrect schedule was the most common type of error followed by incorrect or incomplete regimen. More errors occurred in male patients (P = 0.01), those known to be infected with HIV on admission (P < 0.05), and in patients with an undetectable viral load (P = 0.01). Approximately 30% of ART-related medication errors were resolved prior to discharge, of which pharmacists were responsible for 25%. Incorrect schedule, incorrect or incomplete regimen, and clinically significant drug-drug interaction (DDI) were the most common medication errors that persisted at discharge. Among resolved errors, resolution of clinically significantly DDI or incorrect/incomplete ART were the most common interventions.ConclusionART-related medication errors continue to occur in hospitalized PLWH and frequently persist at discharge. Interventions should be developed to reduce rates of ART-related medication errors on admission. Antimicrobial stewardship programs serve as an ideal platform to incorporate ART stewardship into routine activities to help minimize errors while inpatient and during transitions of care.Disclosures All authors: No reported disclosures.

Stimulant Use and Study Protocol Completion: Assessing the Ability of Men Who Have Sex with Men to Collect Dried Blood Spots for Laboratory Measurement of HIV Viral Load.

Stimulant use is associated with higher HIV viral load (VL) and sexual HIV transmission risk among men who have sex with men (MSM) living with HIV. There is little research on willingness of drug users living with HIV to fully participate in studies, especially those involving self-collection of biomarker data. This study presents findings from an at-home dried blood spot collection study measuring laboratory-quantified VL among U.S. HIV-positive MSM who reported high-risk sexual behavior and/or suboptimal antiretroviral therapy (ART) adherence to assess the association between drug-use behavior and (1) ability to complete a study protocol and (2) VL outcomes. Among recruited participants (n = 766), 35% reported stimulant drug use (amphetamines, cocaine, crack, crystal meth, ecstasy, or a combination of stimulant drugs), 39% reported using other drugs (heroin, marijuana, prescription opioids, and others), and 27% reported no drug use in the past 3 months. In all, 61% of enrolled participants completed the study protocol. Stimulant drug users were less likely (ARR 0.84; 95% CI 0.72-0.98) to complete the protocol than other drug users. Furthermore, other drug users were significantly less likely than non-drug users (ARR 0.52; 95% CI 0.28-0.97) to have an HIV VL result ≥ 1500 copies/mL. This study provides important estimates regarding the likelihood of participation in biomedical research activities among HIV-positive MSM with varying drug-use behaviors, showing that it is feasible to conduct such biomedical studies with drug-using MSM who report high-risk sexual behavior and struggle with their ART adherence.

A randomized controlled efficacy study of the Medido medication dispenser in Parkinson\u2019s disease

BackgroundComplex medication schedules in Parkinson’s disease (PD) result in lower therapy adherence, which contributes to suboptimal therapy and clinical deterioration. Medication reminder systems might improve therapy adherence and subsequently improve symptoms of PD. This randomized controlled study assessed the effect of the electronic medication dispenser Medido on physical disability in PD, as a proxy for changes in therapy adherence.xMethodsEighty-seven patients were randomized into the Medido group or control group. The primary outcome of physical disability was measured by the AMC Linear Disability Scale (ALDS). Secondary outcomes were quality of life (QoL) (PDQ-39), health status (EQ5D-5L, VAS), non-motor symptoms (NMS-Quest), and QoL of the caregiver (PDQ-carer). Measurements were performed at baseline, and after 3 and 6 months follow-up.ResultsWhen using the Medido, a non-significant improvement of 3.0 points (95% CI -5.6;11.6) was seen in ALDS. The exploratory subgroup Hoehn & Yahr classification (H&Y) > 2.5 improved significantly on ALDS with 14.7 points (95% CI -28.5;-0.9, p = 0.029 for group x time interaction). QoL deteriorated with 1.0 point in PDQ-39 (p = 0.01 for group x time interaction) in favor of the control group. Non-significant differences were observed for VAS (0.4 points, p = 0.057) and NMS-Quest (1.3 points, p = 0.095) in favor of the Medido group. No changes over time were observed in EQ5D-5L and PDQ-carer.ConclusionsBased on these data, no firm conclusion can be drawn, but use of the Medido medication dispenser may result in a clinical improvement of physical disability and seems particularly appropriate for more severe patients.Trial registrationNTR3917. Registered 19 March 2013.

The Interpretation of Prescribed Medication Instructions by Diabetes Mellitus Patients at a Selected Clinic in the Capricorn District of Limpopo Province, South Africa: A Pilot Study

Background: Misinterpretation of medications instructions due to poor health literacy is common in diabetic patients, leading to suboptimal medication therapy. The aim of this study was to investigate patients’ interpretation of prescribed medication instructions at a selected Clinic in the Capricorn District of Limpopo Province, South Africa. Methods: The study used a qualitative research approach. Non-Probability purposive sampling was used to select five participants for the study. Semi-structured interviews with a guide were used to collect data. Tesch’s steps for qualitative data analysis were adopted. Results: The study findings revealed inadequate explanation of instructions, poor health outcomes, lack of information related to poor health outcomes, lack of knowledge on using the medication correctly, and medication noncompliance. The findings imply that there is poor education regarding medication use by diabetic patients. Conclusion: The study indicated that diabetic patients have poor medication instructions comprehension such as an inadequate explanation of the medication instructions. Therefore, healthcare professionals must provide in-depth explanation of medication instructions to enhance comprehension.

Expert opinion: Criteria for second-line treatment failure in patients with multiple sclerosis

ObjectivesIn the management of multiple sclerosis (MS), defining criteria for identification of suboptimal therapy responses and switching treatment is essential to avoid worsening. Despite the lack of a standardised definition, criteria for first-line treatment are well documented in the literature, based on clinical measures or magnetic resonance imaging (MRI) (gadolinium enhancing [Gd+] lesions or new/enlarging T2 lesions) assessed during the first 6–18 months after treatment initiation. However, it is unknown whether the same criteria can be used for second-line treatment failure. MethodsFive regional boards involving 36 French MS experts were convened to discuss published literature regarding criteria for first- and second-line treatment failure, and to identify differences in local therapeutic practices. A national board of 11 experts was subsequently conducted to identify convergences and differences between regions, and to propose second-line criteria for the definition of therapeutic failure. ResultsPublished information is lacking regarding second-line treatment failure criteria. In light of this, regional differences in current therapeutic practices are justifiable. Due to the risk-benefit ratio of these treatments and limited options for third-line treatments, the authors recommend a different therapeutic approach when assessing second-line treatment failure. The treatment switch for second-line treatment should be informed by confirmed disease progression, after 6 months, or combined clinical and MRI outcomes, but only after at least 1 year of treatment. ConclusionsExperts compared therapeutic attitudes and practices regarding second-line treatment failure between French regions. They identified convergences that were used to propose a national agreement on second-line treatment failure criteria, which should be evaluated in real-life prospective cohorts.

Social Determinants of Health and Retention in HIV Care Among Recently Incarcerated Women Living with HIV in Canada

Women living with HIV (WLWH) are over-represented in corrections in Canada, yet little is known about women's experiences post-release. We used CHIWOS cross-sectional data from WLWH to estimate associations between social determinants of health and HIV-related care outcomes among WLWH with recent (within past year) or ever (before past year) incarceration experience. Lifetime incarceration prevalence was 36.9% (6.5% recent; 30.4% ever), with significant differences by province of residence (British Columbia: 10% recent; 52% ever; Ontario: 5%; 24%; Quebec: 6%; 22%; p < 0.001). In adjusted multinomial logistic regression analyses, compared with never incarcerated, recent incarceration was associated with Indigenous ancestry, lower annual income (< $20,000 CAD), unstable housing, current sex work, injection drug use (IDU), and sub-optimal antiretroviral therapy (ART) adherence, while ever incarceration was associated with current sex work, IDU, and experiencing adulthood violence. Our findings have implications regarding supports needed by WLWH in the post-release period, including ART adherence and achieving health and social goals.

Childhood constipation

Constipation is a common problem in childhood. It is often under-reported and families may delay seeking help due to fear of embarrassment and a negative response from healthcare professionals. Healthcare professionals may also underestimate the impact of constipation on the child and their family and this may subsequently contribute to poor clinical outcomes. Although it is rarely life-threatening, many children and young people experience psychological, social and educational consequences that require prolonged support. Signs and symptoms of childhood constipation are often poorly recognised. Delayed diagnosis, suboptimal therapy and lack of understanding of the condition often contribute to the ongoing symptoms and multiple medical consultations.

Prognostic factors of a lower CD4/CD8 ratio in long term viral suppression HIV infected children.

BackgroundCombination antiretroviral therapy (cART) is associated with marked immune reconstitution. Although a long term viral suppression is achievable, not all children however, attain complete immunological recovery due to persistent immune activation. We use CD4/CD8 ratio like a marker of immune reconstitution.MethodsPerinatal HIV-infected children who underwent a first-line cART, achieved viral suppression in the first year and maintained it for more than 5 years, with no viral rebound were included. Logistic models were applied to estimate the prognostic factors, clinical characteristics at cART start, of a lower CD4/CD8 ratio at the last visit.Results146 HIV-infected children were included: 77% Caucasian, 45% male and 28% CDC C. Median age at cART initiation was 2.3 years (IQR: 0.5–6.2). 42 (30%) children received mono-dual therapy previously to cART. Time of undetectable viral load was 9.5 years (IQR: 7.8, 12.5). 33% of the children not achieved CD4/CD8 ratio >1. Univariate analysis showed an association between CD4/CD8 <1 with lower CD4 nadir and baseline CD4; older age at diagnosis and at cART initiation; and a previous exposure to mono-dual therapy. Multivariate analysis also revealed relationship between CD4/CD8 <1 and lower CD4 nadir (OR: 1.002, CI 95% 1.000–1.004) as well as previous exposure to mono-dual therapy (OR: 0.16, CI 95% 0.003–0.720).ConclusionsCD4/CD8 >1 was not achieved in 33% of the children. Lower CD4 nadir and previous exposure to suboptimal therapy, before initiating cART, are factors showing independently association with a worse immune recovery (CD4/CD8 < 1).

Use of Analytics to Identify Patients with Sub-Optimal Cardiac Resynchronization Therapy Pacing

Introduction Heart failure (HF) hospitalizations are of growing concern for patients and payers. Cardiac resynchronization therapy patients that achieve high CRT pacing (>90%) are at lower risk of HF hospitalization. There has been no way to identify patients with suboptimal CRT pacing outside of routine office or remote follow up. Analytic software has been developed to identify programming optimization opportunities at a clinic level. Hypothesis Cardiac device analytic software can identify opportunities for programming optimization and enable improvements in CRT pacing percentage. Methods Cardiac device analytic software (Medtronic PaceartTM Analytics) was used to identify CRT patients with suboptimal CRT pacing at a single center. Patients actively followed within the clinic were included. Patients with CRT pacing programmed off, LV leads off due to diaphragmatic stimulation, or who declined further procedures or more aggressive medical therapy were not included. Reduction in HF related healthcare utilization was modeled based on expected reduction in the risk of HF hospitalizations with increased CRT pacing percentage. Cost savings were estimated using national claims payment data. Results A total of 88 out of 642 patients were identified with suboptimal CRT pacing through the analytic tool. There were 42 patients not eligible for improvement for reasons outlined above; 46 patients were considered eligible for intervention. The mean (standard error) baseline CRT pacing was 71.6% (5.5%). With intervention, 21 patients (45.6%) improved CRT pacing to 94.1% (0.6%). 11 patients improved with control of atrial fibrillation, 9 with treatment of PVC's, and 1 with device reprogramming. This improvement of 22.5% was modeled to prevent 7 HF hospitalizations in 1 year, equating to $117,268 in potential savings to the healthcare system from a payer perspective. Conclusions Analytics data can be used to successfully identify patients that have suboptimal CRT pacing and may lead to cost savings through reducing unnecessary HF hospitalizations

Patient-reported outcomes in light of supportive medications in treatment-naïve lung cancer patients.

The impact of supportive medications on patient-reported outcomes (PROs) has not been systematically evaluated. We describe the supportive medications used by treatment-naïve lung cancer patients and assess their association with PROs from MD Anderson Symptom Inventory (MDASI). Treatment-naïve lung cancer patients who completed PROs from MDASI at the initial visit to MD Anderson Cancer Center were included. Medications from the initial visit were abstracted from the electronic medical records system and categorized into therapeutic classes based on U.S. Pharmacopeia v7.0. A chi-square or Mann-Whitney U test was conducted as appropriate. Among 459 patients, ~ 50% took any analgesics and 25% were on opioids. One-third of patients with moderate-severe pain were not on any analgesics. Patients taking opioids had significantly worse median pain scores (6 vs. 0) compared with those not taking any analgesics (p < 0.0001). Higher proportion of patients with moderate-severe pain took opioids compared with those with mild pain (52% vs. 16%, p < 0.0001). Patients on opioids also reported significantly worse scores for five other cancer-specific core symptoms and all six symptoms rating interference with daily life. Only 15% of patients with higher composite score for depression-related symptoms were on antidepressants. However, patients taking antidepressants did not significantly differ in any individual MDASI symptom scores compared with those not on antidepressants (p = 0.4858). Our results suggest a need for better screening for pain and depression and optimization of pain management in treatment-naïve lung cancer patients since their poor functional status may result in suboptimal cancer therapy.

Efficacy of Home-Based Telerehabilitation vs In-Clinic Therapy for Adults After Stroke

Many patients receive suboptimal rehabilitation therapy doses after stroke owing to limited access to therapists and difficulty with transportation, and their knowledge about stroke is often limited. Telehealth can potentially address these issues. To determine whether treatment targeting arm movement delivered via a home-based telerehabilitation (TR) system has comparable efficacy with dose-matched, intensity-matched therapy delivered in a traditional in-clinic (IC) setting, and to examine whether this system has comparable efficacy for providing stroke education. In this randomized, assessor-blinded, noninferiority trial across 11 US sites, 124 patients who had experienced stroke 4 to 36 weeks prior and had arm motor deficits (Fugl-Meyer [FM] score, 22-56 of 66) were enrolled between September 18, 2015, and December 28, 2017, to receive telerehabilitation therapy in the home (TR group) or therapy at an outpatient rehabilitation therapy clinic (IC group). Primary efficacy analysis used the intent-to-treat population. Participants received 36 sessions (70 minutes each) of arm motor therapy plus stroke education, with therapy intensity, duration, and frequency matched across groups. Change in FM score from baseline to 4 weeks after end of therapy and change in stroke knowledge from baseline to end of therapy. A total of 124 participants (34 women and 90 men) had a mean (SD) age of 61 (14) years, a mean (SD) baseline FM score of 43 (8) points, and were enrolled a mean (SD) of 18.7 (8.9) weeks after experiencing a stroke. Among those treated, patients in the IC group were adherent to 33.6 of the 36 therapy sessions (93.3%) and patients in the TR group were adherent to 35.4 of the 36 assigned therapy sessions (98.3%). Patients in the IC group had a mean (SD) FM score change of 8.36 (7.04) points from baseline to 30 days after therapy (P < .001), while those in the TR group had a mean (SD) change of 7.86 (6.68) points (P < .001). The covariate-adjusted mean FM score change was 0.06 (95% CI, -2.14 to 2.26) points higher in the TR group (P = .96). The noninferiority margin was 2.47 and fell outside the 95% CI, indicating that TR is not inferior to IC therapy. Motor gains remained significant when patients enrolled early (<90 days) or late (≥90 days) after stroke were examined separately. Activity-based training produced substantial gains in arm motor function regardless of whether it was provided via home-based telerehabilitation or traditional in-clinic rehabilitation. The findings of this study suggest that telerehabilitation has the potential to substantially increase access to rehabilitation therapy on a large scale. ClinicalTrials.gov identifier: NCT02360488.

Strategies for Clarifying Penicillin Allergies When Skin Testing Is Not an Option.

Patients with reported penicillin allergies have been proven to experience negative health consequences, such as increased cost, suboptimal antimicrobial therapy, and adverse reactions. Though skin testing has been proposed as a method to clarify penicillin allergies, many institutions may lack the resources to perform skin testing on a wide scale. This literature review describes the current literature surrounding the use of penicillin allergy interviews when skin testing is not an option. Specifically, the review highlights the steps in carrying out a successful antibiotic allergy patient interview, summarizes the clinical evidence surrounding antibiotic allergy clarifications, and addresses key advantages and disadvantages of clarifying antibiotic allergies without the availability of skin testing.