Non-exposed Cohort Research Articles

The association between the fluoxetine use and the occurrence of coronary heart disease: a nationwide retrospective cohort study

BackgroundWe explored if the administration of fluoxetine, recognized for its potential in adipocyte browning, entails a differential risk of coronary heart disease (CHD) in comparison to other SSRI medications.MethodsUsing the National Health Insurance Research Database of Taiwan from 2000 to 2013, we conducted a retrospective cohort study. The exposure cohort comprised individuals prescribed fluoxetine for over 90 days (n = 2,228). Conversely, those administered other SSRIs (excluding fluoxetine) for a duration surpassing 90 days were designated as the non-exposed cohort (n = 8,912). CHD incidence served as our primary outcome measure, and we employed Cox proportional hazards models to scrutinize the relationship between fluoxetine exposure and CHD development rates.ResultsCompared with the non-exposed cohort, the fluoxetine use had a significantly decreased 21% risk of developing CHD in the exposed cohort (adjusted hazard ratio: 0.79%, 95% confidence interval: 0.68–0.92). Noticeably, results indicated that there was an inverse association between the fluoxetine exposure and the risk of CHD, regardless of whether men, women or other age groups.ConclusionOur findings suggest that clinical use of fluoxetine was associated with a 21% reduced risk of CHD relative to other SSRI prescriptions.

Semaglutide exposure and its association with adverse outcomes in diabetic patients undergoing transforaminal lumbar interbody fusion for lumbar degenerative disc disease.

Semaglutide, a novel glucagon-like peptide-1 receptor agonist, has transformed the therapeutic landscape for type 2 diabetes mellitus. However, its effect on osteoclast activity and its potential to induce weight-related muscle loss raises concerns about its impact on spine surgery outcomes. As such, evaluating semaglutide's influence on transforaminal lumbar interbody fusion (TLIF) is imperative, given the procedure's reliance on successful bony fusion to prevent postoperative instability and further interventions. Using an all-payer database (MARINER), the authors analyzed data from patients with type 2 diabetes mellitus who were 18-74 years of age and who underwent short-segment fusion (≤ 3-level) TLIFs between January 2018 and October 2022. Patients were either exposed to semaglutide or not. A comprehensive 1:3 (exposure vs no exposure) matching was performed based on age, sex, obesity, hypertension, coronary artery disease, chronic kidney disease, smoking status, osteoporosis, levels of surgery, and basal-bolus insulin dependence. Kaplan-Meier survival curves and log-rank testing were performed to study the probability of additional lumbar fusion surgery within 1 year. After the 1:3 matching, 1781 patients were identified, with 447 in the semaglutide-exposed cohort and 1334 in the nonexposed cohort. Most patients in both groups were 55-69 years old, and 59.3% were female. Analysis showed that the likelihood of undergoing additional lumbar fusion surgery within 1 year post-TLIF was significantly higher in the semaglutide-exposed group than in the nonexposed group (OR 11.79, 95% CI 8.17-17.33). Kaplan-Meier plots and log-rank testing further confirmed a statistically significant divergent probability in the need for additional surgery within 1 year between the cohorts (log-rank, p < 0.001). Semaglutide exposure appears to be associated with a higher likelihood of additional lumbar fusion surgeries within 1 year post-TLIF, especially in patients receiving the medication for longer durations. Although the mechanisms remain speculative, potential impacts on bone turnover and the onset of muscle loss may be contributory factors. Further research is needed to elucidate the exact mechanisms and to develop strategies for optimizing surgical outcomes in these patients.

Psychosocial Factors Associated With Vulvodynia.

We set out to identify the psychosocial factors associated with vulvodynia and the effects on sexuality, mental health, and quality of life. PubMed, LILACS, Embase, CINAHL, Web of Science, Scopus, and PsycINFO were searched in August 2023. Two authors selected and extracted the data independently. The risk of bias was assessed using the Newcastle-Ottawa Scale for Observational Studies. To rank the strength of evidence, the Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE) approach was utilized. A total of 3,182 articles were identified. Twenty-two observational studies (8 cohorts and 14 case-controls) met the eligibility criteria and were included, comprising 2,624 patients. Vulvodynia has been associated with psychological factors (anxiety and depression) and social factors (childhood exposure to physical and sexual abuse, posttraumatic stress, and domestic abuse). Concerning sexual function, the most frequent outcomes were dyspareunia and sexual dysfunction. Only one study assessed quality of life, which showed that women with chronic vulvar pain had greater difficulty performing physical activities and experienced negative moods and feelings. The assessment of the risk of bias showed that the average quality of studies was good to excellent. However, the studies failed to select the nonexposed cohort or control group to describe the results, and often, the study population was rather small, which made it impossible to carry out a meta-analysis. The certainty of evidence for the associations between anxiety and depression, vulvodynia, and sexual functioning suggests that combating these factors could improve overall quality of life in vulvodynia patients.

Post-traumatic growth in later-life cognitive function? Evidence from the 1976 Great Tangshan Earthquake.

This study aimed to explore the long-term impacts of exposure to earthquake in adolescence on later-life cognitive function in China. Data were from the 2015 China Health and Retirement Longitudinal Study (CHARLS). Our analytical sample comprised 4394 participants aged 49 to 78 from two birth cohorts born between 1937 and 1966: exposed cohort during adolescence (born between 1952 and 1966), and non-exposed cohort during adolescence (born between 1937 and 1951). We defined earthquake exposure as the exposure severity of the 1976 Great Tangshan Earthquake (GTE). We selected community environmental characteristics as our key moderators. A difference-in-differences (DID) method was employed to estimate the long-term impact of the GTE on later-life cognitive function. We found that exposure to the earthquake during adolescence resulted in higher scores of later-life cognitive function (for males: β = 2.18; 95% CI: 0.70-3.66; for females: β = 1.22; 95% CI: 0.11-2.33). For males, this impact was moderated by community environmental characteristics including the old-age allowance program (β = 3.07; 95% CI: 1.94-4.19) and the condition of basic community infrastructures (β = 1.52; 95% CI: 0.84-2.19). Our study supports the post-traumatic growth theory. This finding suggest that individuals with early-life traumatic exposure need to be focused on. Additionally, improving the conditions of community infrastructures and establishing a community environment with comfort and security may be pretty important for promoting cognitive function and post-traumatic growth.

Association between Statins Types with Incidence of Liver Cancer: An Updated Meta-analysis.

Previous studies have found a potential role for statins in liver cancer prevention. This study aimed to explore the effect of different types of statins on the incidence of liver cancer. Relevant articles were systematically retrieved from PubMed, EBSCO, Web of Science, and Cochrane Library databases from inception until July 2022 to explore the relationship between lipophilic statins or hydrophilic statins exposure and the incidence of liver cancer. The main outcome was the incidence of liver cancer. Eleven articles were included in this meta-analysis. The pooled results showed a reduced incidence of liver cancer in patients exposed to lipophilic statins (OR=0.54, p < 0.001) and hydrophilic statins (OR=0.56, p</i> < 0.001) compared with the non-exposed cohort. Subgroup analysis showed that both exposures to lipophilic (Eastern countries: OR=0.51, p</i> < 0.001; Western countries: OR=0.59, p</i> < 0.001) and hydrophilic (Eastern countries: OR=0.51, p</i> < 0.001; Western countries: OR=0.66, p</i>=0.019) statins reduced the incidence of liver cancer in Eastern and Western countries, and the reduction was most significant in Eastern countries. Moreover, atorvastatin (OR=0.55, p</i> < 0.001), simvastatin (OR=0.59, p</i> < 0.001), lovastatin (OR=0.51, p</i> < 0.001), pitavastatin (OR=0.36, p</i>=0.008) and rosuvastatin (OR=0.60, p</i>=0.027) could effectively reduce the incidence of liver cancer, unlike fluvastatin, cerivastatin and pravastatin. Both lipophilic and hydrophilic statins contribute to the prevention of liver cancer. Moreover, the efficacy was influenced by the region and the specific type of statins used.

Impact of maternal first trimester treatment regimen on the outcome of valproate exposed pregnancies: an observational Embryotox cohort study

Effects of valproate (VPA) dose and treatment discontinuation during the first trimester of pregnancy on the risks of spontaneous abortions (SAB) and major birth defects were analyzed. Pregnancies with first trimester VPA exposure (n = 484) prospectively recorded by the German Embryotox center in 1997–2016 were compared with a randomly selected, non-exposed cohort (n = 1446). The SAB risk was not significantly increased in the VPA cohort [HRadj 1.31 (95% CI 0.85–2.02)] but major birth defects were significantly more frequent [8.7% vs. 3.4%; ORadj 2.61 (95% CI 1.51–4.50)]. Risk was even higher in pregnancies with no VPA discontinuation in first trimester [ORadj 3.66 (95% CI 2.04–6.54)]. Significant ORs were found for nervous system defects in general [ORadj 5.69 (95% CI 1.73–18.78)], severe microcephaly [ORadj 6.65 (95% CI 1.17–37.68)], hypospadias [ORadj 19.49 (95% CI 1.80–211)] and urinary system defects [ORadj 6.51 (95% CI 1.48–28.67)]. VPA dose had a stronger effect than antiepileptic poly- versus monotherapy; for VPA dose ≥ 1500 mg/day the ORadj was 5.41 (95% CI 2.32–12.66)]. A daily dose increase of 100 mg was calculated to raise the risk for major birth defects by 15% [OR 1.15 (95% CI 1.08–1.23)]. Overall, maternal first trimester treatment regimen had a relevant impact on birth defect risk.

Differential impact of SARS-CoV-2 infection during different outbreak periods on incident diabetes in Japan: a matched cohort study utilizing health insurance claims.

An increased risk of diabetes after COVID-19 exposure has been reported in Caucasians during the early phase of the pandemic, but the effects across viral variants and in non-Caucasians have not been evaluated. To address this gap, survival analyses were performed for five outbreak periods. From an anonymized health insurance database REZULT for the employees and their dependents of large companies or government agencies in Japan, 5 matched cohorts were generated based on age, sex, area of residence (47 prefectures), and 7 ranges of medical bills (COVID-19 exposed:unexposed = 1:4). Observation of each matching group began on the same day. Incident diabetes type 1 (T1D) and type 2 (T2D) were defined as the first claim during the target period, including at least 1 year before the start of observation. T1D accounted for 0.8% of incident diabetes after the first COVID-19 exposure, similar to the non-exposed cohort. Most T2D in the COVID-19 cohort was observed within a few weeks. After further adjustment for the number of days from the start of observation to hospitalization (a time-dependent variable), the hazard ratio for incident T2D ranged from 14.1 to 20.0, with 95% confidence intervals (95%CI) of 8.7 to 32.0, during the 2-month follow-ups from the original strain outbreak to the Delta variant outbreak (by September 2021), and decreased to 2.0, with a 95%CI of 1.6 to 2.5, during the Omicron outbreak (by March 2022). No association was found during the BA.4/5 outbreak (until September 2022). Males had a higher risk, and the trend toward higher risk in older age groups was inconsistent across the periods. Our large dataset, covering 2019-2023, reports for the first time the impact of COVID-19 on incident diabetes in non-Caucasians. The risk intensity and attributes of post-COVID-19 T2D were inconsistent across outbreak periods, suggesting diverse biological effects of different SARS-CoV-2 variants.

Malignant neoplasms of the respiratory tract and thoracic organs in the remote period in males of Altai krai affected by first nuclear test at Semipalatinsk test site

BACKGROUND: The study of remote effects of radiation exposure on tumor-related morbidity in population remains a matter of great social significance in Altai Krai.&#x0D; AIM: To investigate the incidence rate for malignant neoplasms of respiratory tract and thoracic organs in the remote period in the male population born in 1932–1949 and located in the zone of influence of the first nuclear test.&#x0D; METHODS: This retrospective cohort study was based on the analysis of anonymized data and surgical records on morphologically verified cases of primary malignant neoplasms in a male cohort for the period from 2007 to 2016. In this paper, we studied a cohort fixed by the date of the first nuclear test, with a total of 6383 male individuals. The main (exposed) cohort included 2291 men, while the control (non-exposed) cohort included 4092 men who lived in rural communities of the region that were not affected during the first nuclear test. The cohort included 156 cases of morphologically verified diagnosis of primary malignant neoplasms of the respiratory tract and thoracic organs (codes C30–C39 according to the International Classification of Diseases). Person-time incidence rate (PtR), standard error (mPtR) and confidence intervals (95% CI) were calculated. The incidence of respiratory and thoracic malignant neoplasms, structure and relative risk (RR) were assessed. Statistical processing of the data was performed using licensed Microsoft Office 2016 software.&#x0D; RESULTS: The number of person-years spent at risk for respiratory and thoracic malignancies in the male population in the main cohort was 16 731 person-years, and in the control cohort — 30 747 person-years. In the main cohort, PtR was 436.32×105 person-years, with an mPtR of 51.07 and 95% CI of 334.18–538.45; in the control cohort the PtR was 269.95×105 person-years with an mPtR of 29.63 and 95% CI of 210.68–329.21. The leading localizations of malignant neoplasms of the respiratory and thoracic organs in men in the main and control cohorts were bronchial and lung malignancies and laryngeal malignancies.&#x0D; CONCLUSIONS: An increased relative risk of respiratory and thoracic malignant neoplasms manifesting in the remote period in the male population born and living in rural areas of Altai Krai during the first nuclear test conducted at the Semipalatinsk test site was revealed: RR=1.616, 95% CI 1.180–2.214, with the standard error of relative risk equal to 0.160.

Antiepileptic treatment with levetiracetam during the first trimester and pregnancy outcome: An observational study.

Levetiracetam is increasingly used in pregnant women with epilepsy. Although teratogenic effects have not been observed so far, data on the risks of spontaneous abortion and major birth defects are still limited, especially for the frequently used dual therapy of levetiracetam and lamotrigine. Our primary aim was to analyze rates of major birth defects and spontaneous abortion after maternal levetiracetam treatment. This was a cohort study based on pregnancies recorded by the Embryotox Center from 2000 to 2017. Outcomes of prospectively ascertained pregnancies with first trimester levetiracetam monotherapy (n = 221) were compared to pregnancies with lamotrigine monotherapy for epilepsy (n = 469). In addition, all pregnancies with levetiracetam (n = 364) exposure during the first trimester were analyzed in comparison to a nonexposed cohort (n = 729). Pregnancies with the most frequently used combination therapy comprising levetiracetam and lamotrigine (n = 80) were evaluated separately. There was no significantly increased risk of major birth defects or of spontaneous abortions after first trimester exposure to levetiracetam. Birth weight of male neonates was significantly lower after levetiracetam monotherapy compared to lamotrigine monotherapy. Dual therapy with levetiracetam and lamotrigine resulted in a significantly increased risk of spontaneous abortion (adjusted hazard ratio = 3.01, 95% confidence interval [CI] = 1.43-6.33) and a nonsignificant effect estimate for major birth defects (7.7%, n = 5/65, adjusted odds ratio = 1.47, 95% CI = .48-4.47) compared to a nonexposed cohort. Our study confirms the use of levetiracetam as a suitable antiepileptic drug in pregnancy. The lower birth weight of male neonates after maternal levetiracetam monotherapy and the unexpectedly high risk of spontaneous abortion and birth defects after dual therapy with levetiracetam and lamotrigine require further investigation.

Cutaneous T-Cell Lymphoma and Dupilumab Use: A Retrospective Matched Cohort Study of Clinical Characteristics and Treatment Outcomes

Introduction: Dupilumab is a human monoclonal antibody that inhibits signaling of IL-4 and IL-13 and is currently approved by the Food and Drug Administration for the treatment of atopic dermatitis (AD). While causality has not been established, sporadic reports have emerged associating dupilumab use with the onset, progression, or subsequent diagnosis of cutaneous T-cell lymphomas, in particular mycoses fungoides (MF). The natural history of MF diagnosed after dupilumab exposure remains unclear. We performed a retrospective matched cohort study to compare the clinical characteristics and treatment outcomes of patients with MF based on prior dupilumab exposure. Methods: Through the Memorial Sloan Kettering (MSK) Research &amp; Technology data delivery platform (DataLine), we conducted a search for any patient seen by a provider in the MSK Cutaneous Lymphoma Clinic whose electronic record contained the word ‘dupilumab’ or ‘Dupixent.‘ Once the initial query was performed, we individually reviewed each patient to confirm: (1) A histologically-confirmed diagnosis of MF by an MSK dermatopathologist, and (2) Use of dupilumab prior to the histological diagnosis of MF. After identifying a cohort of patients with confirmed MF after dupilumab use (cases), we identified a matched cohort of patients with confirmed MF and no prior dupilumab use (controls). Specifically, we matched patients for stage at diagnosis, date of birth and age at diagnosis (+/- 5 years), and date of presentation (+/- 5 years). Clinical data and treatment outcomes were collected by clinical review. Baseline characteristics were summarized using descriptive statistics and compared between the two groups using the Wilcoxon rank sum test, Pearson's Chi-squared test, and Fisher's exact test. Overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) were estimated as the elapsed time from initial diagnosis to death, disease recurrence, and progression, respectively. Kaplan-Meier estimates were stratified by exposure to dupilumab, and differences between the estimates were compared using the log-rank test. Results: We identified 25 patients who presented with a new, histologically-confirmed diagnosis of MF following dupilumab treatment for a diagnosis of AD. In 16 of these patients, AD was diagnosed based on a skin biopsy, whereas in 9 patients the diagnosis was based on clinical features only. Among 16 patients with known duration of dupilumab use, the median duration of use was 5.0 months (min/max: 1.5-24 months). In total, 14 patients were diagnosed with early-stage disease (IA n=2, IB n=12) and 11 were diagnosed with advanced stage disease (IIB n=4, IIIA n=2, IVA1 n=5). The estimated time from dupilumab treatment to lymphoma diagnosis was 10.2 months, and the median age at lymphoma diagnosis was 53 years (min/max: 28-84). Compared to the cohort of 25 matched patients with MF and no prior dupilumab use ( Table 1), no difference was observed in race, sex, initial therapy (skin-directed vs. systemic), or total number of therapies. The median follow-up time for patients exposed to dupilumab was 13.2 months (95% CI: 6.8-21.9), and 20.7 months (95% CI: 13.4-27.8) for those not exposed. No differences were observed in OS, PFS, or RFS between the exposed (dupilumab) and non-exposed (non-dupilumab) cohorts ( Figure 1). Two-year OS, PFS, and RFS in the non-dupilumab cohort was 85.0%, 47.3%, and 70.7%, compared to 100.0%, 41.5%, and 79.6% in the dupilumab cohort. One patient in the dupilumab-exposed cohort died of a non-lymphoma malignancy, whereas 4 patients in the non-exposed cohort died (3 due to lymphoma, 1 due to unknown causes). Conclusions: In summary, we identified a relatively large cohort of patients with MF diagnosed after dupilumab treatment. Patients presented with early and advanced-stage disease. Outcome were comparable to a matched cohort of non-exposed patients with MF. The causal relationship between dupilumab and MF remains unproven and deserves dedicated biological study.

Competence Development in an Undergraduate Physiotherapy Internship Program during the COVID-19 Pandemic: A Blended Learning Approach

Introduction: The COVID-19 pandemic has led to the creation of different teaching adaptations shared in health degrees, such as blended teaching methods, including face-to-face learning combined with online learning. Objectives: One objective was to compare the academic performance scores aligned to worked competencies during physiotherapy internships between two groups: one exposed to a blended learning (b-learning) educational model and another exposed to a face-to-face teaching system during internships. Another objective was to study the correlation of the marks of the following year’s internship subject. Design: Analytical study of retrospective cohorts. Settings: Physiotherapy university degree program. Participants: Three hundred students working towards attaining Physiotherapy degrees. Methods: Two groups were studied: the Non-Exposed Cohort, which had 100% face-to-face attendance at the clinical center, and the Exposed Cohort, which experienced b-learning and had 50% attendance at the clinical practice center and 50% completion of asynchronous online complementary training during lockdown. Results: The results show that both in the Exposed Cohort and in the Non-Exposed Cohort, the qualifications and, therefore, the competence development achieved by the students were similar. A stronger correlation with skills activities developed in the Exposed Cohort in relation to the final mark of the following year’s internship subject has been found. Discussion and Conclusions: For all the competencies developed during CS II, participants obtained the same grades in both groups, so it is concluded that the online activities implemented during confinement mixed with face-to-face teaching were useful for the achievement of these skills. Thus, b-learning is a good method for developing clinical practice competencies in physiotherapy students. Contribution of the Paper: Blended teaching (b-teaching) is useful for developing internship competencies. It is necessary to align the activities developed in internships with the evaluated skills.

Pregnancy Outcomes in Women Infected With COVID-19: A Retrospective Cohort Study

Introduction: Studies of the impact of the novel coronavirus 2019 (COVID-19) on pregnancy outcomes have yielded conflicting results. Objective: This study examined pregnancy outcomes in COVID-19-infected and non-infected pregnant women. Materials and Methods: In this retrospective cohort study, we included all pregnant women with (n=42) and without COVID-19 infection (n=185) admitted to a training and treatment center in Babol City, Iran, from March to November 2020. We abstracted the records of all pregnancies in women with COVID-19 (exposed cohort) and women without COVID-19 (non-exposed cohort). Patient information was taken from their medical records. The chisquare test and Student t-test were used for data analysis. Modified Poisson regression and mixed linear model were used to assess the adjusted risk ratio (aRR) and adjusted mean difference (aMD) between COVID-19 infection and pregnancy outcomes. Results: A total of 227 pregnant women (42 in the exposure group, 185 in the non-exposed group) were included in the study. The mean age of mothers was 28.12±6.27 years, and also 48.5% of them had their first pregnancy. In comparison with non-infected women, women with COVID-19 faced the highest risk of cesarean section (aRR: 2.22, 95% CI, 1.35%-3.65%, P=0.002) and preterm birth (aRR: 1.22, 95% CI, 1.02%-1.48%, P=0.026). Also, pregnant women with COVID-19 had a significantly higher duration of hospital stay (aMD: 2.20, 95% CI, 1.32%-3.08%, P=0.001) compared to pregnant women without COVID-19. There was no significant difference between the two groups in terms of postpartum hemorrhage and premature rupture of membranes. Conclusion: This study suggests that COVID-19 infection is associated with an increased risk of cesarean section, preterm birth, and increased duration of hospital stay but not with other outcomes. However, the current evidence does not support its causal effects, given the methodological limitations and small sample size.

Do social media interventions increase vaccine uptake?

The Italian mass COVID-19 vaccination campaign has included children aged 5-11 years as part of the target population since December 2021. One of the biggest challenges to vaccine uptake was vaccine hesitancy among parents and children's caregivers. Primary care pediatricians (PCPs), as the first point of contact between the National Health Service (NHS) and parents/caretakers, initiated various communication strategies to tackle this hesitancy. This study aims to evaluate the impact of a PCP-led social media intervention and a digital reminder service (DRS) on parental hesitancy regarding vaccinating their 5-11-year-old children against COVID-19. A prospective cohort study was designed, and the chosen target populations were parents and caretakers of children aged 5-11 years. Two PCP cohorts were recruited. The first group received a social media intervention and a DRS; while the second group did not. Both cohorts had access to traditional face-to-face and telephone-based counseling. The vaccination coverage rate in the two groups was evaluated. A total of 600 children were enrolled. The exposed cohort (277 patients) received social media intervention, DRS, and counseling options (face-to-face and telephone-based), whereas the non-exposed cohort (323 patients) received only counseling options. In total, 89 patients from the exposed cohort did not receive any dose of the COVID-19 vaccine (32.5%), 165 were fully immunized (59.5%), and 23 received only one dose (8.5%). A total of 150 non-exposed patients did not receive any dose of the COVID-19 vaccine (47%), 147 were fully immunized (45.5%), and 24 only received one dose (7.4%). The difference between the two groups was statistically significant (chi square = 11.5016; p = 0.0006). Social media and DRS interventions had a positive impact on vaccine uptake and may be helpful in tackling vaccine hesitancy. Better-designed studies are needed to corroborate these findings.

Sick leave and disability pension among TMD patients with musculoskeletal diseases, mental and behavioural disorders – a SWEREG-TMD population-based cohort study

BackgroundTemporomandibular disorders (TMD) are associated with musculoskeletal diseases (MSD), mental and behavioural disorders (MBD), and patients with TMD have been shown to have 2–3 times more days of sick leave (SL) and disability pension (DP) than the general population. MSD and MBD are two of the most common causes for SL and DP, and the association between TMD and the influence of comorbidities on the need for SL and DP among TMD patients need further clarification. This study investigates the impact of MSD and MBD comorbidity on SL and DP among TMD patients diagnosed in a hospital setting and/or surgically treated.MethodsAll incident TMD patients diagnosed or treated in a hospital setting between 1998 and 2016 and aged 23–59 were included. A non-exposed comparison cohort was collected from the general population. The cohorts were grouped based on the presence of comorbidity: No comorbidity (Group I); MSD comorbidity (Group II); MBD comorbidity (Group III); and combined MSD and MBD comorbidity (Group IV). Main outcomes were mean annual days of SL and DP, and statistical analysis was conducted using generalized estimated equations.ResultsTMD subjects with no comorbidities (Group I) and with MSD/MBD comorbidity (Group II and III) were 2–3 times more often on SL and DP than the corresponding groups from the general population. However, in the group with both MSD and MBD comorbidity (Group IV), the difference between the TMD subjects and the general population was diminishing, suggesting an additive effect.ConclusionTMD patients are more dependent on SL and DP benefits compared to general population and the difference remains even after considering MSD and MBD comorbidity. In individuals with combined MSD and MBD comorbidity, concurrent TMD has less impact on the need for social insurance benefits. The results accentuate the impact TMD has on the patients’ impaired ability to return to work and why TMD should be recognized as having a substantial impact on individual and economic suffering as well as on societal costs, with emphasis on the influence of comorbidities on patient suffering.

The prevalence of primary and secondary hyperparathyroidism and its cardiometabolic implications in primary aldosteronism.

The aim of this study was to analyze the prevalence of primary and secondary hyperparathyroidism in patients with primary aldosteronism (PA), and its implication on cardiovascular and metabolic outcomes. A retrospective study of patients with PA (exposed cohort, N.=44) and all hypertensive (EH) patients with adrenal lesions without PA nor other adrenal hypersecretion (non-exposed cohort, N.=41) on follow-up at our center between 2016 and 2020. The mean age of patients with PA and EH was 55.1±14.13 and 66.3±10.93 (P<0.001), and 50% of PA and 39.0% of EH were women (P=0.309). At diagnosis, the prevalence of primary hyperparathyroidism in PA was of 18.2%, and all were normocalcemic hyperparathyroidism cases. Globally, no differences were found in the prevalence of primary hyperparathyroidism compared to EH (18.2% vs. 29.3%, P=0.229), but hypercalcemic primary hyperparathyroidism was significantly more prevalent in EH patients than in PA (22.0% vs. 0%, P=0.001). There were 47.7% (N.=21) cases of secondary hyperparathyroidism in patients with PA (4 due to chronic kidney disease (CKD) and vitamin D deficiency, and 17 due to vitamin D deficiency alone). The cardiometabolic profile of patients with PA and hyperparathyroidism (N.=29) was similar to of those patients without hyperparathyroidism (N.=15) at diagnosis and after a median follow-up of 3.6 years (interquartile range 1.1-5.9). Although primary and secondary hyperparathyroidism are common in patients with PA, their prevalence was similar than the observed in EH patients. Primary hyperparathyroidism is usually mild in PA, appearing as normocalcemic forms. No negative implications of the hyperparathyroidism in the cardiometabolic profile of PA were observed.

Maternal Hypertensive Disorder of Pregnancy and Mortality in Offspring From Birth to Young Adulthood: National Population-Based Cohort Study

ABSTRACT Worldwide, hypertensive disorders of pregnancy (HDPs) affect up to 10% of pregnancies. It has been associated with adverse pregnancy and birth outcomes, as well as diseases in the offspring later in life, such as metabolic syndrome, and neurodevelopmental and psychiatric disorders. It has been proposed that maternal HDPs may increase the susceptibility of offspring to disease through multiple pathways, such as placental dysfunction, a hypoxic-ischemic environment in pregnancy, abnormal inflammatory levels, and epigenetic changes. However, there is a scarcity of evidence to support this association. The aim of this study was to examine the association between maternal HDPs with mortality in offspring from birth to young adulthood. This was a population-based cohort study based on data from Danish national health registries. Included were all live births in Denmark between 1978 and 2018. Excluded were those with a birth weight &lt;500 g and gestational age at birth &lt;22 weeks and those who died on the day of birth. Live-born individuals were followed from the date of birth until the date of death, emigration, or December 31, 2018, whichever came first. Maternal HDP was categorized as eclampsia, preeclampsia, or hypertension. Overall, 4.2% of 2,437,718 live-born offspring were exposed prenatally to maternal HDP, including 2.8% exposed to preeclampsia or eclampsia and 1.4% to hypertension. During follow-up of up to 41 years (median, 19.4 [interquartile range 9.7–28.7] years), there were 781 deaths (58.94 per 100,000 person years) among offspring exposed to preeclampsia, 17 deaths (133.73 per 100,000) among those exposed to eclampsia, 223 deaths (44.38 per 100,000) among those exposed to hypertension, and 19,119 deaths (41.99 per 100,000) among those not exposed to HDP. The HDP-exposed cohort had a higher cumulative incidence of all-cause mortality than the nonexposed cohort (2.06% [95% confidence interval {CI}, 1.82%–2.34%] vs 1.69% [95% CI, 1.65%–1.73%]), a 0.37% difference (95% CI, 0.11%–0.64%). The HDP-exposed cohort also had a 26% higher risk (hazard ratio, 1.26 [95% CI, 1.18–1.34]) of all-cause mortality than nonexposed offspring. The risks of all-cause mortality were 29% in those exposed to preeclampsia (1.29 [95% CI, 1.20–1.38]), 118% in those exposed to eclampsia (2.88 [95% CI, 1.79–4.63]), and 12% in those exposed to hypertension (1.12 [95% CI, 0.98–1.28]). There were increased risks for cause-specific mortality in the HDP-exposed cohort, including from digestive diseases (2.09 [95% CI, 1.27–3.43]); conditions originating in the perinatal period (2.04 [95% CI, 1.81–2.30]); endocrine, nutritional, and metabolic diseases (1.56 [95% CI, 1.08–2.27]); and cardiovascular diseases (1.52 [95% CI, 1.08–2.13]). In conclusion, maternal HDP was associated with increased risks of all-cause mortality, as well as cause-specific deaths, including digestive diseases; conditions originating in the perinatal period; endocrine, nutritional, and metabolic diseases; and cardiovascular disease.

Reproductive and sexual health of Australian adolescents exposed to family and domestic violence

BackgroundThere is a dearth of research investigating sexually transmitted infections (STIs) in children exposed to family and domestic violence (FDV). Further, there is no research on terminations of pregnancy in...

Neonatal and long-term outcomes of infants with congenital cytomegalovirus infection and negative amniocentesis: systematic review and meta-analysis.

Cytomegalovirus (CMV) DNA is detectable in the amniotic fluid collected by amniocentesis in cases in which the fetus has been infected. However, cases of congenital neonatal CMV infection with a negative amniocentesis result have also been reported in the literature. The aim of the present study was to compare pregnancies with a negative amniocentesis result to those with a positive amniocentesis result in terms of incidence of fetal insult and long-term sequelae. Observational studies that included pregnant women with CMV infection who underwent amniocentesis and that reported their results together with neonatal and/or long-term outcomes of the offspring were included. The risk of bias in included studies was assessed using the Newcastle-Ottawa Scale. The rate of severe symptoms at birth, defined as neurological symptoms or multiorgan involvement at birth, and the rate of severe sensorineural hearing loss (SNHL) and/or neurodevelopmental impairment at follow-up were the main outcomes of the study. The secondary outcome was the rate of pregnancy termination due to the presence of CMV-associated central nervous system (CNS) findings or multiorgan involvement on ultrasound/magnetic resonance imaging (MRI). Seven studies were included in the systematic review and meta-analysis. The pooled false-negative rate of amniocentesis was 8.0% (95% CI, 5.0-13.0%). The pooled rate of severe symptoms at birth was 0.0% (95% CI, 0.0-1.0%; I2 = 0%) in fetuses with a negative amniocentesis result and 22.0% (95% CI, 11.0-38.0%; I2 = 75%) in those with a positive amniocentesis result. The pooled odds ratio (OR) was 0.03 (95% CI, 0.01-0.10; I2 = 0%). The pooled rate of severe SNHL and/or neurodevelopmental impairment at follow-up in fetuses with a negative amniocentesis result was 0.0% (95% CI, 0.0-1.0%; I2 = 0%) and, in those with a positive amniocentesis result, it was 14.0% (95% CI, 7.0-26.0%; I2 = 64%). The pooled OR was 0.04 (95% CI, 0.01-0.14; I2 = 0%). The pooled rate of pregnancy termination due to the presence of CMV-associated CNS findings or multiorgan involvement on ultrasound/MRI was 0.0% (95% CI, 0.0-2.0%; I2 = 0%) in fetuses with a negative amniocentesis result and 20.0% (95% CI, 10.0-36.0%; I2 = 82%) in those with a positive amniocentesis result. The pooled OR was 0.03 (95% CI, 0.01-0.08; I2 = 0%). A subgroup analysis including only pregnancies with primary CMV infection and a sensitivity analysis including only prospective studies were carried out, showing very similar results to those of the main analysis. A negative amniocentesis result in pregnant women with CMV infection ensures lack of fetal insult and long-term sequelae to the child, even if transmission has occurred. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Impact of Fluoxetine on Herbivorous Zooplankton and Planktivorous Fish.

The contamination of freshwater environments by pharmaceuticals is a growing problem. Modern healthcare uses nearly 3000 substances, many of which are designed to work at low dosages and act on physiological systems that have been evolutionarily conserved across taxa. Because drugs affect the organisms from different trophic levels, pharmaceutical pollution is likely to disturb species interactions. However, such effects are still only poorly understood. We investigated the impacts of environmentally relevant concentrations of the common drug fluoxetine (Prozac), an increasingly common contaminant of European waters, on predation behavior of crucian carp (Carassius carassius), a common planktivorous European fish, and the somatic growth of its prey, the water flea (Daphnia magna), a widespread planktonic crustacean. We exposed these two organisms to environmentally relevant levels of fluoxetine (360 ng L-1 ): the fish for 4 weeks and the water fleas for two generations. We tested the growth of the daphnids and the hunting behavior (reaction distance at which fish attacked Daphnia and feeding rate) of the fish under drug contamination. We found that Daphnia exposed to fluoxetine grew larger than a nonexposed cohort. The hunting behavior of C. carassius was altered when they were exposed to the drug; the reaction distance was shorter, and the feeding rate was slower. These effects occurred regardless of Daphnia size and the treatment regime they were subjected to. Our results suggest that contamination of freshwater environments with fluoxetine can disrupt the top-down ecological control of herbivores by reducing the hunting efficiency of fish and, as a consequence, may lead to increases in cladoceran population numbers. Environ Toxicol Chem 2023;42:385-392. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Does Measles, Mumps, and Rubella (MMR) Vaccination Protect against COVID-19 Outcomes: A Nationwide Cohort Study

Cross-protection from previous live attenuated vaccines is proposed to explain the low impact of COVID-19 on children. This study aimed to evaluate the effect of live attenuated MMR vaccines on the risk of being hospitalized for COVID-19 in children. An exposed (MMR vaccine)-non-exposed cohort study was conducted using the nationwide French National Health Data System (SNDS). We included children born between 1 January 2009 and 31 December 2019. Exposure was defined as a claim of at least one dose of MMR vaccine since birth. Hospitalization for COVID-19 was defined using main diagnostic ICD10 codes. Non-conditional logistic regression was used to calculate the adjusted odds ratios (aORs) of the association between MMR exposure and hospitalization for COVID-19, controlling for socio-demographic and socio-economic factors, co-morbidities, and general health. In total, 6,800,542 (median age 6 IQR [3-8] years) children exposed to a MMR vaccine and 384,162 (6 [3-9] years) not exposed were followed up with for 18 months. Among them, 873 exposed to the MMR vaccine and 38 who were not exposed were hospitalized for COVID-19. In a multi-variate analysis, the exposure of children to MMR vaccination was not associated with a decreased risk of COVID-19 hospitalization versus non-exposure (aOR (95%CI) = 1.09 [0.81-1.48]). A stratified analysis by age showed an aOR = 1.03 [0.64-1.66] for children aged 1-4, an aOR = 1.38 [0.82-2.31] for those aged 5-9, and an aOR = 1.11 [0.54-2.29] for those aged 10-12. Our study suggests that the live attenuated MMR vaccine does not protect children against COVID-19 hospitalization.