Prescription Sequence Symmetry Analysis (PSSA) to assess prescribing cascades: a step-by-step guide.

Prescribing cascades occur when patients are prescribed medication to treat the adverse drug reaction of previously prescribed medication. Prescription sequence symmetry analysis (PSSA) can be used to assess the association between two medications in prescription or dispensing databases and thus the potential occurrence of prescribing cascades. In this article, a step-by-step guide is presented for conducting PSSA to assess prescribing cascades. We describe considerations for medication data collection and setting time periods for relevant parameters, including washout window, exposure window, continued exposure interval and blackout period. With two examples, we illustrate the impact of changes in these parameters on the strengths of associations observed. Given the impact seen, we recommend that researchers clearly specify and explain all considerations regarding medication included and time windows set when studying prescribing cascades with PSSA, and conduct subgroup and sensitivity analyses.

Continuing the conversation: a cross-sectional study about the effects of work-related adverse events on the mental health of Dutch (resident) obstetrician-gynaecologists (ObGyns).

BACKGROUND: Obstetrician-Gynaecologists (ObGyns) frequently face work-related adverse events such as severe obstetric complications and maternal or neonatal deaths. In 2014, the WATER-1 study showed that ObGyns are at risk of developing work-related posttraumatic stress disorder (PTSD), while many hospitals lacked a professional support system. The aim of the present study is to evaluate the current prevalence of work-related traumatic events and mental health problems among Dutch ObGyns, as well as to examine the current and desired support. METHODS: In 2022, an online questionnaire was sent to all members of the Dutch Society of Obstetrics and Gynaecology (NVOG), including resident and attending ObGyns. The survey included questions about experienced work-related events, current and desired coping strategies, and three validated screening questionnaires for anxiety, depression, and PTSD (HADS, TSQ, and PCL-5). RESULTS: The response rate was 18.8% and 343 questionnaires were included in the analysis. Of the respondents, 93.9% had experienced at least one work-related adverse event, 20.1% had faced a complaint from the national disciplinary board, and 49.4% had considered leaving the profession at any moment in their career. The prevalence rates of clinically relevant anxiety, depression, and psychological distress were 14.3, 4.4, and 15.7%, respectively. The prevalence of work-related PTSD was 0.9% according to DSM-IV and 1.2% according to DSM-5. More than half of the respondents (61.3%) reported the presence of a structured support protocol or approach in their department or hospital, and almost all respondents (92.6%) rated it as sufficient. CONCLUSIONS: The percentages of anxiety, depression, psychological distress and PTSD are comparable to the similar study performed in 2014. Most Dutch ObGyns experience adverse events at work, which can be perceived as traumatic and, in certain cases, may lead to the development of PTSD. Structured support after adverse work-related events is now available in almost two-thirds of workplaces, and was mostly experienced as good. Despite substantial improvements in the availability and satisfaction of professional support after work-related adverse events, the prevalence rates of mental problems remain considerable, and it is imperative to sustain conversation about the mental well-being of ObGyns.

Unplanned cesarean sections in advanced maternal age: A predictive model.

INTRODUCTION: As maternal age during pregnancy is rising all over the world, there is a growing need for prognostic factors that determine maternal and perinatal outcomes in older women. MATERIAL AND METHODS: This study is a retrospective cohort study of women aged 40 years or older at the time of delivery in four Santeon hospitals across the Netherlands between January 2016 and December 2019. Outcomes were compared between women of 40-44 years (advanced maternal age) and 45 years and older (very advanced maternal age). Primary outcome was unplanned cesarean section, secondary outcomes included postpartum hemorrhage and neonatal outcomes. Multivariate regression analysis was performed to analyze predictive factors for unplanned cesarean sections in women who attempted vaginal delivery. Subsequently, a predictive model and risk scores were constructed to predict unplanned cesarean section. RESULTS: A cohort of 1660 women was analyzed; mean maternal age was 41.4 years, 4.8% of the women were 45 years and older. In both groups, more than half of the women had not delivered vaginally before. Unplanned cesarean sections were performed in 21.1% of the deliveries in advanced maternal age and in 29.1% in very advanced maternal age. Four predictive factors were significantly correlated with unplanned cesarean sections: higher body mass index (BMI), no previous vaginal delivery, spontaneous start of delivery and number of days needed for cervical priming. A predictive model was constructed from these factors with an area under the curve of 0.75 (95% confidence interval 0.72-0.78). A sensitivity analysis in nulliparous women proved that BMI, days of cervical priming, age, and gestational age were risk factors, whereas spontaneous start of delivery and induction were protective factors. There was one occurrence of neonatal death. CONCLUSIONS: Women of advanced maternal age and those of very advanced maternal age have a higher chance of having an unplanned cesarean section compared to the general obstetric population in the Netherlands. Unplanned cesarean sections can be predicted through use of our predictive model. Risk increases with higher BMI, no previous vaginal delivery, and increasing number of days needed for cervical priming, whereas spontaneous start of labor lowers the risk. In nulliparous women, age and gestational age also increase risk, but induction lowers the risk of having an unplanned cesarean section.

Cancer detection and complications of transperineal prostate biopsy with antibiotics when indicated.

OBJECTIVES: To describe the prostate cancer (PCa) detection rate, including clinically significant prostate cancer (csPCa), in a large cohort of patients who underwent transperineal ultrasonography-guided systematic prostate biopsy (TPB-US) using a probe-mounted transperineal access system, with magnetic resonance imaging (MRI) cognitive fusion in case of a Prostate Imaging-Reporting and Data System grade 3-5 lesion, under local anaesthesia in an outpatient setting. Additionally, to compare the incidence of procedure-related complications with a cohort of patients undergoing transrectal ultrasonography-guided (TRB-US) and transrectal MRI-guided biopsies (TRB-MRI). PATIENTS AND METHODS: This was an observational cohort study in men who underwent TPB-US prostate biopsy in a large teaching hospital. For each participant, prostate-specific antigen level, clinical tumour stage, prostate volume, MRI parameters, number of (targeted) prostate biopsies, biopsy International Society of Uropathology (ISUP) grade and procedure-related complications were assessed. csPCa was defined as ISUP grade ≥2. Antibiotic prophylaxis was only given in those with an increased risk of urinary tract infection. RESULTS: A total of 1288 TPB-US procedures were evaluated. The overall detection rate for PCa in biopsy-naive patients was 73%, and for csPCa it was 63%. The incidence of hospitalization was 1% in TPB-US (13/1288), compared to 4% in TRB-US (8/214) and 3% in TRB-MRI (7/219; P = 0.002). CONCLUSIONS: Contemporary combined systematic and target TPB-US with MRI cognitive fusion is easy to perform in an outpatient setting, with a high detection rate of csPCa and a low incidence of procedure-related complications.

How safe is the treatment of pregnant women with fear of childbirth using eye movement desensitization and reprocessing therapy? Obstetric outcomes of a multi-center randomized controlled trial.

INTRODUCTION: Pregnant women with fear of childbirth display an elevated risk of a negative delivery experience, birth-related post-traumatic stress disorder, and adverse perinatal outcomes such as preterm birth, low birthweight, and postpartum depression. One of the therapies used to treat fear of childbirth is eye movement desensitization and reprocessing (EMDR) therapy. The purpose of the present study was to determine the obstetric safety and effectiveness of EMDR therapy applied to pregnant women with fear of childbirth. MATERIAL AND METHODS: A randomized controlled trial (the OptiMUM-study) was conducted in two teaching hospitals and five community midwifery practices in the Netherlands (www.trialregister.nl, NTR5122). Pregnant women (n = 141) with a gestational age between 8 and 20 weeks and suffering from fear of childbirth (i.e. sum score on the Wijma Delivery Expectations Questionnaire ≥85) were randomly allocated to either EMDR therapy (n = 70) or care-as-usual (CAU) (n = 71). Outcomes were maternal and neonatal outcomes and patient satisfaction with pregnancy and childbirth. RESULTS: A high percentage of cesarean sections (37.2%) were performed, which did not differ between groups. However, women in the EMDR therapy group proved seven times less likely to request an induction of labor without medical indication than women in the CAU group. There were no other significant differences between the groups in maternal or neonatal outcomes, satisfaction, or childbirth experience. CONCLUSIONS: EMDR therapy during pregnancy does not adversely affect pregnancy or the fetus. Therefore, therapists should not be reluctant to treat pregnant women with fear of childbirth using EMDR therapy.

An interim oral appliance as a screening tool during drug-induced sleep endoscopy to predict treatment success with a mandibular advancement device for obstructive sleep apnea.

PURPOSE: Previous studies have shown a wide range of efficacy (29 to 71%) of a mandibular advancement device (MAD) in the treatment of obstructive sleep apnea (OSA). Currently, the ability to preselect suitable patients for MAD therapy based on individual characteristics related to upper airway collapsibility is limited. We investigated if the use of non-custom interim MAD during drug-induced sleep endoscopy (DISE) could be a valuable screening tool to predict MAD treatment outcome. METHODS: In a single-center prospective study including a consecutive series of patients with OSA, we compared DISE outcomes with a MAD in situ with polysomnography results after 3 months of using the same MAD that was used during DISE. RESULTS: Of 41 patients who completed the study, the median apnea-hypopnea index (AHI) was 16.0 events/h [IQR 7.4-23.4]. Respiratory outcomes on polysomnography, including apnea index (AI), total AHI, AHI in supine position, and oxygen desaturation index, all significantly improved after 3 months of MAD treatment. With complete improvement of the upper airway obstruction with the MAD in situ during DISE in supine position, patients were 6.3 times more likely to be a responder to MAD treatment compared to patients with a persisting complete obstruction, although not statistically significant (OR 6.3; 95%CI 0.9-42.7; p = 0.060). CONCLUSION: The potential predictive value with regard to MAD therapy outcomes of the use of an interim MAD during DISE would be an important finding, since the prediction of MAD therapy outcome is of great clinical and scientific interest. A study with a larger cohort should be performed to further investigate our findings.

Primary reverse total shoulder arthroplasty for fractures requires more revisions than for degenerative conditions 1 year after surgery: an analysis from the Dutch Arthroplasty Register.

BACKGROUND: Although reverse total shoulder arthroplasty (RTSA) is considered a viable treatment strategy for proximal humeral fractures, there is an ongoing discussion of how its revision rate compares with indications performed in the elective setting. First, this study evaluated whether RTSA for fractures conveyed a higher revision rate than RTSA for degenerative conditions (osteoarthritis, rotator cuff arthropathy, rotator cuff tear, or rheumatoid arthritis). Second, this study assessed whether there was a difference in patient-reported outcomes between these 2 groups following primary replacement. Finally, the results of conventional stem designs were compared with those of fracture-specific designs within the fracture group. MATERIALS AND METHODS: This was a retrospective comparative cohort study with registry data from the Netherlands, generated prospectively between 2014 and 2020. Patients (aged ≥ 18 years) were included if they underwent primary RTSA for a fracture (<4 weeks after trauma), osteoarthritis, rotator cuff arthropathy, rotator cuff tear, or rheumatoid arthritis, with follow-up until first revision, death, or the end of the study period. The primary outcome was the revision rate. The secondary outcomes were the Oxford Shoulder Score, EuroQol 5 Dimensions (EQ-5D) score, numerical rating scale score (pain at rest and during activity), recommendation score, and scores assessing change in daily functioning and change in pain. RESULTS: This study included 8753 patients in the degenerative condition group (mean age, 74.3 ± 7.2 years) and 2104 patients in the fracture group (mean age, 74.3 ± 7.8 years). RTSA performed for fractures showed an early steep decline in survivorship: Adjusted for time, age, sex, and arthroplasty brand, the revision risk after 1 year was significantly higher in these patients than in those with degenerative conditions (hazard ratio [HR], 2.50; 95% confidence interval, 1.66-3.77). Over time, the HR steadily decreased, with an HR of 0.98 at year 6. Apart from the recommendation score (which was slightly better within the fracture group), there were no clinically relevant differences in the patient-reported outcome measures after 12 months. Patients who received conventional stems (n = 1137) did not have a higher likelihood of undergoing a revision procedure than those who received fracture-specific stems (n = 675) (HR, 1.70; 95% confidence interval, 0.91-3.17). CONCLUSION: Patients undergoing primary RTSA for fractures have a substantially higher likelihood of undergoing revision within the first year following the procedure than patients with degenerative conditions preoperatively. Although RTSA is regarded as a reliable and safe treatment option for fractures, surgeons should inform patients accordingly and incorporate this information in decision making when opting for head replacement surgery. There were no differences in patient-reported outcomes between the 2 groups and no differences in revision rates between conventional and fracture-specific stem designs.

SNP rs688 within the low-density lipoprotein receptor (LDL-R) gene associates with HCV susceptibility.

BACKGROUND & AIMS: Despite high-risk behaviour, 10%-20% of HCV multiple exposed individuals remain uninfected (MEU), whilst the remainder become infected (MEI). We hypothesize that host factors play a role in HCV susceptibility. We aimed to identify polymorphisms in host genes that encode for proteins involved in viral entry: CD81, Scavenger receptor 1 (SR-1), Low-density lipoprotein receptor (LDL-R), Claudin-1 (CLDN1), Occludin (OCLN) and Niemann-Pick C1-like 1 (NPC1L1). METHODS: Multiple exposed infected and MEU from two observational cohorts were selected. From the MSM study of acute infection with HCV (MOSAIC), HIV-1 infected MEU cases (n = 30) and HIV-1 infected MEI controls (n = 32) were selected based on reported high-risk behaviour. From the Amsterdam Cohorts Studies (ACS) injecting drug users (IDU) cohort, MEU cases (n = 40) and MEI controls (n = 22) were selected who injected drugs for ≥2 years, in the nineties, when HCV incidence was high. Selected single nucleotide polymorphisms (SNPs) were determined by sequencing or SNP assays. RESULTS: No associations were found for SNPs within genes coding for CD81, SR-1, Claudin-1 or Occludin between the MEU and MEI individuals from either cohort. We did observe a significant association for rs688 within the LDL-R gene with HCV infection (OR: 0.41 P = 0.001), however, LDL cholesterol levels did not vary between individuals carrying the differential SNPs. Additionally, a marginal significant effect was found for rs217434 and rs2072183 (OR: 2.07 P = 0.032 and OR: 1.76 P = 0.039, respectively) within NPC1L1. CONCLUSIONS: Our results demonstrate that the rs688 SNP within the LDL-R gene associates with HCV susceptibility through mucosal as well as intravenous exposure.

Staying hepatitis C negative: A systematic review and meta-analysis of cure and reinfection in people who inject drugs.

BACKGROUND AND AIMS: Direct-acting antivirals (DAAs) are highly effective in treating hepatitis C. However, there is concern that cure rates may be lower, and reinfection rates higher, among people who inject drugs. We conducted a systematic review of treatment outcomes achieved with DAAs in  people who inject drugs (PWID). METHODS: A search strategy was used to identify studies that reported sustained viral response (SVR), treatment discontinuation, adherence or reinfection in recent PWID and/or opioid substitution therapy (OST) recipients. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of proportions was used to estimate pooled SVR and treatment discontinuation rates. The pooled relative risk of achieving SVR and pooled reinfection rate were calculated using generalized mixed effects linear models. RESULTS: The search identified 8075 references; 26 were eligible for inclusion. The pooled SVR for recent PWID was 88% (95% CI, 83%-92%) and 91% (95% CI 88%-95%) for OST recipients. The relative risk of achieving SVR for recent PWID compared to non-recent PWID was 0.99 (95% CI, 0.94-1.06). The pooled treatment discontinuation was 2% (95% CI, 1%-4%) for both recent PWID and OST recipients. Amongst recent PWID, the pooled incidence of reinfection was 1.94 per 100 person years (95% CI, 0.87-4.32). In OST recipients, the incidence of reinfection was 0.55 per 100 person years (95% CI, 0.17-1.76). CONCLUSIONS: Treatment outcomes were similar in recent PWID compared to non-PWID treated with DAAs. People who report recent injecting or OST recipients should not be excluded from hepatitis C treatment.

DC-SIGN Polymorphisms Associate with Risk of Hepatitis C Virus Infection Among Men who Have Sex with Men but not Among Injecting Drug Users.

We aimed to identify whether genetic polymorphisms within L-SIGN or DC-SIGN correlate with hepatitis C virus (HCV) susceptibility. A men who have sex with men (MSM) and an injecting drug users (IDU) cohort of HCV cases and multiple-exposed uninfected controls were genotyped for numerous L-SIGN and DC-SIGN polymorphisms. DC-SIGN single nucleotide polymorphisms (SNPs) -139, -871, and -939 correlated with HCV acquisition in the MSM cohort only. When the same SNPs were introduced into a transcription activity assay they demonstrated a reduction in expression with predicted alteration in binding of transcription factors. DC-SIGN promoter SNPs correlated with risk of HCV acquisition via sexual but not IDU exposure, likely through modulation of mRNA expression levels.

Development and validation of the HCV-MOSAIC risk score to assist testing for acute hepatitis C virus (HCV) infection in HIV-infected men who have sex with men (MSM).

Current guidelines recommend hepatitis C virus (HCV) testing for HIV-infected men who have sex with men (MSM) with ongoing risk behaviour, without specifying the type of risk behaviour. We developed and validated the HCV-MOSAIC risk score to assist HCV testing in HIV-infected MSM. The risk score consisted of six self-reported risk factors identified using multivariable logistic regression using data from the Dutch MOSAIC study (n = 213, 2009-2013). Area under the ROC curve (AUC), sensitivity, specificity, post-test-probability-of-disease and diagnostic gain were calculated. The risk score was validated in case-control studies from Belgium (n = 142, 2010-2013) and the United Kingdom (n = 190, 2003-2005) and in cross-sectional surveys at a Dutch sexually transmitted infections clinic (n = 284, 2007-2009). The AUC was 0.82; sensitivity 78.0% and specificity 78.6%. In the validation studies sensitivity ranged from 73.1% to 100% and specificity from 56.2% to 65.6%. The post-test-probability-of-disease ranged from 5.9% to 20.0% given acute HCV prevalence of 1.7% to 6.4%, yielding a diagnostic gain of 4.2% to 13.6%. The HCV-MOSAIC risk score can successfully identify HIV-infected MSM at risk for acute HCV infection. It could be a promising tool to improve HCV testing strategies in various settings.

Hepatitis C virus (HCV) antibody dynamics following acute HCV infection and reinfection among HIV-infected men who have sex with men.

BACKGROUND: A decline of hepatitis C virus (HCV) antibody titers (anti-HCV), ultimately resulting in seroreversion, has been reported following clearance of viremia in both acute and chronic HCV infection. However, frequency of seroreversion remains unknown in human immunodeficiency virus (HIV)/HCV-coinfected patients. We describe anti-HCV dynamics among HIV-infected men who have sex with men (MSM) following acute HCV infection and reinfection. METHODS: Primary acute HCV infection was assumed when a subject was anti-HCV negative prior to the first positive HCV RNA test. Anti-HCV was measured at least annually in 63 HIV-infected MSM, with a median follow-up of 4.0 years (interquartile range [IQR], 2.5-5.7 years). Time from HCV infection to seroconversion, and from seroconversion to seroreversion, was estimated using the Kaplan-Meier method. Longitudinal anti-HCV patterns were studied using a random-effects model to adjust for repeated measures. RESULTS: Median time from HCV infection to seroconversion was 74 days (IQR, 47-125 days). Subjects who cleared HCV RNA (n = 36) showed a significant decrease in anti-HCV levels (P < .001). Among 31 subjects with sustained virologic response (SVR), anti-HCV became undetectable during follow-up in 8; cumulative incidence of seroreversion within 3 years after seroconversion was 37% (95% confidence interval, 18%-66%). Eighteen subjects became reinfected during follow-up; this coincided with a subsequent increase in anti-HCV reactivity. CONCLUSIONS: A decline of anti-HCV reactivity was associated with HCV RNA clearance. Seroreversion was very common following SVR. Upon reinfection, anti-HCV levels increased again. Monitoring anti-HCV levels might therefore be an effective alternative for diagnosis of HCV reinfection.

Screening for hepatitis B and C in first-generation Egyptian migrants living in the Netherlands.

BACKGROUND: Egypt has high prevalence of hepatitis C virus (HCV) infection and intermediate prevalence of hepatitis B virus (HBV) infection; however, infection prevalence among Egyptian migrants is unknown. Considering the asymptomatic onset and development of disease in chronically-infected patients, many may remain undiagnosed. AIMS: To evaluate an HCV- and HBV-screening programme designed to identify undetected infections among first-generation Egyptian migrants in Amsterdam, the Netherlands. METHODS: In 2009 and 2010, viral hepatitis educational and screening sessions were established at Egyptian meeting places. Data regarding demographics and HCV risk factors were collected. Chronically infected participants were referred and followed up. Phylogenetic analyses were used to ascertain the geographic origin of infections. RESULTS: Eleven of 465 (2.4%; 95% CI = 1.3-4.2%) migrants had HCV antibodies; 10/11 were HCV RNA positive. All had genotype 4a, and strains were typical of those of Egypt and the Middle East. Older age and exposure to parenteral antischistosomal therapy (PAT) were significantly associated with HCV. Anti-HBc prevalence was 16.8% (95% CI = 13.7-20.4%); HBsAg prevalence was 1.1% (95% CI = 0.5-2.5%). All had genotype D, typical of those of the Middle East. Most (9/10 HCV; 3/5 HBV) chronic infections were newly diagnosed; four of the HCV-infected individuals started treatment. CONCLUSIONS: Anti-HCV and HBsAg prevalence among Egyptian migrants was lower compared with the general Egyptian population, but higher than the general population of Western countries. Phylogenetic analyses suggest that all infections were from the region of origin. HCV-screening programmes should target first-generation Egyptian migrants, especially those of older age and those who received PAT.

Effects of demographic and sleep-related factors on snoring sound parameters.

OBJECTIVE: To investigate the effect of frequently reported between-individual (viz., age, gender, body mass index [BMI], and apnea-hypopnea index [AHI]) and within-individual (viz., sleep stage and sleep position) snoring sound-related factors on snoring sound parameters in temporal, intensity, and frequency domains. METHODS: This study included 83 adult snorers (mean ± SD age: 42.2 ± 11.3 yrs; male gender: 59%) who underwent an overnight polysomnography (PSG) and simultaneous sound recording, from which a total of 131,745 snoring events were extracted and analyzed. Data on both between-individual and within-individual factors were extracted from the participants' PSG reports. RESULTS: Gender did not have any significant effect on snoring sound parameters. The fundamental frequency (FF; coefficient = -0.31; P = 0.02) and dominant frequency (DF; coefficient = -12.43; P < 0.01) of snoring sounds decreased with the increase of age, and the second formant increased (coefficient = 22.91; P = 0.02) with the increase of BMI. Severe obstructive sleep apnea (OSA; AHI ≥30 events/hour), non-rapid eye movement sleep stage 3 (N3), and supine position were all associated with more, longer, and louder snoring events (P < 0.05). Supine position was associated with higher FF and DF, and lateral decubitus positions were associated with higher formants. CONCLUSIONS: Within the limitations of the current patient profile and included factors, AHI was found to have greater effects on snoring sound parameters than the other between-individual factors. The included within-individual factors were found to have greater effects on snoring sound parameters than the between-individual factors under study.

Predictors of improved psychological function after bariatric surgery.

BACKGROUND: Negative psychological sequelae have been reported after bariatric surgery. It is unclear which factors affect psychological function in the first postoperative years. OBJECTIVE: Evaluation of significant predictors of improved psychological function following bariatric surgery by analyzing data from the BODY-Q questionnaire. SETTING: Multicenter prospective cohort in 3 centers located in The Netherlands and Denmark. METHODS: The BODY-Q questionnaire was used to assess 6 domains of health-related quality of life. The domain of interest, psychological function, consists of 10 questions from which a converted score of 0 (low) to 100 (high) can be calculated. Linear mixed models were used to analyze which patient characteristics were most predictive of the psychological function score. Secondary outcomes of interest were cross-sectional scores of psychological function and the impact of weight loss, and the effect of major short-term complications on psychological function. RESULTS: Data were analyzed from 836 patients who underwent bariatric surgery from 2015 to 2020. Patients with lower expectations concerning weight loss (<40% desired total weight loss), higher educational level, no history of psychiatric illness, and employment before bariatric surgery demonstrated the highest psychological function scores after bariatric surgery. At 1 and 2 years after bariatric surgery, more weight loss was associated with significantly higher psychological function scores. Experiencing a major short-term complication did not significantly impact psychological function. CONCLUSIONS: Several relevant predictors of improved postoperative psychological function have been identified. This knowledge can be used to enhance patient education preoperatively and identify patients at risk for poor psychological functioning postoperatively.

Cold-activated brown adipose tissue in healthy men.

BACKGROUND: Studies in animals indicate that brown adipose tissue is important in the regulation of body weight, and it is possible that individual variation in adaptive thermogenesis can be attributed to variations in the amount or activity of brown adipose tissue. Until recently, the presence of brown adipose tissue was thought to be relevant only in small mammals and infants, with negligible physiologic relevance in adult humans. We performed a systematic examination of the presence, distribution, and activity of brown adipose tissue in lean and obese men during exposure to cold temperature. Brown-adipose-tissue activity was studied in relation to body composition and energy metabolism. METHODS: We studied 24 healthy men--10 who were lean (body-mass index [BMI] [the weight in kilograms divided by the square of the height in meters], < 25) and 14 who were overweight or obese (BMI, > or = 25)--under thermoneutral conditions (22 degrees C) and during mild cold exposure (16 degrees C). Putative brown-adipose-tissue activity was determined with the use of integrated (18)F-fluorodeoxyglucose positron-emission tomography and computed tomography. Body composition and energy expenditure were measured with the use of dual-energy x-ray absorptiometry and indirect calorimetry. RESULTS: Brown-adipose-tissue activity was observed in 23 of the 24 subjects (96%) during cold exposure but not under thermoneutral conditions. The activity was significantly lower in the overweight or obese subjects than in the lean subjects (P=0.007). BMI and percentage of body fat both had significant negative correlations with brown adipose tissue, whereas resting metabolic rate had a significant positive correlation. CONCLUSIONS: The percentage of young men with brown adipose tissue is high, but its activity is reduced in men who are overweight or obese. Brown adipose tissue may be metabolically important in men, and the fact that it is reduced yet present in most overweight or obese subjects may make it a target for the treatment of obesity.

Pulmonary function in children and adolescents with untreated idiopathic scoliosis: a systematic review with meta-regression analysis.

BACKGROUND CONTEXT: One of the controversies in untreated idiopathic scoliosis is the influence of curve size on respiratory function. Whereas scoliosis patients with curves over 90 to 100 degrees are agreed to be at risk for cardiorespiratory failure in later life, the impairment of curves below 90 degrees is generally considered mild. Although various studies showed that pulmonary function is affected in patients with scoliosis, quantification of the relation between curve size and pulmonary function is lacking. PURPOSE: This systematic review with meta-regression analysis aims to characterize the relation between pulmonary function tests and scoliosis severity in children and adolescents with idiopathic scoliosis. STUDY DESIGN: Systematic review with meta-regression analysis. METHODS: Pubmed, Embase, Cochrane, and CINAHL were systematically searched until November 3, 2020, for original articles that reported (1) severity of scoliosis quantified in Cobb angle, and (2) pulmonary function tests in children and adolescents with untreated idiopathic scoliosis. Exclusion criteria were other types of scoliosis, non-original data, post-treatment data, and case reports. All study designs were included, and relevant study details and patient characteristics were extracted. The primary outcome was the effect of Cobb angle on pulmonary function as expressed by the slope coefficient of a linear meta-regression analysis. RESULTS: A total of 126 studies, including 8,723 patients, were retrieved. Meta-regression analysis revealed a statistically significant inverse relation between thoracic Cobb angle and absolute and predicted forced vital capacity in 1 second, forced vital capacity, vital capacity, and total lung capacity. For these outcomes, the slope coefficients showed a decrease of 1% of the predicted pulmonary function per 2.6 to 4.5 degrees of scoliosis. A multivariable meta-regression analysis of potential confounders (age, year of publication, and kyphosis) hardly affected the majority of the outcomes. CONCLUSION: This meta-regression analysis of summary data (means) from 126 studies showed an inverse relationship between the thoracic Cobb angle and pulmonary function. In contrast to previous conclusions, the decline in pulmonary function appears to be gradual over the full range of Cobb angles between <20 and >120 degrees. These findings strengthen the relevance of minimizing curve progression in children with idiopathic scoliosis.

Correlation between the number of patient-reported adverse events, adverse drug events, and quality of life in older patients: an observational study.

BACKGROUND: Previous studies on medication therapy management services, e.g. medication reconciliation and medication review, do not show consistent improvements in patient's health-related quality of life. However, these services can reduce adverse drug events. AIM: To evaluate the correlation between health-related quality of life and adverse events/adverse drug events reported by patients. METHOD: Older patients (≥ 65 years) with polypharmacy (≥ 5 medicines) admitted to orthopaedic or surgical wards were included. Patients were contacted post-discharge to evaluate patient-reported adverse events, health-related quality of life using the EuroQol questionnaire and self-perceived health status on a 5-point Likert scale. The outcomes were the correlation between health-related quality of life and the number of adverse events/adverse drug events, and potential predictors for these events. Spearman correlation and Poisson regression were used for data analysis. RESULTS: 102 patients were included. The correlation between health-related quality of life and adverse events was weak but significant (Spearman correlation coefficient: - 0.328, p = 0.001). No correlation was found for adverse drug events (- 0.064, p = 0.521). Self-perceived health status was a predictor for adverse events, not for adverse drug events. Health-related quality of life was neither a predictor for adverse events, nor for adverse drug events. CONCLUSION: The correlation between the number of patient-reported adverse events, adverse drug events and health-related quality of life measured by the EuroQol was weak. There is a need for a questionnaire that includes the impact of medication use and is sensitive to outcomes that are affected by medication therapy management services.

Recreational drug use among young, hospitalized patients with acute coronary syndrome: A retrospective study.

Background: Cocaine use is a well-established risk factor for acute coronary syndrome (ACS) although other recreational drugs (RD), are increasingly considered as potential cardiac risk factors. Compared to ACS without RD use, worse outcomes have been described for RD-associated ACS. Objective: The aim of this study was to explore the use of RD in a contemporary cohort of young ACS patients. Methods: Between June 2016 and October 2019, ACS patients aged 18-50 years, admitted to OLVG Hospital in Amsterdam, were retrospectively analysed. Medical chart review was performed to obtain patient and clinical characteristics, RD use, cardiac risk factors, outcome and follow up. Results: A total of 229 patients were included in the study. Recreational drug use prior to ACS was present in 24.9% of all patients, with cannabis (16.2%), cocaine (4.8%), or both (2.6%) most commonly observed. RD users were predominantly young men (87.7%) and had a significantly higher tobacco use compared to non-RD users (89.5% vs. 62.8%, P < 0.001), also after adjusting for age and sex. RD use was associated with larger myocardial infarctions with significantly higher CK-MB levels (104 ± 116 U/L vs 62 ± 96, P = 0.040) and poorer left ventricular function measured by echocardiography as compared to non-users (P = 0.007). Conclusion: Recreational drug use was present in almost 25% of all young ACS patients evaluated for drug use and was associated with larger myocardial infarction resulting in poorer left ventricular function as compared to non-users. Additionally, RD-users were younger and were more often tobacco users, compared to non-users.

Fear of Childbirth in Nulliparous Women.

Purpose: The relation between fear of childbirth (FoC) and gestational age is inconclusive, and self-reported need for help regarding this fear has never been investigated. This study aimed to determine the prevalence and course of FoC according to gestational age, to identify risk factors for the development of FoC, the influence of this fear on preferred mode of delivery, and self-reported need for help. Methods: Nulliparous pregnant women of all gestational ages completed an online survey. The study consisted of a cross-sectional and a longitudinal analysis. Women who completed the survey in the first or second trimester (T0) were approached again in their third trimester (T1). The Wijma Delivery Expectancy Questionnaire Version A (W-DEQ A) was used with a cut-off score ≥ 85 to define presence of fear of childbirth. Questionnaires indexing social support, anxiety, symptoms of depression, preferred mode of delivery, and self-reported need for help were included. Results: In total, 364 women were enrolled at T0, and 118 out of 184 eligible women were included in the longitudinal analysis. Point prevalence of FoC at T0 was 18.4% with no significant difference between trimesters. In the longitudinal sample, the prevalence of FoC decreased from 18.6% (T0) to 11.0% (T1), p = 0.004. Although mean scores for FoC decreased significantly, p < 0.001, scores increased in 41 (34.7%) women. The presence of FoC was associated with elevated anxiety, less family support, prenatal care of the obstetrician by choice, preference for a cesarean section, and for pain relief. Women with FoC were more likely to actively seek for help compared to women without FoC. Conclusion: While FoC is common in each trimester, prevalence decreases over the course of pregnancy. Women with FoC are often actively seeking for help, suggesting that this fear should be addressed better, and help should be offered accordingly.