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Background Anhedonia is a core feature of major depressive disorder (MDD), yet the clinical burden in real-world settings is not well understood. This retrospective cohort study assessed depression symptoms and treatment patterns among patients with MDD with and without prominent anhedonia. Methods Patients with MDD were selected from a real-world dataset of electronic health records from mental health specialists and linked medical and pharmacy claims (OM1, Inc. Boston MA) between January 2013 through August 2023. Patients were included if the first Patient Health Questionnaire 9-item (PHQ-9) score indicated moderate to severe depression (≥ 10) with a MDD diagnosis +/-30 days. The date of the patients’ first PHQ-9 score was used as the index date. Patients with a score ≥ 2 on PHQ-9 item 1 (anhedonia) at the index date were classified as MDD with prominent anhedonia (MDD-ANH) ( n  = 4,255). The remaining patients were classified as Other-MDD ( n  = 1,454). Treatment patterns were assessed using prescription records in the year following the index date. The last PHQ-9 score in the year following the index date was used to assess remission rates (PHQ-9 score < 5) or persistence of moderate to severe depression. Results A total of 5,709 patients with MDD were assessed; 74.5% were in MDD-ANH and 25.5% were in the Other-MDD cohort (met criteria for MDD but not prominent anhedonia). The mean index PHQ-9 score was 18.2 (SD = 4.2) for MDD-ANH patients and 13.5 (SD = 2.9) for Other-MDD patients. The percentage of patients treated with antidepressants was 86.4% in the MDD-ANH group and 84.7% in the Other-MDD group. After adjusting for baseline characteristics, patients with MDD-ANH were more likely to have been treated with atypical antipsychotics (OR = 1.51, p  < 0.001), more likely to have switched medication (OR = 1.24, p  = 0.004), and more likely to have augmented antidepressant therapy (OR = 1.16, p  = 0.021) than Other-MDD patients. Patients with MDD-ANH were less likely to have achieved remission (OR = 0.82, p  = 0.003) and were more likely to have persistent depression (OR = 1.50, p  < 0.001) than patients with Other-MDD. Conclusions Overall, MDD-ANH patients had higher clinical burden reflected in more depressive symptoms, higher treatment utilization and lower rates of remission compared to Other-MDD.

This study assesses the attributable impact of adherence to oral glucose medications as a risk factor for poor glycemic control in population subgroups of a large general population, using an objective medication adherence measure. Using electronic health records data, adherence to diabetes medications over a two-year period was calculated by prescription-based Medication Possession Ratios for adults with diabetes diagnosed before January 1, 2010. Glycemic control was determined by the HbA1c test closest to the last drug prescription during 2010-2012. Poor control was defined as HbA1c>75 mmol/mol (9.0%). Medication adherence was categorized as \"good\" (>80%), \"moderate\" (50-80%), or \"poor\" (<50%). Logistic regression models assessed the role medication adherence plays in the association between disease duration, age, and poor glycemic control. We calculated the change in the attributable fraction of glucose control if the non-adherent diabetic medication population would become adherent by age-groups. Among 228,846 diabetes patients treated by oral antiglycemic medication, 46.4% had good, 28.8% had moderate, and 24.8% had poor adherence. Good adherence rates increased with increasing disease duration, while glycemic control became worse. There was a strong inverse association between adherence level and poor control (OR = 2.50; CI = 2.43-2.58), and adherence was a significant mediator between age and poor control. A large portion of the diabetes population is reported to have poor adherence to oral diabetes medications, which is strongly associated with poor glycemic control in all disease durations. While poor adherence does not mediate the poorer glycemic control seen in patients with longer-standing disease, it is a significant mediator of poor glycemic control among younger diabetes patients. A greater fraction of poorly controlled younger patients, compared to older patients, could be prevented if at least 80% adherence to their medications was achieved. Therefore, our results suggest that interventions to improve adherence should focus on this younger sub-group.

Background. Streptococcus pneumoniae contributes considerably to the burden of pneumonia and invasive pneumococcal disease (IPD), with the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for preventing all-cause pneumonia still undetermined. The aim of this study was to control for common biases and confounders associated with previous observational studies and to assess PPSV23 vaccine effectiveness in preventing IPD and the most resource-intensive type of community-acquired pneumonia, hospital-treated pneumonia (HTP). Methods. This was a retrospective case-control study nested in a population-based cohort, with age-, sex-, and risk-matched controls as the base case. Demographic information, laboratory data, and diagnoses were extracted from the chronic disease registry and from inpatient and outpatient records in the Clalit Health Services database. Vaccine effectiveness for PPSV23 was assessed using multivariable conditional logistic regression. Subgroup, sensitivity, and secondary analyses were conducted to validate findings. Results. A total of 470 070 individuals aged ≥65 years were members of Clalit Health Services during the study period (1 January 2007 through 31 December 2010). The case cohort consisted of 212 participants with IPD and 23 441 with HTP. The adjusted association between vaccination and IPD was protective (odds ratio [OR], 0.58; 95% confidence interval [CI], .41–.81), whereas there was no demonstrated protective effect between vaccination and HTP (OR, 1.01; 95% CI, .97–1.04). The sensitivity analysis and all but 1 subgroup analysis provided consistent results to the base case. Conclusions. The PPSV23 vaccine is effective against the most severe invasive forms of pneumococcal disease, but the lack of effectiveness of PPSV23 in protecting against all-cause HTP should be considered for future vaccine policies.

Decisions on dual antiplatelet therapy (DAPT) duration should balance the opposing risks of ischaemia and bleeding. Our aim was to develop a risk score to identify stable coronary artery disease (SCAD) patients undergoing PCI who would benefit or suffer from extending DAPT beyond 6 months. Retrospective analysis of a cohort of patients who completed 6 months of DAPT following PCI. Predictors of ischaemic and bleeding events for the 6-12 month period post-PCI were identified and a risk score was developed to estimate the likelihood of benefiting from extending DAPT beyond 6 months. Incidence of mortality, ischaemic and bleeding events for patients treated with DAPT for 6 vs. 6-12 months, was compared, stratified by strata of the risk score. The study included 2,699 patients. Over 6 months' follow up, there were 78 (2.9%) ischaemic and 43 (1.6%) bleeding events. Four variables (heart failure, left ventricular ejection fraction ≤30%, left main or three vessel CAD, status post (s/p) PCI and s/p stroke) predicted ischemic events, two variables (age>75, haemoglobin <10 g/dL) predicted bleeding. In the lower stratum of the risk score, 6-12 months of treatment with DAPT resulted in increased bleeding (p = 0.045) with no decrease in ischaemic events. In the upper stratum, 6-12 months DAPT was associated with reduced ischaemic events (p = 0.029), with no increase in bleeding. In a population of SCAD patients who completed 6 months of DAPT, a risk score for subsequent ischaemic and bleeding events identified patients likely to benefit from continuing or stopping DAPT.

Background With increasing diabetes prevalence worldwide, an impending diabetes “pandemic” has been reported. However, definitions of incident cases and the population at risk remain varied and ambiguous. This study analyzed trends in mortality and screening that contribute to diabetes prevalence and incidence, distinguishing between new incident cases and newly detected cases. Methods In an integrated provider-and-payer-system covering 53% of Israel’s population, a composite diabetes case-finding algorithm was built using diagnoses, lab tests, and antidiabetic medication purchases from the organization’s electronic medical record database. Data were extracted on adult members aged 26+ each year from January 1, 2004 through December 31, 2012. Rates of diabetes prevalence, incidence, screening, and mortality were reported, with incidence rates evaluated among the total, “previously-screened,” and “previously-unscreened” at-risk populations. Results There were 343,554 diabetes cases in 2012 (14.4%) out of 2,379,712 members aged 26+. A consistent but decelerating upward trend in diabetes prevalence was observed from 2004-2012. Annual mortality rates among diabetics decreased from 13.8/1000 to 10.7/1000 (p = 0.0002). Total population incidence rates declined from 13.3/1000 in 2006 to 10.8/1000 in 2012 (p < 0.0001), with similar incidence trends (13.2/1000 to 10.2/1000; p = 0.0007) among previously-screened at-risk members, and a rise in testing rates from 53.0% to 66.7% (p = 0.0004). The previously-unscreened group decreased 28.6%, and the incidence rates within this group remained stable. Conclusions The increase in diabetes prevalence is decelerating despite declining mortality and increasing testing rates. A decline in previously-screened incident cases and a shrinking pool of previously-unscreened members suggests that diabetes trends in Israel are moving toward equilibrium, rather than a growing epidemic.

Objective To evaluate the extent to which circulating biomarker and supplements of vitamin D are associated with mortality from cardiovascular, cancer, or other conditions, under various circumstances.Design Systematic review and meta-analysis of observational studies and randomised controlled trials.Data sources Medline, Embase, Cochrane Library, and reference lists of relevant studies to August 2013; correspondance with investigators.Study selection Observational cohort studies and randomised controlled trials in adults, which reported associations between vitamin D (measured as circulating 25-hydroxyvitamin D concentration or vitamin D supplement given singly) and cause specific mortality outcomes.Data extraction Data were extracted by two independent investigators, and a consensus was reached with involvement of a third. Study specific relative risks from 73 cohort studies (849 412 participants) and 22 randomised controlled trials (vitamin D given alone versus placebo or no treatment; 30 716 participants) were meta-analysed using random effects models and were grouped by study and population characteristics.Results In the primary prevention observational studies, comparing bottom versus top thirds of baseline circulating 25-hydroxyvitamin D distribution, pooled relative risks were 1.35 (95% confidence interval 1.13 to 1.61) for death from cardiovascular disease, 1.14 (1.01 to 1.29) for death from cancer, 1.30 (1.07 to 1.59) for non-vascular, non-cancer death, and 1.35 (1.22 to 1.49) for all cause mortality. Subgroup analyses in the observational studies indicated that risk of mortality was significantly higher in studies with lower baseline use of vitamin D supplements. In randomised controlled trials, relative risks for all cause mortality were 0.89 (0.80 to 0.99) for vitamin D3 supplementation and 1.04 (0.97 to 1.11) for vitamin D2 supplementation. The effects observed for vitamin D3 supplementation remained unchanged when grouped by various characteristics. However, for vitamin D2 supplementation, increased risks of mortality were observed in studies with lower intervention doses and shorter average intervention periods.Conclusions Evidence from observational studies indicates inverse associations of circulating 25-hydroxyvitamin D with risks of death due to cardiovascular disease, cancer, and other causes. Supplementation with vitamin D3 significantly reduces overall mortality among older adults; however, before any widespread supplementation, further investigations will be required to establish the optimal dose and duration and whether vitamin D3 and D2 have different effects on mortality risk.

Correspondence to Oren Miron, Clalit Research Institute, Clalit Health Services, Ramat Gan 5252247, Israel; orenmi@clalit.org.il Introduction In the early 2000s, the USA was the global leader in opioid prescription fulfillment rates, which led to an epidemic of misuse and overdoses from prescription opioids.1 Opioid prescription fulfillment has also been increasing in other countries in the Organization for Economic Co-operation and Development, with the largest increase from 2011 to 2016 occurring in Israel.2 3 Opioid prescription fulfillment represents an increased risk in the outpatient setting, where it is less monitored, specifically in young and healthy patients, creating a need to examine the trend in these groups. Methods Data are sourced from Clalit Health Services, Israel’s largest payer/provider healthcare organization, with a total covered population of 4.5 million members in 2018 (52% of the Israeli population). Ethics approval The study was approved by Institutional Review Board of Clalit Health Services as a retrospective analysis of existing data without contacting or disseminating results to participants.

Abstract Background To date, no study has examined influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalizations during pregnancy. Methods The Pregnancy Influenza Vaccine Effectiveness Network (PREVENT) consisted of public health or healthcare systems with integrated laboratory, medical, and vaccination records in Australia, Canada (Alberta and Ontario), Israel, and the United States (California, Oregon, and Washington). Sites identified pregnant women aged 18 through 50 years whose pregnancies overlapped with local influenza seasons from 2010 through 2016. Administrative data were used to identify hospitalizations with acute respiratory or febrile illness (ARFI) and clinician-ordered real-time reverse transcription polymerase chain reaction (rRT-PCR) testing for influenza viruses. Overall IVE was estimated using the test-negative design and adjusting for site, season, season timing, and high-risk medical conditions. Results Among 19450 hospitalizations with an ARFI discharge diagnosis (across 25 site-specific study seasons), only 1030 (6%) of the pregnant women were tested for influenza viruses by rRT-PCR. Approximately half of these women had pneumonia or influenza discharge diagnoses (54%). Influenza A or B virus infections were detected in 598/1030 (58%) of the ARFI hospitalizations with influenza testing. Across sites and seasons, 13% of rRT-PCR-confirmed influenza-positive pregnant women were vaccinated compared with 22% of influenza-negative pregnant women; the adjusted overall IVE was 40% (95% confidence interval = 12%–59%) against influenza-associated hospitalization during pregnancy. Conclusion Between 2010 and 2016, influenza vaccines offered moderate protection against laboratory-confirmed influenza-associated hospitalizations during pregnancy, which may further inform the benefits of maternal influenza vaccination programs. In this retrospective study of hospitals in Australia, Canada, Israel, and the United States from 2010 to 2016, influenza vaccines were 40% effective in preventing laboratory-confirmed influenza-associated hospitalizations during pregnancy.

Abstract Background Influenza vaccine effectiveness (VE) varies by season, circulating influenza strain, age, and geographic location. There have been few studies of influenza VE among hospitalized children, particularly in Europe and the Middle East. Methods We estimated VE against influenza hospitalization among children aged 6 months to 8 years at Clalit Health Services hospitals in Israel in the 2015–2016, 2016–2017, and 2017–2018 influenza seasons, using the test-negative design. Estimates were computed for full and partial vaccination. Results We included 326 influenza-positive case patients and 2821 influenza-negative controls (140 case patients and 971 controls from 2015–2016, 36 case patients and 1069 controls from 2016–2017, and 150 case patients and 781 controls from 2017–2018). Over all seasons, VE was 53.9% for full vaccination (95% confidence interval [CI], 38.6%–68.3%), and 25.6% for partial vaccination (−3% to 47%). In 2015–2016, most viruses were influenza A(H1N1) and vaccine lineage–mismatched influenza B/Victoria; the VE for fully vaccinated children was statistically significant for influenza A (80.7%; 95% CI, 40.3%–96.1%) but not B (23.0%; −38.5% to 59.4%). During 2016–2017, influenza A(H3N2) predominated, and VE was (70.8%; 95% CI, 17.4%–92.4%). In 2017–2018, influenza A(H3N2), H1N1 and lineage-mismatched influenza B/Yamagata cocirculated; VE was statistically significant for influenza B (63.0%; 95% CI, 24.2%–83.7%) but not influenza A (46.3%; −7.2% to 75.3%). Conclusions Influenza vaccine was effective in preventing hospitalizations among fully vaccinated Israeli children over 3 influenza seasons, but not among partially vaccinated children. There was cross-lineage protection in a season where the vaccine contained B/Victoria and the circulating strain was B/Yamagata, but not in a season with the opposite vaccine-circulating strain distribution. Influenza vaccine was effective against influenza-associated hospitalization for fully vaccinated Israeli children, but not for partially vaccinated children. Vaccine-mediated cross-lineage protection against influenza B was seen for a trivalent vaccine containing B/Victoria but not for a B/Yamagata vaccine.

To study the association between vitamin D status and the risk of incident impaired fasting glucose (IFG) and diabetes in a population-based cohort of diabetes-free subjects. In a historical prospective cohort study of subjects from the Clalit Health Services database, which includes information on nearly 4 million people, diabetes-free subjects aged 40-70 years with serum 25-hydroxycholecalciferol (25-OHD) measurements available were followed for 2 years to assess the development of IFG and diabetes in five 25-OHD subgroups: ≥25, 25.1-37.5, 37.6-50, 50.1-75, and >75 nmol/L. The baseline cohort included 117,960 adults: 83,526 normoglycemic subjects and 34,434 subjects with IFG. During follow-up, 8,629 subjects (10.3% of the normoglycemic group) developed IFG, and 2,162 subjects (1.8% of the total cohort) progressed to diabetes. A multivariable model adjusted for age, sex, population group, immigrant status, BMI, season of vitamin D measurement, LDL and HDL cholesterol, triglycerides, estimated glomerular filtration rate, history of hypertension or cardiovascular disease, Charlson comorbidity index, smoking, and socioeconomic status revealed an inverse association between 25-OHD and the risk of progression to IFG and diabetes. The odds of transitioning from normoglycemia to IFG, from normoglycemia to diabetes, and from IFG to diabetes in subjects with a 25-OHD level ≤25 nmol/L were greater than those of subjects with a 25-OHD level >75 nmol/L [odds ratio 1.13 (95% CI 1.03-1.24), 1.77 (1.11-2.83), and 1.43 (1.16-1.76), respectively]. Vitamin D deficiency appears to be an independent risk factor for the development of IFG and diabetes.