Use of prescription opioids in Israel and socio-economic correlations between 2010 and 2020.

BACKGROUND: The use of opioids has increased dramatically over the past several years in Israel. The aim of this study was to explore the trends of opioid consumption in Israel over a decade (2010-2020) stratified by socioeconomic status (SES), residence in the periphery, and ethnic background. METHODS: This cross-sectional study included all adult Maccabi Healthcare Services (MHS) patients who filled at least one prescription for opioids during the past decade. In order to standardize dosages and compare different opioid medications, we used the Morphine Milligram Equivalent (MME) conversion factor. We performed The Mann-Kendall test with autocorrelation correction to assess each trend. We then checked the differences between the trends with the Mann-Whitney test (for periphery) and the Kruskal Wallis (for SES and ethnic background). RESULTS: Between the years 2010-2020, 261,270 MHS members met the study's inclusion criteria. The proportions of opioids consumption were 23.9/1000 patients in 2010 and 27.6/1000 patients in 2020, representing a 15% increase. The average daily consumption of opioids was 4.6 and 10.5 MME in 2010 and 2020, respectively, an increase of 227%. The daily MME during 2020 was higher for residents of the periphery compared to non-periphery residents (daily MME of 14.0 compared to 10.1, respectively). Average daily MME increased gradually during the study period for all levels of SES; the values were highest for the low SES group and the lowest for the high SES group (daily MME in 2020 for the lowest, middle, and high SES groups were 15.2 vs. 11.8 vs. 6.7 respectively). CONCLUSIONS: This study highlights that the primary concern in the increase of opioid use is the increasing dosages. The increase in the number of patients using opioids is also significant but to a minor extent. These phenomena disproportionately impact vulnerable populations. Education programs should be offered to physicians regarding the possible harms of long-term use of opioids. These programs should emphasize the risk factors associated with the development of opioid use disorder (OUD) and the caution needed when increasing dosages or switching to higher-potency drugs. Pain clinics and centers for rehabilitation for patients with chronic pain or OUD should be available, not only in central areas but also in the periphery of the country. These clinics and centers should use a holistic approach and a multidisciplinary team that includes specialists in pain and addiction. They should be financially accessible for patients from low SES group and provide solutions in multiple languages.

Abdominal fat depots are related to lower cognitive functioning and brain volumes in middle-aged males at high Alzheimer's risk.

OBJECTIVE: High BMI, which poorly represents specific fat depots, is linked to poorer cognition and higher dementia risk, with different associations between sexes. This study examined associations of abdominal fat depots with cognition and brain volumes and whether sex modifies this association. METHODS: A total of 204 healthy middle-aged offspring of Alzheimer's dementia patients (mean age = 59.44, 60% females) underwent abdominal magnetic resonance imaging to quantify hepatic, pancreatic, visceral, and subcutaneous adipose tissue and to assess cognition and brain volumes. RESULTS: In the whole sample, higher hepatic fat percentage was associated with lower total gray matter volume (ß = -0.17, p < 0.01). Primarily in males, higher pancreatic fat percentage was associated with lower global cognition (males: ß = -0.27, p = 0.03; females: ß = 0.01, p = 0.93) executive function (males: ß = -0.27, p = 0.03; females: ß = 0.02, p = 0.87), episodic memory (males: ß = -0.28, p = 0.03; females: ß = 0.07, p = 0.48), and inferior frontal gyrus volume (males: ß = -0.28, p = 0.02; females: ß = 0.10, p = 0.33). Visceral and subcutaneous adipose tissue was inversely associated with middle frontal and superior frontal gyrus volumes in males and females. CONCLUSIONS: In middle-aged males at high Alzheimer's dementia risk, but not in females, higher pancreatic fat was associated with lower cognition and brain volumes. These findings suggest a potential sex-specific link between distinct abdominal fat with brain health.

Poor self-rated health is associated with faster cognitive decline and greater small vessel disease in older adults with type 2 diabetes.

OBJECTIVE: Self-rated health (SRH) is a predictor for poor health outcomes and cognition. Older adults with type 2 diabetes mellitus (T2D) have multi-morbidity and greater cognitive impairment. In the present study we investigated the association of SRH with cognitive decline and brain pathology in older adults with T2D. METHODS: Participants (n = 1122) were from the Israel Diabetes and Cognitive Decline study, and SRH was categorised as low (n = 202), moderate (n = 400) or high (n = 520). Cognition was measured by four cognitive domains: episodic memory, executive functions, language, and attention/working memory. Global cognition was the average of the cognitive domains. Statistical models adjusted for sociodemographic, cardiovascular, and clinical variables. In a randomly selected subsample (n = 230) that had magnetic resonance imaging, we examined relationships between baseline SRH and brain characteristics (white matter hyperintensities [WMHs], hippocampal, and total grey matter [GM] volumes). RESULTS: Low SRH was associated with a decline in executive functions, which accelerated over time when compared to high SRH (est = -0.0036; p = <0.001). Compared to high SRH, low SRH was associated with a faster decline in global cognition (est = -0.0024; p = 0.009). Low SRH at baseline was associated with higher volumes of WMHs (est = 9.8420; p < 0.0008). SRH was not associated with other cognitive domains, or with hippocampal and total GM. CONCLUSIONS: Low SRH is associated with cognitive decline in T2D older adults and may serve as a risk assessment. WMHs may represent an underlying mechanism.

Common Bacterial Infections during the 3-Month Period after SARS-CoV-2 Infection: A Retrospective Cohort Study.

INTRODUCTION: Correlations between SARS-CoV-2 and bacterial infections have mainly been studied in hospitals, and these studies have shown that such interactions may be lethal for many. In the context of community flora, less is known of the trends and consequences of viral infections relative to subsequent bacterial infections. PURPOSE: This study aims to explore the prevalence and characteristics of bacterial infections in the three months following SARS-CoV-2 infections, in a community, real-world setting. METHODS: In this retrospective cohort study, we compared patients who completed a polymerase chain reaction (PCR) test or an antigen test for SARS-CoV-2 during January 2022, the peak of the Omicron wave, and examined bacterial infections following the test. We searched these cases for diagnoses of the following four bacterial infections for three months following the test: Group A Streptococcus (GAS) pharyngitis, pneumonia, cellulitis, and urinary tract infections (UTI). RESULTS: During January 2022, 267,931 patients tested positive and 261,909 tested negative for SARS-CoV-2. Test-positive compared to test-negative patients were significantly younger (42.5 years old vs. 48.5 years old, p < 0.001), smoked less, and had fewer comorbidities (including ischemic heart disease, diabetes mellitus, hypertension, chronic obstructive pulmonary disease, and chronic renal failure). In the multivariable analysis, test-positive patients had an increased risk for GAS pharyngitis (adjusted odds ratio [aOR] = 1.25, 95% CI 1.14-1.38, p-value < 0.001) and pneumonia (aOR = 1.25, 95% CI 1.15-1.35, p-value < 0.001), a trend towards an increased prevalence of UTI (aOR = 1.05, 95% CI 0.99-1.12, p-value = 0.092), and lower risk for cellulitis (aOR = 0.92, 95% CI 0.86-0.99, p-value < 0.05). CONCLUSIONS: A history of SARS-CoV-2 infection in the past three months increased susceptibility to respiratory tract bacterial infections and the prevalence of UTI.

Dapagliflozin versus empagliflozin in patients with chronic kidney disease.

Background and Aim: Dapagliflozin and empagliflozin have demonstrated favorable clinical outcomes among patients with chronic kidney disease (CKD). However, their comparative monetary value for improving outcomes in CKD patients is unestablished. We examined the cost-per-outcome implications of utilizing dapagliflozin as compared to empagliflozin for prevention of renal and cardiovascular events in CKD patients. Methods: For calculation of preventable events we divided the allocated budget by the cost needed to treat (CNT) for preventing a single renal or cardiovascular event. CNT was derived by multiplying the annualized number needed to treat (aNNT) by the annual therapy cost. The aNNTs were determined based on data from the DAPA-CKD and EMPEROR-KIDNEY trials. The budget limit was defined based on the threshold recommended by the United States' Institute for Clinical and Economic Review. Results: The aNNT was 42 both dapagliflozin (95% confidence interval [CI]: 34-59) and empagliflozin (CI: 33-66). The CNT estimates for the prevention of one primary event for dapagliflozin and empagliflozin were comparable at $201,911 (CI: $163,452-$283,636) and $209,664 (CI: $164,736-$329,472), respectively. However, diabetic patients had a higher CNT with dapagliflozin ($201,911 [CI: $153,837-$346,133]) than empagliflozin ($134,784 [CI: $109,824-$214,656]), whereas non-diabetic patients had lower CNT for dapagliflozin ($197,103 [CI: $149,029-$346,133]) than empagliflozin ($394,368 [CI: $219,648-$7,093,632]). The CNT for preventing CKD progression was higher for dapagliflozin ($427,858 [CI: $307,673-$855,717]) than empagliflozin ($224,640 [CI: $169,728-$344,448]). For preventing cardiovascular death (CVD), the CNT was lower for dapagliflozin ($1,634,515 [CI: $740,339-∞]) than empagliflozin ($2,990,208 [CI: $1,193,088-∞]). Conclusion: Among patients with CKD, empagliflozin provides a better monetary value for preventing the composite renal and cardiovascular events in diabetic patients while dapagliflozin has a better value for non-diabetic patients. Dapagliflozin provides a better monetary value for the prevention of CVD, whereas empagliflozin has a better value for the prevention of CKD progression.

Liraglutide versus semaglutide for weight reduction-a cost needed to treat analysis.

OBJECTIVE: Higher doses of the glucagon-like peptide-1 agonists liraglutide and, more recently, semaglutide have demonstrated a significant reduction in body weight. However, their comparative value for money for this indication is unclear. METHODS: The cost needed to treat to achieve a 1% reduction in body weight using semaglutide or liraglutide was calculated. The body weight reductions were extracted from the published STEP 1 trial and the SCALE trial results, respectively. A scenario analysis was performed to mitigate the primary differences between the two studies' populations. Drug costs were based on US GoodRx prices as of October 2022. RESULTS: Liraglutide in STEP 1 resulted in a weight loss of 5.4% (95% CI: 5%-5.8%). Semaglutide in SCALE resulted in a weight loss of 12.4% (95% CI: 11.5%-13.4%). The total cost of therapy with liraglutide during the trial was estimated at $17,585 compared with $22,878 with semaglutide. Accordingly, the cost needed to treat per 1% of body weight reduction with liraglutide is estimated at $3256 (95% CI: $3032-$3517) compared with $1845 (95% CI: $1707-$1989) with semaglutide. CONCLUSIONS: Semaglutide provides significantly better value for money than liraglutide for weight reduction.

Effect of Dapagliflozin Versus Empagliflozin on Cardiovascular Death in Patients with Heart Failure Across the Spectrum of Ejection Fraction: Cost per Outcome Analysis.

BACKGROUND: Dapagliflozin and empagliflozin have shown clinical benefits in patients with heart failure (HF). Their comparative monetary value remains undetermined, and we therefore sought to compare the cost-per-outcome implications of utilizing dapagliflozin versus empagliflozin to prevent cardiovascular death (CVD) in patients with HF across the spectrum of ejection fraction. METHODS: We estimated the cost needed to treat (CNT) to prevent one CVD with either dapagliflozin or empagliflozin. CNT was estimated by multiplying the annualized number needed to treat (aNNT) by the annual cost of therapy. The aNNTs were calculated based on data from the DAPA-HF and DELIVER trials for dapagliflozin, and the EMPEROR-Reduced and EMPEROR-Preserved trials for empagliflozin. Drug costs were calculated as 75% of the 2022 US National Average Drug Acquisition Cost. RESULTS: The aNNT to prevent one event of CVD was 110 (95% confidence interval [CI] 58-∞) for dapagliflozin in a pooled analysis of DAPA-HF and DELIVER versus 204 (95% CI 71-∞) for empagliflozin in a pooled analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials. The annual costs of therapy were $4807 and $4992, respectively. The corresponding CNTs were $528,770 (95% CI $278,806-∞) for dapagliflozin and $1,018,368 (95% CI $354,432-∞) for empagliflozin. This remained consistent in Europe, using the price estimates in Germany, with CNT (€77,490 for dapagliflozin and €143,708 for empagliflozin). CONCLUSION: In incorporating data from all four outcomes trials of sodium-glucose cotransporter 2 inhibitors, dapagliflozin provides better monetary value for preventing CVD events in patients with HF across the spectrum of ejection fraction.

Diabetes Control in the Community, Under the Management of a Diabetes-Clinic Nurse Specialist, and the Effect of a Parallel Diabetologist Advice.

INTRODUCTION: Nurses play a key role in managing care and educating people with diabetes in various healthcare systems worldwide, while physicians play this role in others. In addition, some healthcare systems authorize specialist nurses to change patient dose regimens. Therefore, we examined diabetes outcomes in the community by the management of a diabetes-clinic nurse only versus parallel management with a diabetologist. METHODS: Retrospective data were collected for 100 consecutive people with diabetes registered in a community clinic with a diabetes-clinic nurse specialist as a case manager from 1/2018. About half of the patients selected received parallel advice from a diabetologist. Inclusion criteria included poor control of type 2 diabetes (HbA1c above 9%). Patients using an insulin pump, glucose sensor technologies, or multiple injection insulin programs were excluded. RESULTS: One hundred people with diabetes who met the study criteria were included in the study, 64 males and a mean age of 60.03 ± 11.11. In a follow-up of 161.31 ± 68.65 days, HbA1c levels decreased by 3.17% ± 1.95% and did not change in a further follow-up of 162.36 ± 72.75 days. Significant improvement was also observed in controlling the other risk factors examined. Parallel consultation with a diabetologist and the nurse's use of her authority for dose modifications showed no differences in all parameters. Logistic regression for analyzing the effect of the variables related to the patient showed only a moderate effect. CONCLUSIONS: Access to professional services remains a significant challenge for healthcare systems in long-term diabetes control. Monitoring poorly controlled people with diabetes with the help of a diabetes-clinic nurse specialist in the community clinic significantly improved diabetes and risk factors control and persisted long after the intervention. Healthcare systems should consider expanding the service of the diabetes-clinic nurse specialist in the community. Further studies will be required to examine the results in different patient subgroups.

Long COVID symptoms in Israeli children with and without a history of SARS-CoV-2 infection: a cross-sectional study.

OBJECTIVES: To estimate the prevalence of long COVID symptoms in children with and without a history of SARS-CoV-2 infection and to evaluate factors associated with long COVID. DESIGN: A nationwide cross-sectional study. SETTING: Primary care. PARTICIPANTS: 3240 parents of children aged 5-18 with and without SARS-CoV-2 infection completed an online questionnaire (11.9% response rate); 1148 and 2092 with/without a history of infection, respectively. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the prevalence of long COVID symptoms in children with/without a history of infection. Secondary outcomes were the factors associated with the presence of long COVID symptoms and with failure to return to baseline health status in children with a history of infection including gender, age, time from illness, symptomatic illness and vaccine status. RESULTS: Most long COVID symptoms were more prevalent in children with a history of SARS-CoV-2 infection: headaches (211 (18.4%) vs 114 (5.4%), p<0.001), weakness (173 (15.1%) vs 70 (3.3%), p<0.001), fatigue (141 (12.3%) vs 133 (6.4%), p<0.001) and abdominal pain (109 (9.5%) vs 79 (3.8%), p<0.001). Most long COVID symptoms in children with a history of SARS-CoV-2 infection were more prevalent in the older age group (12-18) compared with the younger age group (5-11). Some symptoms were more prevalent in children without a history of SARS-CoV-2 infection, including attention problems with school malfunctioning (225 (10.8%) vs 98 (8.5%), p=0.05), stress (190 (9.1%) vs 65 (5.7%), p<0.001), social problems (164 (7.8%) vs 32 (2.8%)) and weight changes (143 (6.8%) vs 43 (3.7%), p<0.001). CONCLUSION: This study suggests that the prevalence of long COVID symptoms in children with a history of SARS-CoV-2 infection might be higher and more prevalent in adolescents than in young children. Some of the symptoms, mainly somatic symptoms, were more prevalent in children without a history of SARS-CoV-2 infection, highlighting the impact of the pandemic itself rather than the infection.

Decrease in Gait Speed Over Time Is Associated With Increase in Number of Depression Symptoms in Older Adults With Type 2 Diabetes.

BACKGROUND: We examined the cross-sectional and longitudinal relationships of motor functions with depression in older adults with type 2 diabetes (T2D). METHODS: Participants (n = 984) were from the longitudinal Israel Diabetes and Cognitive Decline (IDCD) study. They were initially cognitively normal and underwent evaluations of motor functions (grip strength and gait speed) and of depression (using the 15-item version of the Geriatric Depression Scale [GDS]) approximately every 18 months. We applied Hierarchical Linear Mixed Models (HLMM) to investigate the associations between motor functions and depression adjusting for sociodemographic, cardiovascular factors, overall cognitive score, and subjective report of exhaustion. RESULTS: Participants' baseline characteristics were 72 (±5) years of age (59.6% males), 13 (±4) years of education, Mini-Mental Status Exam (MMSE) score of 28.01 (±1.78), and a GDS score of (2 ± 2.00), consistent with normal cognitive status and lack of major affective symptomatology. Slower gait speed at baseline was associated with higher GDS scores (p = .001) and with their increase over time (p = .049). A decrease in walking speed from baseline was associated with an increase in GDS scores (p = .015). Lower grip strength at baseline was associated with higher GDS scores (p = .002), but not with trajectories in GDS scores over time. A faster decrease in grip strength from baseline was associated with a faster increase in GDS scores (p = .022). CONCLUSIONS: Both gait speed and grip strength are cross-sectionally associated with depression. However, only gait speed and its decrease over time can potentially be used to predict incident depression symptoms, thus facilitating the introduction of depression prevention strategies.

Tirzepatide versus semaglutide for weight loss in patients with type 2 diabetes mellitus: A value for money analysis.

AIMS: Higher doses of the glucagon-like peptide-1 agonist semaglutide and, more recently, tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 agonist showed a significant reduction in body weight in patients with type 2 diabetes mellitus. However, their comparative value for money for this indication is unclear. Therefore, we aimed to establish which provides better value for money. MATERIALS AND METHODS: We calculated the cost needed to treat to achieve a 1% reduction in body weight using high-dose tirzepatide (15 mg) versus semaglutide (2.4 mg). The body weight reductions were extracted from published results of SURMOUNT-1 and STEP 1 trials, respectively. In addition, we performed a scenario analysis to mitigate the primary differences between the two study populations. Drug costs were based on US GoodRx prices as of October 2022. RESULTS: Using tirzepatide resulted in a weight loss of 17.8% (95% CI: 16.3%-19.3%) compared with 12.4% (95% CI: 11.5%-13.4%) for semaglutide. The total cost of 72 weeks of tirzepatide was estimated at $17 527 compared with $22 878 for 68 weeks of semaglutide. Accordingly, the cost needed to treat per 1% of body weight reduction with tirzepatide is estimated at $985 (95% CI: $908-$1075) compared with $1845 (95% CI: $1707-$1989) with semaglutide. Scenario analysis confirmed these findings. CONCLUSIONS: Tirzepatide provides better value for money than semaglutide for weight reduction.

Musculoskeletal Pains among Phlebotomists in Outpatient Clinics: Prevalence and Association with Personal Factors and Ergonomic Analysis of the Workstation.

OBJECTIVE: To investigate the prevalence of musculoskeletal problems reported by phlebotomists, and the association of these problems with workstation characteristics and personal factors. METHODS: Self-administered questionnaires were distributed to phlebotomists (n = 115; 65.2% response rate). In addition to the Nordic Musculoskeletal Questionnaire, we asked respondents to provide sociodemographic data. An ergonomic score was used for the characterization of workstations. RESULTS: Symptoms in at least 1 body area within a year were reported by 80.7% of the participants. The lower back, neck, and shoulders were the most common areas in which symptoms occurred (72.7%, 60.9%, and 59%, respectively); these were also the areas with the highest incidence of symptoms disrupting work. A logistic regression model for predicting pain within a year found adequate leg space as a significant component of the ergonomic score (P = .045, OR = 0.222), which was also a protective factor for neck pain disrupting work (P = .047, OR = 0.385). CONCLUSIONS: Musculoskeletal problems among phlebotomists were high. Therefore, the positive effects of simple ergonomic measures should be confirmed in further research.

Long-COVID in patients with a history of mild or asymptomatic SARS-CoV-2 infection: a Nationwide Cohort Study.

OBJECTIVE: Evaluating the prevalence of long-COVID symptoms in patients with a history of mild or asymptomatic infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the factors associated with developing long-COVID. DESIGN: A nationwide cohort study. Using a centralized database, we have identified patients with and without a history of SARS-CoV-2 infection 1-6 months before data collection. Patients were asked to fill out an online questionnaire through text messages. SETTING: Israeli general practice. SUBJECTS: 2755 persons participated in the study in September 2021 (a response rate of 7.5%): 819 with and, 936 without a history of SARS-CoV-2 infection. MAIN OUTCOME MEASURES: We asked patients to provide details about their demographic status, medical history, COVID-related variables and the presence of long-COVID symptoms. RESULTS: Most prevalent long-COVID symptoms were decreased smell sensation (35.1% vs. 4.3%, p < 0.001), decreased taste sensation (25.2% vs. 3.2%, p < 0.001), memory disturbances (36.9% vs. 14.4%, p < 0.001), dyspnea (24.2% vs. 10.7%, p < 0.001) and arthralgia (33% vs. 16.3%, p < 0.001). Risk factors associated with long-COVID included female gender, symptomatic COVID-19, overweight or obesity and the presence of dyslipidemia. About 34.6% of participants reported not returning to their baseline health condition after the acute illness. CONCLUSION: Long-COVID is frequently seen following a mild symptomatic COVID-19 infection and, to a lesser extent, following an asymptomatic SARS-CoV-2 infection. Primary care physicians should be aware of these symptoms and consider this option in their differential diagnosis. Health policymakers should expect a significant impact of this syndrome on public health.Key PointsLong-COVID has emerged as a significant health problem with a serious impact on normal daily function• Long-COVID symptoms were evident in patients with mild symptomatic disease and in asymptomatic patients to a lesser extent.• Risk factors for having Long-COVID symptoms include female gender, symptomatic disease, increased BMI, and the presence of dyslipidemia.• Fatigue, dyspnea, weakness, decreased libido, weight changes, memory, and sleep disturbances were associated with not returning to the baseline health state.

Aspirin with Low-Dose Ticagrelor or with Low-Dose Rivaroxaban for Secondary Prevention: A Cost per Outcome Analysis.

INTRODUCTION: Secondary prevention of cardiovascular events among patients with diagnosed cardiovascular disease and high ischemic risk poses a significant challenge in clinical practice. The combinations of aspirin with low-dose (LD) ticagrelor or LD rivaroxaban have shown superiority in preventing major adverse cardiovascular events (MACE) compared with aspirin treatment alone. The comparative value for money of these two regimens remains unexplored. METHODS: We analyzed each regimen's annual cost needed to treat (CNT) by multiplying the annualized number needed to treat (aNNT) by the annual cost of each drug. The aNNTs were based on outcome data from PEGASUS TIMI-54 and COMPASS trials. Scenario analyses were performed to overcome variances in terms of population risk. Costs were calculated as 75% of US National Average Drug Acquisition Cost (NADAC), extracted in January 2022. The primary outcome was defined as CNT to prevent one MACE across the two regimens. Secondary value analysis was performed for myocardial infarction (MI), stroke, and cardiovascular death as separate outcomes. RESULTS: The aNNTs to prevent MACE with LD ticagrelor and with LD rivaroxaban were 229 [95% confidence interval (CI) 141-734] and 147 (95% CI 104-252), respectively. At an annual cost of US$3726 versus US$4533, the corresponding CNTs were US$853,254 (95% CI 525,366-2,734,884) with LD ticagrelor and US$666,351 (95% CI 471,432-1,142,316) with LD rivaroxaban. CONCLUSION: Combining aspirin with LD rivaroxaban provides better value for money than with LD ticagrelor for secondary prevention of MACE.

Oral versus subcutaneous semaglutide for prevention of major adverse cardiovascular events: cost per outcome analysis of SUSTAIN-6 and PIONEER-6.

BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP1a), reduces the risk of major adverse cardiovascular events (MACE) in patients with Type 2 diabetes mellitus (T2DM). An oral version of semaglutide is now available, and patients may prefer it over the subcutaneous form. Our objective was to compare the value for money of the two modalities by assessing the cost needed to treat (CNT) to prevent MACE. METHODS: The CNT to prevent MACE was figured by multiplying the one-year number needed to treat (NNT) with either oral or subcutaneous semaglutide by the annual cost of therapy. Efficacy estimates and the resulting NNT figures were extracted from the published results of the SUSTAIN-6 and the PIONEER-6 trials for the injectable and oral versions of semaglutide, respectively. Drug costs were estimated as 75% of the United States national average drug acquisition cost listing in June 2021. We performed a scenario analysis to mitigate the primary differences between the populations in the two trials. Sensitivity analysis was performed to evaluate the effect of price changes of the interventions. RESULTS: The CNT to prevent one MACE with subcutaneous semaglutide in SUSTAIN-6 was $966,693 ($594,888-$5,035,302) compared to $948,689 ($463,465-∞) with oral semaglutide in PIONEER-6. The scenario analysis demonstrated a 17% lower CNT for oral semaglutide. The difference between CNTs was sensitive to price fluctuations of the two interventions. CONCLUSIONS: Oral and subcutaneous semaglutide prescribed to prevent MACE in patients with T2DM provide similar value for money. The choice between both therapies should be guided mainly by patient preferences.

Usefulness of Empagliflozin Versus Oral Semaglutide for Prevention of Cardiovascular Mortality in Patients With Type 2 Diabetes Mellitus.

Empagliflozin and oral semaglutide reduce the incidence of cardiovascular mortality (CVM) in patients with type 2 diabetes mellitus. However, these therapies impose a significant financial burden on healthcare systems. Therefore, we compared the value for money of empagliflozin versus oral semaglutide to prevent CVM. We calculated the cost needed to treat to prevent 1 case of CVM using either drug by multiplying the annualized number needed to treat to prevent 1 event by the annual cost of the therapy. Efficacy estimates were extracted from published randomized controlled trials data. We performed a scenario analysis to mitigate the primary differences between the populations of randomized controlled trials. Drug costs were calculated as 75% of the United States National Average Drug Acquisition Cost listing. The annualized number needed to treat for empagliflozin in EMPA-REG-OUTCOME was 141 (95% confidence interval [CI] 104 to 230) and 141 (95% CI 96 to 879) for oral semaglutide in PIONEER 6. The annual treatment costs are $4,797 for empagliflozin versus $7,133 for oral semaglutide. Therefore, the corresponding costs needed to treat are $676,385 ($498,894-$1,101,039) and $1,005,855 (95% CI $684,837-$6,270,544) respectively. In conclusion, our findings suggest that empagliflozin provides better value for money than oral semaglutide to prevent CVM in patients with type 2 diabetes mellitus at the current United States prices of the interventions.

BNT162b2 mRNA COVID-19 (Comirnaty) Vaccine Effectiveness in Elderly Patients Who Live in Long-Term Care Facilities: A Nationwide Cohort.

INTRODUCTION: In early 2020, the novel SARS-CoV-2 virus began to spread around the world and claim victims. Initially, in the Western world, COVID-19-related mortality was due to illness in long-term care facilities (LTCFs). To manage the COVID-19 crisis in LTCFs in Israel, the Ministry of Health established a task force named "Senior Shield." The task force executed a screening program of weekly polymerase chain reaction (PCR) SARS-CoV-2 tests for LTCF residents and caregivers, and at a later stage, the task force led the Ministry of Health vaccination program at LTCFs. This study aimed to estimate the effectiveness of the BNT162b2 mRNA COVID-19 (Comirnaty) vaccine in reducing COVID-19 morbidity and mortality in LTCF residents. METHODS: We designed a nationwide cohort study utilizing data from the Senior Shield task force. Residents had received the vaccines starting December 2020. The study follow-up period was 5 months (ending May 2021). We defined four outcomes: (a) documented SARS-CoV-2 infection, defined by a positive PCR test, (b) COVID-19 death, defined by a positive PCR test followed by death, (c) all-cause mortality, defined as death regardless of the result of a PCR test, and (d) a composite endpoint which included documented SARS-CoV-2 infection or death, the earliest of both. We used Kaplan-Meier curves with a log-rank comparison and Cox regression with a time-dependent covariate model to estimate adjusted hazard ratios for vaccine effectiveness (VE). The index date was the date of the first vaccine dose. In unvaccinated residents, the index date was the first date of vaccination in their LTCF. RESULTS: A total of 43,596 residents with a mean age of 83 years living in 454 LTCFs were found eligible for this study. Ninety-one percent of the study population received the first vaccine dose (39,482) and 86% received the second vaccine dose (37,656). Estimated VE 28 days after the first vaccine dose (approximately 7 days after the second vaccine dose) was 81.2% for SARS-CoV-2 infection, 85.3% for COVID-related death, 63.7% for all-cause mortality, and 71.1% for the composite endpoint (SARS-CoV-2 infection or death). CONCLUSION: This study shows that the BNT162b2 mRNA COVID-19 vaccine effectively prevents SARS-CoV-2 infection, COVID-19-related death, and all-cause mortality in LTCF residents. Further research is warranted on the effect of the third vaccine (booster) in this population.

Personal growth in early pregnancy: the role of perceived stress and emotion regulation.

OBJECTIVE: Coping with the stress aroused by early pregnancy can not only result in distress, but may constitute an opportunity to experience personal growth. Relying on the model of posttraumatic growth, this study examined the contribution of perceived stress and emotion regulation to women's personal growth during the first trimester of pregnancy. METHOD: A convenience sample of Israeli women (n=170), who were during their first trimester of pregnancy (up to 13 weeks), over 18 years old, and capable to completing the instruments in Hebrew, were recruited through a women's health clinic and through social media during the years 2017-2019. RESULTS: The findings indicate that primiparous mothers report higher personal growth than multiparous. In addition, younger age, being primiparous, and higher cognitive-reappraisal contributed to greater personal growth. Moreover, a curvilinear association was found between perceived stress and personal growth, so that a medium level of stress was associated with the highest level of growth. Finally, cognitive-reappraisal fully mediated the relationship between perceived stress and personal growth. CONCLUSIONS: The findings add to the growing body of knowledge concerning the implications of early pregnancy in general, and personal growth as a result of dealing with the stress typical of this period in particular and highlight the role of the perceived stress as well as the woman's personal characteristics and resources that contribute to this result.

Dapagliflozin Versus Sacubitril-Valsartan to Improve Outcomes of Patients with Reduced Ejection Fraction and Diabetes Mellitus.

BACKGROUND: Comorbid heart failure with reduced ejection fraction (HFrEF) and type 2 diabetes mellitus (DM) is associated with a very high risk of HF events. Sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), and dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, improve HF outcomes in these patients, but their comparative value for money in this patient population has not yet been determined. OBJECTIVE: We aimed to compare the cost needed to treat (CNT) to avoid an HF event with each drug. METHODS: CNT was estimated by multiplying the annualized number needed to treat (NNT) to prevent one HF event by the annual cost of each therapy. HF events were defined as the first event of hospitalization for HF or cardiovascular mortality. Drug efficacy data were extracted from published secondary analyses of patients with DM in the DAPA-HF and PARADIGM-HF trials. Drug costs were estimated as 75% of the 2021 US National Average Drug Acquisition Cost listing. Sensitivity analysis was performed on parameters that may have affected the CNT. RESULTS: The annualized NNT was 24 (95% confidence interval [CI] 16-54) for dapagliflozin and 57 (95% CI 31-433) for the ARNI. At an annual cost of $US4523 and 5099, respectively, the CNT was $US108,563 (95% CI 72,375-244,267) for dapagliflozin and $US290,671 (95% CI 158,084-2,208,079) for the ARNI. CONCLUSIONS: Dapagliflozin seems to offer greater value for money than the ARNI for patients with HFrEF and DM. Our results provide support for contemporary guidelines advocating the use of dapagliflozin in these patients.

Comparison of Smoking Cessation Program Registration, Participation, Smoking Cessation Medication Utilization, and Abstinence Rates Between Smokers With and Without Schizophrenia, Schizo-affective Disorder, or Bipolar Disorder.

INTRODUCTION: People with serious mental illness (SMI) are three times more likely to smoke and be heavy smokers than smokers without SMI. Counseling combined with smoking cessation medication (SCM) is the recommended treatment. However, until 2017, SCM prescription for SMI smokers was discouraged (FDA black box warning). This study compared use of smoking cessation programs (SCP) and SCM between smokers with and without SMI. AIMS AND METHODS: Data regarding SCP and SCM use were extracted from the database of a large HMO that offers free Group and telephone SCP. SCP registration, participation, completion, and abstinence rates between July 2013 and December 2019 were compared between smokers with and without SMI, controlling for demographic and health variables. RESULTS: 48 000 smokers registered for a SCP during the study period. Smokers with SMI were 1.8 times more likely to register for a SCP than smokers without SMI. Smokers without SMI were, however, 1.2 times more likely to start the SCP, 1.5 times more likely to complete the SCP, and 1.6 times more likely to have quit by the end of the program. The strongest factors predicting abstinence were SCP completion and SCM use. Smokers with SMI were less likely to purchase SCM, although their purchase rate increased after the black box warning was lifted. CONCLUSIONS: Smoking cessation programs and SCM use should be encouraged in the SMI population. Providing support during the quit attempt and adapting SCP to the needs of smokers with SMI, combined with SCM prescription promotion, should improve abstinence. IMPLICATIONS: Smokers with serious mental illness (SMI) were more likely to seek professional help to quit smoking than non-SMI smokers, with over 30% achieving abstinence, discrediting healthcare professional beliefs that SMI smokers don't want to and cannot quit. Smoking cessation program (SCP) completion and smoking cessation medication (SCM) utilization were the strongest predictors of abstinence. SMI smokers were more likely to drop out of SCPs and less likely to use SCMs. Providing support during the quit attempt and adapting SCPs to the needs of smokers with SMI, combined with SCM prescription promotion, should improve abstinence.