A meta-analysis identifies factors predicting the future development of freezing of gait in Parkinson's disease.

Freezing of gait (FOG) is a debilitating problem that is common among many, but not all, people with Parkinson's disease (PD). Numerous attempts have been made at treating FOG to reduce its negative impact on fall risk, functional independence, and health-related quality of life. However, optimal treatment remains elusive. Observational studies have recently investigated factors that differ among patients with PD who later develop FOG, compared to those who do not. With prediction and prevention in mind, we conducted a systematic review and meta-analysis of publications through 31.12.2022 to identify risk factors. Studies were included if they used a cohort design, included patients with PD without FOG at baseline, data on possible FOG predictors were measured at baseline, and incident FOG was assessed at follow-up. 1068 original papers were identified, 38 met a-priori criteria, and 35 studies were included in the meta-analysis (n = 8973; mean follow-up: 4.1 ± 2.7 years). Factors significantly associated with a risk of incident FOG included: higher age at onset of PD, greater severity of motor symptoms, depression, anxiety, poorer cognitive status, and use of levodopa and COMT inhibitors. Most results were robust in four subgroup analyses. These findings indicate that changes associated with FOG incidence can be detected in a subset of patients with PD, sometimes as long as 12 years before FOG manifests, supporting the possibility of predicting FOG incidence. Intriguingly, some of these factors may be modifiable, suggesting that steps can be taken to lower the risk and possibly even prevent the future development of FOG.

Healthcare utilization, costs, and epidemiology of Huntington's disease in Israel.

Introduction: Data on Huntington's disease (HD) epidemiology, treatment patterns, and economic burden in Israel are scarce. Methods: Annual prevalence and incidence of HD (ICD-9-CM 333.4) were assessed in the Israel-based Maccabi Healthcare Services (MHS) database 2016-2018. Adherence (medication possession rate [MPR], proportion of disease covered) were assessed for adult people with HD (PwHD) 2013-2018. Healthcare resources utilization (HCRU) and costs related to inpatient and outpatient visits and all medications in 2018 were assessed for PwHD, who were randomly matched to MHS members without HD (1:3) by birth-year and sex. Results: Overall, 164 patients had at least one HD diagnosis. Annual prevalence and incidence were 4.45 and 0.24/100,000, respectively. A total of 67.0% of adult patients (n = 106) were taking tetrabenazine (median MPR and proportion of disease covered, 74.3% and 30.2%, respectively), 65.1% benzodiazepines (75.8% and 32.3%), and 11.3% amantadine (79.2% and 6.0%). Over a 1-year follow-up, PwHD (n = 81) had significantly more neurologist, psychiatrist, physiotherapist, and speech therapist visits (P < 0.05 for each) and more hospitalization days (P < 0.0001) compared with matched controls (n = 243). Total healthcare and medication costs per patient (US dollars) were significantly higher for PwHD than controls ($7,343 vs. $3,625; P < 0.001). Discussion/Conclusion: PwHD have greater annual HCRU and medical costs than MHS members without HD in Israel. Among those who have taken medications, adherence was lower than 80% (both MPR and proportion of disease covered), which may translate into suboptimal symptom relief and quality of life.

Progressive supranuclear palsy's economical burden: the use and costs of healthcare resources in a large health provider in Israel.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare and fatal neurodegenerative movement disorder with no disease modifying therapy currently available. Data on the costs associated with PSP are scarce. This study aims to assess the direct medical expenditure of patients with PSP (PwPSP) throughout disease course. METHODS: This retrospective cohort study is based on the data of a large state-mandated health provider in Israel. We identified PwPSP who were initially diagnosed between 2000 and 2017. Each PwPSP was randomly matched to three health-plan members without PSP by birth-year, sex, and socioeconomic status. Healthcare resources' utilization and related costs were assessed. RESULTS: We identified 88 eligible PwPSP and 264 people in the reference group; mean age at diagnosis was 72.6 years (SD = 8.4) and 53.4% were female. The annual direct costs of PwPSP have risen over time, reaching US$ 21,637 in the fifth year and US$ 36,693 in the tenth year of follow-up vs US$ 8910 in the year prior diagnosis. Compared to people without PSP, PwPSP had substantially higher medical expenditure during the years prior- and post-index date. CONCLUSION: The present study demonstrates higher economic burden, which increases with time, in PwPSP as compared to those without.

Clinical outcomes of COVID-19 in patients with multiple sclerosis treated with ocrelizumab in the pre- and post-SARS-CoV-2 vaccination periods: Insights from Israel.

The coronavirus disease 2019 (COVID-19) pandemic caused challenges in the management of patients living with multiple sclerosis (PLwMS). We investigated the occurrence and severity of COVID-19 infection post-vaccination among PLwMS treated with ocrelizumab and enrolled in the Maccabi Health Services (MHS) (n = 289) or followed at the Hadassah Medical Center (HMC) (n = 80) in Israel. Most patients were fully vaccinated (MHS n = 218; HMC n = 76) and confirmed infection post-vaccination was low (3.7% and 2.6%, respectively). MHS: infection was more severe (hospitalization/intensive care unit/death) in non-vaccinated (33.3%) vs vaccinated patients (25%). HMC: one vaccinated patient required hospitalization with COVID-19 vs two unvaccinated patients. These data from two Israel cohorts suggest that occurrence of COVID-19 after mRNA vaccination is low and limited in severity.

Epidemiology of Progressive Supranuclear Palsy: Real World Data from the Second Largest Health Plan in Israel.

Progressive supranuclear palsy (PSP) is a rare and fatal neurodegenerative movement disorder and no disease modifying therapy (DMT) is currently available. This study aims to assess the epidemiology of PSP in Israel and to describe its clinical features. This retrospective analysis identified patients with PSP between 2000 and 2018 over the age of 40 years at first diagnosis (index date). We identified 209 patients with ≥1 diagnosis of PSP. Of those, 88 patients satisfied the inclusion criteria with a mean age at diagnosis of 72 years (SD = 8) and 53% were female. The 2018 prevalence and incidence rates were 5.3 and 1 per 100,000 persons, respectively. Median survival time was 4.9 years (95% CI 3.6-6.1) and median time from initial symptom to diagnosis was 4.2 years. The most common misdiagnoses were Parkinson's disease, cognitive disorder and depression. The present study demonstrates that the clinic-epidemiological features of PSP in Israel are similar to PSP worldwide. In light of PSP's rarity, investigation of PSP cohorts in different countries may create a proper platform for upcoming DMT trials.

The Clinical and Economic Burden of Tardive Dyskinesia in Israel: Real-World Data Analysis.

PURPOSE/BACKGROUND: Tardive dyskinesia (TD) is a hyperkinetic movement disorder caused by exposure to dopamine-receptor blockers. Data on TD burden in Israel are scarce. This analysis assesses the clinical and economic burden of TD in Israeli patients. METHODS/PROCEDURES: This retrospective analysis used a national health plan database (Maccabi Healthcare Services), representing 25% of the Israeli population. The study included adults alive at index date with an International Classification of Diseases, Ninth Revision, Clinical Modification TD diagnosis before 2018 and more than or equal to 1-year enrollment before diagnosis. Tardive dyskinesia patients were matched to non-TD patients (1:3) by underlying psychiatric condition, birth year, and sex. Treatment patterns and 2018 annual health care resource utilization and costs were assessed. FINDINGS/RESULTS: Of 454 TD patients alive between 2013 and 2018, 333 alive on January 1, 2018, were matched to 999 non-TD patients. At baseline, TD patients had lower socioeconomic status and higher proportion of chronic kidney disease and antipsychotic medication use; all analyses were adjusted accordingly. Tardive dyskinesia patients had significantly more visits to general physicians, neurologists, psychiatrists, physiotherapists, and emergency departments versus non-TD patients (all P < 0.05). Tardive dyskinesia patients also had significantly longer hospital stays than non-TD patients ( P = 0.003). Total healthcare and medication costs per patient were significantly higher in the TD versus non-TD population (US $11,079 vs US $7145, P = 0.018). IMPLICATIONS/CONCLUSIONS: Israeli TD patients have higher clinical and economic burden than non-TD patients. Understanding real-world health care resource utilization and costs allows clinicians and decision makers to quantify TD burden and prioritize resources for TD patients' treatment.

Risk of Parkinson Disease Among Adults With vs Without Posttraumatic Stress Disorder.

Importance: Posttraumatic stress disorder (PTSD) in elderly men may be associated with increased risk of Parkinson disease (PD); thus, this group of patients needs to be monitored closely for timely, customized treatment. Objective: To evaluate the risk of PD in patients with PTSD compared with patients without PTSD. Design, Setting, and Participants: This population-based, retrospective, cohort study used data from Maccabi Health Care Services (MHS), the second largest health plan in Israel, spanning from 2000 to 2019. Participants included MHS members born before 1970 who received a diagnosis of PTSD in 2000 to 2015. Patients with PTSD who had PD before their first diagnosis were excluded. Data analysis was performed from February to June 2022. Exposures: Incident PTSD was denoted by at least 1 diagnosis (1) given by psychiatrists, psychologists, or neurologists; (2) hospital discharge diagnosis; or (3) registered as a chronic diagnosis (defined as such by the primary care physician). The index date was defined as first diagnosis for the patients with PTSD and for the corresponding patients without PTSD. Main Outcomes and Measures: PD incident cases up to 2019 were ascertained by idiopathic PD diagnosis (1) given by a neurologist, (2) extracted from a hospital discharge report, or (3) registered as a chronic diagnosis. Patients with PD-like syndromes documentation after the last mention of PD were excluded. Results: Of 8342 eligible patients, 8336 (99.9%) were matched to nonexposed patients in a 1:1 ratio by birth year and sex; 4303 patients (51.6%) were male, and the mean (SD) age at index was 55.8 (13.2) years. Patients with PTSD had a 1.48-fold (95% CI, 1.10-1.99) excess risk for PD, compared with patients without PTSD. An elevated risk of PD (hazard ratio, 1.95; 95% CI, 1.16-3.28) was recorded among men receiving a diagnosis of PTSD at age 72 years or older. Conclusions and Relevance: These findings suggest that elderly men who receive a diagnosis of PTSD are at an increased risk of PD. Further studies are needed to corroborate these findings and to further assess the association of stress with PD risk.

Advanced-Stage Parkinson's Disease: From Identification to Characterization Using a Nationwide Database.

Background: As Parkinson's disease (PD) progresses, response to oral medications decreases and motor complications appear. Timely intervention has been demonstrated as effective in reducing symptoms. However, current instruments for the identification of these patients are often complicated and inadequate. It has been suggested that anti-PD intensified therapy (IT) can serve as a proxy for increased burden of disease. Objective: To explore whether IT aligns with events reflecting advanced PD (APD) burden. Methods: This was a retrospective analysis of PD beneficiaries in the second-largest healthcare provider in Israel. Patients with PD diagnosed between January 2000 and June 2018 and treated with levodopa (l-dopa) ≥5 times/day and/or ≥1000 mg l-dopa equivalent daily dose were defined as the IT cohort (n = 2037). Treated patients with PD not fulfilling this criterion were defined as the nonintensified therapy (NIT) cohort (n = 3402). Point prevalence and 5- and 10-year cumulative incidence of IT were assessed. Baseline demographic and comorbidities, 1-year healthcare resource use, health costs, and time to clinical events were assessed and compared between cohorts. Results: IT was associated with significantly (P < 0.05) higher healthcare resource use compared with NIT. In turn, IT patients incurred higher healthcare costs (P < 0.001) and were at greater risk for mortality, hospitalization, disability, and device-aided therapy use (P < 0.001, for all comparisons). Conclusions: Treatment intensity can serve as an objective and robust indicator of more APD. This readily extractable marker can be easily integrated into electronic medical record alerts to actively target more advanced patients and to guide risk-appropriate care.

Long-Term Persistence and Monotherapy with Device-Aided Therapies: A Retrospective Analysis of an Israeli Cohort of Patients with Advanced Parkinson's Disease.

INTRODUCTION: Patients with advanced Parkinson's disease (PD) may require device-aided therapies (DAT) for adequate symptom control. However, long-term, real-world efficacy and safety data are limited. This study aims to describe real-world, long-term treatment persistence for patients with PD treated with levodopa-carbidopa intestinal gel (LCIG). The study also aims to describe patient profiles, treatment discontinuation rates, co-medication patterns, monotherapy rates, and rates of healthcare visits and their associated costs for patients receiving all forms of DAT (deep brain stimulation [DBS], continuous subcutaneous apomorphine infusion [CSAI], or LCIG). METHODS: In this retrospective analysis of the Israeli Maccabi Healthcare Services database, adult patients with PD were analyzed in three cohorts, based on DAT (DBS, CSAI, or LCIG). The primary endpoint was LCIG treatment persistence 12 months after initiation. RESULTS: This analysis included 161 DAT-treated patients (LCIG, n = 62; DBS, n = 76; CSAI, n = 23). Among those who discontinued, the mean time to discontinuation was 86.4 months for LCIG and 42.4 months for CSAI (p = 0.046). Twelve months after initiation, 14.3% LCIG, 10.7% DBS, and 5.9% CSAI patients were not receiving any additional anti-parkinsonian therapy. At the last recorded visit, 28.6% LCIG, 13.3% DBS, and 5.9% CSAI patients received DAT as monotherapy. During the first 12 months after initiation, 45.2% LCIG, 65.2% CSAI, and 1.3% DBS patients had no reported hospitalization days. Annual healthcare visit costs decreased following LCIG initiation (US$9491 vs. $8146) and increased following DBS ($4113 vs. $7677) and CSAI ($6378 vs. $8277). CONCLUSION: DAT are well maintained in patients with advanced PD. These retrospective data suggest that patients receiving LCIG may have higher long-term persistence rates compared with patients receiving CSAI. A subgroup of patients was treated with DAT as monotherapy without additional oral anti-parkinsonian therapy, with LCIG showing the highest rates.

Huntington's Disease in Israel: A Population-Based Study Using 20 Years of Routinely-Collected Healthcare Data.

BACKGROUND: Huntington's disease (HD) is a rare, genetic, neurodegenerative disease. Obtaining population-level data on epidemiology and disease management is challenging. OBJECTIVE: To investigate the epidemiology, clinical manifestations, treatment, and healthcare utilization of patients with HD in Israel. METHODS: Retrospective population-based cohort study, including 20 years of routinely collected data from Maccabi Healthcare Services, an insurer and healthcare provider for one-quarter of the Israeli population. RESULTS: The study cohort included 109 adult patients (aged ≥18 years) diagnosed with HD, with mean age of 49.9 years and 56%females. The most common HD-related conditions were anxiety (40%), behavioral problems (34%), sleep disorders (21%), and falls (13%). Annual incidence rates for HD ranged from 0.17 to 1.34 per 100,000 from 2000 to 2018; the 2018 crude prevalence in adults was 4.36 per 100,000. Median survival from diagnosis was approximately 12 years (95%CI: 10.4-15.3). The most frequent symptomatic treatments were antidepressants (69%), antipsychotics (63%), and tetrabenazine (63%), the only drug approved for the treatment of HD chorea in Israel during the examined period. Patterns of healthcare utilization changed as disease duration increased, reflected by increased frequency of emergency department visits and home visits. CONCLUSION: This retrospective population-based study provides insights into the prevalence, incidence, clinical profile, survival, and resource utilization of patients with HD in ethnically diverse Israel. The findings in this study are generally consistent with the international literature and demonstrate the value of routinely collected healthcare data as a complementary resource in HD research.

Longitudinal symptom dynamics of COVID-19 infection.

As the COVID-19 pandemic progresses, obtaining information on symptoms dynamics is of essence. Here, we extracted data from primary-care electronic health records and nationwide distributed surveys to assess the longitudinal dynamics of symptoms prior to and throughout SARS-CoV-2 infection. Information was available for 206,377 individuals, including 2471 positive cases. The two datasources were discordant, with survey data capturing most of the symptoms more sensitively. The most prevalent symptoms included fever, cough and fatigue. Loss of taste and smell 3 weeks prior to testing, either self-reported or recorded by physicians, were the most discriminative symptoms for COVID-19. Additional discriminative symptoms included self-reported headache and fatigue and a documentation of syncope, rhinorrhea and fever. Children had a significantly shorter disease duration. Several symptoms were reported weeks after recovery. By a unique integration of two datasources, our study shed light on the longitudinal course of symptoms experienced by cases in primary care.

Fetal safety of medications used in treating infertility.

INTRODUCTION: The medications used in assisted reproduction are given before and during early pregnancy, and hence, they may potentially result in adverse fetal effects. In this review we present an updated account of their fetal safety and discuss methodological challenges in interpretation of existing data. AREAS COVERED: The fetal safety/risks of clomiphene citrate, aromatase inhibitors, metformin, gonadotropins and progestins are discussed. We searched PubMed, EMBASE, Cochrane, Google, and Google Scholar from inception to 30 April 2020 for publications pertinent to our topic. EXPERT OPINION: There are several major challenges in studying fetal safety of medications used in assisted reproduction. The fact is that the rates of congenital malformations among infertile women giving birth spontaneously is higher than the rates among healthy women conceiving spontaneously. In most clinical studies of assisted reproduction, the primary endpoint is the success in inducing pregnancy, neglecting to report pregnancy outcome and adverse neonatal event. As an example for this reality, it has been estimated that between 1977 and 2005 around 10 million pregnancies were treated with dydrogesterone (DYD), yet till 2019 only very few studies, with a total sample size of less than 600 were reported with regards to fetal safety.

What Factors Increase the Risk of Complications in SARS-CoV-2-Infected Patients? A Cohort Study in a Nationwide Israeli Health Organization.

BACKGROUND: Reliably identifying patients at increased risk for coronavirus disease (COVID-19) complications could guide clinical decisions, public health policies, and preparedness efforts. Multiple studies have attempted to characterize at-risk patients, using various data sources and methodologies. Most of these studies, however, explored condition-specific patient cohorts (eg, hospitalized patients) or had limited access to patients' medical history, thus, investigating related questions and, potentially, obtaining biased results. OBJECTIVE: This study aimed to identify factors associated with COVID-19 complications from the complete medical records of a nationally representative cohort of patients, with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We studied a cohort of all SARS-CoV-2-positive individuals, confirmed by polymerase chain reaction testing of either nasopharyngeal or saliva samples, in a nationwide health organization (covering 2.3 million individuals) and identified those who suffered from serious complications (ie, experienced moderate or severe symptoms of COVID-19, admitted to the intensive care unit, or died). We then compared the prevalence of pre-existing conditions, extracted from electronic health records, between complicated and noncomplicated COVID-19 patient cohorts to identify the conditions that significantly increase the risk of disease complications, in various age and sex strata. RESULTS: Of the 4353 SARS-CoV-2-positive individuals, 173 (4%) patients suffered from COVID-19 complications (all age ≥18 years). Our analysis suggests that cardiovascular and kidney diseases, obesity, and hypertension are significant risk factors for COVID-19 complications. It also indicates that depression (eg, males ≥65 years: odds ratio [OR] 2.94, 95% CI 1.55-5.58; P=.01) as well as cognitive and neurological disorders (eg, individuals ≥65 years old: OR 2.65, 95% CI 1.69-4.17; P<.001) are significant risk factors. Smoking and presence of respiratory diseases do not significantly increase the risk of complications. CONCLUSIONS: Our analysis agrees with previous studies on multiple risk factors, including hypertension and obesity. It also finds depression as well as cognitive and neurological disorders, but not smoking and respiratory diseases, to be significantly associated with COVID-19 complications. Adjusting existing risk definitions following these observations may improve their accuracy and impact the global pandemic containment and recovery efforts.

Fetal safety of methylphenidate-A scoping review and meta analysis.

While for decades attention deficit hyperactivity disorder (ADHD) was regarded as mostly a pediatric condition, it is apparent that many adults continue to be afflicted by this condition, and presently an estimated 30 %-40 % of patients continue with ADHD symptomatology into adulthood. With more adults using stimulants for ADHD, there is evidence of increased numbers using ADHD medications in pregnancy. Till recently the reports on ADHD medication safety have been sparse with insufficient power to address fetal safety. Methylphenidate has been a first line treatment for ADHD, with relatively large numbers of usage. We conducted a scoping review and meta-analysis of observational cohort studies that compared malformation rates among offspring exposed to methylphenidate during early pregnancy, to the rates in the general population. Meta- analysis of 4 cohort studies with almost 3000 women exposed to methylphenidate only, and almost 3 million unexposed controls, yielded an OR of 1.26(95 % confidence interval 1.05-1.51) for major malformations, and 1.59 (95 % confidence interval 1.02-2.49) for cardiac malformations. In conclusion, methylphenidate exposure in early pregnancy is associated with a small but significant increased risk for major malformations, which can be attributed mostly to increased risk of cardiac malformations. It may be advisable to consider fetal echocardiography in pregnant women using methylphenidate during pregnancy.

Gestational diabetes and long-term risk for dyslipidemia: a population-based historical cohort study.

OBJECTIVES: To assess the course of lipid levels over time in postpartum women according to gestational diabetes status, taking into account potential confounders, such as comorbid conditions and body weight. METHODS: The data for the present analysis were collected from a 2.3 million member integrated care provider in Israel. Included were all female members aged 15-50 years who performed a 50 g glucose challenge test (GCT) between March 1995 and May 2009. We collected all follow-up lipid consecration tests performed from date of delivery following the GCT (index date) until April 2017. Data analysis was performed for each lipid component individually (triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)) and the effects of the several risk factors (history of gestational diabetes mellitus (GDM), age at delivery, obesity status and smoking status) were investigated using general linear model taking into account potential confounders. RESULTS: A total of 160 527 women (6.1 million person-years of actual follow-up) were eligible for the analysis, including 10 234 women with GDM (6.4% of the entire cohort). During the study follow-up period, a total of 2.1 million lipid tests were performed. When adjusting for follow-up time, age at index date, body mass index status, and smoking status, GDM was associated with a 1.8-fold risk (95% CI 1.73 to 1.88) for dyslipidemia defined by TG, 1.45-fold risk (95% CI 1.38 to 1.52) for dyslipidemia defined by LDL-C, and 1.44-fold risk (95% CI 1.39 to 1.50) for dyslipidemia defined by HDL-C. DISCUSSION: The results of this retrospective cohort analysis indicate that gestational diabetes confers added risk for developing hyperlipidemia post partum, particularly dyslipidemia defined by TG, as compared with women with normal glucose tolerance.

Assisted reproductive technology and the risk of pediatric cancer: A population based study and a systematic review and meta analysis.

BACKGROUND: There is controversy whether exposure to assisted reproductive technology (ART) is associated with increased risk of pediatric cancer. We aimed at calculating the overall risk of pediatric cancers after ART in a large cohort of exposed women; and to conduct a systematic review and meta- analysis of cohort studies examining overall risk of pediatric cancers after ART. METHODS: All children born in Israel who were members of Maccabi Health Services (MHS) between 1999 and 2016 after ART, were linked to the Israeli Registry of Childhood Cancer (IGS) to identify those with cancer diagnosed before 16 years of age. In parallel we conducted a systematic review and meta-analysis of observational cohort studies with more than 5000 ART- exposed cases that measured pediatric cancer after ART. RESULTS: In the cohort study, the risk ratio for pediatric cancer after ART in general was 0.95 (95% CI, 0.76-1.19). The RR was 1.09 (95% CI, 0.79-1.48) for IVF treatments. Meta- analysis of 13 cohort studies with a total of 750,138 women exposed to ART (with 1152 pediatric cancers) and 214,008,000 unexposed controls (with 30,458 pediatric cancers) did not reveal increased risk for pediatric cancers (RR 0.99; 95% CI, 0.85-1.15). CONCLUSIONS: Based on very large numbers, ART in general, and IVF in particular, are not associated with overall increased risk of pediatric cancer.

Effect of glycaemic control on cardiovascular disease in individuals with type 2 diabetes with pre-existing cardiovascular disease: A systematic review and meta-analysis.

The role of intensive glucose control in people with type 2 diabetes and pre-existing cardiovascular disease (CVD) is controversial. The aim of this systematic review and meta-analysis was to determine in a subset of people with type 2 diabetes and pre-existing CVD, the CV effect of intensive glucose control versus standard of care. We searched Medline, the Cochrane library, EMBASE and the National Institutes of Health Trial registration database for randomized controlled trials that evaluated the effect of intensive glucose control versus standard glucose control in people with type 2 diabetes on incident CVD. Data were extracted using a structured form. When data were not available in the publications, authors were contacted. Eight trials involving 8339 participants were included. Among adults with type 2 diabetes and pre-existing CVD, there was no difference in the risk of CV events in those allocated to intensive glucose control compared with those in the standard care arm (relative risk 0.98, 95% confidence interval 0.87-1.09). In conclusion, in people with diabetes and pre-existing CVD, intensive glucose control versus standard care had a neutral effect on incident CV events.

Circuit resistance training is an effective means to enhance muscle strength in older and middle aged adults: A systematic review and meta-analysis.

BACKGROUND: Physical exercise, particularly resistance training (RT), is proven treatment to reduce the accelerated decline in muscle strength exhibited by older adults, but its effect is hindered by low adherence rate, even under well-structured programs. OBJECTIVE AND DATA SOURCES: We investigated the efficacy of circuit resistance training (CRT) on muscle strength, lean mass and aerobic capacity in older adults based on report in MEDLINE, EMBASE, ClinicalTrials.gov and Cochrane electronic (through 8/2016). STUDY ELIGIBILITY CRITERIA: middle and older aged men and/or women who followed a structured program, assigned to CRT. STUDY APPRAISAL AND SYNTHESIS METHODS: Out of 237 originally identified articles, 10 articles were included with a total of 362 patients with mean: age -64.5±7.4 years; 3±1.15 sessions/week; session duration 41.8±15.9min. RESULTS: Upper body strength modestly increased, by 1.14kg (95% CI; 0.28-2.00), whereas larger increment was seen in lower body strength (11.99; 2.92-21.06). Higher program volume (>24 sessions) positively influenced upper body strength and aerobic capacity. LIMITATIONS: (1) variability in the studies' validity; (2) relatively low number of studies. CONCLUSION: CRT is a valid alternative to conventional RT. Its shorter duration and lower intensity relative to traditional RT, may increase adherence to training in older adults.