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Diabetes control is poor globally and leads to burdensome microvascular and macrovascular complications. We aimed to assess post hoc between-group differences in sustained risk factor control and macrovascular and microvascular endpoints at 6.5 years in the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomized trial. This parallel group individual randomized clinical trial was performed at 10 outpatient diabetes clinics in India and Pakistan from January 2011 through September 2019. A total of 1,146 patients with poorly controlled type 2 diabetes (HbA1c ≥8% and systolic BP ≥140 mm Hg and/or LDL-cholesterol ≥130 mg/dL) were randomized to a multicomponent quality improvement (QI) strategy (trained nonphysician care coordinator to facilitate care for patients and clinical decision support system for physicians) or usual care. At 2.5 years, compared to usual care, those receiving the QI strategy were significantly more likely to achieve multiple risk factor control. Six clinics continued, while 4 clinics discontinued implementing the QI strategy for an additional 4-year follow-up (overall median 6.5 years follow-up). In this post hoc analysis, using intention-to-treat, we examined between-group differences in multiple risk factor control (HbA1c <7% plus BP <130/80 mm Hg and/or LDL-cholesterol <100 mg/dL) and first macrovascular endpoints (nonfatal myocardial infarction, nonfatal stroke, death, revascularization [angioplasty or coronary artery bypass graft]), which were co-primary outcomes. We also examined secondary outcomes, namely, single risk factor control, first microvascular endpoints (retinopathy, nephropathy, neuropathy), and composite first macrovascular plus microvascular events (which also included amputation and all-cause mortality) by treatment group and whether QI strategy implementation was continued over 6.5 years. At 6.5 years, assessment data were available for 854 participants (74.5%; n = 417 [intervention]; n = 437 [usual care]). In terms of sociodemographic and clinical characteristics, participants in the intervention and usual care groups were similar and participants at sites that continued were no different to participants at sites that discontinued intervention implementation. Patients in the intervention arm were more likely to exhibit sustained multiple risk factor control than usual care (relative risk: 1.77; 95% confidence interval [CI], 1.45, 2.16), p < 0.001. Cumulatively, there were 233 (40.5%) first microvascular and macrovascular events in intervention and 274 (48.0%) in usual care patients (absolute risk reduction: 7.5% [95% CI: -13.2, -1.7], p = 0.01; hazard ratio [HR] = 0.72 [95% CI: 0.61, 0.86]), p < 0.001. Patients in the intervention arm experienced lower incidence of first microvascular endpoints (HR = 0.68 [95% CI: 0.56, 0.83), p < 0.001, but there was no evidence of between-group differences in first macrovascular events. Beneficial effects on microvascular and composite vascular outcomes were observed in sites that continued, but not sites that discontinued the intervention. In urban South Asian clinics, a multicomponent QI strategy led to sustained multiple risk factor control and between-group differences in microvascular, but not macrovascular, endpoints. Between-group reductions in vascular outcomes at 6.5 years were observed only at sites that continued the QI intervention, suggesting that practice change needs to be maintained for better population health of people with diabetes. ClinicalTrials.gov NCT01212328.

Achieving and maintaining optimal glycemic targets is the fundamental goal of the management of diabetes. However, failure of oral antidiabetic drugs (OADs) to sustain the targeted glycemic levels in individuals with progressing disease often requires initiation of insulin therapy. This article consolidates the expert opinions of 377 doctors who participated in 34 advisory board meetings held digitally (n=23) and in person (n=11) across India. The present report underscores the need for readily available alternatives, such as biosimilar insulins, in the Indian healthcare market to make insulin accessible to every patient with diabetes. The introduction of biosimilar insulins in the Indian healthcare market is the key to making insulin accessible to every patient with diabetes. Biosimilars are biologic products that closely resemble reference/originator biologics and demonstrate no clinically meaningful differences in safety and effectiveness. The concept of interchangeability serves as a pivotal differentiator for biosimilars, underlining their reliability and safety, and plays a significant role in their broader acceptance and integration into healthcare systems. The 'interchangeability' designation by the United States Food and Drug Administration (USFDA) elevates the biosimilar concept, promoting faster and broader adoption of insulin biosimilars, especially benefiting patients prone to non-adherence to insulin therapy. Healthcare providers are encouraged to consider the option of initiating or transitioning to biosimilar insulin glargine to address the insulin accessibility challenges.

Glucocorticoid treatment is recommended as a standard of care in Duchenne muscular dystrophy; however, few studies have assessed the long-term benefits of this treatment. We examined the long-term effects of glucocorticoids on milestone-related disease progression across the lifespan and survival in patients with Duchenne muscular dystrophy. For this prospective cohort study, we enrolled male patients aged 2–28 years with Duchenne muscular dystrophy at 20 centres in nine countries. Patients were followed up for 10 years. We compared no glucocorticoid treatment or cumulative treatment duration of less than 1 month versus treatment of 1 year or longer with regard to progression of nine disease-related and clinically meaningful mobility and upper limb milestones. We used Kaplan-Meier analyses to compare glucocorticoid treatment groups for time to stand from supine of 5 s or longer and 10 s or longer, and loss of stand from supine, four-stair climb, ambulation, full overhead reach, hand-to-mouth function, and hand function. Risk of death was also assessed. This study is registered with ClinicalTrials.gov, number NCT00468832. 440 patients were enrolled during two recruitment periods (2006–09 and 2012–16). Time to all disease progression milestone events was significantly longer in patients treated with glucocorticoids for 1 year or longer than in patients treated for less than 1 month or never treated (log-rank p<0·0001). Glucocorticoid treatment for 1 year or longer was associated with increased median age at loss of mobility milestones by 2·1–4·4 years and upper limb milestones by 2·8–8·0 years compared with treatment for less than 1 month. Deflazacort was associated with increased median age at loss of three milestones by 2·1–2·7 years in comparison with prednisone or prednisolone (log-rank p<0·012). 45 patients died during the 10-year follow-up. 39 (87%) of these deaths were attributable to Duchenne-related causes in patients with known duration of glucocorticoids usage. 28 (9%) deaths occurred in 311 patients treated with glucocorticoids for 1 year or longer compared with 11 (19%) deaths in 58 patients with no history of glucocorticoid use (odds ratio 0·47, 95% CI 0·22–1·00; p=0·0501). In patients with Duchenne muscular dystrophy, glucocorticoid treatment is associated with reduced risk of losing clinically meaningful mobility and upper limb disease progression milestones across the lifespan as well as reduced risk of death. US Department of Education/National Institute on Disability and Rehabilitation Research; US Department of Defense; National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases; and Parent Project Muscular Dystrophy.

IntroductionPeople with diabetes are at risk of developing chronic kidney disease. However, limited data are available to quantify their risk of kidney function decline in South Asia. This study evaluates the rate and predictors of kidney function decline among people with type 2 diabetes in South Asia.Research design and methodsWe analyzed data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) Trial to quantify the rate of decline in estimated glomerular filtration rate (eGFR) in people with type 2 diabetes (n=1146) over 2.5 years of follow-up. The CARRS Trial evaluated a multicomponent intervention of decision-supported electronic health records and non-physician care coordinator to improve diabetes management at 10 diabetes clinics in India and Pakistan. We used linear mixed models to estimate eGFR slope among all participants and tested the association of eGFR slope with demographic, disease-related, and self-care parameters, accounting for randomization and site.ResultsThe mean age of participants was 54.2 years, with a median duration of diabetes of 7.0 years (IQR: 3.0 - 12.0) and median CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) eGFR of 83.6 (IQR: 67.7 to 97.9) mL/min/1.73 m2. The overall mean eGFR slope was −1.33/mL/min/1.73 m2/year. There were no differences in the eGFR slope by treatment assignment to intervention versus usual care. In the adjusted regression model, pre-existing diabetic retinopathy (slope difference: −2.11; 95% CI: −3.45 to –0.77), previous cardiovascular disease (−1.93; 95% CI: −3.45 to –0.40), and statins use (−0.87; 95% CI: −1.65 to –0.10) were associated with faster eGFR decline.ConclusionsPeople with diabetes receiving care at urban diabetes clinics in South Asia experienced annual eGFR decline at two times higher rate than that reported from other contemporary international diabetes cohorts. Risk factors for faster decline were similar to those previously established, and thus care delivery models must put an additional emphasis on kidney protective therapies among subgroups with microvascular and macrovascular diabetes complications.Trial registration numberNCT01212328.

Purpose This meta-analysis aims to compare the early postoperative recovery, complications encountered, length of hospital stay, and initial functional scores between patellar eversion and non-eversion manoeuvres in patients undergoing during primary total knee arthroplasty (TKA) based on clinical studies available in the literature. Methods A systematic literature search was conducted using PubMed, Embase, Web of Science, and the Cochrane Library databases between January 1, 2000 and August 12, 2022. Prospective trials comparing clinical, radiological, and functional outcomes in patients undergoing TKA with and without patellar eversion manoeuvre were included. The meta-analysis was performed using Rev-Man version 5.41 (Cochrane Collaboration). Pooled-odds ratios (for categorical data) and mean differences with 95% confidence intervals (for continuous data) were calculated ( p  < 0.05 was regarded as statistically significant). Results Ten (out of the 298 publications identified in this subject) were included for the meta-analysis. The patellar eversion group (PEG) had a significantly shorter tourniquet time [mean difference (MD) − 8.91 min; p  = 0.002], although the overall intraoperative blood loss was higher (IOBL; MD 93.02 ml; p  = 0.0003). The patellar retraction group (PRG), on the other hand, revealed statistically better early clinical outcomes in terms of shorter time necessary to perform active straight leg raising (MD 0.66, p  = 0.0001), shorter time to achieve 90° knee-flexion (MD 0.29, p  = 0.03), higher degree of knee flexion achieved at 90 days (MD − 1.90, p  = 0.03), and reduced length of hospital stay (MD 0.65, p  = 0.03). There was no statistically significant difference in the early complication rates, 36-item short-form health survey (1 year), visual analogue scores (1 year), and Insall-Salvati index at follow-up between the groups. Conclusion The implications from the evaluated studies suggest that in comparison with patellar eversion, patellar retraction manoeuvre during surgery provides significantly faster recovery of quadriceps function, earlier attainment of functional knee range of motion (ROM), and shorter length of hospital stay in patients undergoing TKA.

A novel design structure for high gain linearized operational amplifier using cross coupled differential pair is presented in the current article. This proposed circuit exhibits an improved linearity along with the improved high gain. Cross coupled differential amplifier along with positive feedback has been explicated here for linearity improvement and gain enhancement respectively. An intermediate stage has also been introduced to generate the difference signal as the use of positive feedback in conventional differential amplifier leads to unbalance. Utility of all the parameters like less supply voltage, low power consumption, least possible inaccuracy have been considered while designing. A complete analysis of the circuit is done and described in the present paper which demonstrates how the targeted results are achieved. Circuit performance in the presence of parasitic has also been analyzed. On the other hand, Monte Carlo analysis and harmonic distortion analysis at variable supply voltage and different frequency have also been done. The proposed circuit is implemented in Cadence virtuoso analog and digital design environment using 0.18 μm CMOS technology and analyzed with the assistance of tools from Mentor Graphics. The proposed circuit resides in an active area of 25.96 μm × 27.14 μm and guzzles power of 221 μW. A gain of 124 dB, 307 MHz unity gain bandwidth and a phase margin of 69° have been reported. On the other hand, at 1 V along with 1 kHz frequency, − 74.7 dB distortion has been observed with total harmonic distortion analysis. The high bandwidth reported in the analysis allows the proposed circuit to work for high speed applications whereas high gain makes the circuit applicable in almost every field. The active area of pad-limited chip is found to be 0.96 mm 2 .

Introduction Specialist guidelines recommend endoscopic surveillance for Barrett's esophagus to reduce mortality related to esophageal adenocarcinoma, but the setting for optimal Barrett's esophagus monitoring is unclear. We assessed progression rate and disease‐specific mortality in a large cohort of patients followed up at a single Barrett's esophagus expert center. Methods For this prospective longitudinal single center cohort study, we recruited patients with a previous diagnosis of Barrett's esophagus between 2004 and 2022. Endoscopists were trained in Barrett's esophagus surveillance standards and image‐enhanced techniques, and biopsies were reviewed by expert pathologists. Exclusion criteria were a single surveillance endoscopy, high‐grade dysplasia, or esophageal adenocarcinoma at or within 12 months from index endoscopy and patients with < 12 months follow‐up. The primary outcome was the neoplastic progression rate of Barrett's esophagus with intestinal metaplasia to high‐grade dysplasia/esophageal adenocarcinoma. Secondary outcomes included cancer stage and disease‐specific mortality, risk factors for progression and progression rate in patients with Barrett's esophagus with only gastric metaplasia or irregular z‐line and intestinal metaplasia (IZL‐IM). Results A total of 1932 patients were recruited, of which 969 were included in the primary analysis with a median follow‐up of 5.8 years. Of these, 109 developed high‐grade dysplasia or esophageal adenocarcinoma with a progression rate of 1.63%/year. Overall, 48 patients received an esophageal adenocarcinoma diagnosis, of which 89,5% (43/48) had stage 1%, and 0.3% patients (3/969) had disease‐specific mortality. Multivariate analysis showed that age, alcohol consumption, esophagitis, Barrett's esophagus length, hiatus hernia length, low‐grade dysplasia and neutrophil/lymphocyte ratio were risk factors for progression. The rate of progression in patients with Barrett's esophagus—gastric metaplasia or IZL‐IM was 0.06%/year. Conclusions Endoscopic surveillance in an expert Barrett's esophagus center leads to a high neoplastic progression rate, and a low rate of disease‐specific mortality. Further research to correlate disease‐specific mortality and cancer stage with dysplasia detection rate is warranted to develop diagnostic quality indicators specific for Barrett's esophagus.