Ischemia-guided vs routine non-culprit vessel angioplasty for patients with ST segment elevation myocardial infarction and multi-vessel disease: the IAEA SPECT STEMI trial.

BACKGROUND: In patients with multi-vessel disease presenting with ST elevation myocardial infarction (STEMI), the efficacy and safety of ischemia-guided, vs routine non-culprit vessel angioplasty has not been adequately studied. METHODS: We conducted an international, randomized, non-inferiority trial comparing ischemia-guided non-culprit vessel angioplasty to routine non-culprit vessel angioplasty, following primary PCI for STEMI. The primary outcome was the between-group difference in percent ischemic myocardium at follow-up stress MPI. All MPI images were processed and analyzed at a central core lab, blinded to treatment allocation. RESULTS: In all, 109 patients were enrolled from nine countries. In the ischemia-guided arm, 25/48 (47%) patients underwent non-culprit vessel PCI following stress MPI. In the routine non-culprit PCI arm, 43/56 (77%) patients underwent angioplasty (86% within 6 weeks of randomization). The median percentage of ischemic myocardium on follow-up imaging (mean 16.5 months) was low, and identical (2.9%) in both arms (difference 0.13%, 95%CI - 1.3%-1.6%, P < .0001; non-inferiority margin 5%). CONCLUSION: A strategy of ischemia-guided non-culprit PCI resulted in low ischemia burden, and was non-inferior to a strategy of routine non-culprit vessel PCI in reducing ischemia burden. Selective non-culprit PCI following STEMI offers the potential for cost-savings, and may be particularly relevant to low-resource settings. (CTRI/2018/08/015384).

Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: a systematic review and meta-analysis.

BACKGROUND: The safety and efficacy of convalescent plasma in severe coronavirus disease 2019 (COVID-19) remain uncertain. To support a guideline on COVID-19 management, we conducted a systematic review and meta-analysis of convalescent plasma in COVID-19 and other severe respiratory viral infections. METHODS: In March 2020, we searched international and Chinese biomedical literature databases, clinical trial registries and prepublication sources for randomized controlled trials (RCTs) and nonrandomized studies comparing patients receiving and not receiving convalescent plasma. We included patients with acute coronavirus, influenza and Ebola virus infections. We conducted a meta-analysis using random-effects models and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Of 1099 unique records, 6 studies were eligible, and none of these included patients with COVID-19. One nonrandomized study (n = 40) on convalescent plasma in severe acute respiratory syndrome coronavirus (SARS-CoV) provided uninformative results regarding mortality (relative risk [RR] 0.10, 95% confidence interval [CI] CI 0.01 to 1.70). Pooled estimates from 4 RCTs on influenza (n = 572) showed no convincing effects on deaths (4 RCTs, RR 0.94, 95% CI 0.49 to 1.81), complete recovery (2 RCTs, odds ratio 1.04, 95% CI 0.69 to 1.64) or length of stay (3 RCTs, mean difference -1.62, 95% CI -3.82 to 0.58, d). The quality of evidence was very low for all efficacy outcomes. Convalescent plasma caused few or no serious adverse events in influenza RCTs (RR 0.85, 95% CI 0.56 to 1.29, low-quality evidence). INTERPRETATION: Studies of non-COVID-19 severe respiratory viral infections provide indirect, very low-quality evidence that raises the possibility that convalescent plasma has minimal or no benefit in the treatment of COVID-19 and low-quality evidence that it does not cause serious adverse events.

Development of the Instrument to assess the Credibility of Effect Modification Analyses (ICEMAN) in randomized controlled trials and meta-analyses.

BACKGROUND: Most randomized controlled trials (RCTs) and meta-analyses of RCTs examine effect modification (also called a subgroup effect or interaction), in which the effect of an intervention varies by another variable (e.g., age or disease severity). Assessing the credibility of an apparent effect modification presents challenges; therefore, we developed the Instrument for assessing the Credibility of Effect Modification Analyses (ICEMAN). METHODS: To develop ICEMAN, we established a detailed concept; identified candidate credibility considerations in a systematic survey of the literature; together with experts, performed a consensus study to identify key considerations and develop them into instrument items; and refined the instrument based on feedback from trial investigators, systematic review authors and journal editors, who applied drafts of ICEMAN to published claims of effect modification. RESULTS: The final instrument consists of a set of preliminary considerations, core questions (5 for RCTs, 8 for meta-analyses) with 4 response options, 1 optional item for additional considerations and a rating of credibility on a visual analogue scale ranging from very low to high. An accompanying manual provides rationales, detailed instructions and examples from the literature. Seventeen potential users tested ICEMAN; their suggestions improved the user-friendliness of the instrument. INTERPRETATION: The Instrument for assessing the Credibility of Effect Modification Analyses offers explicit guidance for investigators, systematic reviewers, journal editors and others considering making a claim of effect modification or interpreting a claim made by others.

Prevalence and intensity of persistent post-surgical pain following breast cancer surgery: a systematic review and meta-analysis of observational studies.

BACKGROUND: The prevalence and intensity of persistent post-surgical pain (PPSP) after breast cancer surgery are uncertain. We conducted a systematic review and meta-analysis to further elucidate this issue. METHODS: We searched MEDLINE, Embase, CINAHL, and PsycINFO, from inception to November 2018, for observational studies reporting persistent pain (≥3 months) after breast cancer surgery. We used random-effects meta-analysis and the Grading of Recommendations, Assessment, Development and Evaluations approach to rate quality of evidence. RESULTS: We included 187 observational studies with 297 612 breast cancer patients. The prevalence of PPSP ranged from 2% to 78%, median 37% (inter-quartile range: 22-48%); the pooled prevalence was 35% (95% confidence interval [CI]: 32-39%). The pooled pain intensity was 3.9 cm on a 10 cm visual analogue scale (95% CI: 3.6-4.2 cm). Moderate-quality evidence supported the subgroup effects of PPSP prevalence for localized pain vs any pain (29% vs 44%), moderate or greater vs any pain (26% vs 44%), clinician-assessed vs patient-reported pain (23% vs 36%), and whether patients underwent sentinel lymph node biopsy vs axillary lymph node dissection (26% vs 43%). The adjusted analysis found that the prevalence of patient-reported PPSP (any severity/location) was 46% (95% CI: 36-56%), and the prevalence of patient-reported moderate-to-severe PPSP at any location was 27% (95% CI: 10-43%). CONCLUSIONS: Moderate-quality evidence suggests that almost half of all women undergoing breast cancer surgery develop persistent post-surgical pain, and about one in four develop moderate-to-severe persistent post-surgical pain; the higher prevalence was associated with axillary lymph node dissection. Future studies should explore whether nerve sparing for axillary procedures reduces persistent post-surgical pain after breast cancer surgery.

Functional compared to anatomical imaging in the initial evaluation of patients with suspected coronary artery disease: An international, multi-center, randomized controlled trial (IAEA-SPECT/CTA study).

OBJECTIVE: To test the hypothesis that, in the initial evaluation of patients with suspected coronary artery disease (CAD), stress myocardial perfusion imaging (MPI) would result in less downstream testing than coronary computed tomographic angiography (CCTA). METHODS: In this international, randomized trial, mildly symptomatic patients with an intermediate likelihood of having CAD, and asymptomatic patients at intermediate risk of cardiac events, underwent either initial stress-rest MPI or CCTA. The primary outcome was downstream noninvasive or invasive testing at 6 months. Secondary outcomes included cumulative effective radiation dose (ERD) and costs at 12 months. RESULTS: We recruited 303 patients (151 MPI and 152 CTA) from 6 centers in 6 countries. The initial MPI was abnormal in 29% (41/143) and CCTA in 56% (79/141) of patients. Fewer patients undergoing initial stress-rest MPI had further downstream testing at 6 months (adjusted OR 0.51, 95% CI 0.28-0.91, P = 0.023). There was a small increase in the median cumulative ERD with MPI (9.6 vs. 8.8 mSv, P = 0.04), but no difference in costs between the two strategies at 12 months. CONCLUSION: In the management of patients with suspected CAD, a strategy of initial stress MPI is substantially less likely to require further downstream testing than initial testing with CCTA. TRIAL REGISTRATION: clinicaltrials.gov identification number NCT01368770.

Efficacité et innocuité du plasma de convalescent en cas de forme grave de COVID-19, extrapolée de données relatives à d'autres formes graves d'infections respiratoires virales : revue systématique et méta-analyse.

CONTEXTE: On ne connaît pas encore avec certitude l'innocuité et l'efficacité du plasma de convalescent comme traitement de la forme grave de la maladie à coronavirus 2019 (COVID-2019). Afin d'appuyer la conception de lignes directrices sur la prise en charge de la COVID-19, nous avons effectué une revue systématique et une méta-analyse sur l'utilisation du plasma de convalescent pour le traitement de cette maladie et d'autres formes graves d'infections respiratoires virales. MÉTHODES: En mars 2020, nous avons effectué des recherches dans des bases de données biomédicales internationales et chinoises, des registres d'essais cliniques et des sources prépubliées afin de recenser des essais randomisés et contrôlés (ERC) et des études non randomisées comparant les issues de patients ayant reçu du plasma de convalescent à celles de patients n'en ayant pas reçu. Ont été inclus les patients ayant une infection aiguë attribuable à un coronavirus, au virus de l'influenza ou au virus Ebola. Nous avons également réalisé une méta-analyse à l'aide d'un modèle à effets aléatoires et évalué la qualité des données probantes au moyen de l'approche GRADE (Grading of Recommendations Assessment, Development, and Evaluation). RÉSULTATS: Sur les 1099 études uniques initialement repérées, 6 étaient admissibles, et aucune d'entre elles ne portait sur des patients atteints de la COVID-19. Une étude non randomisée (n = 40) sur l'administration de plasma de convalescent à des patients atteints du coronavirus du syndrome respiratoire aigu sévère (SRAS-CoV) a fourni des données peu concluantes sur le taux de mortalité (risque relatif [RR] 0,10; intervalle de confiance [IC] de 95 % 0,01 à 1,70). Des estimations regroupées provenant de 4 ERC sur l'influenza (n = 572) n'ont pas montré d'effet manifeste sur le taux de mortalité (4 ERC; RR 0,94; IC de 95 % 0,49 à 1,81), le rétablissement complet (2 ERC; rapports de cotes [RC] 1,04; IC de 95 % 0,69 à 1,64) et la durée d'hospitalisation (3 ERC; différence moyenne [DM] −1,62; IC de 95 % −3,82 à 0,58 jours). La qualité des données était très faible pour tous les paramètres relatifs à l'efficacité. Dans les ERC sur l'influenza, aucun ou peu d'événements indésirables graves ont été associés au plasma de convalescent (RR 0,85; IC de 95 % 0,56 à 1,29; données de faible qualité). INTERPRÉTATION: Les études portant sur des formes graves d'infections respiratoires virales autres que la COVID-19 ont fourni des données indirectes de très faible qualité semblant indiquer que le plasma de convalescent n'offre aucun bénéfice ou offre des bénéfices minimes pour le traitement de la COVID-19, de même que des données de faible qualité montrant qu'il n'entraîne pas d'événements indésirables graves.

Reproductive healthcare utilization in urban poor settlements of Delhi: Baseline survey of ANCHUL (Ante Natal and Child Health care in Urban Slums) project.

BACKGROUND: Disparity in utilization of reproductive healthcare services between the urban poor and the urban non-poor households in the developing nations is well known. However, disparity may also exist within urban poor households. Our objective was to document the extent of disparity in reproductive healthcare utilization among the urban poor and to identify the socio-demographic determinants of underutilization with a view to characterizing this vulnerable subpopulation. METHODS: A survey of 16,221 households was conducted in 39 clusters from two large urban poor settlements in Delhi. From 13,451 consenting households, socio-demographic data and information on births, maternal and child deaths within the previous year was collected. Details of antenatal care (ANC) was collected from 597 pregnant women. Information on ANC and postnatal care was also obtained from 596 recently delivered (within six months) mothers. All data were captured electronically using a customized and validated smart phone application. Households were categorized into quintiles of socio-economic position (SEP) based on dwelling characteristics and possession of durable assets using principal component analysis. Potential socio-demographic determinants of reproductive healthcare utilization were examined using random effects logistic regression. RESULTS: The prevalence of facility based birthing was 77% (n = 596 mothers). Of the 596 recently delivered mothers only 70% had an ANC registration card, 46.3% had ANC in their first trimester, 46% had visited a facility within 4 weeks post-delivery and 27% were using modern contraceptive methods. Low socio-economic position was the most important predictor of underutilization with a clear gradient across SEP quintiles. Compared to the poorest, the least poor women were more likely to be registered for ANC (OR 1.96, 95%CI 0.95-4.15) and more likely to have made ≥ 4 ANC visits (OR 5.86, 95%CI 2.82-12.19). They were more likely to have given birth in a facility (OR 4.87, 95%CI 2.12-11.16), to have visited a hospital within one month of childbirth (OR 3.18, 95%CI 1.62-6.26). In general, government funded health insurance and conditional cash transfers schemes were underutilized in this community. CONCLUSION: The poorest segment of the urban poor population utilizes reproductive healthcare facilities the least. Strategies to improve access and utilization of healthcare services among the poorest of the poor may be necessary to achieve universal health coverage.

Ante natal care (ANC) utilization, dietary practices and nutritional outcomes in pregnant and recently delivered women in urban slums of Delhi, India: an exploratory cross-sectional study.

BACKGROUND: Antenatal Care (ANC) is one of the crucial factors in ensuring healthy outcomes in women and newborns. Nutrition education and counselling is an integral part of ANC that influences maternal and child health outcomes. A cross sectional study was conducted in Pregnant Women (PW) and mothers who had delivered in the past three months; Recently Delivered Women (RDW) in urban slums of North-east district of Delhi, India, to explore ANC utilization, dietary practices and nutritional outcomes. METHODS: A household survey was conducted in three urban slums to identify PW and RDW. Socio-economic and demographic profile, various components of ANC received including nutrition counselling, dietary intake and nutritional outcomes based on anthropometric indices and anaemia status were assessed. Socio-demographic characteristics, nutrient intake and nutritional status were compared between those who availed ANC versus those who did not using logistic regression. Descriptive summary for services and counselling received; dietary and nutrient intake during ANC were presented. RESULTS: Almost 80% (274 out of 344) women received some form of ANC but the package was inadequate. Determinants for non-utilization of ANC were poverty, literacy, migration, duration of stay in the locality and high parity. Counselling on nutrition was reported by a fourth of the population. Nutrient intake showed suboptimal consumption of protein and micronutrients like iron, calcium, vitamin A, vitamin C, thiamine, riboflavin niacin, zinc and vitamin B12 by more than half of women. A high prevalence of anaemia among PW (85%) and RDW (97.1%) was observed. There was no difference in micronutrient intake and anaemia prevalence among women who received ANC versus who did not. CONCLUSIONS: Pregnant women living in urban poor settlements have poor nutritional status. This may be improved by strengthening the nutrition counselling component of ANC which was inadequate in the ANC package received. Empowering community based health workers in providing effective nutrition counselling should be explored given the overburdened public health system.

Development of a field-friendly automated dietary assessment tool and nutrient database for India.

Studies of diet and disease risk in India and among other Asian-Indian populations are hindered by the need for a comprehensive dietary assessment tool to capture data on the wide variety of food and nutrient intakes across different regions and ethnic groups. The nutritional component of the India Health Study, a multicentre pilot cohort study, included 3908 men and women, aged 35-69 years, residing in three regions of India (New Delhi in the north, Mumbai in the west and Trivandrum in the south). We developed a computer-based, interviewer-administered dietary assessment software known as the 'NINA-DISH (New Interactive Nutrition Assistant - Diet in India Study of Health)', which consisted of four sections: (1) a diet history questionnaire with defined questions on frequency and portion size; (2) an open-ended section for each mealtime; (3) a food-preparer questionnaire; (4) a 24 h dietary recall. Using the preferred meal-based approach, frequency of intake and portion size were recorded and linked to a nutrient database that we developed and modified from a set of existing international databases containing data on Indian foods and recipes. The NINA-DISH software was designed to be easily adaptable and was well accepted by the interviewers and participants in the field. A predominant three-meal eating pattern emerged; however, patterns in the number of foods reported and the primary contributors to macro- and micronutrient intakes differed by region and demographic factors. The newly developed NINA-DISH software provides a much-needed tool for measuring diet and nutrient profiles across the diverse populations of India with the potential for application in other South Asian populations living throughout the world.

Urgent surgery compared with fibrinolytic therapy for the treatment of left-sided prosthetic heart valve thrombosis: a systematic review and meta-analysis of observational studies.

AIMS: Left-sided prosthetic valve thrombosis (PVT) occurs frequently in developing countries and causes major morbidity and mortality. Fibrinolytic therapy (FT) is most commonly used as treatment, but increases the risk of stroke and bleeding. Urgent surgery may be more efficacious and cause fewer complications. Our aim was to compare the efficacy and safety of urgent surgery and FT for the treatment of left-sided PVT. METHODS AND RESULTS: We searched EMBASE and MEDLINE for articles which included at least five patients each treated with surgery and FT. The primary outcome was complete restoration of valve function. Other outcomes were in-hospital death, thrombo-embolism (stroke, transient ischaemic attack, or non-CNS systemic embolism), major bleeding, and recurrence of PVT on follow-up. We calculated odds ratios (ORs) for each outcome and pooled them using a random effects model. We included seven eligible studies with 690 episodes of PVT, 446 treated with surgery, and 244 with FT. There was no significant difference in the occurrence of the primary outcome (86.5 vs. 69.7%, OR 2.53, 95% CI 0.94-6.78, P = 0.066, I(2) = 74%) or death (13.5 vs. 9%, OR 1.95, 95% CI 0.63-5.98, P = 0.244, I(2) = 59%) between the two treatments. However, compared with FT, urgent surgery was associated with significant reductions in thrombo-embolism (1.6 vs. 16%, OR 0.10, 95% CI 0.04-0.24, P < 0.001, I(2) = 0%), major bleeding (1.4 vs. 5%; OR 0.27, 95% CI 0.08-0.98, P = 0.046, I(2) = 0%), and recurrent PVT (7.1 vs. 25.4%; OR 0.25, 95% CI 0.08-0.74, P = 0.013, I(2) = 59%). CONCLUSION: Urgent surgery was not superior to FT at restoring valve function, but substantially reduced the occurrence of thrombo-embolic events, major bleeding, and recurrent PVT. In experienced centres, urgent surgery should probably be preferred over FT for treating left-sided PVT, pending the results of randomized controlled trials.

Mobile and Computer-Based Applications for Rehabilitation Monitoring and Self-Management After Knee Arthroplasty: Scoping Review.

BACKGROUND: Successful post-knee replacement rehabilitation requires adequate access to health information, social support, and periodic monitoring by a health professional. Mobile health (mHealth) and computer-based technologies are used for rehabilitation and remote monitoring. The extent of technology use and its function in post-knee replacement rehabilitation care in low and middle-income settings are unknown. OBJECTIVE: To inform future mHealth intervention development, we conducted a scoping review to map the features and functionality of existing technologies and determine users' perspectives on telerehabilitation and technology for self-management. METHODS: We followed the Joanna Briggs Institute methodology for scoping reviews. We searched the Embase, Medline, PsycINFO via OVID, and Cochrane Central Register of Controlled Trials databases for manuscripts published from 2001 onward. We included original research articles reporting the use of mobile or computer-based technologies by patients, health care providers, researchers, or family members. Studies were divided into the following 3 categories based on the purpose: validation studies, clinical evaluation, and end user feedback. We extracted general information on study design, technology features, proposed function, and perspectives of health care providers and patients. The protocol for this review is accessible in the Open Science Framework. RESULTS: Of the 5960 articles, 158 that reported from high-income settings contributed to the qualitative summary (64 studies on mHealth or telerehabilitation programs, 28 validation studies, 38 studies describing users' perceptions). The highest numbers of studies were from Europe or the United Kingdom and North America regarding the use of a mobile app with or without wearables and reported mainly in the last decade. No studies were from low and middle-income settings. The primary functions of technology for remote rehabilitation were education to aid recovery and enable regular, appropriate exercises; monitoring progress of pain (n=19), activity (n=20), and exercise adherence (n=30); 1 or 2-way communication with health care professionals to facilitate the continuum of care (n=51); and goal setting (n=23). Assessment of range of motion (n=16) and gait analysis (n=10) were the commonly validated technologies developed to incorporate into a future rehabilitation program. Few studies (n=14) reported end user involvement during the development stage. We summarized the reasons for satisfaction and dissatisfaction among users across various technologies. CONCLUSIONS: Several existing mobile and computer-based technologies facilitate post-knee replacement rehabilitation care for patients and health care providers. However, they are limited to high-income settings and may not be extrapolated to low-income settings. A systematic needs assessment of patients undergoing knee replacement and health care providers involved in rehabilitation, involving end users at all stages of development and evaluation, with clear reporting of the development and clinical evaluation can make post-knee replacement rehabilitation care in resource-poor settings accessible and cost-effective.

Surgery compared to fibrinolytic therapy for symptomatic left-sided prosthetic heart valve thrombosis (SAFE-PVT): Rationale and design of a randomized controlled trial.

BACKGROUND: Left-sided mechanical prosthetic heart valve thrombosis (PVT) occurs because of suboptimal anticoagulation and is common in low-resource settings. Urgent surgery and fibrinolytic therapy (FT) are the two treatment options available for this condition. Urgent surgery is a high-risk procedure but results in successful restoration of valve function more often and is the treatment of choice in developed countries. In low-resource countries, FT is used as the default treatment strategy, though it is associated with lower success rates and a higher rate of bleeding and embolic complications. There are no randomized trials comparing the two modalities. METHODS: We performed a single center randomized controlled trial comparing urgent surgery (valve replacement or thrombectomy) with FT (low-dose, slow infusion tissue plasminogen activator, tPA) in patients with symptomatic left-sided PVT. The primary outcome was the occurrence of a complete clinical response, defined as discharge from hospital with completely restored valve function, in the absence of stroke, major bleeding or non-CNS systemic embolism. Outcome assessment was done by investigators blinded to treatment allocation. The principal safety outcome was the occurrence of a composite of in-hospital death, non-fatal stroke, non-fatal major bleed or non-CNS systemic embolism. Outcomes will be assessed both in the intention-to-treat, and in the as-treated population. We will also report outcomes at one year of follow-up. The trial has completed recruitment. CONCLUSION: This is the first randomized trial to compare urgent surgery with FT for the treatment of left-sided PVT. The results will provide evidence to help clinicians make treatment choices for these patients. (Clinical trial registration: CTRI/2017/10/010159).

Colchicine to reduce coronavirus disease-19-related inflammation and cardiovascular complications in high-risk patients post-acute infection with SARS-COV-2-a study protocol for a randomized controlled trial.

BACKGROUND: There is no known effective pharmacological therapy for long COVID, which is characterized by wide-ranging, multisystemic, fluctuating, or relapsing symptoms in a large proportion of survivors of acute COVID. This randomized controlled trial aims to assess the safety and efficacy of an anti-inflammatory agent colchicine, to reduce symptoms among those at high risk of developing long COVID. METHODS: This multi-centre, parallel arm, 1:1 individual randomized, placebo-controlled, double-blind superiority trial will enrol 350 individuals with persistent post-COVID symptoms. Participants will be randomized to either colchicine 0.5 mg once daily (< 70 kg) or twice daily (≥ 70 kg) or matched placebo for 26 weeks and will be followed up until 52 weeks after randomization. The primary trial objective is to demonstrate the superiority of colchicine over a placebo in improving distance walked in 6 min at 52 weeks from baseline. The secondary objectives are to assess the efficacy of colchicine compared to placebo with respect to lung function, inflammatory markers, constitutional symptoms, and mental health state. In a sub-sample of 100 participants, cardiac biomarkers of myocardial injury and myocardial oedema using MRI will be compared. DISCUSSION: Persistent inflammatory response following SARS-CoV-19 is one of the postulated pathophysiological mechanisms of long COVID. Colchicine, a low-cost anti-inflammatory agent, acts via multiple inflammatory pathways and has an established safety profile. This trial will generate evidence for an important health priority that can rapidly translate into practice. TRIAL REGISTRATION: This clinical trial has been registered prospectively on www. CLINICALTRIALS: gov with registration CTRI/2021/11/038234 dated November 24, 2021.

Correlates of markers of dyssynchrony in patients with STEMI and multivessel disease: an analysis from the IAEA SPECT STEMI trial.

BACKGROUND: In this substudy of the Value of Gated-SPECT MPI for Ischemia- Guided PCI of non-culprit vessels in STEMI Patients with Multi vessel Disease after primary PCI trial on the value of myocardial perfusion imaging (MPI) for ischemia-guided percutaneous coronary intervention (PCI) of nonculprit vessels in patients with ST-segment-elevation myocardial infarction (STEMI) and multivessel disease after primary PCI we aim to assess if infarct size affects conventional measures of dyssynchrony at rest. Additionally, we explore if there is an independent correlation of stress-inducible ischemia with dyssynchrony at rest. METHODS: The 48 patients with imaging at randomization were analyzed. Gated-single-photon emission computed tomography (SPECT) MPI with vasodilator stress and technetium-99m-labeled tracers was performed. The phase histogram bandwidth (HBW), phase SD, and entropy were obtained with the QGS software. Correlation between dyssynchrony at rest and infarct size and inducible ischemia was performed using the Spearman test. RESULTS: According to normal database limits dyssynchrony parameters at rest were abnormal for men. In women only HBW was abnormal. Correlation between the summed rest score with dyssynchrony was significant only for entropy (P = 0.035). No correlation was observed for dyssynchrony and stress-induced ischemia. CONCLUSION: Entropy, as a measure of dyssynchrony, has potential in the assessment of patients with STEMI and multivessel disease after primary PCI. Smaller residual myocardial scars in PCI-reperfused patients with STEMI may contribute to the lack of correlation between dyssynchrony at rest and infarct size and stress-induced ischemia, respectively.

Is intravenous iron sucrose the treatment of choice for pregnant anemic women?

Anemia during pregnancy remains an important public health problem in developing countries like India. Anemia is the direct cause of 12-15% of maternal deaths. Iron deficiency is the commonest cause for anemia in the Indian subcontinent. Several preventive and therapeutic approaches are in practice. The available routes of iron supplementation are oral and intravenous. In spite of oral iron being least invasive, cheap and safe, the ineffectiveness of oral iron due to dietary inhibitors and poor compliance are well known. Intravenous iron sucrose can be a promising therapy for moderate to severely anemic pregnant women and has been in practice for quite some time in private and public health practices. In this article, we report the current evidence on the safety and efficacy of intravenous iron sucrose in anemic pregnant women on hematological and clinical outcomes. Though the evidence on its efficacy in improving hemoglobin and serum ferritin is convincing, its effect on maternal and fetal outcomes are unclear. This is primarily due to lack of well-designed and larger studies powered to detect difference in clinical outcomes. Hence, there is a need to gather evidence from a well-designed large randomized clinical trial conducted in a developing country. The results of such a study would feed into the national policy and would form the basis to frame guidelines for management of anemia in developing countries.

Lung Function and Respiratory Morbidity Among Informal Workers Exposed to Cement Dust: A Comparative Cross-Sectional Study.

Background: Cement dust is a significant source of occupational exposure affecting lung function and respiratory health. A higher burden of respiratory morbidity is known among factory workers involved in cement production. Globally or from India, there are no estimates of this burden from informal workers exposed to cement dust. Objective: To assess difference in lung function and respiratory symptoms among informal workers exposed to cement and those unexposed, using a comparative community based cross-sectional study from purposively selected areas in Delhi, India. Methods: Using a portable spirometer we measured lung function and collected respiratory symptoms from conveniently sampled informal workers (n = 100) exposed to cement dust, 50 indoor informal workers (tailors), and 50 outdoor (vegetable) vendors. Regression analyses were performed to compare respiratory symptom score and lung function parameters, adjusted for age, body mass index, smoking, socioeconomic status, and years of occupational exposure. Findings: Exposed workers had significantly lower lung function (PEF = -750 ml/s and -810 ml/s and FEV1/FVC (%) = -3.87 and -2.11) compared to indoor and outdoor groups, with three times higher chronic respiratory symptoms when compared to the unexposed groups. The cement dust exposure was observed to be associated with PEF (mean difference (MD) = -0.75L, 95%CI = -1.36 to -0.15, p = 0.01), %FEV1/FVC (MD = -3.87, 95%CI = -6.77 to -0.96, p = 0.03) and respiratory symptoms (p < 0.001). Conclusion: This study generates evidence regarding the respiratory burden of occupational exposure among vulnerable informal workers. There is an urgent need for policy reforms to safeguard health from occupational exposures, especially among informal workers.

Frailty among middle-aged and older women and men in India: findings from wave 1 of the longitudinal Ageing study in India.

OBJECTIVES: Few studies have examined frailty in Indian adults, despite an increasing population of older adults and an escalating burden of chronic diseases. We aimed to study the prevalence and correlates of frailty in middle-aged and older Indian adults. SETTING: Cross-sectional data from Wave 1 of Longitudinal Ageing Study in India, conducted in 2017-2018 across all states and union territories, were used. PARTICIPANTS: The final analytical sample included 57 649 participants aged 45 years and above who had information on frailty status. PRIMARY OUTCOME MEASURE: The deficits accumulation approach to measuring frailty was employed, creating a frailty index between 0 and 1, based on 40 deficits. Individuals with a frailty index of 0.25 or more were defined as 'frail'. RESULTS: Prevalence of frailty among 45+ adults was 30%. 60+ women were two times as likely to be frail compared with 60+ men, after adjusting for a wide range of sociodemographic, economic and lifestyle factors. The sex difference was more pronounced in adults aged 45-59 years. Odds of hospitalisation in the last 12 months, and having falls in the past 2 years, were two times as high in frail adults compared with non-frail adults. Frail middle-aged and older adults had 33% and 39% higher odds, respectively, of having poor cognition than non-frail adults. The relative increase was higher in women for all three outcomes, although not statistically significant. CONCLUSIONS: There needs to be careful consideration of sex differences when addressing frailty, particularly for optimising frailty interventions. Frailty, although typically assessed in older adults, was shown in this study to be also prevalent and associated with adverse outcomes in middle-aged Indian adults. More research into assessment of frailty in younger populations, its trajectory and correlates may help develop public health measures for prevention of frailty.

Challenges in rehabilitation and continuum of care provision after knee replacement: a mixed-methods study from a low- and middle-income country.

PURPOSE: Continuum-of-care is crucial following knee replacement. This is an understudied area in the context of low- and middle-income countries. We report findings of a mixed-methods study conducted to understand patient's postoperative experiences in following unsupervised home-based physiotherapy protocols and healthcare provider's experiences in providing rehabilitation care. METHODS: Consecutive adults (n = 79) scheduled or had undergone knee replacement, attending an urban tertiary care hospital in India completed a 22-item questionnaire to gauge attitude towards physical rehabilitation. We conducted in-depth interviews with nine patients, ten physiotherapists, and three surgeons using a phenomenology approach. Data were interpreted using the capability, opportunity, and motivation-behaviour (COM-B) framework. RESULTS: Patients were motivated to do exercises and valued family support during the recovery period. However, they desired physiotherapy support, especially during the early recovery period due to post-operative pain. Healthcare providers reported poor adherence with the exercise regimen and desired a mechanism to monitor patient progress after discharge. Patients and health care providers identified accessibility to rehabilitation centre as a major barrier in availing affordable and reliable physiotherapy services. CONCLUSION: There is a need for a continuum of care to improve patient experience during recovery and for health care providers to monitor progress and provide personalised progressive exercise therapy.

In India, regular monitoring following knee replacement is essential in home-based rehabilitation protocols necessitating clinic visits.Barriers to rehabilitation included post-surgical pain and difficulty in accessing physiotherapy services, while patient motivation and family support were facilitators to rehabilitation adherence.There is a need for remote monitoring mechanisms to facilitate health care providers in India, to monitor progress and reduce out of pocket expenditure for patients.

Cancer risk with topical calcineurin inhibitors, pimecrolimus and tacrolimus, for atopic dermatitis: a systematic review and meta-analysis.

BACKGROUND: Atopic dermatitis is a prevalent condition in children and can be effectively managed with medications such as topical calcineurin inhibitors (pimecrolimus or tacrolimus). A key unresolved safety concern is whether use of topical calcineurin inhibitors is associated with cancer. We systematically reviewed the risk of cancer in patients with atopic dermatitis exposed to topical calcineurin inhibitors. METHODS: As part of the 2022 American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters atopic dermatitis guidelines, we searched MEDLINE, Embase, the Latin American and Caribbean Health Sciences Literature database, the Índice Bibliográfico Espanhol de Ciências da Saúde database, the Global Resource of Eczema Trials database, WHO's International Clinical Trials Registry Platform, the US Food and Drug Administration database, the European Medicines Agency database, company registers, and relevant citations from inception to June 6, 2022. We included randomised controlled trials and comparative and non-comparative non-randomised studies in any language addressing cancer risk in patients with atopic dermatitis using topical calcineurin inhibitors. We excluded split-body studies and studies with less than 3 weeks of follow-up. Paired reviewers independently screened records, extracted data, and assessed risk of bias in duplicate. We used Bayesian models to estimate the probability for cancer due to topical calcineurin inhibitor exposure and the GRADE approach to determine the certainty of the evidence. Patients, advocacy groups, and care providers set a priori thresholds of important effects. This study is registered with Open Science Framework, https://osf.io/v4bfc. FINDINGS: We identified and analysed 110 unique studies (52 randomised controlled trials and 69 non-randomised studies [11 were non-randomised study extensions of randomised controlled trials]) including 3·4 million patients followed up for a mean of 11 months (range 0·7-120). The absolute risk of any cancer with topical calcineurin inhibitor exposure was not different from controls (absolute risk 4·70 per 1000 with topical calcineurin inhibitors vs 4·56 per 1000 without; odds ratio 1·03 [95% credible interval 0·94-1·11]; moderate certainty). For all age groups and using data from observational studies and randomised controlled trials, the use of pimecrolimus (OR 1·05 [95% credible interval 0·94-1·15]) or tacrolimus (0·99 [0·89-1·09]) is likely to have had little to no association with cancer compared with no topical calcineurin inhibitor exposure. For pimecrolimus versus tacrolimus, the finding was similar (0·95 [95% credible interval 0·83-1·07]). Findings were similar in infants, children, and adults, and robust to trial sequential, subgroup, and sensitivity analyses. INTERPRETATION: Among individuals with atopic dermatitis, moderate-certainty evidence shows that topical calcineurin inhibitors do not increase the risk of cancer. These findings support the safe use of topical calcineurin inhibitors in the optimal treatment of patients with atopic dermatitis. FUNDING: American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma and Immunology via the Joint Task Force on Practice Parameters.

An extension minimal important difference credibility item addressing construct proximity is a reliable alternative to the correlation item.

OBJECTIVES: Minimal important difference (MID), the smallest change or difference that patients perceive as important, aids interpretation of change in patient-reported outcome measure (PROM) scores. A credibility instrument that assesses the methodological rigor of an anchor-based MID includes one core item addressing the correlation between the PROM and the anchor. However, the majority of MID studies in the literature fail to report the correlation. To address this issue, we extended the anchor-based MID credibility instrument by adding an item addressing construct proximity as an alternative to the correlation item. STUDY DESIGN AND SETTING: Informed by an MID methodological survey, we added an alternative item-a subjective assessment of similarity of the constructs (i.e., construct proximity) between PROM and anchor-to the correlation item and generated principles for the assessment. We sampled 101 MIDs and analyzed the assessments performed by each pair of raters. By calculating weighted Cohen's kappa, we assessed the reliability of the assessments. RESULTS: Construct proximity assessment is based on the anticipated association between the anchor and PROM constructs: the closer the anticipated association, the higher the rating. Our detailed principles address the most frequently used anchors: transition ratings, measures of satisfaction, other PROMs, and clinical measures. The assessments showed acceptable agreement (weighted kappa 0.74, 95% CI 0.55-0.94) between raters. CONCLUSION: In the absence of a reported correlation coefficient, construct proximity assessment provides a useful alternative in the credibility assessment of anchor-based MID estimates.