What is the difference between missing completely at random and missing at random?

The terminology describing missingness mechanisms is confusing. In particular the meaning of 'missing at random' is often misunderstood, leading researchers faced with missing data problems away from multiple imputation, a method with considerable advantages. The purpose of this article is to clarify how 'missing at random' differs from 'missing completely at random' via an imagined dialogue between a clinical researcher and statistician

RATIONALITY ASSESSMENT OF ZINC FORMULATIONS AVAILABLE IN INDIA

Objective: To critically analyze the essentiality and irrational zinc preparations available in Indian market. Methods: This was conducted as cross-sectional analysis by department of pharmacology of our tertiary care hospital between June and December 2016. Data regarding various formulations of zinc were retrieved from current index of medical sciences and drug India database. Rationality assessment was done using prescribed guidelines and approved formulations of zinc by Central drug standard control organisation. Essentiality was checked using National list of essential medicine India, 2013 and latest version of WHO list essential medicine bulletin. Dosage regulation was assessed using Indian pharmacopeia guidelines, National institute of nutrition, India recommendation and upper daily intake toxicity intake, United States of America (USA)Results: Our study results showed wide variation in the number of zinc preparation. Total number of formulation available in the market is 335. Among zinc preparation, the preparation that contains 20 mg of zinc as recommended by various guidelines is 10 in number. About 325 preparations of zinc are added with one or more nutraceuticals. None of these fixed dose combination of zinc containing preparation is recommended as essential fixed regimen.Conclusion: Zinc has lot of relevance in treating recurrent diarrhoeal illness, especially in paediatric cases; however legal, regulatory and educational measures should be followed to curtail all the irrational zinc prescription development, promotion, marketing and prescription

Association between clinical presentations before myocardial infarction and coronary mortality: a prospective population-based study using linked electronic records.

BACKGROUND: Ischaemia in different arterial territories before acute myocardial infarction (AMI) may influence post-AMI outcomes. No studies have evaluated prospectively collected information on ischaemia and its effect on short- and long-term coronary mortality. The objective of this study was to compare patients with and without prospectively measured ischaemic presentations before AMI in terms of infarct characteristics and coronary mortality. METHODS AND RESULTS: As part of the CALIBER programme, we linked data from primary care, hospital admissions, the national acute coronary syndrome registry and cause-specific mortality to identify patients with first AMI (n = 16,439). We analysed time from AMI to coronary mortality (n = 5283 deaths) using Cox regression (median 2.6 years follow-up), comparing patients with and without recent ischaemic presentations. Patients with ischaemic presentations in the 90 days before AMI experienced lower coronary mortality in the first 7 days after AMI compared with those with no prior ischaemic presentations, after adjusting for age, sex, smoking, diabetes, blood pressure and cardiovascular medications [HR: 0.64 (95% CI: 0.57-0.73) P < 0.001], but subsequent mortality was higher [HR: 1.42 (1.13-1.77) P = 0.001]. Patients with ischaemic presentations closer in time to AMI had the lowest seven day mortality (P-trend = 0.001). CONCLUSION: In the first large prospective study of ischaemic presentations prior to AMI, we have shown that those occurring closest to AMI are associated with lower short-term coronary mortality following AMI, which could represent a natural ischaemic preconditioning effect, observed in a clinical setting. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov identifier NCT01604486

Heat and risk of myocardial infarction: hourly level case-crossover analysis of MINAP database.

OBJECTIVE: To quantify the association between exposure to higher temperatures and the risk of myocardial infarction at an hourly temporal resolution. DESIGN: Case-crossover study. SETTING: England and Wales Myocardial Ischaemia National Audit Project (MINAP) database. PARTICIPANTS: 24,861 hospital admissions for myocardial infarction occurring in 11 conurbations during the warmest months (June to August) of the years 2003-09. MAIN OUTCOME MEASURE: Odds ratio of myocardial infarction for a 1 °C increase in temperature. RESULTS: Strong evidence was found for an effect of heat acting 1-6 hours after exposure to temperatures above an estimated threshold of 20 °C (95% confidence interval 16 °C to 25 °C). For each 1 °C increase in temperature above this threshold, the risk of myocardial infarction increased by 1.9% (0.5% to 3.3%, P=0.009). Later reductions in risk seemed to offset early increases in risk: the cumulative effect of a 1 °C rise in temperature above the threshold was 0.2% (-2.1% to 2.5%) by the end of the third day after exposure. CONCLUSIONS: Higher ambient temperatures above a threshold of 20 °C seem to be associated with a transiently increased risk of myocardial infarction 1-6 hours after exposure. Reductions in risk at longer lags are consistent with heat triggering myocardial infarctions early in highly vulnerable people who would otherwise have had a myocardial infarction some time later ("short term displacement"). Policies aimed at reducing the health effects of hot weather should include consideration of effects operating at sub-daily timescales

The effects of hourly differences in air pollution on the risk of myocardial infarction: case crossover analysis of the MINAP database.

OBJECTIVES: To investigate associations between air pollution levels and myocardial infarction (MI) on short timescales, with data at an hourly temporal resolution. DESIGN: Time stratified case crossover study linking clinical data from the Myocardial Ischaemia National Audit Project (MINAP) with PM(10), ozone, CO, NO(2), and SO(2) data from the UK National Air Quality Archive. Pollution effects were investigated with delays (lags) of 1-6, 7-12, 13-18, 19-24, and 25-72 hours in both single and multi-pollutant models, adjusted for ambient temperature, relative humidity, circulating levels of influenza and respiratory syncytial virus, day of week, holidays, and residual seasonality within calendar month strata. SETTING: Population based study in 15 conurbations in England and Wales. SUBJECTS: 79,288 diagnoses of myocardial infarction recorded over the period 2003-6. MAIN OUTCOME MEASURES: Excess risk of myocardial infarction per 10 µg/m(3) increase in pollutant level. RESULTS: In single pollutant models, PM(10) and NO(2) levels were associated with a very short term increase in risk of myocardial infarction 1-6 hours later (excess risks 1.2% (95% confidence interval 0.3 to 2.1) and 1.1% (0.3 to 1.8) respectively per 10 μg/m(3) increase); the effects persisted in multi-pollutant models, though with only weak evidence of an independent PM(10) effect (P = 0.05). The immediate risk increases were followed by reductions in risk at longer lags: we found no evidence of any net excess risk associated with the five pollutants studied over a 72 hour period after exposure. CONCLUSIONS: Higher levels of PM(10) and NO(2), which are typically markers of traffic related pollution, seem to be associated with transiently increased risk of myocardial infarction 1-6 hours after exposure, but later reductions in risk suggest that air pollution may be associated with bringing events forward in time ("short-term displacement") rather than increasing overall risk. The well established effect of air pollution on cardiorespiratory mortality may not be mediated through increasing the acute risk of myocardial infarction, but through another mechanism

Impact of intrathecal morphine analgesia on the incidence of pulmonary complications after cardiac surgery: a single center propensity-matched cohort study.

BACKGROUND: Acute pain and systemic opioids may both negatively impact respiratory function after cardiac surgery. This study analyzes the local practice of using intrathecal morphine analgesia (ITMA) with minimal parenteral opioid administration in cardiac surgery, specifically the impact on postoperative pulmonary complications (PPCs). METHODS: Data from adult patients who underwent elective cardiac surgery between January 2002, and December 2013 in a single center were analyzed. Propensity scores estimating the likelihood of receiving ITMA were used to match (1:1) patients with ITMA and patients with intravenous analgesia (IVA). Primary outcome was PPCs, a composite endpoint including pneumonia, adult respiratory distress syndrome, and any type of acute respiratory failure. Secondary outcomes were in-hospital mortality, cardiovascular complications, and length of stay in the intensive care unit (ICU) and hospital. RESULTS: From a total of 1'543 patients, 920 were treated with ITMA and 623 with IVA. No adverse event consequent to the spinal puncture was reported. Propensity score matching created 557 balanced pairs. The occurrence of PPCs in patients with ITMA was 8.1% vs. 12.8% in patients with IVA (odds ratio, 0.6; 95% CI, 0.40-0.89; p = 0.012). Fewer patients with ITMA had a prolonged stay in the ICU (> 4 days; 16.5% vs. 21.2%, p = 0.047) or in the hospital (> 15 days; 25.5% vs. 31.8%. p = 0.024). In-hospital mortality and cardiovascular complications did not differ significantly between the two groups. CONCLUSION: In this study involving cardiac surgical patients, ITMA was safely applied and was associated with fewer PPCs

Bariatric Surgery in the United Kingdom: A Cohort Study of Weight Loss and Clinical Outcomes in Routine Clinical Care.

BACKGROUND: Bariatric surgery is becoming a more widespread treatment for obesity. Comprehensive evidence of the long-term effects of contemporary surgery on a broad range of clinical outcomes in large populations treated in routine clinical practice is lacking. The objective of this study was to measure the association between bariatric surgery, weight, body mass index, and obesity-related co-morbidities. METHODS AND FINDINGS: This was an observational retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. All 3,882 patients registered in the database and with bariatric surgery on or before 31 December 2014 were included and matched by propensity score to 3,882 obese patients without surgery. The main outcome measures were change in weight and body mass index over 4 y; incident diagnoses of type 2 diabetes mellitus (T2DM), hypertension, angina, myocardial infarction (MI), stroke, fractures, obstructive sleep apnoea, and cancer; mortality; and resolution of hypertension and T2DM. Weight measures were available for 3,847 patients between 1 and 4 mo, 2,884 patients between 5 and 12 mo, and 2,258 patients between 13 and 48 mo post-procedure. Bariatric surgery patients exhibited rapid weight loss for the first four postoperative months, at a rate of 4.98 kg/mo (95% CI 4.88-5.08). Slower weight loss was sustained to the end of 4 y. Gastric bypass (6.56 kg/mo) and sleeve gastrectomy (6.29 kg/mo) were associated with greater initial weight reduction than gastric banding (2.77 kg/mo). Protective hazard ratios (HRs) were detected for bariatric surgery for incident T2DM, 0.68 (95% CI 0.55-0.83); hypertension, 0.35 (95% CI 0.27-0.45); angina, 0.59 (95% CI 0.40-0.87);MI, 0.28 (95% CI 0.10-0.74); and obstructive sleep apnoea, 0.55 (95% CI 0.40-0.87). Strong associations were found between bariatric surgery and the resolution of T2DM, with a HR of 9.29 (95% CI 6.84-12.62), and between bariatric surgery and the resolution of hypertension, with a HR of 5.64 (95% CI 2.65-11.99). No association was detected between bariatric surgery and fractures, cancer, or stroke. Effect estimates for mortality found no protective association with bariatric surgery overall, with a HR of 0.97 (95% CI 0.66-1.43). The data used were recorded for the management of patients in primary care and may be subject to inaccuracy, which would tend to lead to underestimates of true relative effect sizes. CONCLUSIONS: Bariatric surgery as delivered in the UK healthcare system is associated with dramatic weight loss, sustained at least 4 y after surgery. This weight loss is accompanied by substantial improvements in pre-existing T2DM and hypertension, as well as a reduced risk of incident T2DM, hypertension, angina, MI, and obstructive sleep apnoea. Widening the availability of bariatric surgery could lead to substantial health benefits for many people who are morbidly obese

Associations between breast cancer survivorship and adverse mental health outcomes: A matched population-based cohort study in the United Kingdom.

BACKGROUND: Breast cancer is the most common cancer diagnosed in women globally, and 5-year net survival probabilities in high-income countries are generally >80%. A cancer diagnosis and treatment are often traumatic events, and many women struggle to cope during this period. Less is known, however, about the long-term mental health impact of the disease, despite many women living several years beyond their breast cancer and mental health being a major source of disability in modern societies. The objective of this study was to quantify the risk of several adverse mental health-related outcomes in women with a history of breast cancer followed in primary care in the United Kingdom National Health Service, compared to similar women who never had cancer. METHODS AND FINDINGS: We conducted a matched cohort study using data routinely collected in primary care across the UK to quantify associations between breast cancer history and depression, anxiety, and other mental health-related outcomes. All women with incident breast cancer in the Clinical Practice Research Datalink (CPRD) GOLD primary care database between 1988 and 2018 (N = 57,571, mean = 62 ± 14 years) were matched 1:4 to women with no prior cancer (N = 230,067) based on age, primary care practice, and eligibility of the data for linkage to hospital data sources. Cox models were used to estimate associations between breast cancer survivorship and each mental health-related outcome, further adjusting for diabetes, body mass index (BMI), and smoking and drinking status at baseline. Breast cancer survivorship was positively associated with anxiety (adjusted hazard ratio (HR) = 1.33; 95% confidence interval (CI): 1.29-1.36; p < 0.001), depression (1.35; 1.32-1.38; p < 0.001), sexual dysfunction (1.27; 1.17-1.38; p < 0.001), and sleep disorder (1.68; 1.63-1.73; p < 0.001), but not with cognitive dysfunction (1.00; 0.97-1.04; p = 0.88). Positive associations were also found for fatigue (HR = 1.28; 1.25-1.31; p < 0.001), pain (1.22; 1.20-1.24; p < 0.001), receipt of opioid analgesics (1.86; 1.83-1.90; p < 0.001), and fatal and nonfatal self-harm (1.15; 0.97-1.36; p = 0.11), but CI was wide, and the relationship was not statistically significant for the latter. HRs for anxiety and depression decreased over time (p-interaction <0.001), but increased risks persisted for 2 and 4 years, respectively, after cancer diagnosis. Increased levels of pain and sleep disorder persisted for 10 years. Younger age was associated with larger HRs for depression, cognitive dysfunction, pain, opioid analgesics use, and sleep disorders (p-interaction <0.001 in each case). Limitations of the study include the potential for residual confounding by lifestyle factors and detection bias due to cancer survivors having greater healthcare contact. CONCLUSIONS: In this study, we observed that compared to women with no prior cancer, breast cancer survivors had higher risk of anxiety, depression, sleep problems, sexual dysfunction, fatigue, receipt of opioid analgesics, and pain. Relative risks estimates tended to decrease over time, but anxiety and depression were significantly increased for 2 and 4 years after breast cancer diagnosis, respectively, while associations for fatigue, pain, and sleep disorders were elevated for at least 5-10 years after diagnosis. Early diagnosis and increased awareness among patients, healthcare professionals, and policy makers are likely to be important to mitigate the impacts of these raised risks