Medication safety in chronic kidney disease.

PURPOSE OF REVIEW: Several drugs cause nephrotoxicity and accelerate progression of chronic kidney disease (CKD). The objective of this review is to summarize recent evidence on drugs that either increase the risk of nephrotoxicity, progression of CKD or drug induced harm in patients with CKD. RECENT FINDINGS: Bisphosphonates and hypnotics increase the progression of CKD, whereas denosumab does not accelerate progression of CKD. Tenofovir disoproxil fumarate (TDF) increases the risk of renal tubular toxicity and adverse effects on bone, but Tenofovir alafenamide (TAF) and Tenofovir amibufenamide (TMF) have favorable safety profile on the kidneys and bones. Although no dosage adjustment is needed for Oral Nirmatrelvir/Ritonavir in patients with mild renal impairment and coronavirus disease 2019, the dosage is reduced to twice daily in those with moderate renal impairment. It is not recommended in patients with severe renal impairment. The prescribing information does not recommend use of remdesevir below glomerular filtration rate (eGFR) < 30 ml/min but recent studies suggest that remdesevir may be safe and effective in patients with varying levels of CKD severity. Molnupiravir does not require dose adjustment in patients with CKD. SUMMARY: Several medications increase the risk of development of acute kidney injury or progression of CKD. Close attention is needed to select the appropriate dose or safer alternatives to reduce the risk of drug-induced harm in patients with CKD.

Pragmatic guidance for embedding pragmatic clinical trials in health plans: Large simple trials aren't so simple.

BACKGROUND: There are unique opportunities related to the design and conduct of pragmatic trials embedded in health insurance plans, which have longitudinal data on member/patient demographics, dates of coverage, and reimbursed medical care, including prescription drug dispensings, vaccine administrations, behavioral healthcare encounters, and some laboratory results. Such trials can be large and efficient, using these data to identify trial-eligible patients and to ascertain outcomes. METHODS: We use our experience primarily with the National Institutes of Health Pragmatic Trials Collaboratory Distributed Research Network, which comprises health plans that participate in the US Food & Drug Administration's Sentinel System, to describe lessons learned from the conduct and planning of embedded pragmatic trials. RESULTS: Information is available for research on more than 75 million people with commercial or Medicare Advantage health plans. We describe three studies that have used or plan to use the Network, as well as a single health plan study, from which we glean our lessons learned. CONCLUSIONS: Studies that are conducted in health plans provide much-needed evidence to drive clinically meaningful changes in care. However, there are many unique aspects of these trials that must be considered in the planning, implementation, and analytic phases. The type of trial best suited for studies embedded in health plans will be those that require large sample sizes, simple interventions that could be disseminated through health plans, and where data available to the health plan can be leveraged. These trials hold potential for substantial long-term impact on our ability to generate evidence to improve care and population health.

Higher Triad Risk Scores Are Associated With Increased Risk for Trabecular-Rich Bone Stress Injuries in Female Runners.

OBJECTIVE: Bone stress injuries (BSIs) in trabecular-rich bone are associated with greater biological risk factors compared with cortical-rich bone. We hypothesized that female runners with high Female Athlete Triad (Triad)-related risk would be at greater risk for trabecular-rich BSIs than runners with low Triad-related risk. DESIGN: Prospective cohort study. SETTING: Two NCAA institutions. PARTICIPANTS: Female runners were followed prospectively for up to 5 years. INTERVENTION: The intervention consisted of team nutrition presentations focused on optimizing energy availability plus individualized nutrition sessions. Triad Cumulative Risk Assessment (CRA) categories were assigned yearly based on low-energy availability, menstrual status, age of menarche, low body mass index, low bone mineral density, and prior BSI. MAIN OUTCOME MEASURES: The outcome was the annual incidence of trabecular- and cortical-rich BSI. Generalized Estimating Equations (GEE, to account for the correlated nature of the observations) with a Poisson distribution and log link were used for statistical modeling. RESULTS: Cortical-rich BSI rates were higher than trabecular-rich BSI rates (0.32 vs 0.13 events per person-year). Female runners with high Triad-related risk had a significantly higher incidence rate ratio of trabecular-rich BSI (RR: 4.40, P = 0.025) and cortical-rich BSI (RR: 2.87, P = 0.025) than women with low Triad-related risk. Each 1-point increase in Triad CRA score was associated with a significant 26% increased risk of trabecular-rich BSI ( P = 0.0007) and a nonsignificant 14% increased risk of cortical-rich BSI ( P = 0.054). CONCLUSIONS: Increased Triad CRA scores were strongly associated with increased risk for trabecular-rich BSI. Incorporating Triad CRA scores in clinical care could guide BSI prevention.

In vivo intrinsic atomic interaction infer molecular eco-toxicity of industrial TiO2 nanoparticles via oxidative stress channelized steatosis and apoptosis in Paramecium caudatum.

The ecotoxicological effect of after-usage released TiO2 nanoparticles in aquatic resources has been a major concern owing to their production and utilization in different applications. Addressing the issue, this study investigates the detailed in vivo molecular toxicity of TiO2 nanoparticles with Paramecium caudatum. TiO2 nanoparticles were synthesized at a lab scale using high energy ball milling technique; characterized for their physicochemical properties and investigated for their ecotoxicological impact on oxidative stress, steatosis, and apoptosis of cells through different biochemical analysis, flow cytometry, and fluorescent microscopy. TiO2 nanoparticles; TiO2 (N15); of size 36 ± 12 nm were synthesized with a zeta potential of - 20.2 ± 8.8 mV and bandgap of 4.6 ± 0.3 eV and exhibited a blue shift in UV-spectrum. Compared to the Bulk TiO2, the TiO2 (N15) exhibited higher cytotoxicity with a 24 h LC50 of 202.4 µg/ml with P. Caudatum. The mechanism was elucidated as the size and charge-dependent internalization of nanoparticles leading to abnormal physiological metabolism in oxidative stress, steatosis, and apoptosis because of their influential effect on the activity of metabolic proteins like SOD, GSH, MDA, and catalase. The study emphasized the controlled usage TiO2 nanoparticles in daily activity with a concern for ecological and biomedical aspects.

To evaluate the effect of small-group demonstration-based training module in improving clinical skills in undergraduate medical students.

BACKGROUND: In today's modern era, the two most important aspects of medical education are evaluation- and outcome-based learning. Directly Observed Procedural Skills (DOPSs ) is a well-known method of evaluation which constitutes a direct observation of the practical skills being performed by the student and simultaneous written feedback by the teacher. METHOD: A total of 40 undergraduate students were taught by a module based on DOPS. A pre-test and post-test was conducted on DOPS examination pattern and was compared by the Cochran's Q test. RESULTS: In this study, a total of 40 medical undergraduate students and 10 teachers participated. Each student was given one pre-test and five post-test with ultrasound proven mild to moderate splenomegaly. Each student was individually assessed on a module based on DOPS and was given direct feedback by the teachers. A total of 34 (85%) students strongly agreed that they felt comfortable and confident with this methodology. CONCLUSION: The results of this study revealed that DOPS tests can be used as an effective evaluation method to assess medical students because of its appropriate validity and reliability, positive impact on learning, and high satisfaction level amongst students. However, special attention needs to be given to the quality of these tests.

Identifying prescribing cascades in Alzheimer's disease and related dementias: The calcium channel blocker-diuretic prescribing cascade.

PURPOSE: Prescribing cascades occur when a physician prescribes a new drug to address the side-effect of another drug. Persons with Alzheimer's disease and related dementias (ADRD) are at increased risk for prescribing cascades. Our objective was to develop an approach to estimating the proportion of calcium channel blocker-diuretic (CCB-diuretic) prescribing cascades among persons with ADRD in two U.S. health plans. METHODS: We identified patients aged ≥50 on January 1, 2017, dispensed a drug to treat ADRD in the 365-days prior to/on cohort entry date. Patients had medical/pharmacy coverage for 1 year before and through cohort entry. We excluded individuals with an institutional stay encounter in the 45 days prior to cohort entry and censored patients based on: disenrollment from coverage, death, or end of data. We identified incident and prevalent CCB use in the 183-days following cohort entry, and identified subsequent incident diuretic use among incident and prevalent CCB-users within 365-days from cohort entry. RESULTS: There were 121 538 eligible patients. Approximately 62% were female, with a mean age of 79.5 (SD ±8.6). Overall 2.1% of the cohort experienced a prevalent CCB-diuretic prescribing cascade with 1586 incident diuretic-users among 36 462 prevalent CCB-users (4.3%, 95% CI 4.1-4.6%]); and there were161 incident diuretic-users among 3304 incident CCB-users (4.9%, 95% CI 4.2-5.7%) (incident CCB-diuretic cascade). CONCLUSIONS: We describe an approach to identify prescribing cascades in persons with ADRD, which can be used to assess the proportion of prescribing cascades in large cohorts. We determined the proportion of CCB-diuretic prescribing cascades was low.

Dietary Supplement Use According to Sex and Triad Risk Factors in Collegiate Endurance Runners.

ABSTRACT: Barrack, MT, Fredericson, M, Dizon, F, Tenforde, AS, Kim, BY, Kraus, E, Kussman, A, Singh, S, and Nattiv, A. Dietary supplement use according to sex and Triad risk factors in collegiate endurance runners. J Strength Cond Res 35(2): 404-410, 2021-This cross-sectional study evaluated the prevalence in the use of dietary supplements among elite collegiate runners among 2 NCAA Division I cross-country teams. At the start of each season from 2015 to 2017, male and female endurance runners were recruited to complete baseline study measures; the final sample included 135 (male n = 65, female n = 70) runners. Runners completed a health survey, web-based nutrition survey, and Triad risk assessment. The prevalence of dietary supplement use and Triad risk factors, including disordered eating, low bone mass, amenorrhea (in women), low body mass index, and stress fracture history, was assessed. A total of 78.5% (n = 106) runners reported taking 1 or more supplements on ≥4 days per week over the past month, 48% (n = 65) reported use of ≥3 supplements. Products used with highest frequency included multivitamin/minerals 46.7% (n = 63), iron 46.7% (n = 63), vitamin D 34.1% (n = 46), and calcium 33.3% (n = 45). More women, compared with men, used iron (61.4 vs. 30.8%, p < 0.001) and calcium (41.4 vs. 24.6%, p = 0.04); men exhibited higher use of amino acids and beta-alanine (6.2 vs. 0%, p = 0.04). Runners with bone stress injury (BSI) history, vs. no previous BSI, reported more frequent use of ≥3 supplements (61.5 vs. 32.8%, p = 0.001), vitamin D (49.2 vs. 19.4%, p < 0.001), and calcium (47.7 vs. 19.4%, p = 0.001). Low bone mineral density was also associated with higher use of vitamin D and calcium. Most runners reported regular use of 1 or more supplements, with patterns of use varying based on sex, history of BSI, and bone mass.

Identifying monoclonal gammopathy of undetermined significance in electronic health data.

PURPOSE: Monoclonal gammopathy of undetermined significance (MGUS) is a prevalent yet largely asymptomatic precursor to multiple myeloma. Patients with MGUS must undergo regular surveillance and testing, with few known predictors of progression. We developed an algorithm to identify MGUS patients in electronic health data to facilitate large-scale, population-based studies of this premalignant condition. METHODS: We developed a four-step algorithm using electronic health record and health claims data from men and women aged 50 years or older receiving care from a large, multispecialty medical group between 2007 and 2015. The case definition required patients to have at least two MGUS ICD-9 diagnosis codes within 12 months, at least one serum and/or urine protein electrophoresis and one immunofixation test, and at least one in-office hematology/oncology visit. Medical charts for selected cases were abstracted then adjudicated independently by two physicians. We assessed algorithm validity by positive predictive value (PPV). RESULTS: We identified 833 people with at least two MGUS diagnosis codes; 429 (52%) met all four algorithm criteria. We randomly selected 252 charts for review, including 206 from patients meeting all four algorithm criteria. The PPV for the 206 algorithm-identified charts was 76% (95% CI, 70%-82%). Among the 49 cases deemed to be false positives (24%), 33 were judged to have multiple myeloma or another lymphoproliferative condition, such as lymphoma. CONCLUSIONS: We developed a simple algorithm that identified MGUS cases in electronic health data with reasonable accuracy. Inclusion of additional steps to eliminate cases with malignant disease may improve algorithm performance.

Absence of gravin-mediated signaling inhibits development of high-fat diet-induced hyperlipidemia and atherosclerosis.

Gravin, an A-kinase anchoring protein, is known to play a role in regulating key processes that lead to inflammation and atherosclerosis development, namely, cell migration, proliferation, and apoptosis. We investigated the role of gravin in the development of high-fat diet (HFD)-induced atherosclerosis and hyperlipidemia. Five-week-old male wild-type (WT) and gravin-t/t mice were fed a normal diet or an HFD for 16 wk. Gravin-t/t mice showed significantly lower liver-to-body-weight ratio, cholesterol, triglyceride, and very low-density lipoprotein levels in serum as compared with WT mice on HFD. Furthermore, there was less aortic plaque formation coupled with decreased lipid accumulation and liver damage, as the gravin-t/t mice had lower levels of serum alanine aminotransferase and aspartate aminotransferase. Additionally, gravin-t/t HFD-fed mice had decreased expression of liver 3-hydroxy-3-methyl-glutaryl-CoA reductase, an essential enzyme for cholesterol synthesis and lower fatty acid synthase expression. Gravin-t/t HFD-fed mice also exhibited inhibition of sterol regulatory element binding protein-2 (SREBP-2) expression, a liver transcription factor associated with the regulation of lipid transportation. In response to platelet-derived growth factor receptor treatment, gravin-t/t vascular smooth muscle cells exhibited lower intracellular calcium transients and decreased protein kinase A- and protein kinase C-dependent substrate phosphorylation, notably involving the Erk1/2 signaling pathway. Collectively, these results suggest the involvement of gravin-dependent regulation of lipid metabolism via the reduction of SREBP-2 expression. The absence of gravin-mediated signaling lowers blood pressure, reduces plaque formation in the aorta, and decreases lipid accumulation and damage in the liver of HFD mice. Through these processes, the absence of gravin-mediated signaling complex delays the HFD-induced hyperlipidemia and atherosclerosis.NEW & NOTEWORTHY The gravin scaffolding protein plays a key role in the multiple enzymatic pathways of lipid metabolism. We have shown for the first time the novel role of gravin in regulating the pathways related to the initiation and progression of atherosclerosis. Specifically, an absence of gravin-mediated signaling decreases the lipid levels (cholesterol, triglyceride, and VLDL) that are associated with sterol regulatory element binding protein-2 downregulation.

A comparison of two algorithms to identify sudden cardiac deaths in computerized databases.

PURPOSE: Two previously validated algorithms to identify sudden cardiac death using administrative data showed high positive predictive value. We evaluated the agreement between the algorithms using data from a common source population. METHODS: We conducted a cross-sectional study to assess the percent agreement between deaths identified by two sudden cardiac death algorithms using Tennessee Medicaid and death certificate data from 2007 through 2014. The source population included all deceased patients aged 18 to 64 years with Medicaid enrollment in the 6 months prior to death. To identify sudden cardiac deaths, algorithm 1 used only hospital/emergency department (ED) claims from encounters at the time of death, and algorithm 2 required death certificates and used claims data for specific exclusion criteria. RESULTS: We identified 34 107 deaths in the source population over the study period. The two algorithms identified 4372 potential sudden cardiac deaths: Algorithm 1 identified 3117 (71.3%) and algorithm 2 identified 1715 (39.2%), with 460 (10.5%) deaths identified by both algorithms. Of the deaths identified by algorithm 1, 1943 (62.3%) had an underlying cause of death not specified in algorithm 2. Of the deaths identified by algorithm 2, 1053 (61.4%) had no record of a hospital or ED encounter at the time of death, and 202 (11.8%) had a discharge diagnosis code not specified in algorithm 1. CONCLUSIONS: We found low agreement between the two algorithms for identification of sudden cardiac deaths because of differences in sudden cardiac death definitions and data sources.

Bone stress injuries in male distance runners: higher modified Female Athlete Triad Cumulative Risk Assessment scores predict increased rates of injury.

OBJECTIVES: Bone stress injuries (BSI) are common in runners of both sexes. The purpose of this study was to determine if a modified Female Athlete Triad Cumulative Risk Assessment tool would predict BSI in male distance runners. METHODS: 156 male runners at two collegiate programmes were studied using mixed retrospective and prospective design for a total of 7 years. Point values were assigned using risk assessment categories including low energy availability, low body mass index (BMI), low bone mineral density (BMD) and prior BSI. The outcome was subsequent development of BSI. Statistical models used a mixed effects Poisson regression model with p<0.05 as threshold for significance. Two regression analyses were performed: (1) baseline risk factors as the independent variable; and (2) annual change in risk factors (longitudinal data) as the independent variable. RESULTS: 42/156 runners (27%) sustained 61 BSIs over an average 1.9 years of follow-up. In the baseline risk factor model, each 1 point increase in prior BSI score was associated with a 57% increased risk for prospective BSI (p=0.0042) and each 1 point increase in cumulative risk score was associated with a 37% increase in prospective BSI risk (p=0.0079). In the longitudinal model, each 1 point increase in cumulative risk score was associated with a 27% increase in prospective BSI risk (p=0.05). BMI (rate ratio (RR)=1.91, p=0.11) and BMD (RR=1.58, p=0.19) risk scores were not associated with BSI. CONCLUSION: A modified cumulative risk assessment tool may help identify male runners at elevated risk for BSI. Identifying risk factors may guide treatment and prevention strategies.

Determining the scope of attacks on health in four governorates of Syria in 2016: Results of a field surveillance program.

BACKGROUND: Violent attacks on and interferences with hospitals, ambulances, health workers, and patients during conflict destroy vital health services during a time when they are most needed and undermine the long-term capacity of the health system. In Syria, such attacks have been frequent and intense and represent grave violations of the Geneva Conventions, but the number reported has varied considerably. A systematic mechanism to document these attacks could assist in designing more protection strategies and play a critical role in influencing policy, promoting justice, and addressing the health needs of the population. METHODS AND FINDINGS: We developed a mobile data collection questionnaire to collect data on incidents of attacks on healthcare directly from the field. Data collectors from the Syrian American Medical Society (SAMS), using the tool or a text messaging system, recorded information on incidents across four of Syria's northern governorates (Aleppo, Idleb, Hama, and Homs) from January 1, 2016, to December 31, 2016. SAMS recorded a total of 200 attacks on healthcare in 2016, 102 of them using the mobile data collection tool. Direct attacks on health facilities comprised the majority of attacks recorded (88.0%; n = 176). One hundred and twelve healthcare staff and 185 patients were killed in these incidents. Thirty-five percent of the facilities were attacked more than once over the data collection period; hospitals were significantly more likely to be attacked more than once compared to clinics and other types of healthcare facilities. Aerial bombs were used in the overwhelming majority of cases (91.5%). We also compared the SAMS data to a separate database developed by Physicians for Human Rights (PHR) based on media reports and matched the incidents to compare the results from the two methods (this analysis was limited to incidents at health facilities). Among 90 relevant incidents verified by PHR and 177 by SAMS, there were 60 that could be matched to each other, highlighting the differences in results from the two methods. This study is limited by the complexities of data collection in a conflict setting, only partial use of the standardized reporting tool, and the fact that limited accessibility of some health facilities and workers and may be biased towards the reporting of attacks on larger or more visible health facilities. CONCLUSIONS: The use of field data collectors and use of consistent definitions can play an important role in the tracking incidents of attacks on health services. A mobile systematic data collection tool can complement other methods for tracking incidents of attacks on healthcare and ensure the collection of detailed information about each attack that may assist in better advocacy, programs, and accountability but can be practically challenging. Comparing attacks between SAMS and PHR suggests that there may have been significantly more attacks than previously captured by any one methodology. This scale of attacks suggests that targeting of healthcare in Syria is systematic and highlights the failure of condemnation by the international community and medical groups working in Syria of such attacks to stop them.

Targeted sequencing identifies a missense variant in the BEST3 gene associated with antihypertensive response to hydrochlorothiazide.

Chromosome 12q15 was identified in Genetic Epidemiology of Response Assessment (GERA) and replicated in Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) for its association with blood pressure (BP) response to hydrochlorothiazide (HCTZ). However, the functional variant is unknown and we aimed to identify the likely functional variants through targeted sequencing. The chromosome 12q15 region was sequenced in 397 best and worst responders to HCTZ in PEAR (N=199) and GERA (N=198) hypertensive study participants. Logistic regression was used for the association analysis adjusting for age, sex, race, and principal components 1 and 2. For validation, the significant single nucleotide polymorphism was tested for association with the change in systolic (ΔSBP) and diastolic BP (ΔDBP) post-treatment in the entire PEAR (N=370) and GERA (N=570) cohorts. A novel missense polymorphism (G>A, Pro383Leu) in BEST3, rs61747221, was significantly associated with better HCTZ response (P=0.0021, odds ratio=2.05). It was validated in the entire cohort of PEAR (ΔSBP: P=0.021, ß=-1.60, ΔDBP: P=0.023, ß=-1.08) and GERA (ΔSBP: P=0.028, ß=-1.95, ΔDBP: P=0.032, ß=-1.28). BEST3 encodes the calcium sensitive chloride channel in the vascular smooth muscle implicated in the regulation of BP, especially in response to vasoconstrictors like angiotensin II. These results suggest that BEST3 is involved in the chronic BP lowering mechanism of thiazides and highlight its importance as a genetic predictor of the BP response to thiazide diuretics.

Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis.

AIMS: Since 2005, several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved to treat people with type 2 diabetes. These agents are considered for use at the same point in the treatment paradigm as basal insulins. A comprehensive comparison of these drug classes, therefore, can help inform treatment decisions. This systematic review and meta-analysis assessed the clinical efficacy and safety of GLP-1 RAs compared with basal insulins. MATERIALS AND METHODS: MEDLINE, EMBASE, CENTRAL and PubMed databases were searched. Randomized clinical trials (RCTs) of ≥16 weeks' duration comparing GLP-1 RAs vs basal insulins in adults with type 2 diabetes inadequately controlled with oral antihyperglycemic drugs were included. Data on the change from baseline to 26 weeks (±10 weeks) of treatment in hemoglobin A1c (HbA1c) and weight, as well as the proportion of patients experiencing hypoglycaemia, were extracted. Fixed-effect pairwise meta-analyses were conducted where data were available from ≥2 studies. RESULTS: Fifteen RCTs were identified and 11 were meta-analysed. The once-weekly GLP-1 RAs, exenatide long acting release (LAR) and dulaglutide, led to greater, statistically significant mean HbA1c reductions vs basal insulins (exenatide: -0.31% [95% confidence interval -0.42, -0.19], dulaglutide: -0.39% [-0.49, -0.29]) whilst once-daily liraglutide and twice-daily exenatide did not (liraglutide: 0.06% [-0.06, 0.18], exenatide: 0.01% [-0.11, 0.13]). Mean weight reduction was seen with all GLP-1 RAs while mean weight gain was seen with basal insulins. Interpretation of the analysis of hypoglycaemia was limited by inconsistent definitions and reporting. Because of the limited number of available studies sensitivity analyses to explore heterogeneity could not be conducted. CONCLUSIONS: Although weight reduction is seen with all GLP-1 RA's, only the once-weekly agents, exenatide LAR and dulaglutide, demonstrate significant HbA1c reductions when compared to basal insulins.

Social isolation and health in widowhood: A qualitative study of Nepali widows' experiences.

Little research exists on social isolation and health among widows despite their marginalization in South Asia. Using a conceptual framework that delineates distinct forms of social support, our results provide a preliminary analysis of the role social support plays in the well-being of Nepali widows. Between 2011 and 2012, we conducted 42 in-depth interviews in the Kathmandu valley and Surkhet district. Low social support was a common theme, principally lacking in the domains of emotional and instrumental support and was described as increasing women's vulnerability to mistreatment and economic insecurity. Policies and programs that foster these types of support may have positive effects on widows' well-being.

Benefit-harm analysis and charts for individualized and preference-sensitive prevention: example of low dose aspirin for primary prevention of cardiovascular disease and cancer.

BACKGROUND: Clinical practice guidelines provide separate recommendations for different diseases that may be prevented or treated by the same intervention. Also, they commonly provide recommendations for entire populations but not for individuals. To address these two limitations, our aim was to conduct benefit-harm analyses for a wide range of individuals using the example of low dose aspirin for primary prevention of cardiovascular disease and cancer and to develop Benefit-Harm Charts that show the overall benefit-harm balance for individuals. METHODS: We used quantitative benefit-harm modeling that included 16 outcomes to estimate the probability that low dose aspirin provides more benefits than harms for a wide range of men and women between 45 and 84 years of age and without a previous myocardial infarction, severe ischemic stroke, or cancer. We repeated the quantitative benefit-harm modeling for different combinations of age, sex, and outcome risks for severe ischemic and hemorrhagic stroke, myocardial infarction, cancers, and severe gastrointestinal bleeds. The analyses considered weights for the outcomes, statistical uncertainty of the effects of aspirin, and death as a competing risk. We constructed Benefit-Harm Charts that show the benefit-harm balance for different combinations of outcome risks. RESULTS: The Benefit-Harm Charts ( http://www.benefit-harm-balance.com ) we have created show that the benefit-harm balance differs largely across a primary prevention population. Low dose aspirin is likely to provide more benefits than harms in men, elderly people, and in those at low risk for severe gastrointestinal bleeds. Individual preferences have a major impact on the benefit-harm balance. If, for example, it is a high priority for individuals to prevent stroke and severe cancers while severe gastrointestinal bleeds are deemed to be of little importance, the benefit-harm balance is likely to favor low dose aspirin for most individuals. Instead, if severe gastrointestinal bleeds are judged to be similarly important compared to the benefit outcomes, low dose aspirin is unlikely to provide more benefits than harms. CONCLUSIONS: Benefit-Harm Charts support individualized benefit-harm assessments and decision making. Similarly, individualized benefit-harm assessments may allow guideline developers to issue more finely granulated recommendations that reduce the risk of over- and underuse of interventions. The example of low dose aspirin for primary prevention of cardiovascular disease and cancer shows that it may be time for guideline developers to provide combined recommendations for different diseases that may be prevented or treated by the same intervention.

Anti-diabetic therapies and the risk of acute pancreatitis: a nationwide retrospective cohort study from Taiwan.

AIMS: To examine the relationship between different anti-diabetic therapies (dipeptidyl peptidase-4 (DPP-4), metformin and sulfonylureas) and risk of acute pancreatitis among type 2 diabetic patients in Taiwan, and explore each drug's dose-response relationship. MATERIALS AND METHODS: We derived a nationwide retrospective cohort of patients with type 2 diabetes in Taiwan. The inclusion criteria are adult diabetic patients with continuous baseline enrollment, new users of the studied drugs, and without missing demographics. There were 4113/101 498/44 772 DPP-4/Metformin/Sulfonylurea users. Adjusted hazards ratios for pancreatitis associated with DPP-4, derived from Cox proportional hazard models with propensity score weighting, were estimated; dose-response analyses were also conducted. RESULTS: Dipeptidyl peptidase-4 was statistically significantly associated with a decreased risk of acute pancreatitis compared with sulfonylureas (adjusted HR: 0.36, 95%CI [0.17, 0.75]) but not metformin (adjusted HR: 0.67, 95%CI [0.32, 1.41]); metformin was statistically significantly associated with a lower risk of pancreatitis than sulfonylurea (adjusted HR: 0. 53; 95%CI [0.37, 0.76]). In addition, low-dose metformin was statistically significantly associated with a lower risk of pancreatitis compared with high-dose metformin (HR: 0.65; 95%CI [0.44, 0.97]). CONCLUSIONS: Our findings suggest that sulfonylureas may potentially be associated with an increased risk of pancreatitis compared with DPP-4 or metformin. Studies with longer follow up, larger sample sizes, and more precise capture of confounders may be needed to determine the risk of pancreatitis associated with incretin based therapies.

Burden of cardiovascular morbidity and mortality following humanitarian emergencies: a systematic literature review.

BACKGROUND: The global burden of cardiovascular mortality is increasing, as is the number of large-scale humanitarian emergencies. The interaction between these phenomena is not well understood. This review aims to clarify the relationship between humanitarian emergencies and cardiovascular morbidity and mortality. METHODS: With assistance from a research librarian, electronic databases (PubMed, Scopus, CINAHL, and Global Health) were searched in January 2014. Findings were supplemented by reviewing citations of included trials. Observational studies reporting the effect of natural disasters and conflict events on cardiovascular morbidity and mortality in adults since 1997 were included. Studies without a comparison group were not included. Double-data extraction was utilized to abstract information on acute coronary syndrome (ACS), acute decompensated heart failure (ADHF), and sudden cardiac death (SCD). Review Manager 5.0 (Version 5.2, The Nordic Cochrane Centre; Copenhagen Denmark,) was used to create figures for qualitative synthesis. RESULTS: The search retrieved 1,697 unique records; 24 studies were included (17 studies of natural disasters and seven studies of conflict). These studies involved 14,583 cardiac events. All studies utilized retrospective designs: four were population-based, 15 were single-center, and five were multicenter studies. Twenty-three studies utilized historical controls in the primary analysis, and one utilized primarily geographical controls. DISCUSSION: Conflicts are associated with an increase in long-term morbidity from ACS; the short-term effects of conflict vary by study. Natural disasters exhibit heterogeneous effects, including increased occurrence of ACS, ADHF, and SCD. CONCLUSIONS: In certain settings, humanitarian emergencies are associated with increased cardiac morbidity and mortality that may persist for years following the event. Humanitarian aid organizations should consider morbidity from noncommunicable disease when planning relief and recuperation projects.