Self-reported and genetically predicted coffee consumption and smoking in dementia: A Mendelian randomization study.

BACKGROUND AND AIMS: Studies of self-reported coffee consumption and smoking on risk of dementia have shown results conflicting with two-sample Mendelian randomization studies. We tested the hypotheses that coffee consumption and smoking influence risk of dementia using observational and one-sample Mendelian randomization designs with individual level data. METHODS: We included 114,551 individuals from two Danish general population cohorts (median age 58 years). First, we tested whether high self-reported coffee consumption/smoking were associated with risk of dementia. Second, whether genetically predicted high coffee consumption/smoking due to variation near CYP1A1/AHR/CHRNA3 genes were associated with risk of dementia. RESULTS: We observed 3,784 dementia events. Moderate self-reported coffee consumption was associated with low risk of all dementia and non-Alzheimer's dementia, with a similar trend for Alzheimer's disease. Genetically predicted high coffee consumption was associated with high risk of all dementia (hazard ratio [95% confidence interval] per +1 cup/day: 1.20 [1.01-1.42]), with a similar trend for non-Alzheimer's dementia (1.23 [0.95-1.53]). High self-reported smoking was associated with high risk of non-Alzheimer's dementia. High genetically predicted smoking was associated with a trend towards high risk of all dementia and Alzheimer's disease (hazard ratios per +1 pack-year: 1.04 [0.96-1.11]) and 1.06 [0.97-1.16]). CONCLUSIONS: Moderate self-reported coffee consumption was associated with low risk of all and non-Alzheimer's dementia, while high genetically predicted coffee consumption was associated with a trend towards the opposite. High self-reported smoking was associated with high risk of non-Alzheimer's dementia, with a similar trend for genetically predicted smoking on all dementia and Alzheimer's disease.

Causal relationship from coffee consumption to diseases and mortality: a review of observational and Mendelian randomization studies including cardiometabolic diseases, cancer, gallstones and other diseases.

PURPOSE: High coffee consumption is associated with low risk of mortality and morbidity, but the causality remains unclear. This review aims to discuss findings from observational studies on coffee consumption in context of Mendelian randomization studies. METHODS: The PubMed database was searched for all Mendelian randomization studies on coffee consumption and corresponding observational studies. RESULTS: High coffee consumption is associated with low risk of all-cause and cardiovascular mortality in observational studies (HRs of 0.85-0.90 vs. no/low consumers), with no support of causality in Mendelian randomization studies. Moderate/high consumption is associated with low risk of cardiometabolic diseases, including ischemic heart disease (HRs of 0.85-0.90 vs. no/low consumption), stroke (HRs of approximately 0.80 vs. no/low consumption), type 2 diabetes (HRs of approximately 0.70 vs. no/low consumption) and obesity in observational studies, but not in Mendelian randomization studies. High consumption is associated with low risk of endometrial cancer and melanoma and high risk of lung cancer in observational studies, but with high risk of colorectal cancer in Mendelian randomization studies. In observational and Mendelian randomization studies, high coffee consumption is associated with low risk of gallstones (HRs of 0.55-0.70 for high vs. no/low self-reported and 0.81 (0.69-0.96) for highest vs. lowest genetic consumption). CONCLUSION: High coffee consumption is associated with low risk of mortality, cardiometabolic diseases, some cancers and gallstones in observational studies, with no evidence to support causality from Mendelian randomization studies for most diseases except gallstones.

The Obesity Paradox in Elderly Patients Undergoing Emergency Surgery: A Nationwide Analysis.

BACKGROUND: Obesity has long been considered a risk factor for postoperative adverse events in surgery. We sought to study the impact of body mass index (BMI) on the clinical outcomes of the high-risk emergency general surgery (EGS) elderly patients. METHODS: All EGS ≥65 years old patients in the 2007-2016 ACS-NSQIP database, identified using the variables 'emergency' and 'surgspec,' were included. Patients were classified into five groups: normal weight: BMI <25 kg/m2, overweight: BMI ≥25 kg/m2 and <30 kg/m2, Class I: BMI ≥30 kg/m2 and <35 kg/m2, Class II: BMI ≥35 kg/m2 and <40 kg/m2, and Class III: BMI ≥40 kg/m2. Patients with BMI<18.5 kg/m2 were excluded. Multivariable logistic regression models were built to assess the relationship between obesity and 30-day postoperative mortality, overall morbidity, and individual postoperative complications after adjusting for demographics (e.g., age, gender), comorbidities (e.g., diabetes mellitus, heart failure), laboratory tests (e.g., white blood cell count, albumin), and operative complexity (e.g., ASA classification). RESULTS: A total of 78,704 patients were included, of which 26,011 were overweight (33.1%), 13,897 (17.6%) had Class I obesity, 5904 (7.5%) had Class II obesity, and 4490 (5.7%) had Class III obesity. On multivariable analyses, compared to the nonobese, patients who are overweight or with Class I-III obesity paradoxically had a lower risk of mortality, bleeding requiring transfusion, pneumonia, stroke and myocardial infarction (MI). Additionally, the incidence of MI and stroke decreased in a stepwise fashion as BMI progressed from overweight to severely obese (MI: OR: 0.84 [0.73-0.95], OR: 0.73 [0.62-0.86], OR: 0.66 [0.52-0.83], OR: 0.51 [0.38-0.68]; stroke: OR: 0.80 [0.65-0.99], OR: 0.79 [0.62-1.02], OR: 0.71 [0.50-1.00], OR: 0.43 [0.28-0.68]). CONCLUSION: In our study of elderly EGS patients, overweight and obese patients had a lower risk of mortality, bleeding requiring transfusion, pneumonia, reintubation, stroke, and MI. Further studies are needed to confirm and investigate the obesity paradox in this patient population.

Opioids After Surgery in the United States Versus the Rest of the World: The International Patterns of Opioid Prescribing (iPOP) Multicenter Study.

OBJECTIVE: The International Patterns of Opioid Prescribing study compares postoperative opioid prescribing patterns in the United States (US) versus the rest of the world. SUMMARY OF BACKGROUND DATA: The US is in the middle of an unprecedented opioid epidemic. Diversion of unused opioids contributes to the opioid epidemic. METHODS: Patients ≥16 years old undergoing appendectomy, cholecystectomy, or inguinal hernia repair in 14 hospitals from 8 countries during a 6-month period were included. Medical records were systematically reviewed to identify: (1) preoperative, intraoperative, and postoperative characteristics, (2) opioid intake within 3 months preoperatively, (3) opioid prescription upon discharge, and (4) opioid refills within 3 months postoperatively. The median/range and mean/standard deviation of number of pills and OME were compared between the US and non-US patients. RESULTS: A total of 4690 patients were included. The mean age was 49 years, 47% were female, and 4% had opioid use history. Ninety-one percent of US patients were prescribed opioids, compared to 5% of non-US patients (P < 0.001). The median number of opioid pills and OME prescribed were 20 (0-135) and 150 (0-1680) mg for US versus 0 (0-50) and 0 (0-600) mg for non-US patients, respectively (both P < 0.001). The mean number of opioid pills and OME prescribed were 23.1 ±â€Š13.9 in US and 183.5 ±â€Š133.7 mg versus 0.8 ±â€Š3.9 and 4.6 ±â€Š27.7 mg in non-US patients, respectively (both P < 0.001). Opioid refill rates were 4.7% for US and 1.0% non-US patients (P < 0.001). CONCLUSIONS: US physicians prescribe alarmingly high amounts of opioid medications postoperatively. Further efforts should focus on limiting opioid prescribing and emphasize non-opioid alternatives in the US.

Smoking and risk of surgical bleeding: nationwide analysis of 5,452,411 surgical cases.

BACKGROUND: Although smoking is associated with several postoperative complications, a possible association with surgical bleeding remains unclear. We examined if smoking is associated with a higher risk of surgical bleeding. STUDY DESIGN AND METHODS: We included patients from the American College of Surgeons National Surgical Quality Improvement Program 2007-2016 from 680 hospitals across the United States. Patients with information on age, sex, surgical specialty, and smoking status were included. Surgical bleeding was defined as 1 or more red blood cell (RBC) units transfused intraoperatively to 72 hours postoperatively. The association between smoking and surgical bleeding was examined using logistic regressions adjusted for age, sex, body mass index, ethnicity, comorbidities, laboratory values, American Society of Anesthesiologists score, type of anesthesia, duration of surgery, work relative value unit (surrogate for operative complexity), surgical specialty, and procedure year. RESULTS: A total of 5,452,411 cases were recorded, of whom 19% smoked and 6% received transfusion. Odds ratios for transfusion were 1.06 (95% confidence interval [CI], 1.05-1.07) for smokers versus nonsmokers and 1.06 (95% CI, 1.04-1.09) for current smokers versus never-smokers. Odds ratios for cumulative smoking were 0.97 (95% CI, 0.95-1.00) for greater than 0 to 20 versus 0 pack-years, 1.04 (95% CI, 1.01-1.07) for greater than 20 to 40, and 1.12 (95% CI, 1.09-1.15) for greater than 40 (p for trend < 0.001). Hazard ratios for reoperations due to any cause and to bleeding were 1.28 (95% CI, 1.27-1.31) and 0.99 (95% CI, 0.93-1.04). CONCLUSION: Smoking was associated with a higher risk of RBC transfusion as a proxy for surgical bleeding across all surgical specialties combined.

Obesity as protective against, rather than a risk factor for, postoperative Clostridium difficile infection: A nationwide retrospective analysis of 1,426,807 surgical patients.

BACKGROUND: Recent studies suggest that obesity is a risk factor for Clostridium difficile infection, possibly due to disruptions in the intestinal microbiome composition. We hypothesized that body mass index (BMI) is associated with increased incidence of C. difficile infection in surgical patients. METHODS: In this nationwide retrospective cohort study in 680 American College of Surgeons National Surgical Quality Improvement Program participating sites across the United States, the occurrence of C. difficile infection within 30 days postoperatively between different BMI groups was compared. All American College of Surgeons National Surgical Quality Improvement Program patients between 2015 and 2016 were classified as underweight, normal-weight, overweight, or obese class I-III if their BMI was less than 18.5, 18.5 to 25, 25 to 30, 30 to 35, 35 to 40 or greater than 40, respectively. RESULTS: A total of 1,426,807 patients were included; median age was 58 years, 43.4% were male, and 82.9% were white. The postoperative incidence of C. difficile infection was 0.42% overall: 1.11%, 0.56%, 0.39%, 0.35%, 0.33% and 0.36% from the lowest to the highest BMI group, respectively (p < 0.001 for trend). In univariate then multivariable logistic regression analyses, adjusting for patient demographics (e.g., age, sex), comorbidities (e.g., diabetes, systemic sepsis, immunosuppression), preoperative laboratory values (e.g., albumin, white blood cell count), procedure complexity (work relative unit as a proxy) and procedure characteristics (e.g., emergency, type of surgery [general, vascular, other]), compared with patients with normal BMI, high BMI was inversely and incrementally correlated with the postoperative occurrence of C. difficile infection. The underweight were at increased risk (odds ratio, 1.15 [1.00-1.32]) while the class III obese were at the lowest risk (odds ratio, 0.73 [0.65-0.81]). CONCLUSION: In this nationwide retrospective cohort study, obesity is independently and in a stepwise fashion associated with a decreased risk of postoperative C. difficile infection. Further studies are warranted to explore the potential and unexpected association. LEVEL OF EVIDENCE: Prognostic/Epidemiologic, Level IV.

Variation of Opioid Prescribing Patterns among Patients undergoing Similar Surgery on the Same Acute Care Surgery Service of the Same Institution: Time for Standardization?

BACKGROUND: Diversion of unused prescription opioids is a major contributor to the current United States opioid epidemic. We aimed to study the variation of opioid prescribing in emergency surgery. METHODS: Between October 2016 and March 2017, all patients undergoing laparoscopic appendectomy, laparoscopic cholecystectomy, or inguinal hernia repair in the acute care surgery service of 1 academic center were included. For each patient, we systematically reviewed the electronic medical record and the prescribing pharmacy platform to identify: (1) history of opioid abuse, (2) opioid intake 3 months preoperatively, (3) number of opioid pills prescribed, (4) prescription of nonopioid pain medications (eg, acetaminophen, ibuprofen), and (5) the need for opioid prescription refills. The mean and range of opioid pills prescribed, as well as their oral morphine equivalent, were calculated. RESULTS: A total of 255 patients were included (43.5% laparoscopic appendectomy, 44.3% laparoscopic cholecystectomy, and 12.1% inguinal hernia repair). The mean age was 47.5 years, 52.1% were female, 11.4% had a history of opioid use, and 92.5% received opioid prescriptions upon hospital discharge. Only 70.9% of patients were instructed to use nonopioid pain medications. The mean and range of opioid pills prescribed were 17.4; 0-56 (laparoscopic appendectomy), 17.1; 0-75 (laparoscopic cholecystectomy), and 20.9; 0-50 (inguinal hernia repair), while the range of prescribed oral morphine equivalent was 0-600 mg for laparoscopic appendectomy/laparoscopic cholecystectomy and 0-375 mg for inguinal hernia repair. No patients required any opioid medication refills. CONCLUSION: Even within the same surgical service, wide variation of opioid prescription was observed. Guidelines that standardize pain management may help prevent opioid overprescribing.