Observational studies have suggested an association between active smoking and the incidence of type 2 diabetes.
To conduct a systematic review with meta-analysis of studies assessing the association ...between active smoking and incidence of type 2 diabetes.
A search of MEDLINE (1966 to May 2007) and EMBASE (1980 to May 2007) databases was supplemented by manual searches of bibliographies of key retrieved articles, reviews of abstracts from scientific meetings, and contact with experts.
Studies were included if they reported risk of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes in relationship to smoking status at baseline; had a cohort design; and excluded persons with diabetes at baseline.
Two authors independently extracted the data, including the presence or absence of active smoking at baseline, the risk of diabetes, methods used to detect diabetes, and key criteria of study quality. Relative risks (RRs) were pooled using a random-effects model. Associations were tested in subgroups representing different patient characteristics and study quality criteria.
The search yielded 25 prospective cohort studies (N = 1.2 million participants) that reported 45 844 incident cases of diabetes during a study follow-up period ranging from 5 to 30 years. Of the 25 studies, 24 reported adjusted RRs greater than 1 (range for all studies, 0.82-3.74). The pooled adjusted RR was 1.44 (95% confidence interval CI, 1.31-1.58). Results were consistent and statistically significant in all subgroups. The risk of diabetes was greater for heavy smokers (> or =20 cigarettes/day; RR, 1.61; 95% CI, 1.43-1.80) than for lighter smokers (RR,1.29; 95% CI, 1.13-1.48) and lower for former smokers (RR, 1.23; 95% CI, 1.14-1.33) compared with active smokers, consistent with a dose-response phenomenon.
Active smoking is associated with an increased risk of type 2 diabetes. Future research should attempt to establish whether this association is causal and to clarify its mechanisms.
Objective
To examine the association between lifetime lactation and risk and duration of frequent vasomotor symptoms (VMS).
Design
Prospective cohort.
Setting
USA, 1995–2008.
Sample
2356 parous ...midlife women in the Study of Women's Health Across the Nation.
Methods
Lifetime lactation was defined as the duration of breastfeeding across all births in months. We used generalised estimating equations to analyse risk of frequent VMS and Cox regression to analyse duration of frequent VMS in years.
Main outcome measures
Frequent VMS (hot flashes and night sweats) were measured annually for 10 years, defined as occurring ≥6 days in the past 2 weeks.
Results
Overall, 57.1% of women reported hot flashes and 43.0% reported night sweats during follow‐up. Lifetime lactation was inversely associated with hot flashes plateauing at 12 months of breastfeeding (6 months: adjusted odds ratio AOR 0.85, 95% confidence interval (CI) 0.75–0.96; 12 months: AOR 0.78, 95% CI 0.65–0.93) and was inversely associated with night sweats in a downward linear fashion (6 months: AOR 0.93, 95% CI 0.81–1.08; 18 months: AOR 0.82, 95% CI 0.67–1.02; 30 months: AOR 0.73, 95% CI 0.56–0.97). Lifetime lactation was associated with shorter duration of hot flashes and night sweats in a quadratic (bell‐shaped) fashion. The association was strongest at 12–18 months of breastfeeding and significant for hot flashes (6 months: adjusted hazard ratio AHR 1.35, 95% CI 1.11–1.65; 18 months: AHR 1.54, 95% CI 1.16–2.03; 30 months: AHR 1.18, 95% CI 0.83–1.68).
Conclusions
Longer lifetime lactation is associated with decreased risk and duration of frequent VMS.
Background Information on an individual’s risk for death following dialysis therapy initiation may inform the decision to initiate maintenance dialysis for older adults. We derived and validated a ...clinical risk prediction tool for all-cause mortality among older adults during the first 6 months of maintenance dialysis treatment. Study Design Prediction model using retrospective administrative and clinical data. Setting & Participants We linked administrative and clinical data to define a cohort of 2,199 older adults (age ≥ 65 years) in Alberta, Canada, who initiated maintenance dialysis therapy (excluding acute kidney injury) in May 2003 to March 2012. Candidate Predictors Demographics, laboratory data, comorbid conditions, and measures of health system use. Outcomes All-cause mortality within 6 months of dialysis therapy initiation. Analytical Approach Predicted mortality by logistic regression with 10-fold cross-validation. Results 375 (17.1%) older adults died within 6 months. We developed a 19-point risk score for 6-month mortality that included age 80 years or older (2 points), glomerular filtration rate of 10 to 14.9 mL/min/1.73 m2 (1 point) or ≥15 mL/min/1.73 m2 (3 points), atrial fibrillation (2 points), lymphoma (5 points), congestive heart failure (2 points), hospitalization in the prior 6 months (2 points), and metastatic cancer (3 points). Model discrimination (C statistic = 0.72) and calibration (Hosmer-Lemeshow χ2 = 10.36; P = 0.2) were reasonable. As examples, a score < 5 equated to <25% of individuals dying in 6 months, whereas a score > 12 predicted that more than half the individuals would die in the first 6 months. Limitations The tool has not been externally validated; thus, generalizability cannot be assessed. Conclusions We used readily available clinical information to derive and internally validate a 7-variable tool to predict early mortality among older adults after dialysis therapy initiation. Following successful external validation, the tool may be useful as a clinical decision tool to aid decision making for older adults with kidney failure.
Summary Background 35% of patients with pancreatic cancer have unresectable locally advanced disease at diagnosis. Several studies have examined systemic chemotherapy with FOLFIRINOX (leucovorin and ...fluorouracil plus irinotecan and oxaliplatin) in patients with locally advanced pancreatic cancer. We aimed to assess the effectiveness of FOLFIRINOX as first-line treatment in this patient population. Methods We systematically searched Embase, MEDLINE (OvidSP), Web of Science, Scopus, PubMed Publisher, Cochrane, and Google Scholar from July 1, 1994, to July 2, 2015, for studies of treatment-naive patients of any age who received FOLFIRINOX as first-line treatment of locally advanced pancreatic cancer. Our primary outcome was overall survival. Secondary outcomes were progression-free survival; rates of grade 3 or 4 adverse events; and the proportion of patients who underwent radiotherapy or chemoradiotherapy, surgical resection after FOLFIRINOX, and R0 resection. We evaluated survival outcomes with the Kaplan–Meier method with patient-level data. Grade 3 or 4 adverse events, and the proportion of patients who underwent subsequent radiotherapy or chemoradiotherapy or resection, were pooled in a random-effects model. Findings We included 13 studies comprising 689 patients, of whom 355 (52%) patients had locally advanced pancreatic cancer. 11 studies, comprising 315 patients with locally advanced disease, reported survival outcomes and were eligible for patient-level meta-analysis. Median overall survival from the start of FOLFIRINOX ranged from 10·0 months (95% CI 4·0–16·0) to 32·7 months (23·1–42·3) across studies with a pooled patient-level median overall survival of 24·2 months (95% CI 21·7–26·8). Median progression-free survival ranged from 3·0 months (95% CI not calculable) to 20·4 months (6·5–34·3) across studies with a patient-level median progression-free survival of 15·0 months (95% 13·8–16·2). In ten studies comprising 490 patients, 296 grade 3 or 4 adverse events were reported (60·4 events per 100 patients). No deaths were attributed to FOLFIRINOX toxicity. The proportion of patients who underwent radiotherapy or chemoradiotherapy ranged from 31% to 100% across studies. In eight studies, 154 (57%) of 271 patients received radiotherapy or chemoradiotherapy after FOLFIRINOX. The pooled proportion of patients who received any radiotherapy treatment was 63·5% (95% CI 43·3–81·6, I2 90%). The proportion of patients who underwent surgical resection for locally advanced pancreatic cancer ranged from 0% to 43%. The proportion of patients who had R0 resection of those who underwent resection ranged from 50% to 100% across studies. In 12 studies, 91 (28%) of 325 patients underwent resection after FOLFIRINOX. The pooled proportion of patients who had resection was 25·9% (95% CI 20·2–31·9, I2 24%). R0 resection was reported in 60 (74%) of 81 patients. The pooled proportion of patients who had R0 resection was 78·4% (95% CI 60·2–92·2, I2 64%). Interpretation Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24·2 months—longer than that reported with gemcitabine (6–13 months). Future research should assess these promising results in a randomised controlled trial, and should establish which patients might benefit from radiotherapy or chemoradiotherapy or resection after FOLFIRINOX. Funding None.
Background
Although Kaplan-Meier survival analysis is commonly used to estimate the cumulative incidence of revision after joint arthroplasty, it theoretically overestimates the risk of revision in ...the presence of competing risks (such as death). Because the magnitude of overestimation is not well documented, the potential associated impact on clinical and policy decision-making remains unknown.
Questions/purposes
We performed a meta-analysis to answer the following questions: (1) To what extent does the Kaplan-Meier method overestimate the cumulative incidence of revision after joint replacement compared with alternative competing-risks methods? (2) Is the extent of overestimation influenced by followup time or rate of competing risks?
Methods
We searched Ovid MEDLINE, EMBASE, BIOSIS Previews, and Web of Science (1946, 1980, 1980, and 1899, respectively, to October 26, 2013) and included article bibliographies for studies comparing estimated cumulative incidence of revision after hip or knee arthroplasty obtained using both Kaplan-Meier and competing-risks methods. We excluded conference abstracts, unpublished studies, or studies using simulated data sets. Two reviewers independently extracted data and evaluated the quality of reporting of the included studies. Among 1160 abstracts identified, six studies were included in our meta-analysis. The principal reason for the steep attrition (1160 to six) was that the initial search was for studies in any clinical area that compared the cumulative incidence estimated using the Kaplan-Meier versus competing-risks methods for any event (not just the cumulative incidence of hip or knee revision); we did this to minimize the likelihood of missing any relevant studies. We calculated risk ratios (RRs) comparing the cumulative incidence estimated using the Kaplan-Meier method with the competing-risks method for each study and used DerSimonian and Laird random effects models to pool these RRs. Heterogeneity was explored using stratified meta-analyses and metaregression.
Results
The pooled cumulative incidence of revision after hip or knee arthroplasty obtained using the Kaplan-Meier method was 1.55 times higher (95% confidence interval, 1.43–1.68; p < 0.001) than that obtained using the competing-risks method. Longer followup times and higher proportions of competing risks were not associated with increases in the amount of overestimation of revision risk by the Kaplan-Meier method (all p > 0.10). This may be due to the small number of studies that met the inclusion criteria and conservative variance approximation.
Conclusions
The Kaplan-Meier method overestimates risk of revision after hip or knee arthroplasty in populations where competing risks (such as death) might preclude the occurrence of the event of interest (revision). Competing-risks methods should be used to more accurately estimate the cumulative incidence of revision when the goal is to plan healthcare services and resource allocation for revisions.
Background Vasovagal syncope (VVS) is a common problem associated with a poor quality of life, which improves when syncope frequency is reduced. Effective pharmacological therapies for VVS are ...lacking. Metoprolol is a β-adrenergic receptor antagonist that is ineffective in younger patients, but may benefit older (≥40 years) VVS patients. Given the limited therapeutic options, a placebo-controlled clinical trial of metoprolol for the prevention of VVS in older patients is needed. Structure of study The POST5 is a multicenter, international, randomized, placebo-controlled study of metoprolol in the prevention of VVS in patients ≥40 years old. The primary endpoint is the time to first recurrence of syncope. Patients will be randomized 1:1 to receive metoprolol 25 to 100 mg BID or matching placebo, and followed up for 1 year. Secondary end points include syncope frequency, presyncope, quality of life, and cost analysis. Primary analysis will be intention to treat, with a secondary on-treatment analysis. Power calculations A sample size of 222, split equally between the groups achieves 85% power to detect a hazard rate of 0.3561 when the event rates are 50% and 30% in the placebo and metoprolol arms. Allowing for 10% dropout, we propose to enroll 248 patients. Implications This study will be the first adequately powered trial to determine whether metoprolol is effective in preventing VVS in patients ≥40 years. If effective, metoprolol may become the first line pharmacological therapy for these patients.
Contrast-associated acute kidney injury (AKI) is a common complication of coronary angiography and percutaneous coronary intervention (PCI) that has been associated with high costs and adverse ...long-term outcomes.
To determine whether a multifaceted intervention is effective for the prevention of AKI after coronary angiography or PCI.
A stepped-wedge, cluster randomized clinical trial was conducted in Alberta, Canada, that included all invasive cardiologists at 3 cardiac catheterization laboratories who were randomized to various start dates for the intervention between January 2018 and September 2019. Eligible patients were aged 18 years or older who underwent nonemergency coronary angiography, PCI, or both; who were not undergoing dialysis; and who had a predicted AKI risk of greater than 5%. Thirty-four physicians performed 7820 procedures among 7106 patients who met the inclusion criteria. Participant follow-up ended in November 2020.
During the intervention period, cardiologists received educational outreach, computerized clinical decision support on contrast volume and hemodynamic-guided intravenous fluid targets, and audit and feedback. During the control (preintervention) period, cardiologists provided usual care and did not receive the intervention.
The primary outcome was AKI. There were 12 secondary outcomes, including contrast volume, intravenous fluid administration, and major adverse cardiovascular and kidney events. The analyses were conducted using time-adjusted models.
Of the 34 participating cardiologists who were divided into 8 clusters by practice group and center, the intervention group included 31 who performed 4327 procedures among 4032 patients (mean age, 70.3 SD, 10.7 years; 1384 were women 32.0%) and the control group included 34 who performed 3493 procedures among 3251 patients (mean age, 70.2 SD, 10.8 years; 1151 were women 33.0%). The incidence of AKI was 7.2% (310 events after 4327 procedures) during the intervention period and 8.6% (299 events after 3493 procedures) during the control period (between-group difference, -2.3% 95% CI, -0.6% to -4.1%; odds ratio OR, 0.72 95% CI, 0.56 to 0.93; P = .01). Of 12 prespecified secondary outcomes, 8 showed no significant difference. The proportion of procedures in which excessive contrast volumes were used was reduced to 38.1% during the intervention period from 51.7% during the control period (between-group difference, -12.0% 95% CI, -14.4% to -9.4%; OR, 0.77 95% CI, 0.65 to 0.90; P = .002). The proportion of procedures in eligible patients in whom insufficient intravenous fluid was given was reduced to 60.8% during the intervention period from 75.1% during the control period (between-group difference, -15.8% 95% CI, -19.7% to -12.0%; OR, 0.68 95% CI, 0.53 to 0.87; P = .002). There were no significant between-group differences in major adverse cardiovascular events or major adverse kidney events.
Among cardiologists randomized to an intervention including clinical decision support with audit and feedback, patients undergoing coronary procedures during the intervention period were less likely to develop AKI compared with those treated during the control period, with a time-adjusted absolute risk reduction of 2.3%. Whether this intervention would show efficacy outside this study setting requires further investigation.
ClinicalTrials.gov Identifier: NCT03453996.
ObjectivesThe purpose of this study is to estimate the prevalence of comorbidities among people with osteoarthritis (OA) using administrative health data.DesignRetrospective cohort ...analysis.SettingAll residents in the province of Alberta, Canada registered with the Alberta Health Care Insurance Plan population registry.Participants497 362 people with OA as defined by ‘having at least one OA-related hospitalization, or at least two OA-related physician visits or two ambulatory care visits within two years’.Primary outcome measuresWe selected eight comorbidities based on literature review, clinical consultation and the availability of validated case definitions to estimate their frequencies at the time of diagnosis of OA. Sex-stratified age-standardised prevalence rates per 1000 population of eight clinically relevant comorbidities were calculated using direct standardisation with 95% CIs. We applied χ2 tests of independence with a Bonferroni correction to compare the percentage of comorbid conditions in each age group.Results54.6% (n=2 71 794) of people meeting the OA case definition had at least one of the eight selected comorbidities. Females had a significantly higher rate of comorbidities compared with males (standardised rates ratio=1.26, 95% CI 1.25 to 1.28). Depression, chronic obstructive pulmonary disease (COPD) and hypertension were the most prevalent in both females and males after age-standardisation, with 40% of all cases having any combination of these comorbidities. We observed a significant difference in the percentage of comorbidities among age groups, illustrated by the youngest age group (<45 years) having the highest percentage of cases with depression (24.6%), compared with a frequency of 16.1% in those >65 years.ConclusionsOur findings highlight the high frequency of comorbidity in people with OA, with depression having the highest age-standardised prevalence rate. Comorbidities differentially affect females, and vary by age. These factors should inform healthcare programme and delivery.
To determine whether the reported clinical presentation of tension pneumothorax differs between patients who are breathing unassisted versus receiving assisted ventilation.
Animal studies suggest ...that the pathophysiology and physical signs of tension pneumothorax differ by subject ventilatory status.
We searched electronic databases through to October 15, 2013 for observational studies and case reports/series reporting clinical manifestations of tension pneumothorax. Two physicians independently extracted clinical manifestations reported at diagnosis.
We identified 5 cohort studies (n = 310 patients) and 156 case series/reports of 183 cases of tension pneumothorax (n = 86 breathing unassisted, n = 97 receiving assisted ventilation). Hypoxia was reported among 43 (50.0%) cases of tension pneumothorax who were breathing unassisted versus 89 (91.8%) receiving assisted ventilation (P < 0.001). Pulmonary dysfunction progressed to respiratory arrest in 9.3% of cases breathing unassisted. As compared to cases who were breathing unassisted, the adjusted odds of hypotension and cardiac arrest were 12.6 (95% confidence interval, 5.8-27.5) and 17.7 (95% confidence interval, 4.0-78.4) times higher among cases receiving assisted ventilation. One cohort study reported that none of the patients with tension pneumothorax who were breathing unassisted versus 39.6% of those receiving assisted ventilation presented without an arterial pulse. In contrast to cases breathing unassisted, the majority (70.4%) of those receiving assisted ventilation who experienced hypotension or cardiac arrest developed these signs within minutes of clinical presentation.
The reported clinical presentation of tension pneumothorax depends on the ventilatory status of the patient. This may have implications for improving the diagnosis and treatment of this life-threatening disorder.
To characterize and evaluate indications for use of damage control (DC) surgery in civilian trauma patients.
Although DC surgery may improve survival in select, severely injured patients, the ...procedure is associated with significant morbidity, suggesting that it should be used only when appropriately indicated.
Two investigators used an abbreviated grounded theory method to synthesize indications for DC surgery reported in peer-reviewed articles between 1983 and 2014 into a reduced number of named, content-characteristic codes representing unique indications. An international panel of trauma surgery experts (n = 9) then rated the appropriateness (expected benefit-to-harm ratio) of the coded indications for use in surgical practice.
The 1107 indications identified in the literature were synthesized into 123 unique pre- (n = 36) and intraoperative (n = 87) indications. The panel assessed 101 (82.1%) of these indications to be appropriate. The indications most commonly reported and assessed to be appropriate included pre- and intraoperative hypothermia (median temperature <34°C), acidosis (median pH <7.2), and/or coagulopathy. Others included 5 different injury patterns, inability to control bleeding by conventional methods, administration of a large volume of packed red blood cells (median >10 units), inability to close the abdominal wall without tension, development of abdominal compartment syndrome during attempted abdominal wall closure, and need to reassess extent of bowel viability.
This study identified a comprehensive list of candidate indications for use of DC surgery. These indications provide a practical foundation to guide surgical practice while studies are conducted to evaluate their impact on patient care and outcomes.
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