Vinay Pasupuleti

Meta-analysis of the association between obstructive sleep apnoea and postoperative outcome

BACKGROUND Obstructive sleep apnoea (OSA) is often undiagnosed before elective surgery and may predispose patients to perioperative complications. METHODS A literature search of PubMed-Medline, Web of Science, Scopus, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials up to November 2010 was conducted. Our search was restricted to cohort or case-control studies in adults diagnosed with OSA by screening questionnaire, oximetry, or polysomnography. Studies without controls, involving upper airway surgery, and with OSA diagnosed by ICD-9 codes alone were excluded. The primary postoperative outcomes were desaturation, acute respiratory failure (ARF), reintubation, myocardial infarction/ischaemia, arrhythmias, cardiac arrest, intensive care unit (ICU) transfer, and length of stay. RESULTS Thirteen studies were included in the final analysis (n=3942). OSA was associated with significantly higher odds of any postoperative cardiac events [45/1195 (3.76%) vs 24/1420 (1.69%); odds ratio (OR) 2.07; 95% confidence interval (CI) 1.23-3.50, P=0.007] and ARF [33/1680 (1.96%) vs 24/3421 (0.70%); OR 2.43, 95% CI 1.34-4.39, P=0.003]. Effects were not heterogeneous for these outcomes (I(2)=0-15%, P>0.3). OSA was also significantly associated with higher odds of desaturation [189/1764 (10.71%) vs 105/1881 (5.58%); OR 2.27, 95% CI 1.20-4.26, P=0.01] and ICU transfer [105/2062 (5.09%) vs 58/3681 (1.57%), respectively; OR 2.81, 95% CI 1.46-5.43, P=0.002]. Both outcomes showed a significant degree of heterogeneity of the effect among studies (I(2)=57-68%, P<0.02). Subgroup analyses had similar conclusions as main analyses. CONCLUSIONS The incidence of postoperative desaturation, respiratory failure, postoperative cardiac events, and ICU transfers was higher in patients with OSA.

Community-associated Clostridium difficile infection and antibiotics: a meta-analysis

OBJECTIVES Antibiotic exposure is the most important risk factor for Clostridium difficile infection (CDI). Most evaluations of antimicrobial risk factors have been conducted in healthcare settings. The objective of this meta-analysis was to evaluate the association between antibiotic exposure and community-associated CDI (CA-CDI) (i.e. symptom onset in the community with no healthcare facility admission within 12 weeks) and to determine the classes of antibiotics posing the greatest risk. METHODS We searched four electronic databases for subject headings and text words related to CA-CDI and antibiotics. Studies that investigated the risk of CA-CDI associated with antibiotic usage were considered eligible. Data from the identified studies were combined using a random-effects model and ORs were calculated. RESULTS Of 910 citations identified, eight studies (n = 30 184 patients) met our inclusion criteria. Antibiotic exposure was associated with an increased risk of CA-CDI (OR 6.91, 95% CI 4.17-11.44, I(2) = 95%). The risk was greatest with clindamycin (OR 20.43, 95% CI 8.50-49.09) followed by fluoroquinolones (OR 5.65, 95% CI 4.38-7.28), cephalosporins (OR 4.47, 95% CI 1.60-12.50), penicillins (OR 3.25, 95% CI 1.89-5.57), macrolides (OR 2.55, 95% CI 1.91-3.39) and sulphonamides/trimethoprim (OR 1.84, 95% CI 1.48-2.29). Tetracyclines were not associated with an increased CDI risk (OR 0.91, 95% CI 0.57-1.45). CONCLUSIONS Antibiotic exposure was an important risk factor for CA-CDI, but the risk was different amongst different antibiotic classes. The risk was greatest with clindamycin followed by fluoroquinolones and cephalosporins, whereas tetracyclines were not associated with an increased risk.

Postoperative Complications in Patients With Obstructive Sleep Apnea

BACKGROUND Unrecognized obstructive sleep apnea (OSA) is associated with unfavorable perio-perative outcomes among patients undergoing noncardiac surgery (NCS). METHODS The study population was chosen from 39,771 patients who underwent internal medicine preoperative assessment between January 2002 and December 2006. Patients undergoing NCS within 3 years of polysomnography (PSG) were considered for the study, whereas those < 18 years of age, with a history of upper airway surgery, or who had had minor surgery under local or regional anesthesia were excluded. Patients with an apnea-hypopnea index (AHI) ≥ 5 were defined as OSA and those with an AHI < 5 as control subjects. For adjusting baseline differences in age, sex, race, BMI, type of anesthesia, American Society of Anesthesiology class, and medical comorbidities, the patients were classified into five quintiles according to a propensity score. RESULTS Out of a total of 1,759 patients who underwent both PSG and NCS, 471 met the study criteria. Of these, 282 patients had OSA, and the remaining 189 served as control subjects. The presence of OSA was associated with a higher incidence of postoperative hypoxemia (OR, 7.9; P = .009), overall complications (OR, 6.9; P = .003), and ICU transfer (OR, 4.43; P = .069), and a longer hospital length of stay (LOS), (OR, 1.65; P = .049). Neither an AHI nor use of continuous positive airway pressure at home before surgery was associated with postoperative complications (P = .3 and P = .75, respectively) or LOS (P = .97 and P = .21, respectively). CONCLUSIONS Patients with OSA are at higher risk of postoperative hypoxemia, ICU transfers, and longer hospital stay.

Association Between Proton Pump Inhibitor Therapy and Clostridium difficile Infection in a Meta-Analysis

BACKGROUND & AIMS In the past decade, there has been a growing epidemic of Clostridium difficile infection (CDI). During this time, use of proton pump inhibitors (PPIs) has increased exponentially. We evaluated the association between PPI therapy and the risk of CDI by performing a meta-analysis. METHODS We searched MEDLINE and 4 other databases for subject headings and text words related to CDI and PPI in articles published from 1990 to 2010. All observational studies that investigated the risk of CDI associated with PPI therapy and used CDI as an end point were considered eligible. Two investigators screened articles independently for inclusion criteria, data extraction, and quality assessment; disagreements were resolved based on consensus with a third investigator. Data were combined by means of a random-effects model and odds ratios were calculated. Subgroup and sensitivity analyses were performed based on study design and antibiotic use. RESULTS Thirty studies (25 case-control and 5 cohort) reported in 29 articles met the inclusion criteria (n = 202,965). PPI therapy increased the risk for CDI (odds ratio, 2.15, 95% confidence interval, 1.81-2.55), but there was significant heterogeneity in results among studies (P < .00001). This association remained after subgroup and sensitivity analyses, although significant heterogeneity persisted among studies. CONCLUSIONS PPI therapy is associated with a 2-fold increase in risk for CDI. Because of the observational nature of the analyzed studies, we were not able to study the causes of this association. Further studies are needed to determine the mechanisms by which PPI therapy might increase risk for CDI.

Diagnostic Accuracy of Real-time Polymerase Chain Reaction in Detection of Clostridium difficile in the Stool Samples of Patients With Suspected Clostridium difficile Infection: A Meta-Analysis

BACKGROUND Current detection methods for Clostridium difficile infection (CDI) can be time-consuming and have variable sensitivities. Real-time polymerase chain reaction (PCR) may allow earlier and more accurate diagnosis of CDI than other currently available diagnostic tests. A meta-analysis was performed to determine the diagnostic accuracy of real-time PCR. METHODS We searched MEDLINE (Pubmed/Ovid) and 4 other online electronic databases (1995-2010) to identify diagnostic accuracy studies that compared PCR with cell culture cytotoxicity neutralization assay (CCCNA) or anaerobic toxigenic culture (TC) of C. difficile. Screening for inclusion, data extraction, and quality assessment were carried out independently by 2 investigators and disagreements resolved. Data were combined by means of a random-effects model, and summary receiver operating characteristic curves and diagnostic odds ratios were calculated. RESULTS Nineteen studies (7392 samples) met our inclusion criteria. The overall mean sensitivity of PCR was 90% (95% confidence interval [CI]: 88%-91%), specificity 96% (CI: 96%-97%), positive likelihood ratio 26.89 (CI: 20.81-34.74), negative likelihood ratio 0.11 (CI: .08-.15), diagnostic odds ratio 278.23 (CI: 213.56-362.50), and area under the curve 0.98 (CI: .98-.99). Test accuracy depended on the prevalence of C. difficile but not on the reference test used. At C. difficile prevalence of <10%, 10%-20% and >20% the positive predictive value and the negative predictive value were 71%, 79%, 93% and 99%, 98% and 96%, respectively. CONCLUSIONS Real-time PCR has a high sensitivity and specificity to confirm CDI. Overall diagnostic accuracy is variable and depends on CDI prevalence.

Acid‐suppressive therapy is associated with spontaneous bacterial peritonitis in cirrhotic patients: A meta‐analysis

Proton pump inhibitors (PPI) and H2‐receptor antagonists (H2RA) are frequently prescribed in hospitalized patients with cirrhosis. There are conflicting reports regarding the role of acid‐suppressive therapy in predisposing hospitalized patients with cirrhosis to spontaneous bacterial peritonitis (SBP). The aim of this meta‐analysis was to evaluate the association between acid‐suppressive therapy and the risk of SBP in hospitalized patients with cirrhosis.

Risk Factors for Recurrent Clostridium difficile Infection: A Systematic Review and Meta-Analysis

OBJECTIVE An estimated 20-30% of patients with primary Clostridium difficile infection (CDI) develop recurrent CDI (rCDI) within 2 weeks of completion of therapy. While the actual mechanism of recurrence remains unknown, a variety of risk factors have been suggested and studied. The aim of this systematic review and meta-analysis was to evaluate current evidence on the risk factors for rCDI. DESIGN We searched MEDLINE and 5 other databases for subject headings and text related to rCDI. All studies investigating risk factors of rCDI in a multivariate model were eligible. Information on study design, patient population, and assessed risk factors were collected. Data were combined using a random-effects model and pooled relative risk ratios (RRs) were calculated. RESULTS A total of 33 studies (n=18,530) met the inclusion criteria. The most frequent independent risk factors associated with rCDI were age≥65 years (risk ratio [RR], 1.63; 95% confidence interval [CI], 1.24-2.14; P=.0005), additional antibiotics during follow-up (RR, 1.76; 95% CI, 1.52-2.05; P<.00001), use of proton-pump inhibitors (PPIs) (RR, 1.58; 95% CI, 1.13-2.21; P=.008), and renal insufficiency (RR, 1.59; 95% CI, 1.14-2.23; P=.007). The risk was also greater in patients previously on fluoroquinolones (RR, 1.42; 95% CI, 1.28-1.57; P<.00001). CONCLUSIONS Multiple risk factors are associated with the development of rCDI. Identification of modifiable risk factors and judicious use of antibiotics and PPI can play an important role in the prevention of rCDI.

Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis.

AIM It has been suggested that chronic hyperinsulinemia from insulin resistance is involved in the etiology of endometrial cancer (EC). We performed a systematic review and meta-analysis to assess whether insulin resistance is associated with the risk of EC. METHODS We searched PubMed-Medline, Embase, Scopus, and Web of Science for articles published from database inception through 30th September 2014. We included all observational studies evaluating components defining insulin resistance in women with and without EC. Quality of the included studies was assessed by Newcastle-Ottawa scale. Random-effects models and inverse variance method were used to meta-analyze the association between insulin resistance components and EC. RESULTS Twenty-five studies satisfied our inclusion criteria. Fasting insulin levels (13 studies, n = 4088) were higher in women with EC (mean difference [MD] 33.94 pmol/L, 95% confidence interval [CI] 15.04-52.85, p = 0.0004). No differences were seen in postmenopausal versus pre- and postmenopausal subgroup analysis. Similarly, non-fasting/fasting C-peptide levels (five studies, n = 1938) were also higher in women with EC (MD 0.14 nmol/L, 95% CI 0.08-0.21, p < 0.00001). Homeostatic model assessment - insulin resistance (HOMA-IR) values (six studies, n = 1859) in EC patients were significantly higher than in women without EC (MD 1.13, 95% CI 0.20-2.06, p = 0.02). There was moderate-to-high heterogeneity among the included studies. CONCLUSION Currently available epidemiologic evidence is suggestive of significantly higher risk of EC in women with high fasting insulin, non-fasting/fasting C-peptide and HOMA-IR values.

Effect of rural-to-urban within-country migration on cardiovascular risk factors in low- and middle-income countries: a systematic review

Context Limited information is available of effects of rural-to-urban within-country migration on cardiovascular (CV) risk factors in low- and middle- income countries (LMIC). Objective A systematic review of studies evaluating these effects was performed with rural and/or urban control groups. Study selection Two teams of investigators searched observational studies in Medline, Web of Science and Scopus until May 2011. Studies evaluating international migration were excluded. Data extraction Three investigators extracted the information stratified by gender. Information on 17 known CV risk factors was obtained. Results Eighteen studies (n=58 536) were included. Studies were highly heterogeneous with respect to study design, migrant sampling frame, migrant urban exposure and reported CV risk factors. In migrants, commonly reported CV risk factors—systolic and diastolic blood pressure, body mass index, obesity, total cholesterol and low-density lipoprotein—were usually higher or more common than in the rural group and usually lower or less common than in the urban group. This gradient was usually present in both genders. Anthropometric (waist-to-hip ratio, hip/waist circumference, triceps skinfolds) and metabolic (fasting glucose/insulin, insulin resistance) risk factors usually followed the same gradient, but conclusions were weak as information was insufficient. Hypertension, high-density lipoprotein, fibrinogen and C-reactive protein did not follow any pattern. Conclusions In LMIC, most but not all, CV risk factors are higher or more common in migrants than in rural groups but lower or less common than in urban groups. Such gradients may or may not be associated with differential CV events and long-term evaluations are necessary.

Incidence of Pneumonitis With Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Trials

Background Programmed death 1 (PD‐1) programmed death‐ligand 1 (PD‐L1) inhibitors show significant clinical activity in non‐small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune‐mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD‐1 and PD‐L1 inhibitors. We sought to determine the overall incidence of pneumonitis and differences according to type of inhibitors and prior chemotherapy use. Methods MEDLINE, Embase, and Scopus databases were searched up to November 2016. Rates of pneumonitis of any grade and grade ≥ 3 from all clinical trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab as single agents in NSCLC were collected. The incidence of pneumonitis across trials was calculated using DerSimonian‐Laird random effects models. We compared incidences between PD‐1 and PD‐L1 inhibitors and between treatment naive and previously treated patients. Results Nineteen trials (12 with PD‐1 inhibitors [n = 3,232] and 7 with PD‐L1 inhibitors [n = 1,806]) were identified. PD‐1 inhibitors were found to have statistically significant higher incidence of any grade pneumonitis compared with PD‐L1 inhibitors (3.6%; 95% CI, 2.4%‐4.9% vs 1.3%; 95% CI, 0.8%‐1.9%, respectively; P = .001). PD‐1 inhibitors were also associated with higher incidence of grade 3 or 4 pneumonitis (1.1%; 95% CI, 0.6%‐1.7% vs 0.4%; 95% CI, 0%‐0.8%; P = .02). Treatment naive patients had higher incidence of grade 1 through 4 pneumonitis compared with previously treated patients (4.3%; 95% CI, 2.4%‐6.3% vs 2.8%; 95% CI, 1.7%‐ 4%; P = .03). Conclusions There was a higher incidence of pneumonitis with use of PD‐1 inhibitors compared with PD‐L1 inhibitors. Higher rate of pneumonitis was more common in treatment naive patients.