Jasjeet K. Minhas-Sandhu

Sitagliptin use in patients with diabetes and heart failure: a population-based retrospective cohort study.

OBJECTIVES The study objective was to evaluate the effects of sitagliptin in patients with type 2 diabetes (T2D) and heart failure (HF). BACKGROUND There is uncertainty in the literature about whether dipeptidyl peptidase (DPP)-4 inhibitors cause harm in patients with HF and T2D. METHODS We analyzed data from a national commercially insured U.S. claims database. Patients with incident HF were identified from individuals with T2D initially treated with metformin or sulfonylurea and followed over time. Subjects subsequently using sitagliptin were compared with those not using sitagliptin in the 90 days before our primary outcome of all-cause hospital admission or death using a nested case-control analysis after adjustment for demographics and clinical and laboratory data. HF-specific hospital admission or death also was assessed. RESULTS A total of 7,620 patients with diabetes and incident HF met our inclusion criteria. Mean (SD) age was 54 years (9), and 58% (3,180) were male. Overall, 887 patients (12%) were exposed to sitagliptin therapy (521 patient years of exposure) after incident HF. Our primary composite endpoint occurred in 4,137 patients (54%). After adjustment, sitagliptin users were not at an increased risk for the primary endpoint (7.1% vs. 9.2%, adjusted odds ratio [aOR]: 0.84, 95% confidence interval [CI]: 0.69 to 1.03) or each component (hospital admission 7.5% vs. 9.2%, aOR: 0.93, 95% CI: 0.76 to 1.14; death 6.9% vs. 9.3%, aOR: 1.16, 95% CI: 0.68 to 1.97). However, sitagliptin use was associated with an increased risk of HF hospitalizations (12.5% vs. 9.0%, aOR: 1.84, 95% CI: 1.16 to 2.92). CONCLUSIONS Sitagliptin use was not associated with an increased risk of all-cause hospitalizations or death, but was associated with an increased risk of HF-related hospitalizations among patients with T2D with pre-existing HF.

Ten-Year Mortality after Community-acquired Pneumonia. A Prospective Cohort

RATIONALE Information on the long-term prognosis after community-acquired pneumonia (CAP) is limited. OBJECTIVES To determine if CAP increases adverse long-term outcomes relative to a control population. METHODS Between 2000 and 2002, 6,078 adults with CAP from six hospitals and seven emergency departments in Edmonton (AB, Canada) were prospectively recruited and matched on age, sex, and site of treatment with five control subjects without pneumonia (n = 29,402). Mortality, hospitalizations, and emergency department admissions through 2012 were evaluated using multivariable Cox proportional hazards analyses adjusted for socioeconomic status and comorbidities. MEASUREMENTS AND MAIN RESULTS Average age was 59 years (2,682 [44%] ≥ 65 yr), 3,214 (53%) were men, and 3,425 (56%) were managed as outpatients. Over a median of 9.8 years, 2,858 patients with CAP died compared with 9,399 control subjects (absolute risk difference, 30 per 1,000 patient years [py]; adjusted hazard ratio [aHR], 1.65; 95% confidence interval, 1.57-1.73; P < 0.001). Patients with CAP who were younger than 25 years old had the lowest absolute rate difference for mortality (4 per 1,000 py; aHR, 2.40), and patients older than 80 years old had the highest absolute rate difference (92 per 1,000 py; aHR, 1.42). Absolute rates of all-cause hospitalization, emergency department visits, and CAP-related visits were all significantly higher in patients with CAP compared with control subjects (P < 0.001 for all comparisons). CONCLUSIONS Our results indicate that an episode of CAP confers a high risk of long-term adverse events compared with the general population who have not experienced CAP, and this is irrespective of age.

Obesity and outcomes in patients hospitalized with pneumonia

Studies suggest obesity is paradoxically associated with better outcomes for patients with pneumonia. Therefore, we examined the impact of obesity on short-term mortality in patients hospitalized with pneumonia. For 2 years clinical and radiographic data were prospectively collected on all consecutive adults admitted with pneumonia to six hospitals in Edmonton, Alberta, Canada. We identified 907 patients who also had body mass index (BMI, kg/m(2)) collected and categorized them as underweight (BMI < 18.5), normal (18.5 to <25), overweight (25 to <30) and obese (>30). Overall, 65% were >65 years, 52% were female, and 15% reported recent weight loss. Eighty-four (9%) were underweight, 358 (39%) normal, 228 (25%) overweight, and 237 (26%) obese. Two-thirds had severe pneumonia (63% PSI Class IV/V) and 79 (9%) patients died. In-hospital mortality was greatest among those that were underweight (12 [14%]) compared with normal (36 [10%]), overweight (21 [9%]) or obese (10 [4%], p <0.001 for trend). Compared with those of normal weight, obese patients had significantly lower rates of in-hospital mortality in multivariable logistic regression analyses: adjusted odds ratio (OR), 0.46; 95% CI, 0.22-0.97; p 0.04. However, compared with patients with normal weight, neither underweight (adjusted OR, 1.13; 95% CI, 0.54-2.4; p 0.7) nor overweight (adjusted OR, 0.94; 95% CI, 0.52-1.69; p 0.8) were associated with in-hospital mortality. In conclusion, in patients hospitalized with pneumonia, obesity was independently associated with lower short-term mortality, while neither being underweight nor overweight were. This suggests a protective influence of BMIs > 30 kg/m(2) that requires better mechanistic understanding.

Impact of guideline-concordant antibiotics and macrolide/β-lactam combinations in 3203 patients hospitalized with pneumonia: prospective cohort study

For patients hospitalized with pneumonia, guidelines provide empirical antibiotic recommendations and some studies suggest that macrolide/β-lactam combinations are preferable. We hypothesized that guideline-concordant regimens, particularly macrolide/β-lactams, would reduce mortality and ICU admissions. All patients hospitalized with pneumonia in Edmonton, Alberta, Canada, were managed according to a clinical pathway and enrolled in a population-based registry. Clinical data, Pneumonia Severity Index and treatments were collected. Guideline-concordant regimens were macrolides/β-lactams or respiratory fluoroquinolone monotherapy. The main outcome was in-hospital mortality. The study included 3203 patients and most had severe pneumonia (63% PSI Class IV-V). Three hundred and twenty-one (10.0%) patients died, 306 (9.6%) were admitted to the ICU and 570 (17.8%) achieved the composite of death or ICU admission. Most (n = 2506) patients received guideline-concordant antibiotics. Receipt of guideline-concordant antibiotics was not associated with a reduction in mortality alone (231 (9.2%) vs. 90 (12.9%); adjusted odds ratio (aOR), 0.82; 95% CI, 0.61-1.09; p 0.16), but was associated with decreased death or ICU admission (14.7% vs. 29.0%; aOR, 0.44; 95% CI, 0.36-0.54; p < 0.0001). Within guideline-concordant subgroups, there was no difference in mortality between macrolide/β-lactams and respiratory fluoroquinolone monotherapy (22 (8.3%) vs. 209 (9.3%); aOR, 1.09; 95% CI, 0.66-1.81; p 0.73) but macrolide/β-lactams were associated with increased odds of death or ICU admission (17.4% vs. 14.4%; aOR, 1.58; 95% CI, 1.09-2.27; p 0.01). In conclusion, guideline-concordant antibiotics were not associated with decreased mortality for patients hospitalized with pneumonia, but were associated with a decrease in the composite endpoint of death or ICU admission. Our findings do not support any clinical advantage of macrolide/β-lactam compared with respiratory fluoroquinolone monotherapy.

Stress Hyperglycemia and Newly Diagnosed Diabetes in 2124 Patients Hospitalized with Pneumonia

OBJECTIVE Our goal was to determine the association between random admission hyperglycemia and new diagnosis of diabetes after discharge in patients hospitalized with pneumonia. METHODS Clinical data, including the Pneumonia Severity Index, were prospectively collected on all 2124 patients without diabetes admitted with pneumonia to 6 hospitals in Edmonton, Alberta, Canada. Admission glucose was classified as: normal (4.0-6.0 mmol/L, reference group) versus mild (6.1-7.7 mmol/L), moderate (7.8-11.0 mmol/L), and severe (11.1-20.0 mmol/L) stress hyperglycemia. New diagnosis of diabetes over 5 years was ascertained using well-validated criteria within linked administrative databases. Multivariable Cox models were used, and sensitivity, specificity, and likelihood ratios were calculated. RESULTS Mean age was 68 years; 1091 (51%) were male, and 1418 (67%) had stress hyperglycemia. Over 5 years, 194 (14%) with stress hyperglycemia were diagnosed with diabetes. Compared with the 45 of 706 (6%) incidences of diabetes in normal glycemia patients (4.0-6.0 mmol/L), a strong graded increase in risk of new diabetes existed with increasing hyperglycemia: mild (59 of 841 [7%]; adjusted hazard ratio [aHR] 1.09; 95% confidence interval [CI], 0.74-1.61) versus moderate (86 of 473 [18%]; aHR 2.99; 95% CI, 2.07-4.31) versus severe (49 of 104 [47%]; aHR 11.43; 95% CI, 7.50-17.42). Among moderate-to-severe hyperglycemia (≥7.8 mmol/L) patients, the sensitivity, specificity, and positive and negative likelihood ratios for new diabetes were 57%, 77%, 2.1, and 0.6, respectively, with a number-needed-to-evaluate of 5 to detect one new case of diabetes. CONCLUSION Moderate-to-severe random hyperglycemia in pneumonia patients admitted to the hospital is strongly associated with new diagnosis of diabetes. Opportunistic evaluation for diabetes may be warranted in this group.

Pneumococcal vaccination and risk of acute coronary syndromes in patients with pneumonia: population-based cohort study

Background It is vigorously debated whether pneumococcal polysaccharide vaccination (PPV) reduces risk of acute coronary syndrome (ACS) events in patients with community-acquired pneumonia (CAP). Methods Clinical data were prospectively collected on a population-based cohort of adults presenting with CAP in Edmonton (Alberta, Canada). Multivariable Cox models and propensity matching were used to examine the association between PPV status and ACS events within 90 days of pneumonia. Sensitivity analyses related to PPV administration (before pneumonia vs after) and duration of benefit (90 days vs 1 year) were conducted to rule out confounding. Results Overall, 6171 patients were included; mean age 59 (SD 21) years, 53% male subjects, 18% had ischaemic heart disease and 2738 (44%) were hospitalised. Within 90 days of pneumonia, ACS events occurred in 175 (3%) patients and most were non-fatal (162 (93%)). In multivariable analyses, PPV exposure was associated with a 58% reduction in ACS events (12 vs 16 events per 100 patient-years, adjusted HR (aHR) 0.42 (0.27 to 0.66)) and results were nearly identical with propensity matching (aHR 0.46 (0.28 to 0.73)). However, indepth sensitivity analyses, with some with large assumptions, could not refute the existence of a small protective benefit of PPV. Conclusion Even after extensive adjustment using clinical data, the authors observed that PPV exposure was associated with a 60% reduction in ACS events among patients with pneumonia. Sensitivity analyses demonstrated that these findings, at least in part, were probably a result of confounding, most likely the ‘healthy-vaccinee’ effect. Previous observational studies using administrative data suggesting a very large protective benefit of PPV on ACS events may have been heavily confounded.

Incidence, Correlates, and Chest Radiographic Yield of New Lung Cancer Diagnosis in 3398 Patients With Pneumonia

BACKGROUND One reason chest radiographs are recommended after pneumonia is to exclude underlying lung cancer. Our aims were to determine the incidence and correlates of new lung cancer and the diagnostic yield of new lung cancer by chest radiography in patients with pneumonia. METHODS We conducted a population-based cohort study of patients with chest radiography-confirmed pneumonia, who were discharged alive from hospitals and emergency departments in Edmonton, Alberta, Canada. Patients were enrolled from 2000 through 2002 and followed up for 5 years. We determined incidence of new lung cancer and receipt of chest radiographs within 90 days, 1 year, and 5 years. Multivariable proportional hazards analyses were used to determine independent correlates of lung cancer. RESULTS There were 3398 patients; 59% were 50 years or older, 52% were male, and 17% were smokers. Half (49%) were admitted to hospital. At 90 days, 36 patients (1.1%) had new lung cancer; at 1 year, 57 patients (1.7%); and over 5 years, 79 patients (2.3%). The median time to diagnosis was 109 days (interquartile range, 27-423 days). Characteristics independently associated with lung cancer included age 50 years or older (adjusted hazard ratio [aHR], 19.0; 95% confidence interval [CI], 5.7-63.6), male sex (aHR, 1.8; 95% CI, 1.1-2.9), and smoking (aHR, 1.7; 95% CI, 1.0-3.0). Of the patients, 1354 (40%) had follow-up chest radiographs within 90 days, and the diagnostic yield of lung cancer was 2.5%; if radiographs were restricted to patients 50 years or older, the yield would have been 2.8%. CONCLUSIONS The incidence of new lung cancer after pneumonia is low: approximately 1% within 90 days and 2% over 5 years. Routine chest radiographs after pneumonia for detecting lung cancer are not warranted, although our study suggests that patients 50 years or older should be targeted for radiographic follow-up.

Risk of heart failure after community acquired pneumonia: prospective controlled study with 10 years of follow-up

Abstract Objective To determine the attributable risk of community acquired pneumonia on incidence of heart failure throughout the age range of affected patients and severity of the infection. Design Cohort study. Setting Six hospitals and seven emergency departments in Edmonton, Alberta, Canada, 2000-02. Participants 4988 adults with community acquired pneumonia and no history of heart failure were prospectively recruited and matched on age, sex, and setting of treatment (inpatient or outpatient) with up to five adults without pneumonia (controls) or prevalent heart failure (n=23 060). Main outcome measures Risk of hospital admission for incident heart failure or a combined endpoint of heart failure or death up to 2012, evaluated using multivariable Cox proportional hazards analyses. Results The average age of participants was 55 years, 2649 (53.1%) were men, and 63.4% were managed as outpatients. Over a median of 9.9 years (interquartile range 5.9-10.6), 11.9% (n=592) of patients with pneumonia had incident heart failure compared with 7.4% (n=1712) of controls (adjusted hazard ratio 1.61, 95% confidence interval 1.44 to 1.81). Patients with pneumonia aged 65 or less had the lowest absolute increase (but greatest relative risk) of heart failure compared with controls (4.8% v 2.2%; adjusted hazard ratio 1.98, 95% confidence interval 1.5 to 2.53), whereas patients with pneumonia aged more than 65 years had the highest absolute increase (but lowest relative risk) of heart failure (24.8% v 18.9%; adjusted hazard ratio 1.55, 1.36 to 1.77). Results were consistent in the short term (90 days) and intermediate term (one year) and whether patients were treated in hospital or as outpatients. Conclusion Our results show that community acquired pneumonia substantially increases the risk of heart failure across the age and severity range of cases. This should be considered when formulating post-discharge care plans and preventive strategies, and assessing downstream episodes of dyspnoea.