Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of ...bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay.
We performed a systematic literature review of studies providing information on the relative yield of various diagnostic assays (BinaxNOW® S. pneumoniae urine antigen test (UAT) with blood and/or sputum culture) in diagnosing pneumococcal pneumonia. We estimated the proportion of pneumococcal pneumonia that is bacteremic, the proportion of CAP attributable to pneumococcus, and the additional contribution of the Binax UAT beyond conventional diagnostic techniques, using random effects meta-analytic methods and bootstrapping. We included 35 studies in the analysis, predominantly from developed countries. The estimated proportion of pneumococcal pneumonia that is bacteremic was 24.8% (95% CI: 21.3%, 28.9%). The estimated proportion of CAP attributable to pneumococcus was 27.3% (95% CI: 23.9%, 31.1%). The Binax UAT diagnosed an additional 11.4% (95% CI: 9.6, 13.6%) of CAP beyond conventional techniques. We were limited by the fact that not all patients underwent all diagnostic tests and by the sensitivity and specificity of the diagnostic tests themselves. We address these resulting biases and provide a range of plausible values in order to estimate the burden of pneumococcal pneumonia among adults.
Estimating the adult burden of pneumococcal disease from bacteremic pneumococcal pneumonia data alone significantly underestimates the true burden of disease in adults. For every case of bacteremic pneumococcal pneumonia, we estimate that there are at least 3 additional cases of non-bacteremic pneumococcal pneumonia.
Urinary culture sensitivity after antibiotics administration is unknown. This study aimed to describe the diagnostic sensitivity of urine cultures from patients' first, second, and third micturition ...samples after a single dose of empirical antibiotics given for upper and/or febrile urinary tract infections, as well as searched for factors influencing diagnostic sensitivity over time.
We collected consecutive urine samples from adult patients with an upper or febrile urinary tract infection diagnosed at four secondary hospital emergency rooms. One sample was collected before a first dose of empirical antibiotic treatment and up to three samples were collected from consecutive postadministration micturition. The main outcome was the number of positive cultures growing uropathogens with ≥103 colony forming units (CFUs) for men and ≥104 for women. Identical analyses were performed for any identified CFU and ≥105 CFU cut-off points. Time between antibiotic administration and first negative urinary culture was noted, which could have been at the time of any of the three postantibiotic urine samples. We used a Cox regression analysis for age- and sex-adjusted analyses.
A total of 86 of 87 patients' preantibiotic cultures (99%) were positive compared with 26 of 75 (35%; p < 0.001), 15 of 50 (30%; p < 0.001), and 1 of 15 (7%; p < 0.001) of the first, second, and third postantibiotic samples, respectively, and missing 14 of 21 (67%), 13 of 17 (76%), and 7 of 7 (100%) of uropathogens with antibiotic resistance, respectively. The times needed for 25%, 50%, and 75% of cultures to be negative were 1.5, 2.9, and 9 hours, respectively, after antibiotic administration. Older age, male sex, non-Escherichia coli pathogens, urinary tract disease, comorbidity burdens, and urinary catheters prolonged time to negative culture, but were not significantly associated after adjustment. Uropathogens were found at ≥105 CFU in 15 of 75 (20%), 7 of 50 (14%), and 0 of 15 (0%) of the three postantibiotic micturition samples, respectively, and in any identified CFU in 48 of 75 (64%), 23 of 50 (46%), and 1 of 15 (7%), respectively.
Urinary culture sensitivity decreases rapidly after administering antibiotics.
Background/Aims Insulin resistance reduces the response to interferon alfa-based therapy of chronic hepatitis C patients. It has been speculated that improvement of insulin sensitivity might increase ...the chances of responding to treatment of such individuals. Methods We started a multicenter clinical trial of retreatment of chronic hepatitis C patients, who had failed to respond to the pegylated interferon alfa/ribavirin combination, with a triple therapy consisting in these same antivirals plus an insulin-sensitizer (pioglitazone) (The INSPIRED-HCV study). Results None of the first five patients fulfilling the inclusion criteria and included in the trial achieved a satisfactory virological response after 12 weeks of retreatment, despite the fact that in at least three of them the insulin resistance score improved. As a result, the study was terminated. Conclusions Different schedules are warranted to improve insulin sensitivity prior to attempting retreatment of chronic hepatitis C patients with insulin resistance.
Recent European Association of Urology (EAU) guidelines and a clinical prediction rule developed by Van Nieuwkoop et al. suggest simple criteria for performing radiological imaging for patients with ...a febrile urinary tract infection (UTI). We analysed the records of patients with a UTI from four hospitals in Switzerland. Of 107 UTI patients, 58% underwent imaging and 69% (95%CI: 59–77%) and 64% (95%CI: 54–73%) of them were adequately managed according to Van Nieuwkoop’s clinical rule and EAU guidelines, respectively. However, only 47% (95%CI: 33–61%) and 57% (95%CI: 44–69%) of the imaging performed would have been recommended according to their respective rules. Clinically significant imaging findings were associated with a history of urolithiasis (OR = 11.8; 95%CI: 3.0–46.5), gross haematuria (OR = 5.9; 95%CI: 1.6–22.1) and known urogenital anomalies (OR = 5.7; 95%CI: 1.8–18.2). Moreover, six of 16 (38%) patients with a clinically relevant abnormality displayed none of the criteria requiring imaging according to Van Nieuwkoop’s rule or EAU guidelines. Thus, adherence to imaging guidelines was suboptimal, especially when imaging was not recommended. However, additional factors associated with clinically significant findings suggest the need for a new, efficient clinical prediction rule.
Objectives
The aim of the study was to analyse the proportion of evidence-based medication displayed in pharmacies and compare it between the different linguistic regions of the country, at different ...times of the year to determine the amount of proven effective medications indirectly recommended to the public in different parts of Switzerland.
Design
This is an observational study conducted by medical doctors in the department of internal medicine at the Spitalzentrum Biel, Switzerland.
Setting
The observation took place from July 2019 to May 2020. From a total of 1800 pharmacies in Switzerland, 68 different pharmacies were selected across the 3 main linguistic regions and the medication on display in their windows were examined 4 times a year regarding their efficacy. The displays of medication with or without evidence-based efficacy were described using absolute numbers and proportions and compared between the different linguistic regions at different seasons using χ
2
.
Participants
There were no human or animal participants involved in this study.
Primary and secondary outcome measures
The primary outcome is the proportion of medication displayed in pharmacy windows with a proven effectiveness in medical literature. The secondary outcome was the variability of the primary outcome over time (seasonal changes), over the different linguistic regions of Switzerland and between chains and privately owned pharmacies.
Results
We examined 970 medications and found that over the whole year, there is a high proportion of non-evidence-based drugs (56,9%) displayed in pharmacies. Swiss German cantons display significantly more non-evidence-based medications in winter. We found no statistical difference for other seasons or between chains and privately owned pharmacies.
Conclusion
Pharmacies in Switzerland tend to display significantly more non-evidence-based drugs, thus indirectly recommending them to the public. In a time of necessary expansion of self-medication by the population, this could incite consumers to buy drugs without proven effectiveness.
Among smokers, the presence of tobacco stains on fingers has recently been associated with a high prevalence of tobacco related conditions and alcohol abuse.
we aimed to explore tobacco stains as a ...marker of death and hospital readmission.
Seventy-three smokers presenting tobacco-tar staining on their fingers and 70 control smokers were followed during a median of 5.5 years in a retrospective cohort study. We used the Kaplan-Meier survival analysis and the log-rank test to compare mortality and hospital readmission rates among smokers with and smokers without tobacco stains. Multivariable Cox models were used to adjust for confounding factors: age, gender, pack-year unit smoked, cancer, harmful alcohol use and diabetes. The number of hospital admissions was compared through a negative binomial regression and adjusted for the follow-up time, diabetes, and alcohol use.
Forty-three patients with tobacco-stained fingers died compared to 26 control smokers (HR 1.6; 95%CI: 1.0 to 2.7; p 0.048). The association was not statistically significant after adjustment. Patients with tobacco-stained fingers needed a readmission earlier than smokers without stains (HR 2.1; 95%CI: 1.4 to 3.1; p<0.001), and more often (incidence rate ratio (IRR) 1.6; 95%CI: 1.1 to 2.1). Associations between stains and the first hospital readmission (HR 1.6; 95%CI: 1.0 to 2.5), and number of readmissions (IRR 1.5; 95%CI: 1.1 to 2.1) persisted after adjustment for confounding factors.
Compared to other smokers, those presenting tobacco-stained fingers have a high unadjusted mortality rate and need early and frequent hospital readmission even when controlling for confounders.
The association between early antibiotic administration and outcomes remains controversial in patients hospitalized for community-acquired pneumonia.
We performed a secondary analysis of a randomized ...controlled trial comparing two antibiotic treatment strategies for patients hospitalized for moderately severe CAP. The univariate and multivariate associations between time to antibiotic administration (TTA) and time to clinical stability were assessed using a Cox proportional hazard model. Secondary outcomes were death, intensive care unit admission and hospital readmission up to 90days.
371 patients (mean age 76years, CURB-65 score≥2 in 52%) were included. Mean TTA was 4.35h (SD 3.48), with 58.5% of patients receiving the first antibiotic dose within 4h.
In multivariate analysis, number of symptoms and signs (HR 0.876, 95% CI 0.784–0.979, p=0.020), age (HR 0.986, 95% CI 0.975–0.996, p=0.007), initial heart rate (HR 0.992, 95% CI 0.986–0.999, p=0.023), and platelets count (HR 0.998, 95% CI 0.996–0.999, p=0.004) were associated with a reduced probability of reaching clinical stability. The association between TTA and time to clinical stability was not significant (HR 1.009, 95% CI 0.977–1.042, p=0.574). We found no association between TTA and the risk of intensive care unit admission, death or readmission up to 90days after the initial admission.
In patients hospitalized for moderately severe CAP, a shorter time to antibiotic administration was not associated with a favorable outcome. These findings support the current recommendations that do not assign a specific time frame for antibiotics administration.
•Guidelines do not assign a specific time frame for the first antibiotic dose in CAP•We evaluated the benefit of early antibiotics in moderately severe pneumonia•Time to treatment was not associated with a shorter time to clinical stability•These results should not be extrapolated to patients with more severe disease
The clinical benefit of adding a macrolide to a β-lactam for empirical treatment of moderately severe community-acquired pneumonia remains controversial.
To test noninferiority of a β-lactam alone ...compared with a β-lactam and macrolide combination in moderately severe community-acquired pneumonia.
Open-label, multicenter, noninferiority, randomized trial conducted from January 13, 2009, through January 31, 2013, in 580 immunocompetent adult patients hospitalized in 6 acute care hospitals in Switzerland for moderately severe community-acquired pneumonia. Follow-up extended to 90 days. Outcome assessors were masked to treatment allocation.
Patients were treated with a β-lactam and a macrolide (combination arm) or with a β-lactam alone (monotherapy arm). Legionella pneumophila infection was systematically searched and treated by addition of a macrolide to the monotherapy arm.
Proportion of patients not reaching clinical stability (heart rate <100/min, systolic blood pressure >90 mm Hg, temperature <38.0°C, respiratory rate <24/min, and oxygen saturation >90% on room air) at day 7.
After 7 days of treatment, 120 of 291 patients (41.2%) in the monotherapy arm vs 97 of 289 (33.6%) in the combination arm had not reached clinical stability (7.6% difference, P = .07). The upper limit of the 1-sided 90% CI was 13.0%, exceeding the predefined noninferiority boundary of 8%. Patients infected with atypical pathogens (hazard ratio HR, 0.33; 95% CI, 0.13-0.85) or with Pneumonia Severity Index (PSI) category IV pneumonia (HR, 0.81; 95% CI, 0.59-1.10) were less likely to reach clinical stability with monotherapy, whereas patients not infected with atypical pathogens (HR, 0.99; 95% CI, 0.80-1.22) or with PSI category I to III pneumonia (HR, 1.06; 95% CI, 0.82-1.36) had equivalent outcomes in the 2 arms. There were more 30-day readmissions in the monotherapy arm (7.9% vs 3.1%, P = .01). Mortality, intensive care unit admission, complications, length of stay, and recurrence of pneumonia within 90 days did not differ between the 2 arms.
We did not find noninferiority of β-lactam monotherapy in patients hospitalized for moderately severe community-acquired pneumonia. Patients infected with atypical pathogens or with PSI category IV pneumonia had delayed clinical stability with monotherapy.
clinicaltrials.gov Identifier: NCT00818610.
Hospital readmissions are frequent, costly, and sometimes preventable. Although these issues have been well publicized and incentives to reduce them introduced, the best interventions for reducing ...readmissions remain unclear.
To evaluate the effects of a multimodal transitional care intervention targeting patients at high risk of hospital readmission on the composite outcome of 30-day unplanned readmission or death.
A single-blinded, multicenter randomized clinical trial was conducted from April 2018 to January 2020, with a 30-day follow-up in 4 medium-to-large-sized teaching hospitals in Switzerland. Participants were consecutive patients discharged from general internal medicine wards and at higher risk of unplanned readmission based on their simplified HOSPITAL score (≥4 points). Data were analyzed between April and September 2022.
The intervention group underwent systematic medication reconciliation, a 15-minute patient education session with teach-back, a planned first follow-up visit with their primary care physician, and postdischarge follow-up telephone calls from the study team at 3 and 14 days. The control group received usual care from their hospitalist, plus a 1-page standard study information sheet.
Thirty-day postdischarge unplanned readmission or death.
A total of 1386 patients were included with a mean (SD) age of 72 (14) years; 712 (51%) were male. The composite outcome of 30-day unplanned readmission or death was 21% (95% CI, 18% to 24%) in the intervention group and 19% (95% CI, 17% to 22%) in the control group. The intention-to-treat analysis risk difference was 1.7% (95% CI, -2.5% to 5.9%; P = .44). There was no evidence of any intervention effects on time to unplanned readmission or death, postdischarge health care use, patient satisfaction with the quality of their care transition, or readmission costs.
In this randomized clinical trial, use of a standardized multimodal care transition intervention targeting higher-risk patients did not significantly decrease the risks of 30-day postdischarge unplanned readmission or death; it demonstrated the difficulties in preventing hospital readmissions, even when multimodal interventions specifically target higher-risk patients.
ClinicalTrials.gov Identifier: NCT03496896.