Management of recurrent urinary tract infections in adults

Many women will experience one or more urinary tract infection (UTI) during their life. The most unfortunate will have many. Men presenting with infections, and women with recurrent episodes, require further investigation. A diagnosis of a UTI is often based on a typical spectrum of symptoms, with confirmatory urine cultures lagging a few days behind. Unfortunately, symptoms of a UTI may not be typical, and other conditions can manifest similarly. Treatment of UTI with antibiotics is usually required, but there is increasing awareness of the need for antimicrobial stewardship to avoid the misuse and overuse of antibiotics, even as patients are increasingly reluctant to take them. Recurrent UTI can cause significant morbidity and disruption to daily activities yet investigations rarely demonstrate a reversible cause. There are a host of different antibiotic and non-antibiotic interventions that aim to lower the risk of further infections. However, these are not reliably effective, bring side effects of their own and are often proposed to this desperate population of patients on the back of weak evidence of efficacy.     

Helicobacter pylori and gastric hyperacidity,and their association with recurrent aphthous stomatitis

Helicobacter pylori is an established cause of gastric ulcers. Its role in causing recurrent aphthous stomatitis (RAS) remains controversial. Fifty-two RAS patients and 52 sex-matched controls were recruited in this case–control study. All subjects were screened for hematinic deficiencies and H. pylori. The latter was assessed quantitatively using the ¹⁴C-urea breath test. The χ² test and Wilcoxon signed ranks test were used to compare H. pylori and hematinic indices between cases and controls, while conditional logistic regression was used to assess the associations between the occurrence of RAS and independent factors. H. pylori was positive in 56.7% of the overall sample, with no difference between RAS patients (50.8%) and controls (49.2%) (P = 0.843). The median H. pylori and haematological indices values did not show any association with ulcer diameter, number, or frequency. Interestingly, gastric hyperacidity was significantly associated with RAS, and this association was independent from tobacco smoking, alcohol drinking, and H. pylori (odds ratio 14.99, 95% confidence interval 2.47–90.95; P = 0.003). This study found no association between H. pylori and RAS. The association between RAS and gastric hyperacidity suggests that gastric refluxate, not H. pylori, has an effect on the oral mucosa that favours an ulcerative change.     

On estimands arising from misspecified semiparametric rate-based analysis of recurrent episodic conditions

Marginal rate-based analyses are widely used for the analysis of recurrent events in clinical trials. In many areas of application, the events are not instantaneous but rather signal the onset of a symptomatic episode representing a recurrent infection, respiratory exacerbation, or bout of acute depression. In rate-based analyses, it is unclear how to best handle the time during which individuals are experiencing symptoms and hence are not at risk. We derive the limiting value of the Nelson-Aalen estimator and estimators of the regression coefficients under a semiparametric rate-based model in terms of an underlying two-state process. We investigate the impact of the distribution of the episode durations, heterogeneity, and dependence on the asymptotic and finite sample properties of standard estimators. We also consider the impact of these features on power in trials designed to test intervention effects on rate functions. An application to a trial of individuals with herpes simplex virus is given for illustration.