Discontinuation of alpha-blocker therapy in men with lower urinary tract symptoms: a systematic review and meta-analysis.

OBJECTIVES: We aimed to synthesise the available data for the effect of stopping alpha-blocker therapy among men with lower urinary tract symptoms. The focus was on symptom, uroflowmetry and quality of life outcomes, but we also reviewed the adverse events (AEs) and the number of patients who restarted therapy. DATA SOURCES: We searched MEDLINE/PubMed, EMBASE/Ovid and The Cochrane Central Register of Controlled Trials from inception to May 2018. ELIGIBILITY CRITERIA: We selected studies regardless of study design in which men were treated with an alpha-blocker for at least 3 months and in which the effects of alpha-blocker discontinuation were subsequently studied. Only controlled trials were used for the primary objective. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed the risk of bias for the controlled studies only using the Cochrane Collaboration's tool for assessing risk of bias. Data were pooled using random-effects meta-analyses. RESULTS: We identified 10 studies (1081 participants) assessing the primary objective. Six studies (733 participants) assessed differences in AEs between continuation and discontinuation, and six studies (501 participants) reported the numbers of subjects that restarted treatment after discontinuation. No studies in primary care were identified. After discontinuing monotherapy, symptom scores increased and peak flow rates decreased at 3 and 6 months, but not at 12 months; however, neither parameter changed when alpha-blockers were stopped during combination therapy. Small differences in post-void residual volumes and quality of life scores were considered clinically irrelevant. We also found that 0%-49% of patients restarted after stopping alpha-blocker therapy and that AEs did not increase with discontinuation. CONCLUSIONS: Discontinuing alpha-blocker monotherapy leads to a worsening compared with continuing therapy. Discontinuing the alpha-blocker after combination therapy had no significant effects on outcomes in either the short or long term. Discontinuation may be appropriate for the frail, elderly or those with concomitant illness or polypharmacy. However, studies in primary care are lacking. PROSPERO REGISTRATION NUMBER: CRD42016032648.

Diagnostic Accuracy of Fecal Calprotectin for Pediatric Inflammatory Bowel Disease in Primary Care: A Prospective Cohort Study.

PURPOSE: In specialist care, fecal calprotectin (FCal) is a commonly used noninvasive diagnostic test for ruling out inflammatory bowel disease (IBD) in children with chronic gastrointestinal symptoms. The aim of this study was to evaluate the diagnostic accuracy of FCal for IBD in symptomatic children in primary care. METHODS: We studied 2 prospective cohorts of children with chronic diarrhea, recurrent abdominal pain, or both: children initially seen in primary care (primary care cohort) and children referred to specialist care (referred cohort). FCal (index test) was measured at baseline and compared with 1 of the 2 reference standards for IBD: endoscopic assessment or 1-year follow-up. Physicians were blinded to FCal results, and values greater than 50 µg/g feces were considered positive. We determined specificity in the primary care cohort and sensitivity in the referred cohort. RESULTS: None of the 114 children in the primary care cohort ultimately received a diagnosis of IBD. The specificity of FCal in the primary care cohort was 0.87 (95% CI, 0.80-0.92). Among the 90 children in the referred cohort, 17 (19%) ultimately received a diagnosis of IBD. The sensitivity of FCal in the referred cohort was 0.99 (95% CI, 0.81-1.00). CONCLUSIONS: The findings of this study suggest that a positive FCal result in children with chronic gastrointestinal symptoms seen in primary care is not likely to be indicative of IBD. A negative FCal result is likely to be a true negative, which safely rules out IBD in children in whom a primary care physician considers referral to specialist care.

Noninvasive Tests for Inflammatory Bowel Disease: A Meta-analysis.

BACKGROUND: The clinical presentation of pediatric inflammatory bowel disease (IBD) is often nonspecific and overlaps with functional gastrointestinal disorders. OBJECTIVE: To determine the diagnostic accuracy of symptoms, signs, noninvasive tests, and test combinations that can assist the clinician with the diagnosis of IBD in symptomatic children. METHODS: A literature search was conducted of Medline and Embase. Two reviewers independently selected studies reporting on the diagnostic accuracy of tests for IBD, with confirmation by endoscopy and histopathology or clinical follow-up, in children with chronic gastrointestinal symptoms. Two reviewers independently extracted data and assessed study quality with the QUADAS-2, an evidence-based quality assessment tool for diagnostic accuracy studies. RESULTS: Nineteen studies were included (N = 2806). Symptoms (abdominal pain, diarrhea, rectal bleeding, and weight loss) had pooled sensitivities ranging from 0.48 to 0.82 and specificities ranging from 0.17 to 0.78. Of all the blood markers, C-reactive protein (CRP) (9 studies) and albumin (6 studies) had the best performance, with pooled sensitivities of 0.63 (0.51-0.73) and 0.48 (0.31-0.66), respectively, and specificities of 0.88 (0.80-0.93) and 0.94 (0.86-0.98). Assessment of fecal calprotectin (FCal) (10 studies) had a pooled sensitivity of 0.99 (0.92-1.00) and a specificity of 0.65 (0.54-0.74). One limitation was that none of the studies was conducted in nonreferred children. CONCLUSIONS: In children whose pediatrician is considering an endoscopy, symptoms are not accurate enough to identify low-risk patients in whom an endoscopy can be avoided. FCal, CRP, and albumin findings are potentially of clinical value, given their ability to select children at low risk (negative FCal test result) or high risk (positive CRP or albumin test result) for IBD.

Avoid Endoscopy in Children With Suspected Inflammatory Bowel Disease Who Have Normal Calprotectin Levels.

In children with suspected inflammatory bowel disease, adding calprotectin stool testing to the screening strategy has been recommended to distinguish organic from nonorganic disease. In this cohort study with historical controls, we could not confirm that screening with stool calprotectin improves the diagnostic yield (ratio inflammatory bowel disease-positive endoscopies and total number of endoscopies); however, in patients with normal fecal calprotectin levels (<50 µg/g) endoscopic and histological abnormalities were not seen. We propose to refrain from endoscopy when stool calprotectin levels are normal.

Effect of pelvic floor muscle training compared with watchful waiting in older women with symptomatic mild pelvic organ prolapse: randomised controlled trial in primary care.

OBJECTIVE: To compare the effects of pelvic floor muscle training and watchful waiting on pelvic floor symptoms in a primary care population of women aged 55 years and over with symptomatic mild pelvic organ prolapse. DESIGN: Randomised controlled trial. SETTING: Dutch primary care. PARTICIPANTS: Women aged 55 years or over with symptomatic mild prolapse (leading edge above the hymen) were identified by screening. Exclusion criteria were current prolapse treatment or treatment in the previous year, malignancy of pelvic organs, current treatment for another gynaecological disorder, severe/terminal illness, impaired mobility, cognitive impairment, and insufficient command of the Dutch language. INTERVENTIONS: Pelvic floor muscle training versus watchful waiting. MAIN OUTCOME MEASURES: The primary outcome was change in bladder, bowel, and pelvic floor symptoms measured with the Pelvic Floor Distress Inventory-20 (PFDI-20), three months after the start of treatment. Secondary outcomes were changes in condition specific and general quality of life, sexual function, degree of prolapse, pelvic floor muscle function, and patients' perceived change in symptoms. RESULTS: Of the 287 women who were randomised to pelvic floor muscle training (n=145) or watchful waiting (n=142), 250 (87%) completed follow-up. Participants in the intervention group improved by (on average) 9.1 (95% confidence interval 2.8 to 15.4) points more on the PFDI-20 than did participants in the watchful waiting group (P=0.005). Of women in the pelvic floor muscle training group, 57% (82/145) reported an improvement in overall symptoms from the start of the study compared with 13% (18/142) in the watchful waiting group (P<0.001). Other secondary outcomes showed no significant difference between the groups. CONCLUSIONS: Although pelvic floor muscle training led to a significantly greater improvement in PFDI-20 score, the difference between the groups was below the presumed level of clinical relevance (15 points). Nevertheless, 57% of the participants in the intervention group reported an improvement of overall symptoms. More studies are needed to identify factors related to success of pelvic floor muscle training and to investigate long term effects.Trial registration Dutch Trial Register (www.trialregister.nl) identifier: NTR2047.

Sexual function in older women with pelvic floor symptoms: a cross-sectional study in general practice.

BACKGROUND: Pelvic floor symptoms are common and are negatively associated with sexual function which, in turn, is an important aspect of quality of life. The majority of older women with pelvic floor symptoms are treated in general practice but evidence from studies in general practice on the sexual functioning of these women is scarce. AIM: This study examined predictors of sexual inactivity in older women with pelvic floor symptoms in general practice and of sexual functioning in those women who are sexually active. DESIGN AND SETTING: Cross-sectional study in women (aged ≥55 years) from 20 general practices who screened positive on a pelvic floor symptom questionnaire. METHOD: Logistic and linear regression analyses were used to determine predictors of sexual inactivity and sexual functioning (PISQ-12) by assessing their association with patient characteristics, symptoms (PFDI-20) and degree of prolapse (POP-Q). RESULTS: A total of 639 women were included (sexually active n = 393, sexually inactive n = 246). Predictors of sexual inactivity were increasing age (odds ratio [OR] = 1.13; 95% confidence interval [CI] = 1.10 to 1.17) and lower education (OR = 2.31; 95% CI = 1.50 to 3.54; Nagelkerke R(2) = 0.208). In sexually active women, sexual functioning was associated with pelvic floor symptom distress (P<0.001) and pelvic floor surgery (P = 0.018; R(2) = 0.138). CONCLUSION: In older women with pelvic floor symptoms, increasing age and lower educational level are predictors of sexual inactivity. Many of these older women are sexually active and pelvic floor symptom distress is negatively associated with sexual functioning. These results may encourage GPs to ask about sexual problems in women with pelvic floor symptoms.

Challenges in diagnostic accuracy studies in primary care: the fecal calprotectin example.

BACKGROUND: Low disease prevalence and lack of uniform reference standards in primary care induce methodological challenges for investigating the diagnostic accuracy of a test. We present a study design that copes with these methodological challenges and discuss the methodological implications of our choices, using a quality assessment tool for diagnostic accuracy studies (QUADAS-2). DESIGN: The study investigates the diagnostic value of fecal calprotectin for detecting inflammatory bowel disease in children presenting with chronic gastrointestinal symptoms in primary care. It is a prospective cohort study including two cohorts of children: one cohort will be recruited in primary care and the other in secondary/tertiary care. Test results of fecal calprotectin will be compared to one of the two reference standards for inflammatory bowel disease: endoscopy with histopathological examination of mucosal biopsies or assessment of clinical symptoms at 1-year follow-up. DISCUSSION: According to QUADAS-2 the use of two reference standards and the recruitment of patients in two populations may cause differential verification bias and spectrum bias, respectively. The clinical relevance of this potential bias and methods to adjust for this are presented. This study illustrates the importance of awareness of the different kinds of bias that result from choices in the design phase of a diagnostic study in a low prevalence setting. This approach is exemplary for other diagnostic research in primary care.