Reasons for No Colonoscopy After an Unfavorable Screening Result in Dutch Colorectal Cancer Screening: A Nationwide Questionnaire.

PURPOSE: We aimed to assess participant-reported factors associated with non-follow-up with colonoscopy in colorectal cancer (CRC) screening. METHODS: In May 2019, we distributed a nationwide cross-sectional questionnaire (n = 4,009) to participants in the Dutch CRC screening program who received a positive fecal immunochemical test (FIT). Among respondents who reported no colonoscopy, we assessed the presence of a contraindication, and those without were compared with those who reported colonoscopy by logistic regression analysis. RESULTS: Of 2,225 respondents (56% response rate), 730 (33%) reported no colonoscopy. A contraindication was reported by 55% (n = 404). Decisional difficulties (odds ratio [OR] = 0.29; 95% CI, 0.18-0.47), lacking the opportunity to discuss the FIT outcome (OR = 0.45; 95% CI, 0.28-0.72), and a low estimated risk of CRC (OR = 0.45; 95% CI, 0.26-0.76) were negatively associated with follow-up. Knowledge items negatively associated with follow-up included having an alternative explanation for the positive FIT (OR = 0.3; 95% CI, 0.21-0.43), having trust in the ability to self-detect CRC (OR = 0.42; 95% CI, 0.27-0.65), and thinking that polyp removal is ineffective (OR = 0.59; 95% CI, 0.43-0.82). The belief that the family physician would support colonoscopy showed the strongest positive association with follow-up (OR = 2.84; 95% CI, 2.01-4.02) CONCLUSIONS: Because decisional difficulties and certain convictions regarding CRC and screening are associated with non-follow-up, personalized screening counseling might be an intervention worth exploring as a means of improving follow-up in the Dutch CRC screening program. Involving family physicians might also prove beneficial.

Toward a simple diagnostic index for acute uncomplicated urinary tract infections.

PURPOSE: Whereas a diagnosis of acute uncomplicated urinary tract infection (UTI) in clinical practice comprises a battery of several diagnostic tests, these tests are often studied separately (in isolation from other test results). We wanted to determine the value of history and urine tests for diagnosis of uncomplicated UTIs, taking into account their mutual dependencies and information from preceding tests. METHODS: Women with painful and/or frequent micturition answered questions about their signs and symptoms (history) of UTIs and underwent urine tests. A culture was the reference standard (10(3) colony-forming units per milliliter). A diagnostic index was derived using logistic regression with bootstrapped backward selection and parameter-wise shrinkage. Risk thresholds for UTI of 30% and 70% were used to analyze discriminative properties. Six models were compared: (1) history only, (2) history+ urine dipstick, (3) history+ urine dipstick + urinary sediment, (4) history+ urine dipstick+ dipslide, and (5) history+ urine dipstick+ urinary sediment+ dipslide; we then added (6) a test only for patients with an intermediate risk (between 30% and 70%) after the preceding test. RESULTS: One hundred ninety-six women were included (UTI prevalence 61%). Seven variables were selected from history (3), dipstick (2), sediment (1), and dipslide (1). History correctly classified 56% of patients as having a UTI risk of either <30% or >70%. History and urine dipstick raised this to 73%. The 3 models with the addition of urinary sediment and dipslide, separately and in combination, performed hardly better. The sixth model, in which those at intermediate risk after history and received an additional test, correctly classified 83%. The patient's suspicion of a UTI and a positive nitrite test were the strongest indicators of a UTI. CONCLUSIONS: Most women with painful and/or frequent micturition can be correctly classified as having either a low or a high risk of UTI by asking 3 questions: Does the patient think she has a UTI? Is there at least considerable pain on micturition? Is there vaginal irritation? Other women require additional urine dipstick investigation. Sediment and dipslide have little added value. External validation of these recommendations is required before they are implemented in practice.

Women with symptoms of uncomplicated urinary tract infection are often willing to delay antibiotic treatment: a prospective cohort study.

BACKGROUND: Women presenting with symptoms of acute uncomplicated urinary tract infection (UTI) are often prescribed antibiotics. However, in 25 to 50% of symptomatic women not taking antibiotics, symptoms recover spontaneously within one week. It is not known how many women are prepared to delay antibiotic treatment. We investigated how many women presenting with UTI symptoms were willing to delay antibiotic treatment when asked by their general practitioner (GP). METHODS: From 18 April 2006 until 8 October 2008, in a prospective cohort study, patients were recruited in 20 GP practices in and around Amsterdam, the Netherlands. Healthy, non-pregnant women who contacted their GP with painful and/or frequent micturition for no longer than seven days registered their symptoms and collected urine for urinalysis and culture. GPs were requested to ask all patients if they were willing to delay antibiotic treatment, without knowing the result of the culture at that moment. After seven days, patients reported whether their symptoms had improved and whether they had used any antibiotics. RESULTS: Of 176 women, 137 were asked by their GP to delay antibiotic treatment, of whom 37% (51/137) were willing to delay. After one week, 55% (28/51) of delaying women had not used antibiotics, of whom 71% (20/28) reported clinical improvement or cure. None of the participating women developed pyelonephritis. CONCLUSIONS: More than a third of women with UTI symptoms are willing to delay antibiotic treatment when asked by their GP. The majority of delaying women report spontaneous symptom improvement after one week.

Comparative effectiveness of antibiotics for uncomplicated urinary tract infections: network meta-analysis of randomized trials.

BACKGROUND: The efficacies and adverse effects of different antibiotics for uncomplicated urinary tract infections (UTIs) have been studied by standard meta-analytic methods using pairwise direct comparisons of antimicrobial treatments: the effects of one treatment are compared to those of either another treatment or placebo. However, for clinical decisions, we need to know the effectiveness of each possible treatment in comparison with all relevant alternatives, not with just one. OBJECTIVES: To compare the efficacies and adverse effects of all relevant antibiotics for UTI treatment simultaneously by performing a network meta-analysis using direct and indirect treatment comparisons. METHODS: Using logistic regression analysis, we performed a network meta-analysis of randomized controlled trials (RCTs) published after 1999 that compared different oral antibiotic or placebo regimens for UTI treatment in general practice or outpatient settings. We looked at five binary outcomes: early clinical, early bacteriological, late clinical and late bacteriological outcomes, as well as adverse effects. Consequently, a ranking of the antibiotic regimens could be composed. RESULTS: Using a network structure, we could compare and rank nine treatments from 10 studies. Overall, ciprofloxacin and gatifloxacin appeared the most effective treatments, and amoxicillin-clavulanate appeared the least effective treatment. In terms of adverse effects, there were no significant differences. DISCUSSION: Network meta-analysis shows some clear efficacy differences between different antibiotic treatments for UTI in women. It provides a useful tool for clinical decision making in everyday practice. Moreover, the method can be used for meta-analyses of RCTs across primary care and beyond.

Decision-making given surrogate outcomes.

BACKGROUND: Opinions differ about the extent to which intervention research should and can directly assess the main patient-important health outcomes, what role surrogate endpoints can play, and which requirements should then apply to the scientific underpinning of clinical and policy decisions. METHOD: In a commentary we elaborate on this and provide guidance for dealing with related dilemmas. CONCLUSIONS: Ethical, methodological and practical reasons for decision making based on surrogate endpoints can be that (1) reaching the intended patient-important health outcome would take too long to await direct RCT-based evidence, (2) experimental conditions have limited sustainability over time; and (3) the plausibility of an intervention's clinical efficacy, given the already available evidence regarding surrogate endpoints, goes beyond equipoise. Given an expected increase of interventions with a long term patient-important health outcome perspective, dealing with surrogate endpoints will remain an important challenge. Appropriately dealing with a surrogate endpoint includes (1) the assessment of its predictive value for the intended patient-important outcome, where GRADE guidelines for assessing 'indirectness' and 'causal chain analysis' can be helpful; (2) transparency of (absence of) evidence; (3) adequately updating the 'knowledge mosaic'; (4) weighing different perspectives and values, and (5) monitoring whether adjustments need to be made. The remaining level of uncertainty must be balanced against the urgency of clinical or societal decision making and the disadvantages of postponing this. Criteria for using surrogate endpoints are suggested. Patients, citizens and policy makers can be involved in agreeing upon these criteria.

Impact of a Machine Learning-Based Decision Support System for Urinary Tract Infections: Prospective Observational Study in 36 Primary Care Practices.

BACKGROUND: There is increasing attention on machine learning (ML)-based clinical decision support systems (CDSS), but their added value and pitfalls are very rarely evaluated in clinical practice. We implemented a CDSS to aid general practitioners (GPs) in treating patients with urinary tract infections (UTIs), which are a significant health burden worldwide. OBJECTIVE: This study aims to prospectively assess the impact of this CDSS on treatment success and change in antibiotic prescription behavior of the physician. In doing so, we hope to identify drivers and obstacles that positively impact the quality of health care practice with ML. METHODS: The CDSS was developed by Pacmed, Nivel, and Leiden University Medical Center (LUMC). The CDSS presents the expected outcomes of treatments, using interpretable decision trees as ML classifiers. Treatment success was defined as a subsequent period of 28 days during which no new antibiotic treatment for UTI was needed. In this prospective observational study, 36 primary care practices used the software for 4 months. Furthermore, 29 control practices were identified using propensity score-matching. All analyses were performed using electronic health records from the Nivel Primary Care Database. Patients for whom the software was used were identified in the Nivel database by sequential matching using CDSS use data. We compared the proportion of successful treatments before and during the study within the treatment arm. The same analysis was performed for the control practices and the patient subgroup the software was definitely used for. All analyses, including that of physicians' prescription behavior, were statistically tested using 2-sided z tests with an α level of .05. RESULTS: In the treatment practices, 4998 observations were included before and 3422 observations (of 2423 unique patients) were included during the implementation period. In the control practices, 5044 observations were included before and 3360 observations were included during the implementation period. The proportion of successful treatments increased significantly from 75% to 80% in treatment practices (z=5.47, P<.001). No significant difference was detected in control practices (76% before and 76% during the pilot, z=0.02; P=.98). Of the 2423 patients, we identified 734 (30.29%) in the CDSS use database in the Nivel database. For these patients, the proportion of successful treatments during the study was 83%-a statistically significant difference, with 75% of successful treatments before the study in the treatment practices (z=4.95; P<.001). CONCLUSIONS: The introduction of the CDSS as an intervention in the 36 treatment practices was associated with a statistically significant improvement in treatment success. We excluded temporal effects and validated the results with the subgroup analysis in patients for whom we were certain that the software was used. This study shows important strengths and points of attention for the development and implementation of an ML-based CDSS in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04408976; https://clinicaltrials.gov/ct2/show/NCT04408976.

[Urinary tract infections in general practice; diagnostics and treatment can be improved]. / Urineweginfecties op de huisartsenpost.

This is a commentary on the article of Van der Spek et al. on the workload, diagnostic work-up and treatment of urinary tract infections in adults during out-of-hours primary care. Despite a well-established Dutch guideline on urinary tract infections, correctly diagnosing and prescribing antibiotics for urinary tract infections is a challenge that needs major improvement, especially during out-of-hours GP care.

Optimizing the diagnostic work-up of acute uncomplicated urinary tract infections.

BACKGROUND: Most diagnostic tests for acute uncomplicated urinary tract infections (UTIs) have been previously studied in so-called single-test evaluations. In practice, however, clinicians use more than one test in the diagnostic work-up. Since test results carry overlapping information, results from single-test studies may be confounded. The primary objective of the Amsterdam Cystitis/Urinary Tract Infection Study (ACUTIS) is to determine the (additional) diagnostic value of relevant tests from patient history and laboratory investigations, taking into account their mutual dependencies. Consequently, after suitable validation, an easy to use, multivariable diagnostic rule (clinical index) will be derived. METHODS: Women who contact their GP with painful and/or frequent micturition undergo a series of possibly relevant tests, consisting of patient history questions and laboratory investigations. Using urine culture as the reference standard, two multivariable models (diagnostic indices) will be generated: a model which assumes that patients attend the GP surgery and a model based on telephone contact only. Models will be made more robust using the bootstrap. Discrimination will be visualized in high resolution histograms of the posterior UTI probabilities and summarized as 5th, 10th, 25th 50th, 75th, 90th, and 95th centiles of these, Brier score and the area under the receiver operating characteristics curve (ROC) with 95% confidence intervals. Using the regression coefficients of the independent diagnostic indicators, a diagnostic rule will be derived, consisting of an efficient set of tests and their diagnostic values. The course of the presenting complaints is studied using 7-day patient diaries. To learn more about the natural history of UTIs, patients will be offered the opportunity to postpone the use of antibiotics. DISCUSSION: We expect that our diagnostic rule will allow efficient diagnosis of UTIs, necessitating the collection of diagnostic indicators with proven added value. GPs may use the rule (preferably after suitable validation) to estimate UTI probabilities for women with different combinations of test results. Finally, in a subcohort, an attempt is made to identify which indicators (including antibiotic treatment) are useful to prognosticate recovery from painful and/or frequent micturition.

Cost-effectiveness of different strategies for diagnosis of uncomplicated urinary tract infections in women presenting in primary care.

BACKGROUND: Uncomplicated Urinary Tract Infections (UTIs) are common in primary care resulting in substantial costs. Since antimicrobial resistance against antibiotics for UTIs is rising, accurate diagnosis is needed in settings with low rates of multidrug-resistant bacteria. OBJECTIVE: To compare the cost-effectiveness of different strategies to diagnose UTIs in women who contacted their general practitioner (GP) with painful and/or frequent micturition between 2006 and 2008 in and around Amsterdam, The Netherlands. METHODS: This is a model-based cost-effectiveness analysis using data from 196 women who underwent four tests: history, urine stick, sediment, dipslide, and the gold standard, a urine culture. Decision trees were constructed reflecting 15 diagnostic strategies comprising different parallel and sequential combinations of the four tests. Using the decision trees, for each strategy the costs and the proportion of women with a correct positive or negative diagnosis were estimated. Probabilistic sensitivity analysis was used to estimate uncertainty surrounding costs and effects. Uncertainty was presented using cost-effectiveness planes and acceptability curves. RESULTS: Most sequential testing strategies resulted in higher proportions of correctly classified women and lower costs than parallel testing strategies. For different willingness to pay thresholds, the most cost-effective strategies were: 1) performing a dipstick after a positive history for thresholds below €10 per additional correctly classified patient, 2) performing both a history and dipstick for thresholds between €10 and €17 per additional correctly classified patient, 3) performing a dipstick if history was negative, followed by a sediment if the dipstick was negative for thresholds between €17 and €118 per additional correctly classified patient, 4) performing a dipstick if history was negative, followed by a dipslide if the dipstick was negative for thresholds above €118 per additional correctly classified patient. CONCLUSION: Depending on decision makers' willingness to pay for one additional correctly classified woman, the strategy consisting of performing a history and dipstick simultaneously (ceiling ratios between €10 and €17) or performing a sediment if history and subsequent dipstick are negative (ceiling ratios between €17 and €118) are the most cost-effective strategies to diagnose a UTI.

[Unambiguous practice guidelines on urinary tract infections in primary and secondary care]. / Eenduidige richtlijnen voor de eerste en tweede lijn inzake urineweginfecties.

The Dutch College of General Practitioners (NHG) practice guideline 'Urinary tract infections' intended for primary health care and the Dutch Working Party on Antibiotic Policy (SWAB) practice guideline 'Antimicrobial therapy in complicated urinary tract infections' intended for specialists in secondary care, were reviewed together. - In the NHG guideline the differentiation between 'complicated' and 'uncomplicated' urinary tract infections has been replaced by categorisation into age, sex, risk group and the presence of fever, or invasion of tissues.- If urinary tract infection has been diagnosed, a dip slide test can be used to determine resistance.- The guidelines recommend the most narrow-spectrum antibiotic to reduce further increase in antimicrobial resistance.- A chapter about women with recurrent urinary tract infections has been added to the SWAB guideline. Amongst other things, the chapter provides information on the prescription of prophylactic lactobacillus in secondary care.