Ongoing efforts to improve clinical trial design in irritable bowel syndrome have been hindered by high placebo response rates and ineffective outcome measures. We assessed established strategies to minimize placebo effect as well as the various approaches to placebo effect which can affect trial design. These include genetic markers such as catechol-O-methyltransferase, opioidergic and dopaminergic neurobiologic theory, pre-cebo effect centered on expectancy theory, and side effect unblinding grounded on conditioning theory. We reviewed endpoints used in the study of IBS over the past decade including adequate relief and subjective global relief, emphasizing their weaknesses in fully evaluating the IBS condition, specifically their motility effects based on functional net value and relative benefit-harm based on dropouts due to adverse events. The focus of this review is to highlight ongoing efforts to improve clinical trial design which can lead to better outcomes in a real-world setting.
Catechol O-Methyltransferase ; Genetic Markers ; Humans ; Irritable Bowel Syndrome* ; Outcome Assessment (Health Care) ; Patient Dropouts ; Placebo Effect* ; Placebos

Biopsy, Fine-Needle ; methods ; Bronchi ; diagnostic imaging ; pathology ; Endosonography ; methods ; Humans ; Lung Neoplasms ; pathology ; Lymph Nodes ; pathology ; Neoplasm Staging

An 8-month old female presented with spontaneous subarachnoid hemorrhage and was treated successfully with endovascular coil embolization of the ruptured aneurysm. Transcranial Doppler ultrasound performed four days later demonstrated middle cerebral artery (MCA) velocities greater than 350 cm/sec on the right and greater than 200 cm/sec on the left, despite medical management. The patient demonstrated no focal neurological deficits, though examination was limited by our patient's sedation and intubation. Angiography revealed severe vasospasm of the supraclinoid internal carotid and MCA territories, bilaterally. The vasospasm was refractory to the administration of intra-arterial verapamil. Balloon angioplasty was attempted, but the device could not be advanced safely due to the small size of the patient's vessels and the stiffness of the device. A microcatheter (0.0165" diameter) was advanced over a J-shaped soft microwire (0.014" diameter) to perform mechanical angioplasty in the internal carotid artery and MCA vessels bilaterally. Dramatic improvement was seen angiographically and on transcranial Doppler, and no complications were seen.
Aneurysm ; Aneurysm, Ruptured ; Angiography ; Angioplasty ; Angioplasty, Balloon ; Carotid Artery, Internal ; Embolization, Therapeutic ; Female ; Humans ; Infant* ; Intubation ; Middle Cerebral Artery ; Subarachnoid Hemorrhage ; Ultrasonography ; Vasospasm, Intracranial* ; Verapamil

BACKGROUND/AIMS: Recent studies reveal that acute gastroenteritis can precipitate irritable bowel syndrome (IBS) symptoms leading to the concept of post-infectious IBS. However, the overall contribution of gastroenteritis to the total IBS prevalence is unknown. In this exercise we try to estimate the contribution of gastroenteritis in IBS using the published literature and a longitudinal approach. METHODS: Existing literature was reviewed to determine the incidence of IBS after gastroenteritis, the rate of remission over time, data on rates of gastroenteritis in a given population and any patterns of resistance to these effects in human populations. This produced 3 models. The first assumed all humans were susceptible to gastroenteritis and its ability to produce IBS. The second assumed (using meta-analysis data) that 90% of humans in a given outbreak would be resistant to this effect. The third model used a high gastroenteritis exposure rate as might be seen in military deployment. RESULTS: In model 1, the prevalence was unrealistically high with an eventual steady state of 43.6% of the population affected by IBS. In a very conservative approach (model 2), steady state was achieved after 10 years to an overall prevalence of 8.9%. Interestingly, based on a high 1 year exposure rate such as military deployment, the maximum prevalence (steady state) was reached before 1 year suggesting high risk. CONCLUSIONS: Although hypothetical in approach, based on conservative estimates in existing literature the contribution of gastroenteritis to the overall prevalence of IBS is substantial.
Gastroenteritis ; Humans ; Incidence ; Irritable Bowel Syndrome ; Military Personnel ; Prevalence

Background: The aerosol box was rapidly developed and disseminated to minimize viral exposure during aerosolizing procedures during the COVID-19 pandemic, yet users may not understand how to use and clean the device. This could potentially lead to increased viral exposure to subsequent patients and practitioners. We evaluated intraoperative contamination and aerosol box decontamination and the impact of a preoperative educational visual aid. Methods: Using a double-blinded randomized design, forty-four anesthesiology trainees and faculty completed a simulated anesthetic case using an aerosol box contaminated with a fluorescent marker; half of the subjects received a visual aid prior to the simulation. Intraoperative contamination was evaluated at 10 standardized locations using an ultraviolet (UV) light. Next, subjects were instructed to clean the aerosol box for use on the next patient. Following cleaning, the box was evaluated for decontamination using an UV light. Results: Median total contamination score was significantly reduced in the experimental group (5.0 vs. 10.0, P < 0.001). The aerosol box was completely cleaned by 36.4% of subjects in the experimental group compared to 4.5% in the control group (P = 0.009). Conclusions The use of a visual aid significantly decreased intraoperative contamination and improved box cleaning. Despite these findings, a potentially clinically significant amount of viral exposure may exist. Thorough evaluation of the risks and benefits of the aerosol box should be completed prior to use. If an aerosol box is used, a visual aid should be considered to remind practitioners how to best use and clean the box.

BACKGROUND/AIMS: We evaluated the distribution of lower and upper gastrointestinal (GI) symptoms among individuals with irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in a nationwide survey. METHODS: Individuals (≥ 18 years of age) were identified from a nationwide sample of > 70 000 United States adults. Participants completed the National Institutes of Health GI Patient Reported Outcomes Measurement Information System (NIH GI-PROMIS) questionnaire. Symptom frequency and intensity in the prior 7 days were assessed using validated PROMIS scores. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to compare symptom prevalence in IBS-C vs CIC, and one-way ANOVA was used to assess differences in PROMIS scores. Regression analysis was performed to adjust for demographic variables. RESULTS: Nine hundred and seventy adults met eligibility criteria (275 with IBS-C, 734 with CIC). Demographics were similar among groups except for education, marital and employment status, and income. Adjusting for demographic differences, GI-PROMIS scores of global GI symptoms were higher in IBS-C (251.1; 95% CI, 230.0–273.1) compared to CIC (177.8; 95% CI 167.2–188.4) (P < 0.001). Abdominal pain was more prevalent (OR, 4.3; 95% CI, 2.9–6.6) and more severe (P = 0.007) in IBS-C. Constipation was more severe in IBS-C (P = 0.011). Incontinence was more common (OR, 2.9; 95% CI, 1.3–6.3) but just as severe (P = 0.389) in IBS-C versus CIC. Regarding upper GI symptoms, the prevalence of dysphagia, heartburn, and nausea were similar. However, IBS-C individuals had more severe heartburn (P = 0.001). CONCLUSION: GI symptoms are generally more severe in IBS-C compared to CIC, however abdominal pain, bloating, and upper GI symptoms still commonly occur in CIC.
Abdominal Pain ; Adult ; Constipation ; Cross-Sectional Studies ; Deglutition Disorders ; Demography ; Education ; Employment ; Heartburn ; Humans ; Information Systems ; Irritable Bowel Syndrome ; National Institutes of Health (U.S.) ; Nausea ; Odds Ratio ; Prevalence ; Surveys and Questionnaires ; Symptom Assessment ; United States

Background: The aerosol box was rapidly developed and disseminated to minimize viral exposure during aerosolizing procedures during the COVID-19 pandemic, yet users may not understand how to use and clean the device. This could potentially lead to increased viral exposure to subsequent patients and practitioners. We evaluated intraoperative contamination and aerosol box decontamination and the impact of a preoperative educational visual aid. Methods: Using a double-blinded randomized design, forty-four anesthesiology trainees and faculty completed a simulated anesthetic case using an aerosol box contaminated with a fluorescent marker; half of the subjects received a visual aid prior to the simulation. Intraoperative contamination was evaluated at 10 standardized locations using an ultraviolet (UV) light. Next, subjects were instructed to clean the aerosol box for use on the next patient. Following cleaning, the box was evaluated for decontamination using an UV light. Results: Median total contamination score was significantly reduced in the experimental group (5.0 vs. 10.0, P < 0.001). The aerosol box was completely cleaned by 36.4% of subjects in the experimental group compared to 4.5% in the control group (P = 0.009). Conclusions The use of a visual aid significantly decreased intraoperative contamination and improved box cleaning. Despite these findings, a potentially clinically significant amount of viral exposure may exist. Thorough evaluation of the risks and benefits of the aerosol box should be completed prior to use. If an aerosol box is used, a visual aid should be considered to remind practitioners how to best use and clean the box.

There have been many significant scientific advances in the diagnostics and treatment modalities in the field of male infertility in recent decades. Examples of these include assisted reproductive technologies, sperm selection techniques for intracytoplasmic sperm injection, surgical procedures for sperm retrieval, and novel tests of sperm function. However, there is certainly a need for new developments in this field. In this review, we discuss advances in the management of male infertility, such as seminal oxidative stress testing, sperm DNA fragmentation testing, genetic and epigenetic tests, genetic manipulations, artificial intelligence, personalized medicine, and telemedicine. The role of the reproductive urologist will continue to expand in future years to address different topzics related to diverse questions and controversies of pathophysiology, diagnosis, and therapy of male infertility, training researchers and physicians in medical and scientific research in reproductive urology/ andrology, and further development of andrology as an independent specialty.

Purpose: Varicocele has been associated with high seminal oxidative stress (OS), impaired semen quality, and reduced male fertility potential. However, the exact mechanism(s) underlying the development of varicocele-mediated infertility and the cause-effect relationship between varicocele and testicular dysfunction are not fully understood. The aim of this systematic review and meta-analysis (SRMA) is to investigate the impact of varicocele on testicular OS markers and sperm parameters in experimental animals with varicocele as compared to animals without varicocele. Materials and Methods: A literature search was performed using the Scopus and PubMed databases on studies that investigated testicular OS markers and sperm parameters in animals with varicocele. The primary outcomes included malondialdehyde (MDA) (nmol/mg) levels whereas the secondary outcomes included total sperm count (×106), sperm vitality (%), total sperm motility (%), and sperm DNA fragmentation (SDF) (%). Standardized mean difference (SMD) (95% confidence interval [CI]) was chosen to express the effect size. The quality of the included studies was evaluated using the Cambridge Quality Checklist. Results: Out of 76 identified articles, 6 studies on rats were included in the meta-analysis. The analysis showed a significant increase of MDA (SMD: 15.61 [1.93, 29.29]; p=0.03) in rats with varicocele vs. controls. We also observed a significant decrease in total sperm count (SMD: -17.45 [-28.97, -5.93]; p<0.01), sperm vitality (SMD: -16.41 [-26.30, -6.52]; p<0.01), total sperm motility (SMD: -17.67 [-24.90, -10.44]; p<0.01), and a significant increase of SDF (SMD: 7.41 [1.23, 13.59]; p=0.02), in rats with varicocele vs. controls. The quality of the included studies was ranked as high. Conclusions This SRMA indicates a significant increase in levels of testicular MDA and SDF and a reduction of sperm quality in experimental animals with varicocele. These findings support the potential role of testicular OS in the development of varicocele-induced testicular damage.

Background: and Purpose Intracranial arterial stenosis (ICAS)-related stroke occurs due to three primary mechanisms with distinct infarct patterns: (1) borderzone infarcts (BZI) due to impaired distal perfusion, (2) territorial infarcts due to distal plaque/thrombus embolization, and (3) plaque progression occluding perforators. The objective of the systematic review is to determine whether BZI secondary to ICAS is associated with a higher risk of recurrent stroke or neurological deterioration. Methods: As part of this registered systematic review (CRD42021265230), a comprehensive search was performed to identify relevant papers and conference abstracts (with ≥20 patients) reporting initial infarct patterns and recurrence rates in patients with symptomatic ICAS. Subgroup analyses were performed for studies including any BZI versus isolated BZI and those excluding posterior circulation stroke. The study outcome included neurological deterioration or recurrent stroke during follow-up. For all outcome events, corresponding risk ratios (RRs) and 95% confidence intervals (95% CI) were calculated. Results: A literature search yielded 4,478 records with 32 selected during the title/abstract triage for full text; 11 met inclusion criteria and 8 studies were included in the analysis (n=1,219 patients; 341 with BZI). The meta-analysis demonstrated that the RR of outcome in the BZI group compared to the no BZI group was 2.10 (95% CI 1.52–2.90). Limiting the analysis to studies including any BZI, the RR was 2.10 (95% CI 1.38–3.18). For isolated BZI, RR was 2.59 (95% CI 1.24–5.41). RR was 2.96 (95% CI 1.71–5.12) for studies only including anterior circulation stroke patients. Conclusion This systematic review and meta-analysis suggests that the presence of BZI secondary to ICAS may be an imaging biomarker that predicts neurological deterioration and/or stroke recurrence.