2.Placebo Effect in Clinical Trial Design for Irritable Bowel Syndrome.
Journal of Neurogastroenterology and Motility 2014;20(2):163-170
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
3.Estimating the Contribution of Acute Gastroenteritis to the Overall Prevalence of Irritable Bowel Syndrome.
Eric D SHAH ; Mark S RIDDLE ; Christopher CHANG ; Mark PIMENTEL
Journal of Neurogastroenterology and Motility 2012;18(2):200-204
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
4.Treatment of Cerebral Vasospasm in an Infant Using a Modified Dotter Technique.
Brian M SNELLING ; Samir SUR ; Sumedh S SHAH ; Eric C PETERSON
Journal of Cerebrovascular and Endovascular Neurosurgery 2017;19(1):48-51
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
5.Lower and Upper Gastrointestinal Symptoms Differ Between Individuals With Irritable Bowel Syndrome With Constipation or Chronic Idiopathic Constipation
Eric D SHAH ; Christopher V ALMARIO ; Brennan M R SPIEGEL ; William D CHEY
Journal of Neurogastroenterology and Motility 2018;24(2):299-306
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
6.Intraoperative aerosol box use: does an educational visual aid reduce contamination?
Garrett W. BURNETT ; George ZHOU ; Eric A. FRIED ; Ronak S. SHAH ; Chang PARK ; Daniel KATZ
Korean Journal of Anesthesiology 2021;74(2):158-164
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.
7.Intraoperative aerosol box use: does an educational visual aid reduce contamination?
Garrett W. BURNETT ; George ZHOU ; Eric A. FRIED ; Ronak S. SHAH ; Chang PARK ; Daniel KATZ
Korean Journal of Anesthesiology 2021;74(2):158-164
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.
8.Male Infertility: New Developments, Current Challenges, and Future Directions
Murat GÜL ; Giorgio Ivan RUSSO ; Hussein KANDIL ; Florence BOITRELLE ; Ramadan SALEH ; Eric CHUNG ; Parviz KAVOUSSI ; Taymour MOSTAFA ; Rupin SHAH ; Ashok AGARWAL
The World Journal of Men's Health 2024;42(3):502-517
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.
9.Global Practice Patterns and Variations in the Medical and Surgical Management of NonObstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations
Amarnath RAMBHATLA ; Rupin SHAH ; Imad ZIOUZIOU ; Priyank KOTHARI ; Gianmaria SALVIO ; Murat GUL ; Taha HAMODA ; Parviz KAVOUSSI ; Widi ATMOKO ; Tuncay TOPRAK ; Ponco BIROWO ; Edmund KO ; Mohamed ARAFA ; Ramy Abou GHAYDA ; Vilvapathy Senguttuvan KARTHIKEYAN ; Giorgio Ivan RUSSO ; Germar-Michael PINGGERA ; Eric CHUNG ; Ashok AGARWAL ;
The World Journal of Men's Health 2025;43(1):92-122
Purpose:
Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA.
Materials and Methods:
A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process.
Results:
Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12–19 IU/mL by 22.5% of participants and 20–40 IU/mL by 27.8%, while 31.8% reported no upper limit.
Conclusions
This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.
10.Global Practice Patterns and Variations in the Medical and Surgical Management of NonObstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations
Amarnath RAMBHATLA ; Rupin SHAH ; Imad ZIOUZIOU ; Priyank KOTHARI ; Gianmaria SALVIO ; Murat GUL ; Taha HAMODA ; Parviz KAVOUSSI ; Widi ATMOKO ; Tuncay TOPRAK ; Ponco BIROWO ; Edmund KO ; Mohamed ARAFA ; Ramy Abou GHAYDA ; Vilvapathy Senguttuvan KARTHIKEYAN ; Giorgio Ivan RUSSO ; Germar-Michael PINGGERA ; Eric CHUNG ; Ashok AGARWAL ;
The World Journal of Men's Health 2025;43(1):92-122
Purpose:
Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA.
Materials and Methods:
A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process.
Results:
Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12–19 IU/mL by 22.5% of participants and 20–40 IU/mL by 27.8%, while 31.8% reported no upper limit.
Conclusions
This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.