Publication Bias in Clinical Trials in Cataract Therapies: Implications for Evidence-Based Decision-Making: Publication Bias in Clinical Trials in Cataract Therapies.

ABSTRACT: Evidence-based decision-making is generally based on published evidence. Therefore, if the published evidence is biased, so will the decision-making. One possible bias is the "positive-results" publication bias. This study attempts to characterize this phenomenon in cataract therapy trials. Studies were categorized as "positive" if their results were congruent with the hypothesis and "negative" if not. Secondary outcomes included the influence of funding source and differences in publication metrics between "positive" and "negative" publications. The US NLM Clinical Trials database was reviewed for cataract trials, yielding 248 trials. Trials with less than 2 treatment arms, less than 5 participants, or insufficient reporting were excluded. Data was collected on intervention, treatment arms, funding type, publication rates, citation rate, and the impact factor/H-index of journals. Of the 132 trials included, there were 69 positive and 63 negative results. Publication rate for positive results (71%) was significantly greater than negative results (17%), (p<0.01), with no significant difference in the other publication metrics. In conclusion, "negative" result trials are published less frequently, but are equally valued, if published. There are implications for evidence-based medicine with these findings.

Evaluation of body mass index, ponderal index, visceral cross-sectional area, subcutaneous fat cross-sectional area, and liver volume as predictive factors for obesity-related comorbidities: a retrospective cohort study.

BACKGROUND: The body mass index (BMI) is an imperfect clinical measure of obesity that should be used in conjunction with other valid measures of weight-related risk. We studied whether there is a superior measure of obesity-related comorbidities. METHODS: Records of bariatric clinic patients who had an abdominal computed tomography (CT) within 1 year of visit were reviewed. The presence of obesity-related comorbidities was determined at the time of the scan. BMI and ponderal index (PI) were calculated, and CT scans were reviewed to determine the visceral cross-sectional area (VCSA), subcutaneous fat cross-sectional area (SFCSA), and liver volume (LV). Data were analyzed using the Kruskal-Wallis test and Mann-Whitney U test. RESULTS: A higher number of comorbidities were found to be associated with a larger BMI (P = .011), VCSA (P = .014), SFCSA (P = .007), and LV (P = .014), but not a larger PI (P = .11). Of the 16 comorbidities assessed, VCSA and LV were associated with more than BMI and SFCSA. However, each measure could be associated with different comorbidities. A higher BMI was associated with increased insulin use (P = .034), hypertension (P = .007), and history of obstructive sleep apnea (P = .015), none of which were associated with PI. BMI and PI were the only measures associated with a history of deep vein thrombosis/pulmonary embolism (both P < .01). Only SFCSA was found to be associated with gastroesophageal reflux disease (P = .029). VCSA (P = .038) and LV (P = .001) were associated with nonalcoholic fatty liver disease. CONCLUSION: No measure could account for all obesity-related comorbidities, implying the need for targeted measurements. However, PI was the least effective measure.

Publication Bias in Upper Gastrointestinal Oncology Clinical Trials.

PURPOSE: Evidence-based medicine requires evaluation of the medical literature to guide clinical reasoning and treatment recommendations. The presence of publication bias towards exclusion of non-statistically significant clinical trials may be leading to an incomplete evaluation of the literature and cause potentially incomplete guidance for patients. We aimed to compare publication rates and impact of publications of positive and negative outcome clinical trials. METHODS: We queried the US National Library of Medicine Clinical Trials database identifying clinical trials with reported results on the topics of pancreatic, liver, and gastric cancer. A "positive" trial was defined as having a statistically significant difference between the treatment arms, while a "negative" did not. Data collected included termination cause, intervention, funding type, publication rates, and journal characteristics. RESULTS: In total, 535 clinical trials were examined, across all pathologies clinical trials with significant findings for the primary outcome were published at a higher rate (99%) compared to those with non-significant findings (77%) (p < 0.01). Significantly, more studies with significant findings reached at least 80% of their estimated enrollment goal versus non-significant studies, 72% and 53% respectively (p < 0.01). Three of four metrics for impact of publication showed no difference between significant and non-significant studies once they reached publication. CONCLUSION: These findings suggest that clinical trials of three of the most common upper gastrointestinal malignancies have a publication bias towards studies with significant primary outcome findings. This study has implications to the way evidence-based medicine is practiced as the medical literature appears to be failing to capture important data for consideration of clinical decision making.

Examining surgeon stress in robotic and laparoscopic surgery.

Robotic surgery may decrease surgeon stress compared to laparoscopic. To evaluate intraoperative surgeon stress, we measured salivary alpha-amylase and cortisol. We hypothesized robotic elicited lower increases in surgeon salivary amylase and cortisol than laparoscopic. Surgical faculty (n = 7) performing laparoscopic and robotic operations participated. Demographics: age, years in practice, time using laparoscopic vs robotic, comfort level and enthusiasm for each. Operative data included operative time, WRVU (surgical "effort"), resident year. Saliva was collected using passive drool collection system at beginning, middle and end of each case; amylase and cortisol measured using ELISA. Standard values were created using 7-minute exercise (HIIT), collecting saliva pre- and post-workout. Linear regression and Student's t test used for statistical analysis; p values < 0.05 were significant. Ninety-four cases (56 robotic, 38 laparoscopic) were collected (April-October 2022). Standardized change in amylase was 8.4 ± 4.5 (p < 0.001). Among operations, raw maximum amylase change in laparoscopic and robotic was 23.4 ± 11.5 and 22.2 ± 13.4; raw maximum cortisol change was 44.21 ± 46.57 and 53.21 ± 50.36, respectively. Values normalized to individual surgeon HIIT response, WRVU, and operative time, showing 40% decrease in amylase in robotic: 0.095 ± 0.12, vs laparoscopic: 0.164 ± 0.16 (p < 0.02). Normalized change in cortisol was: laparoscopic 0.30 ± 0.44, robotic 0.22 ± 0.4 (p = NS). On linear regression (p < 0.001), surgeons comfortable with complex laparoscopic cases had lower change in normalized amylase (p < 0.01); comfort with complex robotic was not significant. Robotic may be less physiologically stressful, eliciting less increase in salivary amylase than laparoscopic. Comfort with complex laparoscopic decreased stress in robotic, suggesting laparoscopic experience is valuable prior to robotic.

Modern insights into the pathophysiology and treatment of pseudoachalasia.

BACKGROUND: Secondary achalasia or pseudoachalasia is a clinical presentation undistinguishable from achalasia in terms of symptoms, manometric, and radiographic findings, but associated with different and identifiable underlying causes. METHODS: A literature review was conducted on the PubMed database restricting results to the English language. Key terms used were "achalasia-like" with 63 results, "secondary achalasia" with 69 results, and "pseudoachalasia" with 141 results. References of the retrieved papers were also manually reviewed. RESULTS: Etiology, diagnosis, and treatment were reviewed. CONCLUSIONS: Pseudoachalasia is a rare disease. Most available evidence regarding this condition is based on case reports or small retrospective series. There are different causes but all culminating in outflow obstruction. Clinical presentation and image and functional tests overlap with primary achalasia or are inaccurate, thus the identification of secondary achalasia can be delayed. Inadequate diagnosis leads to futile therapies and could worsen prognosis, especially in neoplastic disease. Routine screening is not justifiable; good clinical judgment still remains the best tool. Therapy should be aimed at etiology. Even though Heller's myotomy brings the best results in non-malignant cases, good clinical judgment still remains the best tool as well.

Artificial Intelligence in Surgical Research: Accomplishments and Future Directions.

MINI-ABSTRACT: The study introduces various methods of performing conventional ML and their implementation in surgical areas, and the need to move beyond these traditional approaches given the advent of big data. OBJECTIVE: Investigate current understanding and future directions of machine learning applications, such as risk stratification, clinical data analytics, and decision support, in surgical practice. SUMMARY BACKGROUND DATA: The advent of the electronic health record, near unlimited computing, and open-source computational packages have created an environment for applying artificial intelligence, machine learning, and predictive analytic techniques to healthcare. The "hype" phase has passed, and algorithmic approaches are being developed for surgery patients through all stages of care, involving preoperative, intraoperative, and postoperative components. Surgeons must understand and critically evaluate the strengths and weaknesses of these methodologies. METHODS: The current body of AI literature was reviewed, emphasizing on contemporary approaches important in the surgical realm. RESULTS AND CONCLUSIONS: The unrealized impacts of AI on clinical surgery and its subspecialties are immense. As this technology continues to pervade surgical literature and clinical applications, knowledge of its inner workings and shortcomings is paramount in determining its appropriate implementation.

Effects of Spinal Deformities on Hiatal Hernia Occurrence and Recurrence.

BACKGROUND: Spinal deformities such as kyphosis, lordosis, and scoliosis have demonstrated a possible association between these deformities. Our hypothesis is that the presence of spinal deformities will increase the risk of hiatal hernia recurrence after repair. METHODS: The following data was retrospectively gleaned for patients undergoing hiatal hernia repair (1997-2022): age, sex, date of hiatal hernia repair, presence and type of spinal deformity, Cobb angle, type of hiatal hernia and size, type of hiatal hernia repair, recurrence and size, time to recurrence, reoperation, type of reoperation, and time to reoperation. RESULTS: Spinal deformities were present in 15.8% of 546 patients undergoing hiatal hernia repair, with a distribution of 21.8% kyphosis, 2.3% lordosis, 58.6% scoliosis, and 17.2% multiple. There was no difference in sex or age between groups. Spinal deformity patients were more likely to have types III and IV hiatal hernias (52.3% vs. 38.9%, p = 0.02) and larger hernias (median 5 [3-8] vs. 4 [2-6], p = 0.01). There was no difference in access, fundoplication use, or mesh use between groups. However, these patients had a higher recurrence rate (47.7% vs 30.0%, p = 0.001) and a shorter time to recurrence (months) (10.3 [5.6-25.1] vs 19.2 [9.8-51.0], p = 0.02). Cobb angle did not affect recurrence. CONCLUSIONS: Spinal deformity patients were more likely to have more complex and larger hiatal hernias. They were at higher risk of hiatal hernia recurrence after repair with shorter times to recurrence. This is a group that requires special attention with additional preoperative counseling and possibly use of surgical adjuncts in repair.

A neural network analysis of the effect of high and low frailty index indicators on predicting elective surgery discharge destinations.

BACKGROUND: Frailty is frequently used by clinicians to help determine surgical outcomes. The frailty index, which represents the frequency of frailty indicators present in an individual, is one method for evaluating patient frailty to predict surgical outcomes. However, the frailty index treats all indicators of frailty that are used in the index as equivalent. Our hypothesis is that frailty indicators may be divided into groups of high and low-impact indicators and this separation will improve surgical discharge outcome prediction accuracy. DATA AND METHODS: Population data for inpatient elective operations was collected from the 2018 American College of Surgeons National Surgical Quality Improvement Program Participant Use Files. Artificial neural network (ANN) models trained using backpropagation are used to evaluate the relative accuracy for predicting surgical outcome of discharge destination using a traditional modified frailty index (mFI) or a new joint mFI that separates high-impact and low-impact indicators into distinct groups as input variables. Predictions are made across nine possible discharge destinations. A leave-one-out method is used to indicate the relative contribution of high and low-impact variables. RESULTS: Except for the surgical specialty of cardiac surgery, the ANN model using distinct high and low-impact mFI indexes uniformly outperformed the ANN models using a single traditional mFI. Prediction accuracy improved from 3.4% to 28.1%. The leave-one-out experiment shows that except for the case of otolaryngology operations, the high-impact index indicators provided more support when determining surgical discharge destination outcomes. CONCLUSION: Frailty indicators are not uniformly similar and should be treated differently in clinical outcome prediction systems.

Novel Per-Oral Cricopharyngotomy for Cricopharyngeal Bar: Feasibility Study With Emphasis on Technical Limitations.

Per-oral endoscopic cricopharyngotomy (c-POEM) is a treatment for cricopharyngeal dysfunction, specifically cricopharyngeal bars (CPB). C-POEM differs from other endoscopic surgical procedures, such as per-oral endoscopic myotomy (POEM), gastric per-oral endoscopic myotomy (g-POEM), and Zenker per-oral endoscopic myotomy (z-POEM). We report three patients who underwent c-POEM for CPB, their clinical course, and outcomes. We underwent a single institution retrospective chart review of three patients who underwent c-POEM and their immediate postoperative course. These three patients represent all patients who underwent c-POEM. The operating surgeons were experienced endoscopists who regularly performed endoscopic myotomy. The three patients were female, over 50 years old, and presented with dysphagia secondary to the CPB. All three patients had perioperative complications consistent with esophageal leaks requiring prolonged hospital courses and recovery. All three patients had improved but persistent dysphagia up to nine months following the procedure. The results of this small case series exemplify the high rate of complications, specifically postoperative esophageal leak, when performing c-POEM for CPB. Thus, we stress caution and recommend against performing c-POEM for CPB.

LAPAROSCOPIC ANTIREFLUX SURGERY: ARE OLD QUESTIONS ANSWERED? MESH HERNIOPLASTY.

Hiatal hernias are at high risk of recurrence. Mesh reinforcement after primary approximation of the hiatal crura has been advocated to reduce this risk of recurrence, analogous to mesh repair of abdominal wall hernias. However, the results of such repairs have been mixed, at best. In addition, repairs using some type of mesh have led to significant complications, such as erosion and esophageal stricture. At present, there is no consensus as to (1) whether mesh should be used, (2) indications for use, (3) the type of mesh, and (4) in what configuration. This lack of consensus is likely secondary to the notion that recurrence occurs at the site of crural approximation. We have explored the theory that many, if not most, "recurrences" occur in the anterior and left lateral aspects of the hiatus, normally where the mesh is not placed. We theorized that "recurrence" actually represents progression of the hernia, rather than a true recurrence. This has led to our development of a new mesh configuration to enhance the tensile strength of the hiatus and counteract continued stresses from intra-abdominal pressure.

Voice Hoarseness with Reflux as a Suspected Etiology: Incidence, Evaluation, Treatment, and Symptom Outcomes.

PURPOSE: To describe the clinical evaluation course, treatments, and outcomes of patients with a primary complaint of hoarseness due to suspected laryngopharyngeal reflux (LPR). METHODS: A retrospective chart review was conducted of patients with a primary complaint of hoarseness with acid reflux as the suspected cause at a single institution between October 2011 and March 2020 who underwent clinical evaluation, treatment, and follow-up. Data collected included diagnostic procedures and treatments received, subjective symptom outcomes, and final diagnosis as determined by the treating physician. RESULTS: A total of 134 patients met the inclusion criteria. Videostroboscopy was the most performed procedure (n = 59, 44%) followed by endoscopy (n = 38, 28%) and pH monitoring (n = 28, 21%). Three patients were removed for statistical analysis of treatment differences and outcomes due to variant treatment plans. Most patients received sole medical management (n = 86, 66%), 7 patients received only voice therapy (5%), and 10 patients underwent surgical management (8%). Several patients received combined medical management and voice therapy (n = 21, 16%). Final diagnoses included gastroesophageal reflux disease (GERD) (25%), followed by multifactorial causes (17%) and dysphonia with unclear etiology (13%). Among all patients, 82 (61%) reported symptom improvement. Twenty-eight patients were diagnosed with LPR or LPR with GERD (21%), and 22 reported symptom improvement (79%). There was a statistically significant relationship between a final diagnosis with a reflux component and symptom improvement (p = .038). There was no statistically significant difference between treatment types and symptom outcomes both within the total patient population (p = .051) and patients diagnosed with a reflux condition (p = .572). CONCLUSION: LPR remains a difficult diagnosis to establish and represents a minority of patients with voice complaints. Despite varying evaluation and treatment modalities, most patients with LPR improved during their treatment and evaluation period without a clear association with any specific type of treatment. Further studies should explore diagnostic criteria for LPR, the necessary and efficient clinical evaluation to establish a diagnosis, and possible beneficial treatments.

Multi-society consensus conference and guideline on the treatment of gastroesophageal reflux disease (GERD).

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common diseases in North America and globally. The aim of this guideline is to provide evidence-based recommendations regarding the most utilized and available endoscopic and surgical treatments for GERD. METHODS: Systematic literature reviews were conducted for 4 key questions regarding the surgical and endoscopic treatments for GERD in adults: preoperative evaluation, endoscopic vs surgical or medical treatment, complete vs partial fundoplication, and treatment for obesity (body mass index [BMI] ≥ 35 kg/m2) and concomitant GERD. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Recommendations for future research were also proposed. RESULTS: The consensus provided 13 recommendations. Through the development of these evidence-based recommendations, an algorithm was proposed for aid in the treatment of GERD. Patients with typical symptoms should undergo upper endoscopy, manometry, and pH-testing; additional testing may be required for patients with atypical or extra-esophageal symptoms. Patients with normal or abnormal findings on manometry should consider undergoing partial fundoplication. Magnetic sphincter augmentation or fundoplication are appropriate surgical procedures for adults with GERD. For patients who wish to avoid surgery, the Stretta procedure and transoral incisionless fundoplication (TIF 2.0) were found to have better outcomes than proton pump inhibitors alone. Patients with concomitant obesity were recommended to undergo either gastric bypass or fundoplication, although patients with severe comorbid disease or BMI > 50 should undergo Roux-en-Y gastric bypass for the additional benefits that follow weight loss. CONCLUSION: Using the recommendations an algorithm was developed by this panel, so that physicians may better counsel their patients with GERD. There are certain patient factors that have been excluded from included studies/trials, and so these recommendations should not replace surgeon-patient decision making. Engaging in the identified research areas may improve future care for GERD patients.