metamedian: An R package for meta-analyzing studies reporting medians.

When performing an aggregate data meta-analysis of a continuous outcome, researchers often come across primary studies that report the sample median of the outcome. However, standard meta-analytic methods typically cannot be directly applied in this setting. In recent years, there has been substantial development in statistical methods to incorporate primary studies reporting sample medians in meta-analysis, yet there are currently no comprehensive software tools implementing these methods. In this paper, we present the metamedian R package, a freely available and open-source software tool for meta-analyzing primary studies that report sample medians. We summarize the main features of the software and illustrate its application through real data examples involving risk factors for a severe course of COVID-19.

Robust rank-based meta-analyses for two-sample designs with application to platelet counts of malaria infection data.

In this paper, we propose robust meta-analysis procedures for individual studies that report a broad range of robust summary statistics for a two-sample problem. Summary statistics of individual studies could be presented in different forms including full data, medians of the two samples, the Hodges-Lehman and Wilcoxon estimates of the location shift parameters. Data synthesis is made under both fixed-effect and random-effect meta-analysis models. We systematically compare these robust meta-analysis procedures via simulation studies to meta-analysis procedure based on sample means and variances from individual studies under a wide range of error distributions. We show that the coverage probabilities of the robust meta-analysis confidence intervals are quite close to the nominal confidence level. We also show that mean square error (MSE) of the robust meta-analysis estimator is considerably smaller than that of the non-robust meta-analysis estimator under the contaminated normal, heavy tailed and skewed error distributions. The robust meta-analysis procedures are then applied to platelet count reduction for malaria infected patients in Ghana.

Models for cluster randomized designs using ranked set sampling.

Cluster randomized designs (CRD) provide a rigorous development for randomization principles for studies where treatments are allocated to cluster units rather than the individual subjects within clusters. It is known that CRDs are less efficient than completely randomized designs since the randomization of treatment allocation is applied to the cluster units. To mitigate this problem, we embed a ranked set sampling design from survey sampling studies into CRD for the selection of both cluster and subsampling units. We show that ranking groups in ranked set sampling act like a covariate, reduce the expected mean squared cluster error, and increase the precision of the sampling design. We provide an optimality result to determine the sample sizes at cluster and sub-sample level. We apply the proposed sampling design to a dental study on human tooth size, and to a longitudinal study from an education intervention program.

Pneumatic Dilation in Geriatric Achalasia Patients.

BACKGROUND: The aim of the study was to share the effectiveness of pneumatic dilation in geriatric achalasia patients. METHODS: Achalasia patients over the age of 65 and those under the age of 65 as the control group who received pneumatic dilation as the first-line treatment were evaluated in the study. RESULTS: The average age of geriatric patients was 72.5 ± 55.92 years (65-90), with 50.3% of them being male. Follow-up was conducted for a mean of 64.52 ± 38.73 months. While pneumatic dilation was successful in 98.6% (141/143) of geriatric patients, it was also successful in 94% (141/150) of non-geriatric patients. Remission after single balloon dilatation was observed in 81.8% of geriatric patients, while it was observed in only 52.7% of non-geriatric patients (P = .000). When comparing remission after single dilatation and multiple dilatations, it was observed that geriatric patients who achieved remission after multiple balloon dilatation had higher lower esophageal sphincter pressure and Eckardt scores at the diagnosis and higher lower esophageal sphincter pressure and esophageal body resting pressures after the first balloon dilatation. CONCLUSIONS: The proportion of elders in the world population is increasing daily and this disease has been known to disproportionately afflict this group. Although surgical treatments, in particular per-oral endoscopic myotomy, have recently gained popularity as therapies for achalasia, pneumatic dilation remains the most commonly used in geriatric patients.

Performance of indirect immunofluorescence test and immunoblot tests in the evaluation of antinuclear and antimitochondrial antibodies.

BACKGROUND: Antinuclear antibodies (ANA) and antimitochondrial antibodies (AMA) have essential markers for the diagnosis of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). These autoantibodies are detecting different laboratory methods. In this study, we studied the diagnostic performance of used methods in detecting ANA and AMA. METHODS: The autoantibody profiles of patients with AIH and PBC groups were analyzed with the indirect immunofluorescence test (IIF) and liver-specific antigens containing immunoblot test (IB). RESULTS: There were 45 (87%) women in the study group and 8 (53%) women in the control group. The mean age of the patients was 50.5 ± 14.21 years old. The serum ALT and AST levels were higher in AIH, and ALP, GGT, and Ig M were higher in PBC. IIF test results among AIH/PBC groups; there was no difference in overall ANA positivity (p: 0.078). AMA was negative in all patients with AIH but positive in 83.3% of patients with PBC. IB test results among AIH/PBC groups; antibodies against PDGH, LKM-1, and Scl-70 were not observed in any patient with AIH/PBC. Except for M2 (p: 0.001) and M23E (p: 0.007) antibodies, there was no significant difference in antibodies between groups. Out of five PBC patients with negative AMA by IIF method, one was positive for AMA-M2, two were positive anti-gp210, and three were positive anti-M2-3E, but anti-sp100 was negative in all of them by the IB. DISCUSSION: AIH/PBC has complex associations with different autoantibodies, and some of these antibodies are not readily detected by the IIF test. IB assays with a wide variety of liver-specific antigens may be helpful in the diagnosis (especially in patients with AMA negative PBC) and follow-up in AIH/PBC patients.

Relationship Among Helicobacter Pylori, Lower Esophagus Sphincter Pressure, and Gastroesophageal Reflux: A Single-Center Experience.

Objectives: The aim of the study was to evaluate the relationship among lower esophageal sphincter pressure (LESP), Helicobacter pylori (Hp), and gastroesophageal reflux (GER). Methods: The retrospective study included patients with isolated hypertensive or hypotensive lower esophageal sphincter (LES) who underwent esophageal manometry in our gastroenterology motility laboratory and had normal manometry results. Demographic characteristics, complaints on admission, upper endoscopy findings, 24-h esophageal pH monitoring results, and presence of Hp in gastric biopsy were evaluated. Results: A total of 1226 patients were included in the study, among whom women comprised 54% of all patients. Mean age was 45.4±13.4 years. Most common presenting complaint was pyrosis (85.4%). Pathological reflux was detected in 61.4% of the patients in 24-h esophageal pH monitoring. Reflux esophagitis was detected in 22.9% and LES laxity was present in 17.4% of the patients. In gastric biopsy, Hp was positive in 40% of the patients. The age of patients with hypertensive LES was significantly higher and female gender and body mass index (BMI) were associated with hypertensive LES. Pyrosis was significantly less prevalent in patients with hypertensive LESP. Esophagitis and LES laxity were significantly more prevalent in patients with hypotensive LES. No significant difference was found among the three groups with regard to reflux and Hp positivity. No significant difference was found between Hp-positive and Hp-negative groups with regard to reflux and reflux esophagitis. Conclusion: No clear relationship was found among LES disorders, GER, and Hp. Moreover, no significant difference was found among LES disorders with regard to GER, while the presence of hypotensive LESP, rather than Hp, was found to be an important factor in the development of reflux esophagitis.

The Relationship Between Achalasia and Esophageal Cancer: The Experience of a Tertiary Center.

OBJECTIVE: We examined the prevalence of esophageal cancer in 828 patients diagnosed with achalasia and the characteristics of patients who developed esophageal cancer. MATERIAL AND METHODS: The demographic characteristics and medical records of the patients who were followed up with a diagnosis of achalasia between 1995 and 2019 were investigated from the patient files. RESULTS: The mean age of the patients was 51 ± 17.3, 390 of them were males (47.1%) and 438 were females (52.9%). The mean diagnosis age of the patients was 45.4 years. The median follow-up duration of the patients was 73 months (12-480). Esophageal cancer developed in 5 patients (0.6%) during follow-up. Three of these 5 patients had squamous cell carcinoma (60%) and 2 had adenocarcinoma (40%). Three of these patients were males (60%) and 2 were females (40%). The mean age of the patients was 68 (56-78), and cancer developed after a median of 156 months (24-216) after the achalasia diagnosis. Balloon dilation therapy was performed for the treatment of achalasia in all 5 patients who developed esophageal cancer. CONCLUSION: Achalasia patients have an increased risk of developing esophageal cancer compared to the general population, and patients should be followed closely for cancer development.

Using combined environmental-clinical classification models to predict role functioning outcome in clinical high-risk states for psychosis and recent-onset depression.

BACKGROUND: Clinical high-risk states for psychosis (CHR) are associated with functional impairments and depressive disorders. A previous PRONIA study predicted social functioning in CHR and recent-onset depression (ROD) based on structural magnetic resonance imaging (sMRI) and clinical data. However, the combination of these domains did not lead to accurate role functioning prediction, calling for the investigation of additional risk dimensions. Role functioning may be more strongly associated with environmental adverse events than social functioning. AIMS: We aimed to predict role functioning in CHR, ROD and transdiagnostically, by adding environmental adverse events-related variables to clinical and sMRI data domains within the PRONIA sample. METHOD: Baseline clinical, environmental and sMRI data collected in 92 CHR and 95 ROD samples were trained to predict lower versus higher follow-up role functioning, using support vector classification and mixed k-fold/leave-site-out cross-validation. We built separate predictions for each domain, created multimodal predictions and validated them in independent cohorts (74 CHR, 66 ROD). RESULTS: Models combining clinical and environmental data predicted role outcome in discovery and replication samples of CHR (balanced accuracies: 65.4% and 67.7%, respectively), ROD (balanced accuracies: 58.9% and 62.5%, respectively), and transdiagnostically (balanced accuracies: 62.4% and 68.2%, respectively). The most reliable environmental features for role outcome prediction were adult environmental adjustment, childhood trauma in CHR and childhood environmental adjustment in ROD. CONCLUSIONS: Findings support the hypothesis that environmental variables inform role outcome prediction, highlight the existence of both transdiagnostic and syndrome-specific predictive environmental adverse events, and emphasise the importance of implementing real-world models by measuring multiple risk dimensions.

The Efficacy of Biofeedback Therapy in Patients with Solitary Rectal Ulcer and Dyssynergic Defecation.

BACKGROUND: The treatment of solitary rectal ulcer (SRU) is challenging and controversial; generally, no response to conventional treatments can be obtained, particularly in patients with dyssynergic defecation (DD). We assessed the efficiency of biofeedback therapy (BFT) in patients who did not respond to conservative treatments and had coexistence of SRU and DD. METHODS: BFT responses, as well as anorectal manometry and rectoscopy results of 20 patients with the coexistence of SRU and DD, were assessed. RESULTS: Mean age was 32.5 years. Of the patients, 12 were female, and 8 of them were male. An average of 12 sessions of BFT was performed on the patients. Ulcer disappeared in 11 patients (55%) after BFT, and the ulcer size decreased in 3 patients (15%). However, ulcers healed in 9 (90%) of 10 patients whose DD pattern disappeared following BFT, and ulcers healed in only 20% of patients whose DD pattern continued (p = 0.005). The change in anal resting pressure after BFT was significant (p = 0.016). Ulcers were healed in 87.5% (7/8) of the patients whose anal resting pressure decreased after BFT and whose DD disappeared, while ulcers remained untreated in 85.7% of the patients whose anal resting pressure decreased, but the DD pattern continued (p = 0.005). CONCLUSIONS: SRU patients with DD are typically unresponsive to medical treatments. Ameliorating anorectal dyssynergia should be the priority of treatment in these patients. BFT is an effective treatment for DD. BFT enhances the healing of ulcers in patients with SRU by restoring coordination of the pelvic floor.

Unstable Belief Formation and Slowed Decision-making: Evidence That the Jumping-to-Conclusions Bias in Schizophrenia Is Not Linked to Impulsive Decision-making.

BACKGROUND: Jumping-to-conclusions (JTC) is a prominent reasoning bias in schizophrenia (SCZ). While it has been linked to not only psychopathological abnormalities (delusions and impulsive decision-making) but also unstable belief formation, its origin remains unclear. We here directly test to which extend JTC is associated with delusional ideation, impulsive decision-making, and unstable belief formation. METHODS: In total, 45 SCZ patients were compared with matched samples of 45 patients with major depressive disorder (MDD) and 45 healthy controls (HC) as delusions and JTC also occur in other mental disorders and the general population. Participants performed a probabilistic beads task. To test the association of JTC with measures of delusions (Positive and Negative Syndrome Scale [PANSS]positive, PANSSpositive-factor, and Peter Delusions Inventory [PDI]), Bayesian linear regressions were computed. For the link between JTC and impulsive decision-making and unstable beliefs, we conducted between-group comparisons of "draws to decision" (DTD), "decision times" (DT), and "disconfirmatory evidence scores" (DES). RESULTS: Bayesian regression obtained no robust relationship between PDI and DTD (all |R2adj| ≤ .057, all P ≥ .022, all Bayes Factors [BF01] ≤ 0.046; α adj = .00833). Compared with MDD and HC, patients with SCZ needed more time to decide (significantly higher DT in ambiguous trials: all P ≤ .005, r2 ≥ .216; numerically higher DT in other trials). Further, SCZ had unstable beliefs about the correct source jar whenever unexpected changes in bead sequences (disconfirmatory evidence) occurred (compared with MDD: all P ≤ .004 and all r2 ≥ .232; compared with HC: numerically higher DES). No significant correlation was observed between DT and DTD (all P ≥ .050). CONCLUSIONS: Our findings point toward a relationship of JTC with unstable belief formation and do not support the assumption that JTC is associated with impulsive decision-making.

Role of hepatosteatosis in HBsAg seroconversion in HBeAg-negative chronic hepatitis B patients.

BACKGROUND: In chronic Hepatitis B virus (HBV) infection, certain individual and viral characteristics such as advanced age, presence of hepatic steatosis (HS), normal ALT levels, initially negative HBeAg and HBV DNA, and genotype of the virus are associated with HBsAg seroclearance and seroconversion. Herein, we report the results of our study evaluating the association between hepatosteatosis and HbsAg seroconversion. METHODS: The clinical and biochemical data of patients with CHB and hepatosteatosis (HS) (HBsAg seroconversion, n:52, and non-HbsAg seroconversion, n:352), and the rate of development of HBsAg seroconversion were evaluated. RESULTS: We collected data from 404 patients with HBeAg negative CBH (mean age ± SD: 36.2 ± 11 years; 223 [55.2%] men, 181 [44.8%] women). The mean age at diagnosis of disease was 36.2 ± 11 years. The mean duration of the disease was 10.6 ± 7 years. Seroconversion developed in 52 patients (12.8%) with serum HBsAg positive (mean ± SD: 12.7 ± 5.8). Elderly age and the duration of disease time were significantly associated with seroconversion (P < .001). The presence of serum HBsAg seroconversion was significantly associated with hepatosteatosis (OR: 3.06, 95% CI 1.64-5.71, P < .01). Serum HBsAg seroconversion was more frequent in patients with mild HS than patients with moderate-severe HS (P = .04). In multivariate regression analysis, the presence of HS was found to be an independent factor predicting the development of HBsAg seroconversion (OR: 2.07 95% GA:1.07-4.0 P = .03). CONCLUSION: The presence of mild HS in HBeAg negative chronic hepatitis B patients contributes to HBsAg seroconversion. Further studies are required to better understand the relationship between steatosis and HBsAg seroconversion.

The Efficacy of Biofeedback Treatment in Patients with Fecal Incontinence.

BACKGROUND: The initial treatment for fecal incontinence (FI) includes supportive treatment and medical treatment. If the initial treatment fails, biofeedback therapy (BFT) is recommended. However, there are limited and conflicting results in the literature supporting the beneficial effect of BFT for FI. The aim of the study is to analyze the efficacy of BFT in 126 patients who have FI due to several causes. METHODS: The data of 126 patients (88 females (69.8%) and 38 males (30.2%)) were collected retrospectively. Colonoscopy, anorectal manometry (ARM), and 3D-Endoanal ultrasonography (EAUS) were performed for all patients before applying BFT. In addition, all patients received toilet training instruction and training in Kegel and other pelvic floor strengthening exercises from an experienced nurse, before BFT. RESULTS: The median age of participants was 54 years (range 18-75 years). While 80 patients (63.5%) had clinical and manometric benefit from BFT, 46 patients (36.5%) did not respond to BFT. According to the EAUS and ARM findings, BFT was beneficial in patients who had partial external sphincter failure, and was unsuccessful in patients who had both internal and external sphincter failure, both internal and external sphincter tears, and external sphincter tear rates of more than 25%. After BFT, significant increases in squeeze pressures were observed, with this increase being higher in the positive-response group. CONCLUSION: The results suggest that BFT is effective in the treatment of FI for specific patient populations.

One-year real life data of our patients with moderate-severe Crohn's disease who underwent ustekinumab therapy.

AIM: The aim of this study was to present one-year real-life data of our patients with CD who showed unresponsiveness and/or intolerance to biological agents and then received ustekinumab treatment through an early access program. MATERIALS AND METHODS: The retrospective study reviewed the 52-week clinical data of 10 patients with moderate or severe CD who underwent ustekinumab therapy. RESULTS: The 10 patients comprised 7 (70%) men and 3 (30%) women with a mean age of 38 ± 11.3 years. Mean disease duration was 13.5 ± 8.5 years. Mean pretreatment CDAI score was 273.5 ± 92 and mean pretreatment HBI score was 11.6 ± 3.8. At the end of the 8-week intravenous induction treatment, 5 (55%) patients showed clinical remission according to the CDAI and HBI scores. Additionally, 62.5% of the patients were in clinical remission at the end of week 52 according to the CDAI and HBI scores. No drug-related side effects were observed in any patient throughout the treatment. CONCLUSION: Ustekinumab appears to be effective and safe in the treatment of moderate and severe CD, particularly in cases of unresponsiveness and intolerance to biological agents such as anti-TNF, and in the achievement of clinical remission.

Comprehensive assessment of levodopa-carbidopa intestinal gel for Turkish advanced Parkinson's disease patients

Background/aim: Levodopa-carbidopa intestinal gel (LCIG) is an effective treatment modality in the management of advanced Parkinson's disease (PD) despite frequent adverse events and different rates of dropouts. Efficacy and safety data regarding Turkish patients on LCIG are limited. This study aims to report in detail the efficacy and adverse effect profile of LCIG among advanced PD patients from a Turkish center for movement disorders. Materials and methods: Twenty-two patients (50% male) who started receiving LCIG between December 2014 and March 2020 were recruited. The efficacy of LCIG was assessed with the Unified Parkinson's Disease Rating Scale (UPDRS III), Clinical Global Improvement (CGI) scale, and Quality of Life scale (PDQ8). Improvements in gait disorders and nonmotor features were also questioned. Adverse events (AE) were collated into 3 topics: related to percutaneous endoscopic gastrojejunostomy (PEG-J), device-related, and LCIG infusion-related. Results: Mean age and pre-LCIG disease duration were 66.7 (8.8) and 13.3 (8.0) years respectively. UPDRS III scores and H-Y scale assessments significantly improved. Better quality of life scores, clinical global improvements, and improvements in dysarthria, dysphagia, and gait were observed. None of our patients dropped out or died during a mean 17.5-month (12.3) period. Overall 20 (90.9%) patients experienced at least one AE. Twelve patients had PEG-J­related complications; three had acute abdomen. Eight (36.4%) patients had device-associated problems. Half of the patients required at least one additional endoscopic procedure and 7 had a device replaced. Mean body weight decreased from 69.5 to 62.5 kg and seven patients had newly onset PNP at a follow-up electromyography. Dyskinesia related to LCIG infusion was observed in 5 (22.7%) patients. There was no significant increase in hallucination among patients. Conclusion: LCIG is an efficient treatment modality in the management of Turkish patients with advanced Parkinson's disease. Although most of the patients had at least one AE, none of them dropped out. Patient selection, patient compliance, and collaborative management are important steps affecting the success of modality.

Meta-analysis of quantile intervals from different studies with an application to a pulmonary tuberculosis data.

After the completion of many studies, experimental results are reported in terms of distribution-free confidence intervals that may involve pairs of order statistics. This article considers a meta-analysis procedure to combine these confidence intervals from independent studies to estimate or construct a confidence interval for the true quantile of the population distribution. Data synthesis is made under both fixed-effect and random-effect meta-analysis models. We show that mean square error (MSE) of the combined quantile estimator is considerably smaller than that of the best individual quantile estimator. We also show that the coverage probability of the meta-analysis confidence interval is quite close to the nominal confidence level. The random-effect meta-analysis model yields a better coverage probability and smaller MSE than the fixed-effect meta-analysis model. The meta-analysis method is then used to synthesize medians of patient delays in pulmonary tuberculosis diagnosis in China to provide an illustration of the proposed methodology.