Evaluation of Alternative Treatment Strategies for Bile Acid Malabsorption in Inflammatory Bowel Disease Patients: A Network Meta-Analysis.

Background: Bile acid malabsorption (BAM) is characterized by chronic watery diarrhea resulting from excessive bile acids in the feces. BAM is often an overlooked cause of chronic diarrhea, with its prevalence not being sufficiently researched. This review aimed to assess existing literature that explores diverse treatment strategies, to review the published studies that examine the various therapies for BAM patients, emphasizing their influence on clinical results. Methods: We conducted a comprehensive review of various databases, including PubMed, Scopus, Web of Science, Cochrane Database, and EMBASE. Our criteria for inclusion focused on randomized controlled studies (RCTs) that evaluated the effectiveness of different treatment options for patients with BAM. To rank the treatments, we adopted the frequentist approach through the "netrank" function of the network meta-analysis (NMA). Moreover, we utilized the "netsplit" function in the NMA to separate direct and indirect evidence. Our analysis was carried out using RStudio version 1.4.1717 (2009 - 2021 RStudio, Inc.), and we used the "netmeta" and "meta" packages for NMA. Results: We found seven relevant articles involving 213 participants, the average age being approximately 50 years, including 53 males and 92 females. Of the drugs examined, tropifexor was proved to be the most effective in raising the fibroblast growth factor 19 (FGF19) levels and reducing the 7 alpha-hydroxy-4-cholesten-3-one (C4) levels, compared to the placebo (mean difference (MD) = 335.30, 95% confidence interval (CI) (334.86, 335.74), MD = -24.60, 95% CI (-25.37, -23.83); respectively). Compared to colesevelam and the placebo, liraglutide was more efficient in decreasing fecal bile acid concentration (liraglutide; MD = -19, 95% CI (-37.61, -0.39)). Conclusions: Tropifexor has been identified as the most successful medication in mitigating BAM symptoms. To ensure more accurate results, there is a need for randomized controlled clinical trials that involve a larger participant pool.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response in adults with predominantly antibody deficiency.

Background: Patients with predominantly antibody deficiency (PAD) have lower anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibody levels after initial 2-dose SARS-CoV-2 vaccination than healthy controls do; however, the anti-spike antibody responses and neutralization function in patients with PAD following subsequent immunizations remain understudied. Objective: We sought to characterize anti-spike antibody responses in adults with PAD over the course of 5 SARS-CoV-2 vaccine doses and identify diagnostic and immunophenotypic risk factors for low antibody response. Methods: We evaluated anti-spike antibody levels in 117 adult patients with PAD and 192 adult healthy controls following a maximum of 5 SARS-CoV-2 immunizations. We assessed neutralization of the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant and analyzed infection outcomes. Results: The patients with PAD had significantly lower mean anti-spike antibody levels after 3 SARS-CoV-2 vaccine doses than the healthy controls did (1,439.1 vs 21,890.4 U/mL [P < .0001]). Adults with secondary PAD, severe primary PAD, and high-risk immunophenotypes had lower mean anti-spike antibody levels following vaccine doses 2, 3, and/or 4 but not following vaccine dose 5. Compared with patients with mild and moderate PAD, patients with severe PAD had a higher rate of increase in anti-spike antibody levels over 5 immunizations. A strong positive correlation was observed between anti-spike antibody levels and neutralization of both the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant. Most infections were managed on an outpatient basis. Conclusions: In all of the patients with PAD, anti-spike antibody levels increased with successive SARS-CoV-2 immunizations and were correlated with neutralization of both the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant. Secondary PAD, severe primary PAD, and high-risk immunophenotypes were correlated with lower mean anti-spike antibody levels following vaccine doses 2 through 4. Patients with severe PAD had the highest rate of increase in anti-spike antibody levels over 5 immunizations. These data suggest a clinical benefit to sequential SARS-CoV-2 immunizations, particularly among high-risk patients with PAD.

Transvenous Compared With Leadless Pacemakers: A meta-analysis comparing TP versus LP.

This study aims to compare the effectiveness of leadless pacemakers (LPs) and transvenous pacemakers and to examine the safety of both methods. We included patients undergoing single-chamber pacemaker implantation, either LP or TVP. Our outcomes were successful implantation rate, major complication, vascular injury, tamponade, and pneumothorax. We performed a double-arm analysis comparing LP versus TVP, with risk ratio (RR) and 95% confidence interval. A total of 10 studies were included in this meta-analysis. Regarding efficacy endpoints, RR revealed no significant difference between the LP and transvenous pacemaker groups in terms of successful rate of implantation (RR = 1.00; P = 0.77). Regarding safety outcomes, LP experienced lower incidence of major complications (RR = 0.47; P = 0.01), infection (RR = 0.24; P = 0.001), and tamponade (RR = 0.36; P = 0.01). There was no significant difference between both groups regarding pneumothorax (RR = 0.35; P = 0.22) and vascular injury (RR = 1.55; P = 0.25). The study findings suggest that both LPs and TVPs have similar effectiveness. Moreover, the incidences of pneumothorax, vascular injuries, and major complications were found to be comparable between the 2 methods. However, LPs were found to have lower rates of infection and tamponade.

Efficacy and Safety of Rifaximin in the Prevention of Recurrent Episodes of Hepatic Encephalopathy: A Systematic Review and Meta-analysis.

BACKGROUND: Rifaximin is an oral antimicrobial drug with a broad-spectrum effect. It locally regulates the function and structure of intestinal bacteria and decreases intestinal endotoxemia. We aimed to investigate the preventive role of rifaximin in recurrent episodes of hepatic encephalopathy in cases with a history of hepatic diseases. METHODS: We searched PubMed, Scopus, and Web of Science for the relevant studies using the following search strategy: "(Rifaximin) OR (Xifaxan) AND (cirrhosis) OR (encephalopathy)." We assessed the risk of bias using Cochrane's risk of bias tool. We included the following outcomes: recurrence of hepatic encephalopathy, adverse events, mortality rate, and time to the first episode of hepatic encephalopathy from the time of randomization (days). We performed the analysis of homogeneous data under the fixed-effects model, while analysis of heterogeneous data was performed under the random-effects model. RESULTS: We analyzed data obtained from 999 patients from 7 included trials. The overall risk ratio proved that the rifaximin group was associated with a lower recurrence rate than the control group (risk ratio [RR] = 0.61[0.50, 0.73], P = .001). We found no significant variation in both groups regarding adverse events (RR = 1.08 [0.89, 1.32], P = .41), and mortality rates (RR = 0.98 [0.61, 1.57], P = .93). The overall risk of bias results was low. CONCLUSION: The meta-analysis showed that in patients allocated to the rifaximin group, the incidence rate of hepatic encephalopathy was significantly lower when compared with those in the control group with no difference in both groups regarding adverse events and mortality rates.

Evaluation of the Safety and Efficacy of Dual Therapy Perindopril/Amlodipine in the Management of Hypertension. A Systematic Review and Meta-Analysis.

INTRODUCTION: Hypertension represent the commonest cause of death in 2017. Hypertension is classified into two types which are primary or essential hypertension and secondary hypertension. The perindopril-amlodipine combination showed a significant effect in reduction of the elevated BP and the cardiovascular complications. AIM: To evaluate the efficacy and safety of a fixed-dose single-pill combination of perindopril-amlodipine in hypertensive patients. METHODS: We searched PubMed, Medline, SCOPUS, and Web of Science for relevant clinical trials. Quality appraisal was evaluated according to GRADE and we assessed the risk of bias using Cochrane's risk of bias tool. We included the following outcomes: systolic blood pressure, diastolic blood pressure, pulse pressure, mean blood pressure, heart rate, cough, dizziness, headache, and peripheral edema. We performed the analysis of homogeneous data under the fixed-effects model, while analysis of heterogeneous data was analyzed under the random-effects model. We conducted a meta-regression according to the dose. RESULTS: We included ten clinical trials. The pooled analysis showed that there was a significant reduction of the systolic blood pressure, diastolic blood pressure, pulse plessure, mean blood pressure, and heart rate after the the perindopril-amlodipine combination (MD = 18.96 [14.32, 23.60], P < 0.0001), (MD = 11.90 [8.45, 15.35], P < 0.0001), (MD = 8.44 [6.91, 9.97], P = 0.0001), (MD = 13.07 [5.86, 20.29], P = 0.0004), and (MD = 2.93 [0.89, 4.96], P = 0.005), respectively. The results of the meta-regression revealed that the efficacy is increased by increasing the dose (P < 0.001) CONCLUSION: The use of the perindopril-amlodipine combination had a significant effect on the reduction of SBP, DBP, mean blood pressure, pulse pressure, and HR.

Impact of sustained virologic response in regression of portal hypertension in Egyptian patients with hepatitis C virus-associated cirrhosis and portal hypertension.

Background: Portal hypertension (PH) is a common consequence in hepatitis C virus cirrhotic patients. With interferon alpha-based therapy, SVR was linked to improved PH and fibrosis regression. SVR to oral antiviral regimens is linked to reduced portal pressure in patients with clinically significant portal hypertension (CSPH) at baseline. However, CSPH continues in most of the patients. This study aims to assess the reversibility and/or improvement of PH in Egyptian patients with HCV-related cirrhosis and CSPH after achieving SVR with DAAs. The second aim is to evaluate performance of the noninvasive markers of fibrosis in prediction of the presence and/or reversibility of the CSPH in correlation to radiological and endoscopic parameters. Subjects and methods: We evaluated noninvasive parameters, radiological and endoscopic signs of PH at baseline, and/or SVR 24 and SVR 48 post-DAA therapy in 40 patients with cirrhosis and CSPH (group A) and another 40 patients with cirrhosis only (group B). Results: In group A, the spleen diameter decreased from baseline (15.74 ± 1.53 cm), and SVR 24 (15.48 ± 1.51), to SVR 48 (15.35 ± 1.49 cm). No ascites detected at SVR 48 in 62.5%. Portal vein diameter and portal vein blood velocity reduced to 13.53 ± 1.07 mm and 14.14 ± 2.2 cm/s at SVR 48, with reversibility of hepatic vein waveform towards the triphasic pattern. Medium to large esophageal varices regressed from 52.5% to 2.5%, and up to 70% of patients showed no EVs at SVR 48. In group A, 24 patients showed complete reversibility of CSPH, and 16 patients showed improvement of CSPH. Child-Pugh score, FIB-4 index, King's score, and Lok index revealed higher significance for detection of the presence of PH. Child-Pugh score, PC/SD ratio, and Lok index revealed higher significance for detection of reversibility of PH. Conclusion: We concluded that CSPH improved after SVR with DAAs and completely regressed in some patients. Upon predicting the presence of PH, Child-Pugh score, FIB-4 index, King's score, and Lok index were the most significant noninvasive scores. While for predicting the reversibility of PH, Child-Pugh score, PC/SD ratio, and Lok index were the most significant scores.

Efficacy of Single-Pill, Triple Antihypertensive Therapy in Patients with Uncontrolled Hypertension: A Systematic Review and Meta-analysis.

INTRODUCTION: Systemic arterial hypertension is the most common preventable risk factor for all causes of morbidity and mortality worldwide with a prevalence of 35-40% of the adults. Despite the wide variety of effective antihypertensive medications, most hypertensive patients remain uncontrolled. However, the combination of ACE inhibitor, diuretics, and calcium antagonist for the triple therapy in a single Pill Combination (SPC) is an efficient regimen in hypertension management. It is recommended by the ESH 2018 guideline, which offers better efficacy and compliance to treatment. AIM: To evaluate the efficacy of perindopril/indapamide/amlodipine single-pill combination in patients with uncontrolled hypertension. METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL for relevant clinical trials. We conducted the risk of bias assessment using Cochrane's risk of bias tool. We performed the analysis of continuous data using mean difference (MD) and relative 95% confidence interval (CI), while dichotomous data were analyzed using risk ratio (RR) and relative 95% CI. We included the analysis of the following outcomes: systolic blood pressure (SBP), Diastolic blood pressure (DBP), Heart rate (HR), 24 h Ambulatory blood pressure monitoring (ABPM) for SBP, and 24 h ABPM for DBP. RESULTS: We included six clinical trials. We found that the triple therapy significantly reduces SBP by 24 mmHg (MD = - 24.65 [22.41, 26.89], (P < 0.01)), DBP by 12 mmHg (MD = 12.41 [11.53, 13.29], (P < 0.01)), 24-h ABPM for SBP by 14 mmHg (MD = 14.08 [9.10, 19.05], (P < 0.01)), and ABPM 24 h DBP by 7 mmHg (MD = 7.01 [5.37, 8.65], (P < 0.01)). We noted no significant difference of the single pill on heart rate (MD = 0.81 [- 0.04, 1.67], (P = 0.06). CONCLUSION: perindopril/indapamide/amlodipine is effective in reducing systolic and diastolic blood pressures by 24 and 12 mmHg respectively. Over 24 h, the combination reduced systolic and diastolic blood pressures by 14 and 7 mmHg respectively.

KAP-COVIDGLOBAL: a multinational survey of the levels and determinants of public knowledge, attitudes and practices towards COVID-19.

OBJECTIVE: The adherence to public health recommendations to control COVID-19 spread is influenced by public knowledge, attitudes and practices (KAP). We performed this cross-sectional study to assess the levels and determinants of public KAP towards COVID-19 in a large, multinational sample. DESIGN: Cross-sectional study (survey). SETTING: The questionnaire was distributed to potential respondents via online platforms. PARTICIPANTS: 71 890 individuals from 22 countries. METHODS: We formulated a four-section questionnaire in English, followed by validation and translation into seven languages. The questionnaire was distributed (May to June 2020) and each participant received a score for each KAP section. RESULTS: Overall, the participants had fair knowledge (mean score: 19.24±3.59) and attitudes (3.72±2.31) and good practices (12.12±1.83) regarding COVID-19. About 92% reported moderate to high compliance with national lockdown. However, significant gaps were observed: only 68.2% knew that infected individuals may be asymptomatic; 45.4% believed that antibiotics are an effective treatment; and 55.4% stated that a vaccine has been developed (at the time of data collection). 71.9% believed or were uncertain that COVID-19 is a global conspiracy; 36.8% and 51% were afraid of contacting doctors and Chinese people, respectively. Further, 66.4% reported the pandemic had moderate to high negative effects on their mental health. Female gender, higher education and urban residents had significantly (p≤0.001) higher knowledge and practice scores. Further, we observed significant correlations between all KAP scores. CONCLUSIONS: Although the public have fair/good knowledge and practices regarding COVID-19, significant gaps should be addressed. Future awareness efforts should target less advantaged groups and future studies should develop new strategies to tackle COVID-19 negative mental health effects.

Vedolizumab Dose Escalation Improves Therapeutic Response in a Subset of Patients with Ulcerative Colitis.

BACKGROUND: The Gemini trial failed to detect a significant difference in response rate for patients with ulcerative colitis (UC) randomized to standard (every 8 week) vedolizumab dosing vs escalated (every 4 week) dosing. Subsequent real-world data imply the Gemini trial design may have obscured a benefit of escalated dosing. AIMS: We investigated outcomes after vedolizumab dose escalation for patients with UC. We also explored potential clinical predictors of dose escalation requirement. METHODS: In this retrospective study, we included patients with UC who received vedolizumab between 1/2017-1/2019. We compared rates of clinical response (decrease in partial Mayo score by ≥ 2) and remission (partial Mayo < 2) for standard vs escalated dosing. RESULTS: Among the 90 patients reviewed, 52 achieved and maintained remission on standard dosing. The average time to remission with standard dosing was 33.3 ± 6.6 weeks. After an average of 56.3 ± 7.4 weeks standard dosing, 24 patients (22 "partial responders" and 2 "non-responders") were dose-escalated. Of the 22 "partial responders" dose-escalated, 10 (45%) achieved remission, 10 (45%) achieved further improvement. Neither "non-responder" demonstrated further clinical benefit. Prior anti-tumor necrosis factor (anti-TNF) biologic exposure predicted dose escalation requirement (p = 0.008). Patients requiring dose escalation had more severe disease at baseline as measured by both full Mayo (p = 0.009) and partial Mayo scores (p = 0.01). CONCLUSIONS: We show dose escalation benefited patients with UC who exhibit a "partial response" to standard dosing. Early vedolizumab dose escalation should be considered in both patients with severe disease and those with prior anti-TNF experience.

Syphilis Hepatitis Presenting as a Mimic of Primary Biliary Cholangitis.

Syphilis hepatitis is a rare cause of acute liver injury. Primary biliary cholangitis (PBC) is a progressive autoimmune disease characterized by the typical presentation of a cholestatic liver injury and the presence of antimitochondrial antibodies (AMAs). We present a case of syphilis hepatitis that presented as a mimic to PBC with positive AMA. The eradication of syphilis led to the resolution of the liver injury and down trending of the antibody level. We recommend excluding syphilis in patients with high-risk behaviors presenting with a cholestatic liver injury and positive AMA before the diagnosis of PBC.

Double Biologic Therapy for Refractory Stricturing Crohn's Disease: A Successful Case of Deep Remission with Ustekinumab and Vedolizumab.

Stricturing Crohn's disease (CD) is a severe phenotype that presents unique challenges to therapeutic management. Emerging literature suggests that anti-TNF monoclonal antibody (mAb) therapies are inadequate for preventing progression to stricture. We hereby present a case of a patient with refractory CD who required multiple surgical resections despite several anti-TNF treatment regimens. Subsequent surgical complications were avoided after changing to combination vedolizumab and ustekinumab therapies every 4 weeks. This case argues for a tailored approach to CD therapy based on disease phenotype and demonstrates that combination therapy with ustekinumab and vedolizumab is a viable option for patients with stricturing disease.