Systematic review and meta-analysis of endoscopic versus medical management of peptic ulcers with adherent clots.

Peptic ulcer disease is an important cause of upper gastrointestinal bleeding. Current guidelines recommend endoscopic treatment for ulcers with active bleeding or non-bleeding visible vessels, but the optimal management of ulcers with adherent clots is unclear. We performed a systematic review of the efficacy of endoscopic versus medical management of peptic ulcers with adherent clots. A systematic literature search was performed through September 2022 (MEDLINE, Embase, and CENTRAL). Randomized controlled trials (RCTs) comparing the effect of endoscopic versus medical management alone for peptic ulcers with adherent clots on the outcome of recurrent bleeding were incuded. A random-effects meta-analysis was performed to estimate the overall treatment effect. We included seven RCTs reporting on the endoscopic versus medical management of peptic ulcers with adherent clots. The pooled cohort comprised 268 patients with a mean age of 62.8 years and a mean follow up of 20 days. There was a significant reduction in the risk of recurrent bleeding with endoscopic hemostatic treatment for peptic ulcers with adherent clots, compared with medical management alone (risk ratio [RR] = 0.40, 95% confidence interval [CI] 0.16-0.95, 268 participants). However, there was no difference in mortality (RR = 0.90, 95% CI 0.23-3.59, 52 participants) or need for ulcer surgery (RR = 0.48, 95% CI 0.10-2.28, 52 participants) between endoscopic and medical management groups. In summary, there was evidence for a reduction in recurrent bleeding from peptic ulcers with adherent clots treated with endoscopic hemostatic techniques compared with medical management alone but no difference in rates of mortality or need for surgery.

Risk factors for malignancy and serious infection in patients with inflammatory bowel disease: a retrospective analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of malignancy and infection compared to the general population. AIMS: We aim to identify risk factors for malignancy or serious infection in our IBD cohort. METHODS: Patients with IBD from a single tertiary referral centre were included. Demographic and clinical details, including immunosuppressant exposure, were collected and medical records retrospectively screened for adverse events, including malignancy or infection requiring hospitalisation. Logistic regression was used to evaluate risk factors for adverse events. RESULTS: Five hundred and forty-nine patients with IBD (340 Crohn disease (CD) and 209 ulcerative colitis (UC)) were studied. Forty-eight malignancies, including 39 (81.3%) non-melanoma skin cancers, 3 (6.3%) haematologic malignancies and 6 (15.4%) solid-organ malignancies, were identified, and 92 cases of serious infection were detected. IBD duration (odds ratio (OR) = 1.08; 95% confidence interval (CI) = 1.03-1.13) and ileocolonic CD (OR = 4.96; 95% CI = 1.13-21.71) were associated with increased odds of overall cancer. Compared with patients not previously exposed to the given class of immunosuppression assessed, the development of overall malignancy was not higher with thiopurine exposure (OR = 1.00; 95% CI = 0.50-2.24) or anti-tumour necrosis factor-alpha (TNF-α) exposure (OR = 0.78; 95% CI = 0.37-1.64). Similarly, compared with patients not exposed, infection risk was not affected by thiopurine (OR = 0.74; 95% CI = 0.46-1.20) or anti-TNF exposure (OR = 0.60; 95% CI = 0.38-0.95). CONCLUSIONS: Factors including ileocolonic CD and increasing IBD duration were associated with higher malignancy risk in this cohort. Compared with non-exposure, patients exposed to thiopurines were not at increased risk of malignancy or serious infection. Similarly, patients exposed to anti-TNF treatment did not experience increased rates of malignancy or serious infection compared to patients not exposed to this treatment.

Antibody response to the COVID-19 ChAdOx1nCov-19 and BNT162b vaccines after temporary suspension of DMARD therapy in immune-mediated inflammatory disease (RESCUE).

OBJECTIVE: To assess the antibody response to disease-modifying antirheumatic drug (DMARD) therapy after the first and second dose of the ChAdOx1nCov-19 (AstraZeneca (AZ)) and BNT162b (Pfizer) vaccines in patients with immune-mediated inflammatory disease (IMID) compared with controls and if withholding therapy following the first vaccination dose has any effect on seroconversion and SARS-CoV-2 antibody (Ab) levels. METHODS: A multicentre three-arm randomised controlled trial compared the immunogenicity of the Pfizer and AZ vaccines in adult patients on conventional synthetic (csDMARD), biologic (bDMARD) or targeted synthetic (tsDMARD) therapy for IMID (n=181) with a control group (n=59). Patients were randomised to continue or withhold DMARD therapy for 1-2 weeks post first dose vaccination only. Serum SARS-CoV-2 IgG detection (IgG ≥1.0 U/mL) and titres against the S1/S2 proteins were measured at baseline, 3-4 weeks post first vaccination and 4 weeks post second vaccination. RESULTS: AZ vaccination was given to 47.5%, 41.5% and 52.5% in the continue, withhold and control groups, respectively while Pfizer vaccination was given to 52.5%, 58.5% and 47.5% among the continue, withhold and control groups, respectively. Seroconversion rates following the first dose in the AZ and Pfizer groups were only 27.3% vs 79.2% (p=0.000) and 64.58% vs 100% (p=0.000), respectively in the IMID groups who continued therapy compared with the AZ and Pfizer controls, respectively. Withholding DMARD therapy following the first vaccination dose resulted in higher seroconversion to 67.7% and 84.1% in the AZ and Pfizer groups, respectively. Following the second AZ and Pfizer vaccinations when all DMARDs were continued, despite a slightly lower seroconversion rate (83.7% vs 100%, p=0.000 and 95.9% vs 100%, p=0.413), respectively, the mean SARS-CoV2 IgG Ab titres were not significantly different in the csDMARD and bDMARD groups compared with the controls regardless of hold while it was significantly lower in patients taking tsDMARD (12.88 vs 79.49 U/mL, p=0.000). CONCLUSIONS: Following the first vaccination dose, antibody responses were lower in IMID on DMARD therapy, however the final responses were excellent regardless of hold with the exception of the tsDMARD group where withholding therapy is recommended. At least 2 vaccinations are therefore recommended preferably with an messenger RNA vaccine. TRIAL REGISTRATION NUMBER: ANZCTR: 12621000661875.

Systematic Review: The Impact and Importance of Body Composition in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Alterations in body composition are common in inflammatory bowel disease [IBD] and have been associated with differences in patient outcomes. We sought to consolidate knowledge on the impact and importance of body composition in IBD. METHODS: We performed a systematic search of MEDLINE, EMBASE and conference proceedings by combining two key research themes: inflammatory bowel disease and body composition. RESULTS: Fifty-five studies were included in this review. Thirty-one focused on the impact of IBD on body composition with a total of 2279 patients with a mean age 38.4 years. Of these, 1071 [47%] were male. In total, 1470 [64.5%] patients had Crohn's disease and 809 [35.5%] had ulcerative colitis. Notably, fat mass and fat-free mass were reduced, and higher rates of sarcopaenia were observed in those with active IBD compared with those in clinical remission and healthy controls. Twenty-four additional studies focused on the impact of derangements in body composition on IBD outcomes. Alterations in body composition in IBD are associated with poorer prognoses including higher rates of surgical intervention, post-operative complications and reduced muscle strength. In addition, higher rates of early treatment failure and primary non-response are seen in patients with myopaenia. CONCLUSIONS: Patients with IBD have alterations in body composition parameters in active disease and clinical remission. The impacts of body composition on disease outcome and therapy are broad and require further investigation. The augmentation of body composition parameters in the clinical setting has the potential to improve IBD outcomes in the future.

Immunosuppression as a risk factor for COVID-19: a meta-analysis.

BACKGROUND: While immunosuppression poses a theoretical increase in the risk of COVID-19, the nature of this relationship is yet to be ascertained. AIMS: To determine whether immunosuppressed patients are at higher risk of COVID-19 to help inform the management of patients receiving immunosuppressant therapies during the pandemic. METHODS: We performed a random-effects meta-analysis of data from studies that reported on the prevalence of immunosuppression among patient cohorts with COVID-19. RESULTS: Sixty full-text publications were identified. In total, six individual studies were included in the final analysis, contributing a total of 10 049 patients with COVID-19 disease. The prevalence of immunosuppressed patients among the study cohorts with COVID-19 ranged from 0.126% to 1.357%. In the pooled cohort a total of 64/10 049 (0.637%) patients with COVID-19 disease was immunosuppressed. Observed to expected ratios were used to compare the prevalence of immunosuppression in cohorts with confirmed COVID-19 disease to the background prevalence of immunosuppression in the general community. The observed to expected ratio of immunosuppression among patients with COVID-19 illness, relative to the general community, was 0.12 (95% confidence interval: 0.05-0.27). CONCLUSIONS: Compared to the general population, immunosuppressed patients were not at significantly increased risk of COVID-19 infection. This finding provides support for current expert consensus statements, which have recommended the continuation of immunosuppressant therapy in the absence of COVID-19.

Variation in a novel antipseudomonal antimicrobial consumption metric across hospital inpatient units at a Veterans Affairs hospital: A retrospective cohort study.

A novel antimicrobial consumption metric designed to identify the proportion of carbapenem consumption (PoCC) among broad-spectrum antipseudomonal antimicrobials has been shown to vary significantly by US Census Bureau region. This retrospective surveillance study identified significant total PoCC variability (27%; P = .001) across 8 inpatient units from January 2017 through June 2018. This metric may be useful in identifying and comparing inpatient units that may be overusing antipseudomonal carbapenems.

Warfarin-antibiotic interactions in older adults of an outpatient anticoagulation clinic.

BACKGROUND: Several classes of drugs, such as antibiotics, may interact with warfarin to cause an increase in warfarins anticoagulant activity and the clinical relevance of warfarin-antibiotic interactions in older adults is not clear. OBJECTIVE: The aim of this study was to determine the effect of oral antibiotics, such as amoxicillin, azithromycin, cephalexin, ciprofloxacin, levofloxacin, and moxifloxacin, on the international normalized ratio (INR) in patients ≥65 years on stable warfarin therapy. The secondary objective was to compare the effect of warfarin-antibiotic interactions on outcomes of overanticoagulation. METHODS: Data for this retrospective cohort study were collected through a medical record review of patients in an outpatient anticoagulation clinic of a Veterans Affairs medical center. Patients aged ≥65 years on stable warfarin therapy and with at least 1 prescription of an oral antibiotic of interest during the period from January 1, 2003 to March 1, 2011 were included. A mixed-effects repeated-measures ANOVA model was used to determine the effect of antibiotics on the mean change in patients' INR. The Fisher exact test was used to determine the association between the antibiotics and secondary outcomes of overanticoagulation, using cephalexin as the control. Statistical significance was defined as a P value <0.05. RESULTS: A total of 205 patients had 364 prescriptions for warfarin and antibiotics concomitantly, and there was a significant interaction between antibiotic and time (F(15, 358) = 1.9; P = 0.0221). Antibiotics with a significant increase in INR were amoxicillin (P = 0.0019), azithromycin (P < 0.0001), ciprofloxacin (P = 0.002), levofloxacin (P < 0.0001) and moxifloxacin (P < 0.0001). There was a significant association between type of antibiotic and secondary outcomes of overanticoagulation. CONCLUSIONS: In older patients on stable warfarin therapy, antibiotics may lead to an increase in INR. However, this may not result in clinically significant outcomes of bleeding or hospitalization, suggesting that antibiotics may be prescribed for older adults taking warfarin as long as their INR is being routinely monitored.

Pregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders.

BACKGROUND: The US Food and Drug Administration (FDA) approved pregabalin in December 2004 for the treatment of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. Pregabalin is the first drug approved in the United States and in Europe for both conditions. In June 2005, pregabalin was approved as an adjunctive treatment in adults with partial-onset seizures. The FDA currently is considering the approval of pregabalin as adjunctive therapy in adults with generalized anxiety disorder (GAD) or social anxiety disorder (SAD). OBJECTIVES: The goals of this review were to summarize the pharmacology, pharmacokinetics, efficacy, and tolerability of pregabalin; review its approved uses in the management of neuropathic pain and refractory partial-onset seizures; and investigate its potential use in patients with GAD or SAD. METHODS: Relevant English-language literature was identified through a search of MEDLINE (1993-June 2006) and International Pharmaceutical Abstracts (2000-June 2006). The search terms included pregabalin, Lyrica, S-(+)-3 isobutyl-gaba, PN, DPN, diabetic peripheral neuropathy, PHN, postherpetic neuralgia, partial seizures, epilepsy, generalized anxiety disorder, and CI-1008. RESULTS: In 4 clinical trials in a total of 1068 patients with diabetic peripheral neuropathy, the patients receiving pregabalin 300 to 600 mg/d had significantly greater improvement in mean pain scores than placebo recipients (P < or = 0.01). Patients with postherpetic neuralgia receiving pregabalin 450 to 600 mg/d had significantly greater improvement in relief of pain and pain-related sleep interference than placebo recipients (P < or = 0.002). Patients with refractory partial-onset seizures who received pregabalin 150 to 600 mg/d (divided into 2 or 3 doses) concomitantly with antiepileptic drugs had significantly fewer seizures than placebo recipients (P < or = 0.001). In the 3 studies that evaluated the efficacy of pregabalin in patients with GAD or SAD, the patients receiving pregabalin 200 to 600 mg/d (divided into 2 or 3 daily doses) had a significantly greater reduction in mean pain scores on the Hamilton Anxiety Scale than placebo recipients (P < or = 0.01). Across all the reviewed clinical trials, the most commonly reported adverse effects (AEs) were those affecting the central nervous system, including somnolence (< or =50%), dizziness (< or =49%), and headache (< or =29%). AEs resulted in withdrawal from the study in < or =32% of patients. CONCLUSIONS: Pregabalin appears to be an effective therapy in patients with diabetic peripheral neuropathy, postherpetic neuralgia, and adults with refractory partial-onset seizures. The available data suggest that pregabalin may be beneficial as an adjunctive therapy in adult patients with GAD or SAD.

Posttraumatic stress disorder in male military veterans with comorbid overweight and obesity: psychotropic, antihypertensive, and metabolic medications.

UNLABELLED: Posttraumatic stress disorder (PTSD) is an important syndrome among military veterans. Little has been written about comorbid medical conditions of PTSD, particularly overweight and obesity. We focus on psychotropic and non-psychotropic drugs, their interactions, and metabolic issues most relevant to primary care physicians. METHOD: Data from the recently constituted PTSD program at the Department of Veterans Affairs Medical Center in Richmond, Va., were retrospectively reviewed to assess the prevalence and severity of comorbid overweight and obesity in male veterans with PTSD. Also, our database allowed us to correlate various drugs used to treat hypertension, diabetes mellitus, and dyslipidemia with body mass index (BMI). RESULTS: The mean BMI of 157 veterans with PTSD (DSM-IV criteria) in this sample was in the obese range (30.3 ± 5.6 kg/m²). The number of drugs a given patient was taking for treatment of hypertension, diabetes mellitus, and dyslipidemia correlated with BMI. Psychotropic drugs associated with weight gain did not explain our findings. CONCLUSIONS: Overweight and obesity among our male veterans with PTSD strikingly exceeded national findings. The administration of psychotropic drugs associated with weight gain did not explain these findings. The number of medications used to treat hypertension, diabetes mellitus, and dyslipidemia correlated significantly with BMI. Rather than these medications explaining the high prevalence of overweight and obesity in our study population, obesity probably worsened these components of the metabolic syndrome, necessitating more aggressive treatment reflected in the high number of drugs prescribed.