Short term effectiveness of ustekinumab versus vedolizumab in Crohn's disease after failure of anti-TNF agents: An observational comparative study design with a Bayesian analysis.

BACKGROUND: Crohn's disease (CD) is a debilitating gastrointestinal disease with complex etiology. Although effective, recipients of anti-tumor necrosis factor (TNF) agents may experience primary or secondary nonresponse, necessitating alternative treatments. This study is intended to compare the short-term effectiveness of ustekinumab and vedolizumab in treating CD after failure of multiple lines of anti-TNF therapy using real-world data. METHODS: A retrospective study was conducted at a tertiary hospital in Dammam, Saudi Arabia, including adults (≥18 years old) with CD who did not respond to anti-TNF therapy. Primary endpoints were clinical improvement per the Harvey-Bradshaw Index (HBI) scores and remission at 12 weeks on an ordinal outcome scale. Secondary endpoints included clinical, biochemical, and endoscopic remission; clinical response; corticosteroid-free days; and cumulative steroid dose. Proportional odds and logistic regression Bayesian models were used to analyze outcomes, and the probability of treatment effectiveness was calculated from the posterior distribution. RESULTS: The study included 101 patients (ustekinumab, n = 71 and vedolizumab, n = 30) with a median age of 32 years (IQR: 26.0-38.0); 54.4% were male. At 12 weeks, the HBI endpoint showed an adjusted odds ratio (aOR) = 0.60 (95% confidence interval [CI]: 0.25-1.31), favoring ustekinumab, with a 75% probability of treatment effectiveness over vedolizumab. The clinical ordinal scale had an aOR = 0.61 (95% CI: 0.26-1.35) with a 73% probability of effectiveness for ustekinumab. Ustekinumab was also associated with favorable outcomes in secondary endpoints, reaching up to a 90% probability of effectiveness. CONCLUSION: In CD patients with anti-TNF failure, ustekinumab was more effective than vedolizumab in the short term. These real-world insights contribute to understanding CD management but require validation in larger prospective studies and randomized controlled trials.

Association between COVID-19 severity and tobacco smoking status: a retrospective cohort study using propensity score matching weights analysis.

INTRODUCTION: The COVID-19 pandemic continues to be a global threat to public health, with over 766 million confirmed cases and more than 6 million reported deaths. Patients with a smoking history are at a greater risk of severe respiratory complications and death due to COVID-19. This study investigated the association between smoking history and adverse clinical outcomes among COVID-19 patients admitted to a designated medical centre in Saudi Arabia. METHODS: A retrospective observational cohort study was conducted using patient chart review data from a large tertiary medical centre in the eastern region of the country. Patients admitted between January and December 2020 were screened. The inclusion criteria were ≥18 years of age and confirmed COVID-19 infection via reverse-transcription-PCR. The exclusion criteria were unconfirmed COVID-19 infection, non-COVID-19 admissions, unconfirmed smoking status, vaccinated individuals, essential chart information missing or refusal to consent. Statistical analyses comprised crude estimates, matching weights (as the main analysis) and directed acyclic graphs (DAGs) causal pathway analysis using an ordinal regression model. RESULTS: The sample comprised 447 patients (never-smoker=321; ever-smoker=126). The median age (IQR) was 50 years (39-58), and 73.4% of the sample were males. A matching weights procedure was employed to ensure covariate balance. The analysis revealed that the odds of developing severe COVID-19 were higher in the ever-smoker group with an OR of 1.44 (95% CI 0.90 to 2.32, p=0.130). This was primarily due to an increase in non-invasive oxygen therapy with an OR of 1.05 (95% CI 0.99 to 1.10, p=0.101). The findings were consistent across the different analytical methods employed, including crude estimates and DAGs causal pathway analysis. CONCLUSION: Our findings suggest that smoking may increase the risk of adverse COVID-19 outcomes. However, the study was limited by its retrospective design and small sample size. Further research is therefore needed to confirm the findings.

The influence of telemedicine in primary healthcare on diabetes mellitus control and treatment adherence in Riyadh region.

Several studies have found that telemedicine has the potential to enhance the outcomes of patients with diabetes. This study aimed to determine the impact of telemedicine on the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) in Saudi Arabia. We conducted a cross-sectional study among T2DM patients in selected primary healthcare centers in Riyadh, Saudi Arabia, from March 1, 2023, to August 20, 2023. We looked at how telemedicine affected HbA1c control, adherence, the number of diabetic complications, and polypharmacy using adjusted multivariable logistic regression models. Among the 583 patients, 140 (24.05 %) received care via telemedicine, while 442 (75.95 %) received in-person care. Patients who utilized telemedicine had significantly better glycemic control than those who received in-person care only (AOR = 5.123, 95 % CI = 3.107-8.447). Telemedicine also showed positive effects on treatment adherence (AOR = 2.552, 95 % CI = 1.6284-4.2414). Telemedicine can effectively reduce diabetic complications (AOR = 0.277, 95 % CI = 0.134-0.571). Regarding polypharmacy, patients with telemedicine use were less likely to report polypharmacy (AOR = 0.559, 95 % CI = 0.361-0.866). Telemedicine is considered one of the factors that improve HbA1c management and might increase therapeutic adherence and reduce diabetic complications and polypharmacy.

Retraction: Emphysematous Cystitis: A Radiological Diagnosis of Potentially Life-Threatening Infection.

[This retracts the article DOI: 10.7759/cureus.20201.].

Clinical and Socioeconomic Determinants of Angiotensin Receptor-Neprilysin Inhibitor Prescription at Hospital Discharge in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Angiotensin receptor-neprilysin inhibitor (ARNI) prescription in the United States remains suboptimal despite strong evidence for efficacy and value in heart failure with reduced ejection fraction. Factors responsible for under prescription are not completely understood. Economic limitations may play a disproportionate role in reduced access for some patients. METHODS: This is an analysis of the Get With The Guidelines-Heart Failure registry, supplemented with data from the Distressed Community Index. Data were fit to a mixed-effects regression model to investigate clinical and socioeconomic factors associated with ARNI prescription at hospital discharge. Missing data were handled by multilevel multiple imputation. RESULTS: Of the 136 144 patients included in analysis, 12.6% were prescribed an ARNI at discharge. The dominant determinants of ARNI prescription were ARNI use while inpatient (odds ratio [OR], 72 [95% CI, 58-89]; P<0.001) and taking an ARNI before hospitalization (OR 9 [95% CI, 7-13]; P<0.001). Having an ACE (angiotensin-converting enzyme) inhibitor/angiotensin receptor blocker (ARB)/ARNI contraindication was associated with lower likelihood of ARNI prescription at discharge (OR, 0.11 [95% CI, 0.10-0.12]; P<0.001). Socioeconomic factors associated with lower likelihood of ARNI prescription included having no insurance (OR, 0.60 [95% CI, 0.50-0.72]; P<0.001) and living in a ZIP Code identified as distressed (OR, 0.81 [95% CI, 0.70-0.93]; P=0.010). The rate of ARNI prescription is increasing with time (OR, 2 [95% CI, 1.8-2.3]; P<0.001 for patients discharged in 2020 as opposed to 2017), but the disparity in prescription rates between distressed and prosperous communities appears to be increasing. CONCLUSIONS: Multiple medical and socioeconomic factors contribute to low rates of ARNI prescription at hospital discharge. Potential targets for improving ARNI prescription rates include initiating ARNIs during hospitalization and aggressively addressing patients' access barriers with the support of inpatient social services and pharmacists.

Assessing tobramycin levels and renal function following the implantation of CaSO4 beads impregnated with tobramycin: A prospective cohort study.

This study aimed to evaluate the risk of serum tobramycin concentrations exceeding therapeutic levels after administration of calcium sulfate (CaSO4) beads containing either 240 mg or 400 mg tobramycin and 1000 mg vancomycin. This single-center, prospective. This single-center, prospective study included included Piedmont Columbus, Regional orthopedic surgery patients. Following the implantation of tobramycin into CaSO4 beads, serially measured serum tobramycin concentrations were evaluated after 6, 12, 24, and 48 hours. In addition to that, serum tobramycin concentration was evaluated after 5 days. None of the patients who received 240 mg tobramycin-impregnated beads had a tobramycin level >2 µg/mL. Six hours after implantation, the tobramycin level in 2 out of 2 (100%) patients who received 400 mg of tobramycin-impregnated beads was >2 µg/mL. One day following the surgery, the median serum creatinine was 0.85 mg/dL, with an interquartile range of 0.73 to 1.04 mg/dL. No cases of acute kidney injury were observed. This cohort demonstrated that non-nephrotoxic serum tobramycin levels could be achieved in CaSO4 beads mixed with 240 mg or 400 mg of tobramycin.

Is there still a role for talimogene laherparepvec (T-VEC) in advanced melanoma? An indirect efficacy comparison of T-VEC plus ipilimumab combination therapy versus T-VEC alone as salvage therapy in unresectable metastatic melanoma.

BACKGROUND: Talimogene laherparepvec (T-VEC) improves overall survival (OS) in unresectable stage IIIB/C-IV melanoma T-VEC may have synergistic effects with CTLA-4 inhibitors In the absence of a trial comparing T-VEC and ipilimumab (T-VEC + IPI) to T-VEC, we applied a novel indirect comparison method using extrapolated OS curves to estimate OS outcomes in a simulated trial comparing both regimens in stage IIIB/C-IV unresectable melanoma. RESEARCH DESIGN AND METHODS: Two trials with extractable OS curves for a T-VEC versus T-VEC + IPI comparison were identified. Outcomes were adjusted for heterogeneity in prognostic factors using a calculated adjustment factor. T-VEC and adjusted/unadjusted T-VEC+IPI curves were plotted with 95% CIs. RESULTS: Unadjusted indirect OS comparison of T-VEC versus T-VEC + IPI revealed no significant difference up to 15 months. Extrapolation beyond 15 months showed significant survival benefits for T-VEC + IPI over T-VEC, confirmed in adjusted analyses. The expected OS percentage at 48 months is 32.0% (95% CI = 26.6-37.3) for T-VEC, 60.0% (95% CI = 46.2-69.1) for unadjusted, and 81.1% (95% CI = 72.3-85.9) for adjusted T-VEC + IPI. CONCLUSIONS: Our novel indirect comparison suggests that T-VEC + IPI may demonstrate a significantly improved OS versus T-VEC alone. Findings may portend a possible role for the addition of T-VEC to advanced melanoma treatment regimens in select patients as salvage therapy.

Emphysematous Cystitis: A Radiological Diagnosis of Potentially Life-Threatening Infection.

Urinary tract infections are very prevalent among women. The majority of urinary tract infections are uncomplicated and can be managed empirically with no further investigations. However, imaging studies may be indicated in patients with severe or persistent symptoms. Complicated urinary tract infections typically develop in the setting of diabetes mellitus. We report a case of a 52-year-old woman who presented to the emergency department with severe lower abdominal pain for two days that was associated with nausea, vomiting, and fever. There was no history of change in urine or bowel habits. Besides the history of well-controlled asthma, the patient was not known to have any comorbid medical condition. Upon examination, the patient had tachycardia, low-grade fever, and a localized suprapubic tenderness with guarding. Laboratory investigation revealed leukocytosis, elevated erythrocyte sedimentation rate and C-reactive protein, and deranged renal functions. Further, urinalysis revealed numerous white blood cells, red blood cells, positive nitrite, and leukocyte esterase. A computed tomography scan demonstrated the presence of small locules of gas within the lumen and the wall of the bladder representing emphysematous cystitis. The patient was admitted to the intensive care unit. She received aggressive hydration therapy and a short course of opioid therapy for pain control. Broad-spectrum antibiotic therapy in the form of piperacillin-tazobactam was initiated. Over the following few days, the patient exhibited significant improvement in his symptoms and resolution of the laboratory parameters. Emphysematous cystitis is a rare infection of the lower urinary tract with gas formation. The case highlighted that such a condition may develop in the absence of diabetes mellitus or other risk factors. Prompt treatment is crucial as emphysematous cystitis can be life-threatening if the diagnosis is missed or delayed.