Does colchicine reduce mortality in patients with COVID-19 clinical syndrome? An umbrella review of published meta-analyses.

Background: Despite significant improvements in both treatment and prevention strategies, as well as multiple commissioned reviews, there remains uncertainty regarding the survival benefit of repurposed drugs such as colchicine in patients with Coronavirus Disease 2019 (COVID-19) clinical syndrome. Methods: In this umbrella review, we carried out a comprehensive search of PubMed, EMBASE, Cochrane Database of Systematic Reviews, Science Citation Index, and the Database of Abstracts of Reviews of Effectiveness between January 1, 2020 and January 31, 2023 for systematic reviews and meta-analyses evaluating the mortality-reducing benefits of colchicine in patients with COVID-19. This was to ascertain the exact relationship between colchicine exposure and mortality outcomes in these cohorts of patients. We utilized A Measurement Tool to Assess systematic Reviews-2 (AMSTAR-2) to conduct an exhaustive methodological quality and risk of bias assessment of the included reviews. Results: We included eighteen meta-analyses (n = 199,932 participants) in this umbrella review. Colchicine exposure was associated with an overall reduction of about 32% in the risk of mortality (odds ratio 0.68, confidence interval [CI] 0.58-0.78; I2 = 94%, p = 0.001). Further examination of pooled estimates of mortality outcomes by the quality effects model (corrected for the methodological quality and risk of bias of the constituent reviews) reported similar point estimates (OR 0.73; CI 0.59 to 0.91; I2 = 94%). Conclusion: In a pooled umbrella evaluation of published meta-analyses of COVID-19 patient cohorts, exposure to colchicine was associated with a reduction in overall mortality. Although it remains uncertain if this effect could potentially be attenuated or augmented by COVID-19 vaccination.

Prevalence and global trends of polypharmacy among people living with HIV: a systematic review and meta-analysis.

Background: There has been a rising prevalence of polypharmacy among people living with HIV (PLWH). Uncertainty however remains regarding the exact estimates of polypharmacy among these cohorts of patients. Methods: We conducted a systematic search of PubMed; EMBASE, CROI, Cochrane Database of Systematic Reviews; Science Citation Index and Database of Abstracts of Reviews of Effects for studies between 1 January 2000 and 30 June 2021 that reported on the prevalence of polypharmacy (ingestion of > 5 non-ART medications) among PLWH on antiretroviral therapy regimen (ART). Prevalence of polypharmacy among HIV-positive patients on ART with Clopper-Pearson 95% confidence intervals were presented. The heterogeneity between studies was evaluated using I 2 and τ 2 statistics. Results: One hundred ninety-seven studies were initially identified, 23 met the inclusion criteria enrolling 55,988 PLWH, of which 76.7% [95% confidence interval (CI): 76.4-77.1] were male. The overall pooled prevalence of polypharmacy among PLWH was 33% (95% CI: 25-42%) (I 2 = 100%, τ2 = 0.9170, p < 0.0001). Prevalence of polypharmacy is higher in the Americas (44%, 95% CI: 27-63%) (I 2 = 100%, τ2 = 1.0886, p < 0.01) than Europe (29%, 95% CI: 20-40%) (I 2 = 100%, τ2 = 0.7944, p < 0.01). Conclusion: The pooled prevalence estimates from this synthesis established that polypharmacy is a significant and rising problem among PLWH. The exact interventions that are likely to significantly mitigate its effect remain uncertain and will need exploration by future prospective and systematic studies. Registration: PROSPERO: CRD42020170071. Plain Language Summary: Background: In people living with HIV (PLWH), what is the prevalence of polypharmacy and is this influenced by sociodemographic factors?Methods and Results: In this systematic review and meta-analysis of 23 studies comprising 55,988 participants, we have for the first time found an estimated polypharmacy pooled prevalence of 33% among PLWH. There was a relatively higher pooled prevalence of polypharmacy among the America's compared with European cohorts of PLWH.Conclusion: Polypharmacy among PLWH is a rising morbidity that needs urgent intervention both at policy and patient levels of care.

The determination of causality of drug induced liver injury in patients with COVID-19 clinical syndrome.

BACKGROUND: Drug induced liver injury (DILI) is a rising morbidity amongst patients with COVID-19 clinical syndrome. The updated RUCAM causality assessment scale is validated for use in the general population, but its utility for causality determination in cohorts of patients with COVID-19 and DILI remains uncertain. METHODS: This retrospective study was comprised of COVID-19 patients presenting with suspected DILI to the emergency department of Weill Cornell medicine-affiliated Hamad General Hospital, Doha, Qatar. All cases that met the inclusion criteria were comparatively adjudicated by two independent rating pairs (2 clinical pharmacist and 2 physicians) utilizing the updated RUCAM scale to assess the likelihood of DILI. RESULTS: A total of 72 patients (mean age 48.96 (SD ± 10.21) years) were examined for the determination of DILI causality. The majority had probability likelihood of "possible" or "probable" by the updated RUCAM scale. Azithromycin was the most commonly reported drug as a cause of DILI. The median R-ratio was 4.74 which correspond to a mixed liver injury phenotype. The overall Krippendorf's kappa was 0.52; with an intraclass correlation coefficient (ICC) of 0.79 (IQR 0.72-0.85). The proportion of exact pairwise agreement and disagreement between the rating pairs were 64.4%, kappa 0.269 (ICC 0.28 [0.18, 0.40]) and kappa 0.45 (ICC 0.43 [0.29-0.57]), respectively. CONCLUSION: In a cohort of patients with COVID-19 clinical syndrome, we found the updated RUCAM scale to be useful in establishing "possible" or "probable" DILI likelihood as evident by the respective kappa values; this results if validated by larger sample sized studies will extend the clinical application of this universal tool for adjudication of DILI.

Clinical, Radiological, and Outcome Characteristics of Acute Pulmonary Embolism: A 5-year Experience from an Academic Tertiary Center.

BACKGROUND: Acute pulmonary embolism (PE) is a common and potentially life-threatening condition. This comprehensive study from a Gulf Cooperation Council (GCC) country aimed to evaluate the clinical, radiological, and outcome characteristics associated with acute PE. METHODS: This retrospective observational study analyzed data of patients with confirmed acute PE who were admitted to the largest academic tertiary center in the State of Qatar from January 1, 2014, to December 31, 2018. Data on the clinical presentation, radiologic, and echocardiographic findings, as well as outcomes were collected. RESULTS: A total of 436 patients were diagnosed with acute PE during the study period (male, 53%). Approximately 56% of the patients were < 50 years old at presentation, with a median age of 47 years. In approximately 69% of cases, the PE occurred outside the hospital. The main associated comorbidities were obesity (34.6%), hypertension (29.4%), and diabetes (25%). Immobilization (25.9%) and recent surgery (20.6%) were the most common risk factors. The most frequent presenting symptom was dyspnea (39.5%), and the most frequent signs were tachycardia (49.8%) and tachypnea (45%). Cardiac arrest was the initial presentation in 2.2% of cases. Chest X-ray findings were normal in 41%. On computed tomography pulmonary angiography (CTPA), 41.3% of the patients had segmental PE, 37.1% had central PE, and 64.1% had bilateral PE. The main electrocardiographic (ECG) abnormality was sinus tachycardia (98%). In patients who underwent echocardiography, right ventricular (RV) enlargement was the main echocardiographic finding (36.4%). Low-, intermediate-, and high-risk PE constituted 49.8%, 31.4%, and 18.8% of the cases, respectively. Thrombolysis was prescribed in 8.3% of the total and 24.4% of the high-risk PE cases. Complications of PE and its treatment (from admission up to 6 months post-discharge) included minor bleeding (14%), major bleeding (5%), PE recurrence (4.8%), and chronic thromboembolic pulmonary hypertension (CTEPH) (5%). A total of 15 (3.4%) patients died from PE. CONCLUSIONS: Acute PE can manifest with complex and variable clinical and radiological syndromes. Striking findings in this study are the younger age of acute PE occurrence and the low PE-related mortality rate.

Evolution of gastroesophageal reflux disease symptoms after bariatric surgery: A dose-response meta-analysis.

BACKGROUND: Obesity is associated with increased prevalence of gastroesophageal reflux disease, with recent reports suggesting improvement in gastroesophageal reflux disease symptoms and weight loss following bariatric surgical intervention. However, the exact impact of the type of bariatric surgery on the evolution of gastroesophageal reflux disease symptoms has remained unexamined. METHODS: We systematically searched electronic databases (PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to December 2018) for eligible studies that satisfy prespecified inclusion criteria. We included clinical trials of all designs that reported on gastroesophageal reflux disease outcomes following laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass. Two independent reviewers extracted relevant data based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Data were pooled using a random-effects model. Main outcomes were symptomatic improvement in gastroesophageal reflux disease symptoms following bariatric surgery. RESULTS: A total of 31 studies were analyzed, and a robust-error meta-regression model was used to conduct a dose-response meta-analysis synthesizing data on 31 studies that reported gastroesophageal reflux disease outcomes after bariatric surgery. Of 5,295 patients who underwent either laparoscopic sleeve gastrectomy (n = 4,715 patients) or laparoscopic Roux-en-Y gastric bypass (n = 580 patients), 63.4% experienced improvement in gastroesophageal reflux disease symptoms (95% CI 32.46-72.18). The dose-response meta-analysis demonstrated a window period of 2 years for sustained improvement after which symptoms began to recur in those that were asymptomatic. CONCLUSION: Bariatric surgery may improve gastroesophageal reflux disease symptoms in obese patients who underwent laparoscopic sleeve gastrectomy; however, the most favorable effect is likely to be found after Roux-en-Y gastric bypass surgery. The effects were not sustained and returned to baseline within 4 years.

Rhino-orbital Mucormycosis as a complication of severe COVID-19 pneumonia.

Mucormycosis has multiple clinical phenotypes, which are more common in immunocompromised patients, especially those with diabetes mellitus. Debilitating rhino-orbital-cerebral and pulmonary infections by far represent the most typical clinical phenotypes associated with these fungi. Mucormycosis is an uncommon infection; however, there have been isolated sporadic tiny outbreaks around the world. With the substantial increase in COVID-19 cases in India, there is a parallel increase in the number of cases of Mucormycosis. A few reports raising unusual concomitant mucormycosis in COVID-19 patients have raised a possible association between the two diseases. We report a 59-year-old male with an established history of uncontrolled diabetes mellitus admitted to the hospital with severe COVID-19 pneumonia (severity ascertained according to WHO classification) treated with steroids and discharged home following full recovery. However, one week later, he presented with right eye ophthalmoplegia and complete loss of vision, which was subsequently established as orbital Mucormycosis. This case highlights the need for heightened awareness of this atypical secondary infection (especially systemic mycosis) in patients recovering from COVID-19 infection.

SGLT-2 inhibitors associated euglycemic and hyperglycemic DKA in a multicentric cohort.

Euglycemic diabetic ketoacidosis (EuDKA) secondary to Sodium-glucose co-transporter-2 inhibitors (SGLT2i) in type 2 diabetes mellitus (T2D) is a rare but increasingly reported phenomenon. Not much is known about the burden of EuDKA in patients on SGLT2i or the associated factors. This retrospective cohort study tries to delineate the differences in factors associated with the development of EuDKA as compared to hyperglycemic DKA. We conducted a multicentre, retrospective study across three tertiary care centers under Weill Cornell affiliated-Hamad Medical Corporation, Qatar. The cohort comprised of T2D patients on SGLT2i who developed DKA between January 2015 to December 2020. The differences between the subjects who developed EuDKA or hyperglycaemic DKA (hDKA) were analyzed. A total of 9940 T2D patients were on SGLT2i during 2015-2020, out of which 43 developed DKA (0.43%). 25 developed EuKDA, whereas 18 had hDKA. The point prevalence of EuDKA in our cohort was 58.1%. EuDKA was most common in patients using canagliflozin, followed by empagliflozin and Dapagliflozin (100%, 77%, and 48.3%, respectively). Overall, infection (32.6%) was the most common trigger for DKA, followed by insulin non-compliance (13.7%). Infection was the only risk factor with a significant point estimate between the two groups, being more common in hDKA patients (p-value 0.006, RR 2.53, 95% CI 1.07-5.98). Canagliflozin had the strongest association with the development of EuDKA and was associated with the highest medical intensive care unit (MICU) admission rates (66.6%). In T2D patients on SGLT2i, infection is probably associated with an increased risk of developing EuDKA. The differential role of individual SGLT2i analogs is less clear and will need exploration by more extensive prospective studies.

Albumin administration in patients with decompensated liver cirrhosis: a meta-analytic update.

End-stage liver disease and its related complications exert a huge disease burden and reduce the survival rates of many patients. Albumin administration for patients with decompensated liver cirrhosis has been a controversial topic of discussion. The aim of this study is to investigate whether albumin reduces the mortality and complications of liver cirrhosis compared to standard medical therapy (SMT) alone. Clinical trials in which albumin administration was compared to SMT in patients with liver cirrhosis were included in this meta-analysis. The primary outcome of this study was to evaluate the effect on reducing all-cause mortality. Ascites control, renal failure and hepatic encephalopathy were evaluated as secondary outcomes. Nine clinical trials with 1231 patients were recruited and analyzed using the quality effect model. Mortality rate was significantly reduced in the albumin group [relative risk (RR) 0.73, 95% confidence interval (CI) 0.56-0.96]. Heterogeneity was mild across all studies (I2 23.3%). Studies reporting long-term albumin (LTA) administration were found to have a significant decrease in mortality (RR 0.57, 95% CI 0.44-0.73). However, studies reporting short-term albumin administration were found to have no effect on mortality (RR 0.90, 95% CI 0.56-1.45). Furthermore, there was a significant decrease in the incidence of all secondary outcomes. This meta-analysis provides evidence that LTA administration is significantly effective in reducing the mortality of liver cirrhosis compared to SMT. Albumin administration was also shown to reduce the occurrence of ascites, renal failure and hepatic encephalopathy as complications of liver cirrhosis.

An Investigation into the Association Between Inflammatory Bowel Disease and Cardiac Arrhythmias: An Examination of the United States National Inpatient Sample Database.

BACKGROUND: Inflammatory bowel diseases (IBD) associated-chronic inflammation and autonomic dysregulation may predispose to arrhythmias. However, its exact prevalence is unknown. Thus, we aimed to ascertain the prevalence of arrhythmias in patients with IBD. METHODS: We queried the Nationwide Inpatient Sample (the largest publicly available all-payer inpatient USA database) from 2012 to 2014. We used the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9 CM) discharge codes to identify adult patients (⩾18 years) with IBD and dysrhythmias (supraventricular tachycardia (SVT), atrial fibrillation, atrial flutter, ventricular tachycardia (VT), or ventricular fibrillation). Furthermore, we identified risk factors for cardiovascular disease. We divided patients into 2 cohorts, IBD cohorts, and non-IBD cohort. The independent effect of a diagnosis of IBD on the risk of dysrhythmias was examined using a multivariable logistic regression model controlling for multiple confounders. RESULTS: We identified 847 235 and 84 757 349 weighted hospitalizations among patients with IBD and non-IBD cohorts, respectively. Patients with IBD were less likely to be hospitalized for dysrhythmias than the non-IBD (9.7% vs 14.2%, P < .001). The hospitalization odds for dysrhythmias among patients with IBD were less than the general population (OR 0.87; 95% CI 0.85-0.88). However, the prevalence of SVT and VT was indifferent between the 2 groups. Male sex, age of over 60, and white race were risk factors for dysrhythmias. CONCLUSION: Despite prior reports of a higher prevalence of arrhythmias among patients with IBD, in a nationwide inpatient database, we found lower rates of hospitalization-related-arrhythmias in the IBD population compared to that of the general population.

Polypharmacy and drug interactions amongst cirrhotic patients discharged from a tertiary center: Results from a national quality improvement audit.

BACKGROUND AND STUDY AIMS: Auditing of polypharmacy is particularly essential in patients with cirrhosis because of the crucial role of liver in drug metabolism. The aim of this study was to audit the drug prescribed in this group of patients and analyzed the quantity and severity of potential drug-drug interaction. PATIENTS AND METHODS: In this cross-sectional study we analyzed the last prescription as recorded in the Electronic Medical Record at the time of discharge for cirrhotic patients who were hospitalized during 24-months study period. Data were also collected for age, gender, and diagnoses. The drugs were analyzed for cross interactions using the Lexicomp-online e-formulary. The drug interactions are classified as: class A: no known interaction, class B: no action needed, Class C: monitor therapy, class D: consider therapy modification, and Class X: the drug should be avoided. RESULTS: A total of 333 patients with cirrhosis were audited, whereas complete and relevant data were available for 181 patients (134 males, 74%) with a mean age ± SD 59.7 ± 10.1. Out of these, 168 (92.8%) patients were using at least one medicine and the total number of medications used was 808 drugs. The observed average of utilization was 7.8 ± 3.1 drugs (range = 1-17) and 102 (56.3%) patients used polypharmacy. A total of 198 (24.5%) consumed drugs were related to cirrhosis and its complications. Six (3.3%), 30 (16.6%) and 65 (35.9%) patients had Class-X, Class D, and Class C, respectively. Utilization of polypharmacy was statistical significant in patients with class X (83.3%, p = 0.03), class D (16.6%, p = 0.01), and class C (35.9%, p = 0.02). CONCLUSION: The findings highlight the importance of auditing for polypharmacy to recognize and prevent potential drug-related problems in patients with cirrhosis. Implementation of strategies to optimize medication use in patients with cirrhosis should be considered necessary as it can have a bearing on length of stay and morbidity.

The utility of kidney injury molecule-1 as an early biomarker of kidney injury in people living with HIV.

There are increasing reports of antiretroviral therapy (ART) drug-related kidney dysfunction. Traditional markers of kidney dysfunction such as urine protein/creatinine ratio and estimated glomerular filtration rate (eGFR) have thus far proven ineffective at detecting some sub-clinical forms of ART-related kidney injury. This is a cross-sectional examination of 114 people living with HIV (PLWH), either naïve (N =104) or treatment experienced (N =10). Urinary kidney injury molecule-1 (KIM-1 ng/mg) thresholds were estimated using electrochemiluminescent assays from stored urine samples and normalised for urinary creatinine excretion (KIM-1/Cr). Correlation coefficients and predictors of kidney tubular injury were compared and derived for both adjusted and unadjusted urinary KIM-1/CR (ng/mg). In PLWH (both ART-naïve and treatment experienced) had a higher baseline unadjusted and adjusted median (≥3.7 ng/mg) and upper tertile (≥6.25 ng/mg) urinary KIM-1/Cr levels compared to either non-normal volunteers (0.39 ng/mg) or those with acute kidney injury in the general population (0.57 ng/mg). When upper tertile KIM-1/Cr (≥6.25 ng/mg) was utilised as a marker of kidney injury, eGFR (ml/min/1.73 m2), white Caucasian ethnicity, and protease inhibitor exposure were significantly associated with increased risk of kidney injury in multivariate analyses (odds ratio 0.91, confidence interval [CI] 0.68-0.98, P = 0.02; odds ratio 8.9, CI 1.6-48.6, p = 0.01; and odds ratio 0.05, CI 0.03-0.9, p =0.04, respectively). We found a significant degree of sub-clinical kidney injury (high unadjusted and adjusted KIM-1/Cr) in PLWH with normal kidney function (eGFR ≥60 ml/min/1.73 m2). We also found a higher baseline KIM-1/Cr (ng/mg) in our study cohort than reported both in normal volunteers and patients with kidney injury in the general population.

Pharmacotherapy in COVID-19 patients: a review of ACE2-raising drugs and their clinical safety.

The COVID-19 pandemic is caused by the severe acute-respiratory-syndrome-coronavirus-2 that uses ACE2 as its receptor. Drugs that raise serum/tissue ACE2 levels include ACE inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) that are commonly used in patients with hypertension, cardiovascular disease and/or diabetes. These comorbidities have adverse outcomes in COVID-19 patients that might result from pharmacotherapy. Increasing ACE2 could potentially increase the risk of infection, severity or mortality in COVID-19 or it might be protective as it forms angiotensin-(1-7) which exhibits anti-inflammatory/anti-oxidative effects and prevents diabetes- and/or hypertension-induced end-organ damage. Thus, there existed clinical uncertainty. Here, we review studies implicating 15 classes of drugs in increasing ACE2 levels in vivo and the available literature on the clinical safety of these drugs in COVID-19 patients. Further, in a re-analysis of clinical data from a meta-analysis of 9 studies, we show that ACEIs/ARBs usage was not associated with an increased risk of all-cause mortality. Literature suggests that ACEIs/ARBs usage generally appears to be clinically safe though their use in severe COVID-19 patients might increase the risk of acute renal injury. For definitive clarity, further clinical and mechanistic studies are needed in assessing the safety of all classes of ACE2 raising medications.

Therapeutic challenges in the management of osmotic demyelination syndrome: A case report of a favorable outcome from a tertiary center.

RATIONALE: There is an increasing and compelling need for early recognition of features of osmotic demyelination syndrome (ODS), and a further attempt at correcting this even where presentation is late. PATIENT CONCERNS: A 49-year-old male admitted into the emergency department with a complaint of lethargy and severe hyponatremia, with subsequent ODS supervening on initial attempts at correction. DIAGNOSIS: Rapid rise in serum sodium concentration (121 mmol/L in 8 hours from a nadir of 101 mmol/L), concomitant deterioration in patient's conscious level support the diagnosis of ODS. INTERVENTION: Concomitant administration of 5% dextrose water with desmopressin with a therapeutic objective of gradual relowering of serum sodium concentration. OUTCOMES: Significant improvement in patients' conscious level and motor function with the commencement of sodium relowering therapy. The patient was eventually discharged home. LESSONS: Regardless of the temporal profile of neurologic sequelae following ODS due to hyponatremia, its worthwhile attempting initial sodium relowering with dextrose 5% and desmopressin and then monitoring of biochemical and neurologic markers.

An Unusual Case of Modified Lemierre's Syndrome Caused by Staphylococcus aureus Cellulitis.

BACKGROUND Lemierre's syndrome is a potential life-threatening disease commonly occurring in young, healthy individuals. It is often preceded by an oropharyngeal infection causing bacteremia. This may rapidly progress into thrombophlebitis of the internal jugular venous system, its branches, and septic embolization and often fulminant organ failure. CASE REPORT A previously healthy 31-year-old male with recent history of facial herpes zoster infection, presented with 1-week history of increasingly painful nasal, and periorbital swelling. Imaging confirmed superior ophthalmic vein thrombosis. Staphylococcus aureus was isolated in blood cultures and had an uncomplicated hospital course with full recovery. CONCLUSIONS Early recognition of Lemierre's syndrome contributes significantly in reducing morbidity and mortality associated with it. Staphylococcus aureus skin infection is a very rare cause of Lemierre's syndrome, and its association with superior ophthalmic vein thrombosis has not yet been reported in literature.

Polymorphisms of tenofovir disoproxil fumarate transporters and risk of kidney tubular dysfunction in HIV-positive patients: genetics of tenofovir transporters.

The association between single nucleotide polymorphisms of genes encoding transport proteins involved in the bio-disposition of tenofovir disoproxil fumarate (TDF) and kidney tubular dysfunction (KTD) in HIV-positive patients was examined in this study. Fifty-eight patients who received TDF were screened for KTD using retinol-binding protein (RBP) concentration in urine. We defined KTD as the top quartile of urinary RBP/creatinine ratio (>17 µg/mmol), regardless of estimated glomerular filtration rate (eGFR) or proteinuria. Genotyping of genes encoding transport proteins involved in the disposition of TDF was undertaken using validated Taqman 5' nuclease assays. Patients with KTD (N = 15) had higher current CD4 cell counts, lower eGFR and were less likely to possess the genotype CC at position 24 of the ABBC2 (MRP2, rs717620) gene. In multivariate analysis, genotype CC at position 24 of the ABBC2 gene was significantly associated with KTD (odds ratio =0.05, 95% confidence interval = 0.003-0.7, P = 0.027). Genotype CC at position 24 of the ABBC2 (MRP2 rs717620) gene was significantly associated with a reduced risk of elevated urinary RBP in HIV-positive patients exposed to TDF.