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This article summarizes the top 20 research studies of 2021 identified as POEMs (patient-oriented evidence that matters) that did not address the COVID-19 pandemic. Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists prevent adverse cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and also reduce all-cause and cardiovascular mortality. Most older adults (mean age, 75 years) with prediabetes do not progress to diabetes. Among patients in this age group with type 2 diabetes treated with medication, an A1C level of less than 7% is associated with increased risk of hospitalization for hypoglycemia, especially when using a sulfonylurea or insulin. For patients with chronic low back pain, exercise, nonsteroidal anti-inflammatory drugs, duloxetine, and opioids were shown to be more effective than control in achieving a 30% reduction in pain, but self-discontinuation of duloxetine and opioids was common. There is no clinically important difference between muscle relaxants and placebo in the treatment of nonspecific low back pain. In patients with chronic pain, low- to moderate-quality evidence supports exercise, yoga, massage, and mindfulness-based stress reduction. For acute musculoskeletal pain, acetaminophen, 1,000 mg, plus ibuprofen, 400 mg, without an opioid is a good option. Regarding screening for colorectal cancer, trial evidence supports performing fecal immunochemical testing every other year. For chronic constipation, evidence supports polyethylene glycol, senna, fiber supplements, magnesium-based products, and fruit-based products. The following abdominal symptoms carry a greater than 3% risk of cancer or inflammatory bowel disease: dysphagia or change in bowel habits in men;rectal bleeding in women;and abdominal pain, change in bowel habits, or dyspepsia in men and women older than 60 years. For secondary prevention in those with established arteriosclerotic cardiovascular disease, 81 mg of aspirin daily appears to be effective. The Framingham Risk Score and the Pooled Cohort Equations both overestimate the risk of cardiovascular events. Over 12 years, no association between egg consumption and cardiovascular events was demonstrated. Gabapentin, pregabalin, duloxetine, and venlafaxine provide clinically meaningful improvements in chronic neuropathic pain. In patients with moderate to severe depression, initial titration above the minimum starting dose of antidepressants in the first eight weeks of treatment is not more likely to increase response. In adults with iron deficiency anemia, adding vitamin C to oral iron has no effect. In children with pharyngitis, rhinosinusitis, acute bronchitis, or acute otitis media, providing education combined with a take-and-hold antibiotic prescription results in 1 in 4 of those children eventually taking an antibiotic.Copyright © 2022 American Academy of Family Physicians.
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BACKGROUND: The coronavirus pandemic has had an extremely negative impact on the patients with diabetes mellitus (DM both in terms of a more severe course of COVID -19 and an increased risk of death. AIM: Analysis of risk factors for death due to COVID -19 in patients with DM type 1 and type 2 (DM1 and DM2). MATERIALS AND METHODS: Retrospective analysis of the database of the national diabetes register (NDR), which included DM patients with COVID-19 and reported virus infection outcome (recovery/or death) in 15 712 DM1 and 322 279 DM2 patients during a 2-year follow-up period (01/02/2020 to 03/04/2022) (discharge date)). RESULT(S): Case fatality rate in patients with DM, who underwent COVID -19 was 17.1% (DM1-8.8%;DM2-17.5%). As a result of multivariate regression analysis of seven significant factors in DM1 and thirteen in DM2 (evaluated by univariate anlisys), a number of the most important predictors of risk for fatal outcome were identified: in DM1 these were age >=65 years (OR =4.01, 95% CI: 1.42-11.36), presence of arterial hypertension (AH) (OR =2.72, 95% CI: 1.03 -7.16) and diabetic foot syndrome (DFS) (OR = 7.22, 95% CI: 1.98-26.29);for T2DM: age >= 65 years (OR =2.53, 95% CI: 1.96-3.27), male (OR =1.51, 95% CI: 1.23-1.84), duration DM >=10 years (OR =2.01, 95% CI: 1.61-2.51), BMI >= 30 kg/m2 (OR =1.26, 95% CI: 1.02-1.55), ASCVD/CKD (OR =1.49, 95% CI: 1.01-2.04), history of diabetic coma (OR =12.97, 95% CI: 1.89-88.99) and presence of disability (OR =1.40, 95% CI: 1.14-1.73). In T2DM, the type of antidiabetic therapy (ADT) prior to COVID -19 (last visit before the development of infection) had a significant impact: Insulin therapy (OR = 1.64, 95% CI: 1.30-2.07), sulfonylureas (SU) (OR =1.51, 95% CI: 1.23-1.84));dipeptidyl peptidase-4 inhibitor (iDPP-4) therapy (OR =0.57, 95% CI: 0.39-0.83) and sodium-glucose cotransporter-2 inhibitor (iSGLT2) therapy (OR =0.64, 95% CI: 0.46-0.88). Vaccination was the most important protective factor in both types of DM: DM1 OR =0.19, 95% CI: 0.06-0.59;SD2 OR =0.20, 95% CI: 0.16-0.26. CONCLUSION(S): The common risk factor for fatal outcome in both DM1 and DM2 was age >=65 years;in DM1 - history of hypertension and DFS, in DM2 - male sex, diabetes duration >=10 years, BMI >=30 kg/m2, history of ASCVD/CKD and diabetic coma, disability. In T2DM, significant differences in risk were observed depending on the type of ADT: insulin and SU therapy were factors that increased the risk of death, whereas therapy with iDPP-4 and iSGLT2 reduced the risk of death. Vaccination reduced the risk of death in DM1 and DM2 by 5.2 and 5-fold, respectively. Copyright © Endocrinology Research Centre, 2022.
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Introduction In a study involving > 10,000 patients hospitalized with COVID-19, we found that liver injury, which was present in ~70% of patients upon hospital admission, correlates with in-hospital mortality (Satapathy et al., Eur J Gastroenterol Hepatol 2021). Curiously, severe liver chemistry abnormalities (LCA) were seen less often in patients with diabetes or hypertension, although these diseases confer increased risk of severe disease. This raises the question whether home medications protect from COVID-19 associated liver injury. We now analyzed associations between LCA and twenty-six groups of antidiabetic, antihypertensive, and other common mediations. Results 9898 patients hospitalized with COVID-19 in 13 hospitals in New York between March 1 to August 31, 2020, who had an complete records on admission were retrospectively analyzed. LCA measured were alanine and aspartate aminotransferases, alkaline phosphatase, and bilirubin, and were defined as absent, mildmoderate (up to four times elevated), or severe. Diseases and socioeconomic factors were similar to the initial study. 67.2% had hypertension, and 40.8% had diabetes. The most common medications included insulin (12.2%), metformin (18.3%), sulfonylureas (6.8%), DDP4 inhibitors (6.3%), ACE inhibitors (14.8%), ARBs (18.6%), beta-blockers (33.2%), calcium-channel blockers (26.5%), diuretics (21.6%), statins (41.5%), PPIs (22.1%), H2- blockers (6.8%), antiplatelets (31.0%), anticoagulants (20.5%). Comparisons between groups were analyzed using Kruskal-Wallis test, chi-squared test, and Fisher's exact test. Univariate and multivariate regression analysis were performed. Univariate analysis showed a higher risk for severe LCA in men, Asian and Black race, non-Hispanic ethnicity. As in our prior analysis, hypertension and diabetes were associated with less frequent severe LCA. In addition, hyperlipidemia, CAD, CHF, atrial fibrillation, CKD, ESRD, GERD, asthma, COPD, cancer, and liver disease were inversely associated with severe LCA. Medications that were associated with less frequent severe LCA included statins, ACE, ARBs, calcium-channel blockers, betablockers, diuretics, antiplatelet medications, insulin, biguanide, sulfonylureas, PPIs, H2- blockers, and anticoagulants, but not oral steroids. In multivariate analysis, male gender, Asian and Black race were associated with increased risk of severe LCA. Hypertension, ESRD and asthma were associated with less frequent severe LCA, but not diabetes. Among medications, only metformin showed a statistically significant correlation with severe LCA on admission, with a hazard ratio 0.57 (p 0.0002). Conclusions Metformin use was inversely associated with severe liver chemistry abnormalities upon hospital admission with COVID- 19 in a large cohort of patients during the initial pandemic in New York.
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A 64 year-old Caucasian woman was admitted profoundly unwell with lethargy and generalised weakness. She had rheumatoid arthritis, with no history of diabetes or long-term steroid-use. Blood tests revealed pancytopaenia secondary to methotrexate (stopped on admission), acute kidney injury and severe metabolic acidosis. CT demonstrated lung base ground-glass changes. The patient had been double-vaccinated for covid-19 and all covid swabs were negative. Despite receiving Tazocin, respiratory symptoms worsened. High-dose co-trimoxazole was commenced to treat potential Pneumocystis infection from being immunocompromised. Subsequently she developed new confusion. Random blood glucose at midday was 1.2mmol/l. After treatment, hypoglycaemia recurred and persisted despite repeated intravenous dextrose boluses and glucagon injection. Blood glucose only improved with continuous 10% dextrose infusion. Causes were explored -a recent CT scan showed no pancreatic or intra-abdominal pathology;morning cortisol was normal. Literature review revealed very rarely Co-trimoxazole causes hypoglycaemia;hence this was stopped. Hypoglycaemia resolved within 48 hours;confusion improved. When serum glucose was 3.3mmol/l, c-peptide measured was inappropriately high (5175pmol/L). Co-trimoxazole is biochemically similar to sulfonylureas, mimicking their action on pancreatic beta-cells. Endogenous insulin hypersecretion raises c-peptide levels during hypoglycaemia. As Co-trimoxazole is renally excreted, when renal function is impaired it accumulates, with exacerbation of side effects such as protracted hypoglycaemia, especially at higher doses, as in our case. Hypoglycaemia will likely resolve after a 24-48h washout period, especially if renal function improves back to baseline. We recommend awareness of hypoglycaemia risk with co-trimoxazole treatment and blood glucose monitoring for inpatients taking high doses, especially in the setting of renal impairment.
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Background: While vaccination is the most important way to combat the SARS-CoV- 2 pandemic, there may still be a need for early outpatient treatment that is safe, inexpensive, and currently widely available in parts of the world that do not have access to the vaccine. There are in-silico, in-vitro, and in-tissue data suggesting that metformin (MET) inhibits the viral life cycle, as well as observational data suggesting that MET use before infection with SARS-CoV2 is associated with less severe COVID-19. Previous observational analyses from single-center cohorts have been limited by size. Methods: Objective: Conduct a retrospective cohort analysis for associations between MET use and COVID-19 outcomes with an active comparator design of prevalent users of therapeutically equivalent diabetes monotherapy: MET versus dipeptidyl-peptidase- 4- inhibitors (DPP4i) and sulfonylureas (SU). Participants: Adults with type 2 diabetes (T2DM) in the National COVID Cohort Collaborative (N3C) longitudinal U.S. cohort of adults with +SARS-CoV- 2 result between January 1 2020 to June 1 2021. Exposures: Diabetes monotherapy with MET, DPP4i, or SU within 90 days prior to the +SARS-CoV- 2 result. Outcome: Hospitalization or ventilation or mortality from COVID-19. Back pain assessed as a negative control outcome. Results: 6,626 adults with T2DM and +SARS-CoV- 2 from 36 sites. Mean age was 60.7 +/-12.0 years;48.7% male;56.7% White, 21.9% Black, 3.5% Asian, and 16.7% Latinx. Mean BMI was 34.1 +/-7.8kg/ m2. Overall 14.5% of the sample was hospitalized;1.5% received mechanical ventilation;and 1.8% died. In adjusted outcomes, compared to DPP4i, MET had non-significant associations with reduced need for ventilation (RR 0.68, 0.32-1.44), and mortality (RR 0.82, 0.41-1.64). Compared to SU, MET was associated with a lower risk of ventilation (RR 0.5, 95% CI 0.28 -0.98, p = 0.044) and mortality (RR 0.56, 95%CI 0.33 -0.97, p = 0.037). There was no difference in adjusted or unadjusted results of the negative control outcome. Conclusions: There were clinically significant associations between MET use and less severe COVID-19 compared to SU, but not compared to DPP4i. New-user studies and randomized trials are needed to assess early outpatient treatment and post-exposure prophylaxis with therapeutics that are safe in adults, children, pregnancy and available worldwide.
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Aim: The aim of the study was to explore the impact of the coronavirus disease 19 (COVID-19) lockdown on the clinical outcome of patients with Type 2 diabetes mellitus (DM) attending a primary care Diabetes Clinic in Lagos State, Nigeria, in terms of their compliance with medication intake, blood pressure (BP), and glycemic control and ability to modify medication through telephone consultation. Methodology: A retrospective review of the clinical characteristics of patients was carried out. Telephone calls were made to patients with Type 2 DM who attended the chronic medical disorder clinic of the Family Medicine Department, Lagos State University Teaching Hospital, Lagos, Nigeria. The information obtained included questions on demographic data, type of medications used, and medication compliance, use of self-monitoring devices for BP, and blood glucose levels. Data analysis was performed using SPSS program version 26. Results: A total of 178 patients were eligible. Most (87%) reported using their medication as prescribed, 74% of patients had self-monitoring of blood glucose (SMBG) during lockdown, though only 29% checked glucose level regularly and 54% practiced home monitoring of BP (HMBP). Medication was modified in 34% of patients by the doctor who called in. Biguanides and Sulfonylureas were the most prescribed oral antidiabetic medications, while Renin Angiotensin Aldosterone System (RAAS) blockers were the most prescribed antihypertensive class. The HMBP was associated with lower systolic BP (t-test 3.49, P = 0.0008). Conclusions: Type 2 diabetic patients managed through telephone during the COVID-19 lockdown reported good level of drug compliance, while improved practice of SMBG, and HMBP resulted in better level of control. The findings of this review suggest that the use of e-consultation can play a role in patient management of Type 2 diabetes even beyond the COVID-19 era including reaching patients in distant locations who are unable to come to the hospital. There is a need for further studies on e-medicine role on various aspects of medical care.
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Introduction: Neonatal diabetes mellitus (NDM) is a rare monogenic form of diabetes occurring mainly in the first 6 months of life. Approximately 30% of transient NDM cases have an activating mutation in the KATP channel genes ABCC8 and KCNJ11. The majority of transfers from insulin to sulfonylureas in patients with KCNJ11 mutations are done inside the hospital. Objectives: To report a case of transient neonatal diabetes mellitus (TNDM) where precision medicine, defining treatment based on molecular diagnosis and technology (intermittent continuous glucose monitoring-iCGM) allowed to make treatment adjustments with the patient safely at home, in times of COVID-19 pandemic. Methods: Case report of a patient with TNDM in use of iCGM. Results: A boy with transient NDM due to the p.E227K mutation in the KCNJ11 gene. Diabetes remitted at 30 months and relapsed at 6 years of age. Insulin was initiated and soon transition to glibenclamide was proposed with the use of iCGM, which allowed the patient to safely stay at home during the transition, especially important in the context of the COVID-19 pandemic. The data was uploaded to an online platform that allowed the medical team to perform remote daily checks on glucose levels and suggest treatment changes. During insulin therapy, the device's 14-day analysis revealed a glucose management index (GMI) of 7,2% and 72% of time in range (TIR). Patient's glucose profile improved rapidly after SU was initiated so that insulin therapy was discontinued. After four months of SU treatment, GMI was 6,2% with 93% of TIR (Figure 1). Conclusions: NDM is a model of a genetic disease that can benefit from precision medicine, where treatment is defined after molecular diagnosis, and that iCGM is a valuable tool that should be considered to monitor glucose, increase safety and speed up dose adjustments in outpatient transition from insulin to glibenclamide. As far as we understand the use of iCGM was not reported in this situation previously.
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NLRP3 inflammasome mediated release of interleukin-1ß (IL-1ß) has been implicated in various diseases, including COVID-19. In this study, rationally designed alkenyl sulfonylurea derivatives were identified as novel, potent and orally bioavailable NLRP3 inhibitors. Compound 7 was found to be potent (IL-1ß IC50 = 35 nM; IL-18 IC50 = 33 nM) and selective NLRP3 inflammasome inhibitor with excellent pharmacokinetic profile having oral bioavailability of 99% in mice.