Alpha-lipoic acid for diabetic peripheral neuropathy.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a frequent complication in people living with type 1 or type 2 diabetes. There is currently no effective treatment for DPN. Although alpha-lipoic acid (ALA, also known as thioctic acid) is widely used, there is no consensus about its benefits and harms. OBJECTIVES: To assess the effects of alpha-lipoic acid as a disease-modifying agent in people with diabetic peripheral neuropathy. SEARCH METHODS: On 11 September 2022, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and two clinical trials registers. We also searched the reference lists of the included studies and relevant review articles for additional references not identified by the electronic searches. SELECTION CRITERIA: We included randomised clinical trials (RCTs) that compared ALA with placebo in adults (aged 18 years or older) and that applied the study interventions for at least six months. There were no language restrictions. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. The primary outcome was change in neuropathy symptoms expressed as changes in the Total Symptom Score (TSS) at six months after randomisation. Secondary outcomes were change in neuropathy symptoms at six to 12 months and at 12 to 24 months, change in impairment, change in any validated quality of life total score, complications of DPN, and adverse events. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: Our analysis incorporated three trials involving 816 participants. Two studies included people with type 1 or type 2 diabetes, while one study included only people with type 2 diabetes. The duration of treatment was between six months and 48 months. We judged all studies at high risk of overall bias due to attrition. ALA compared with placebo probably has little or no effect on neuropathy symptoms measured by TSS (lower score is better) after six months (mean difference (MD) -0.16 points, 95% confidence interval (CI) -0.83 to 0.51; 1 study, 330 participants; moderate-certainty evidence). The CI of this effect estimate did not contain the minimal clinically important difference (MCID) of 0.97 points. ALA compared with placebo may have little or no effect on impairment measured by the Neuropathy Impairment Score-Lower Limbs (NIS-LL; lower score is better) after six months (MD -1.02 points, 95% CI -2.93 to 0.89; 1 study, 245 participants; low-certainty evidence). However, we cannot rule out a significant benefit, because the lower limit of the CI surpassed the MCID of 2 points. There is probably little or no difference between ALA and placebo in terms of adverse events leading to cessation of treatment within six months (risk ratio (RR) 1.48, 95% CI 0.50 to 4.35; 3 studies, 1090 participants; moderate-certainty evidence). No studies reported quality of life or complications associated with DPN. AUTHORS' CONCLUSIONS: Our analysis suggests that ALA probably has little or no effect on neuropathy symptoms or adverse events at six months, and may have little or no effect on impairment at six months. All the studies were at high risk of attrition bias. Therefore, future RCTs should ensure complete follow-up and transparent reporting of any participants missing from the analyses.

The Impact of Antibiotic Use on Mortality in Patients Hospitalized in a COVID-19 Centre from Romania: A Retrospective Study.

Background and Objectives: Considering the significant number of patients worldwide that received empirical antibiotic therapy for COVID-19 infection due to their critical condition and the lack of therapeutical guidelines, we wanted to find out the consequences of antibiotic use in our study population. Materials and Methods: We conducted a retrospective cohort study including symptomatic patients older than 18 years, hospitalized for SARS-CoV-2 between March and December 2020 in the Internal Medicine and Pneumology Departments of Colentina Clinical Hospital. The elected outcome was death, while independent variables were antibiotic therapy and literature-cited parameters associated with mortality in this disease. Results: Out of 198 included patients, 96 (48.48%) patients received antibiotic therapy during hospitalization. Female gender (OR = 2.61, p = 0.04), history of neoplasm (OR = 7.147, p = 0.01), heart failure (OR = 8.62, p = 0.002), and diabetes mellitus (OR = 3.05, p = 0.02) were significantly associated with death in multivariate analysis. Antibiotic treatment showed a higher probability of death both in bivariate (OR = 5.333, p < 0.001) and multivariate analysis adjusted for the aforementioned prognostic factors (OR = 3.55, p = 0.01). Conclusions: After adjusting for confounders, in-hospital antibiotic administration did not improve survival in COVID-19 patients.

Quality of life status determinants in hypertrophic cardiomyopathy as evaluated by the Kansas City Cardiomyopathy Questionnaire.

PURPOSE: The present study evaluated how heart failure (HF) negatively impacts health-related quality of life (HRQoL) in hypertrophic cardiomyopathy (HCM) patients and explored the major clinical determinants associated with HRQoL impairment in this population. METHODS: This was a cross-sectional single-center study of health-related HRQoL that included 91 consecutive patients with HCM. Evaluation was performed based on a comprehensive protocol that included the recommended diagnostic studies, as well as administration of the translated validated version of the Kansas City Cardiomyopathy Questionnaire (KCCQ) (CV Outcomes Inc) as a health status measure. RESULTS: The cohort included 52 (57%) males, median age 58 (20-85) years. The median global KCCQ score was 67 (12.5-100) corresponding to a moderate impairment in HRQoL. There was an inverse correlation between the median global KCCQ score and NYHA class (Kendall's tau b coefficient r - 0.33, p = 0.001). Patients with pulmonary hypertension (PHT), defined as resting pulmonary artery systolic pressure of ≥ 45 mmHg, presented a significantly worse HRQoL as compared to those without PHT (median KCCQ score 56.2 vs 77.5, p = 0.013). The KCCQ score mildly correlated with age (r - 0.18, p = 0.014), history of syncope (r - 0.18, p = 0.045), estimated glomerular filtration rate (eGFR) (r 0.31, p < 0.001), plasmatic creatinine (r - 0.18, p = 0.017) and urea levels (r - 0.27, p < 0.001), left ventricular (LV) end-systolic dimensions (r - 0.18, p = 0.014), maximal provoked intraventricular gradient (r 0.20, p = 0.039), LV ejection fraction (r 0.15, p = 0.04), average E/e' (r - 0.16, p = 0.039), pulmonary acceleration time (r 0.21, p = 0.007), pulmonary artery systolic pressure (r - 0.20, p = 0.016). In ordinal regression, the independent predictors of HRQoL were NYHA class and eGFR. CONCLUSIONS: Patients with HCM and HF present a moderate degree of alteration in HRQoL. This is especially true for patients with PHT and more severe functional impairment. Renal failure and NYHA class are potential markers of HRQoL in clinical practice.

Diet as an environmental trigger in inflammatory bowel disease: a retrospective comparative study in two European cohorts.

BACKGROUND AND AIMS: inflammatory bowel disease development has been associated with several environmental factors, among which, diet can play a key role, probably due to a westernized lifestyle. However, its involvement in the pathogenesis of inflammatory bowel disease (IBD) is difficult to demonstrate. The aim of this study was to analyze dietary composition in a Romanian and Belgian population with IBD. METHODS: an observational retrospective comparative study was performed using two European cohorts (Romanian and Belgian). The IBD group included 76 Romanian and 53 Belgian patients with an IBD diagnosis, while the control group included a total of 56 healthy people (35 Romanians and 21 Belgians). All subjects were interviewed and asked to fill in a questionnaire regarding diet. RESULTS: in the entire IBD cohort (Romanian + Belgian), a significantly increased consumption of sweets (OR 3.36 [95 % CI 1.6,7]), processed and high fat meat (OR 2.5 [95 % CI 1.4, 4.7], fried food (OR 9.5 [3.8, 23.6]), salt (OR 2.8 [1.5, 5.3]), ice cream (OR 3.25 [1.1, 9.8]), mayonnaise (OR 3.49 [1.1, 10.3]), margarine (OR 5.63 [1.64, 19.33]) and chips/nachos/other snacks (OR 2.3 [0.97, 5.73]) were found compared to the healthy control group. The intake of seeds, nuts (OR 0.26 [0.14, 0.52]) and yoghurt consumption (OR 0.44 [0.23, 0.83]) was lower in the IBD group compared to the control group. CONCLUSION: a westernized diet with increased consumption of sweets, processed food, high fat meat, fried food, salt, margarine, snacks, ice cream and mayonnaise seems to be a risk factor for IBD in Romanian and Belgian IBD patients. Intake of seeds, nuts and yoghurt may be a protective factor.

Impaired ankle-brachial index in antiphospholipid syndrome: Beyond the traditional risk factors.

INTRODUCTION: The patients with antiphospholipid syndrome (APS) associate an increased risk of atherosclerosis. OBJECTIVE: To determine the predictors of an abnormal ankle-brachial index (ABI), surrogate measure of atherosclerosis, in patients with APS. METHODS: The ABI was measured according to standard recommendations in 106 patients. Traditional cardiovascular risk factors were assessed in all cases. A large spectrum of APS antibodies was determined in 73 patients. RESULTS: A total of 106 patients diagnosed with APS were included. 28.3% patients included were found to have low ABI. Anti-beta 2-glycoprotein I (aß2GPI) IgG antibodies [4.00 (1.00-79.00) vs 3.00 (0.00-29.00) U/mL, P = 0.02] and antiprothrombin (aPT) IgM antibodies [4.50 (0.00-82.00) vs 3.00 (0.00-14.00) U/mL, P = 0.05] titers were found to be higher in patients with abnormal ABI. However, after multivariate regression analysis, only the aß2GPI IgG titer remained predictor of low ABI (P = 0.04). CONCLUSIONS: aß2GPI IgG associated with impaired ABI in patients with APS. This relation might reflect their involvement in the atherosclerosis occurrence.

Real-world efficacy and safety of ombitasvir, paritaprevir/r+dasabuvir+ribavirin in genotype 1b patients with hepatitis C virus cirrhosis.

BACKGROUND: Direct antiviral agents (DAA) showed very good results in terms of efficacy and safety in clinical trials, but real-life data are still needed in order to confirm this profile. MATERIAL AND METHODS: In Romania, through a nationwide government-funded programme in 2015-2016, approx.5800 patients with virus C cirrhosis received fully reimbursed DAA therapy with OBV/PTV/r+DSV+RBV for 12 weeks. We analysed a national prospective cohort enrolling the first 2070 patients, all with genotype 1b. The only key inclusion criteria was advanced fibrosis (Metavir stage F4) confirmed by Fibromax testing (or liver biopsy/Fibroscan). Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). RESULTS: Forty patients stopped the treatment because of hepatic decompensation (1.9%), 21 stopped because of other adverse events and one was lost to follow-up. This cohort was 51% females, mean age 60 years (25÷82), 67% pretreated, 70% associated NASH, 67% with severe necro-inflammation (severity score 3-Fibromax), 37% with comorbidities, 10.4% with Child Pugh A6, 0.5% B7. The median MELD score was 8.09 (6 ÷ 22). SVR by intention-to-treat was reported in 1999/2070(96.6%), 55/2070 failed to respond. Liver decompensation was statistically associated in multivariate analysis with platelets< 105 /mm3 (P = .03), increased total bilirubin (P < .001), prolonged INR (P = .02), and albumin<3.5 g/dL (P = .03). CONCLUSIONS: OBV/PTV/r+DSV+RBV proved to be highly efficient in our population of cirrhotics with a 96.6% SVR. Serious adverse events related to therapy were reported in 61/2070(2.9%), most of them liver decompensation (1.9%), related to hepatic dysfunction, and lower platelet count.

The impact of anti-U1-RNP positivity: systemic lupus erythematosus versus mixed connective tissue disease.

Anti-U1-RNP positivity remains mandatory for the mixed connective tissue disease (MCTD) diagnosis, reason for which anti-U1-RNP occurrence in patients with lupus clinical features might determine diagnostic issues. Thus, the prevalence of 25-30% for anti-RNP was reported in John Hopkins and LUMINA lupus cohorts and also 13% prevalence for the anti-U1-RNP in Euro-Lupus cohort. Presence of anti-U1-RNP antibodies in patients fulfilling SLE criteria (but not the MCTD ones) was associated with manifestations such as Raynaud phenomenon, musculoskeletal and lung impairment or nail fold capillaroscopy changes, some clinical features frequently encountered in MCTD patients and only rarely described in lupus population. The use of more specific markers such as 70 kDa anti-U1-RNP or anti-Sm-D was proposed for discriminating between SLE and MCTD. In addition, the IgM serotype of anti-U1-RNP seems more frequently expressed in SLE, while the IgG serotype alone in MCTD. Better acknowledgement of possible clinical involvements in lupus subsets, such as the peculiarities related to the anti-U1-RNP positivity, could provide access to early diagnosis of rather rare but possible severe lupus organ impairments (e.g. pulmonary arterial hypertension).

Influence of decision aids on oral anticoagulant prescribing among physicians: a randomised trial.

BACKGROUND: Oral anticoagulants (OAC) are underused in treatment of atrial fibrillation (AF), with differences in patient and physician preferences. For risk communication, the graphic showing risks on treatment contains all the information, therefore, the graphic showing risks without treatment may not be necessary. Here, our objective was to assess whether decision aids require information of risks without treatment and specifically whether presentation of 5-year stroke risk in patients with AF increases use of OACs compared with presentation of 1-year risk and whether decisions on treatment are different when physicians decide their own treatment vs. that of the patient. DESIGN: Randomised controlled trial with 23 factorial design, performed at 12 university hospitals, one internal medicine course and one national medical conference. RESULTS: Of 968 physicians who participated, 83·3% prescribed anticoagulation therapy. Treatment decisions were not influenced by the number of graphics or by the time frame of risk estimation, with risk differences of 0·5% (95% confidence interval, -4·0% to 5·4%) and 3·4% (-1·3% to 8·1%). However, physician-to-patient prescription rates were 5·4% (0·2-10·6%) more frequent after seeing the 5-year risk graphic. Physician-to-self intentions to prescribe occurred less frequently, with risk difference of 15·4% (10·8-20%). Physicians considered the baseline risk and the absolute risk reduction only when prescribing to patients but not to themselves. CONCLUSIONS: Risks could be communicated using decision aids with only one graphic. Showing the risk of stroke at 5 years could increase the prescription of OACs to patients with AF. Faced with the same risk of stroke, physicians prescribed less to themselves than to patients.

Circulating Reticulocalbin 1 and Reticulocalbin 3 in Systemic Sclerosis Patients: Results of a Case Control Study.

BACKGROUND: Proteomic candidate biomarkers for systemic sclerosis (Ssc) useful for appropriate patient evaluation and follow-up were identified in mass-spectrometry studies; however, most of these biomarkers were not evaluated and confirmed on independent patient samples. Up-regulation of reticulocalbin 1 (RCN1) and reticulocalbin 3 (RCN3) in the dermal fibroblast secretome originating from Ssc patients was previously described. The aim of the study was to evaluate circulating RCN1 and RCN3 as candidate biomarkers for Ssc clinical expression. METHODS: 40 consecutive Ssc patients and 20 gender and age matched controls were included. Serum RCN1 and RCN3 was evaluated using commercial ELISA kits. RESULTS: Serum RCN1 and RCN3 were not statistically significant different between Ssc patients and healthy controls. Serum RCN1 and RCN3 were correlated in both Ssc and healthy control groups (p < 0.001). Serum RCN1 was positively correlated with Ssc disease activity score (EUSTAR, p = 0.02) and remained associated with EUSTAR after adjusting for disease duration in multivariate analysis. 6 Ssc patients (15%) had elevated RCN1 values compared to reference values obtained from healthy control samples. These patients had higher prevalence of digital ulcers, higher disease activity scores, and tended to have esophageal hypomotility, calcinosis, telangiectasia, and diffuse Ssc subtype. CONCLUSIONS: RCN1 and RCN3 expression was not statistically significantly different to healthy controls. However, RCN1 was associated with disease activity score and could be used as a stratification biomarker for Ssc patients, as patients with high RCN1 shared a particular disease pattern.