Efficacy of early treatment with hydroxychloroquine in people with mild to moderate COVID-19: A systematic review and meta-analysis

IntroductionNo early treatment intervention for COVID-19 has proven effective to date. We systematically reviewed the efficacy of hydroxychloroquine as early treatment for COVID-19.Material and methodsRandomized controlled trials (RCTs) evaluating hydroxychloroquine for early treatment of COVID-19 were searched in five engines and preprint websites until September 14, 2021. Primary outcomes were hospitalization and all-cause mortality. Secondary outcomes included COVID-19 symptom resolution, viral clearance, and adverse events. Inverse variance random-effects meta-analyses were performed and quality of evidence (QoE) per outcome was assessed with GRADE methods.ResultsFive RCTs (n=1848) were included. The comparator was placebo in four RCTs and usual care in one RCT. The RCTs used hydroxychloroquine total doses between 1,600 and 4,400 mg and had follow up times between 14 and 90 days. Compared to the controls, early treatment with hydroxychloroquine did not reduce hospitalizations (RR 0.80, 95%CI 0.47-1.36, I2=2%, 5 RCTs, low QoE), all-cause mortality (RR 0.77, 95%CI 0.16-3.68, I2=0%, 5 RCTs, very low QoE), symptom resolution (RR 0.94, 95%CI 0.77-1.16, I2=71%, 3 RCTs, low QoE) or viral clearance at 14 days (RR 1.02, 95%CI 0.82-1.27, I2=65%, 2 RCTs, low QoE). There was a higher non-significant increase of adverse events with hydroxychloroquine vs. controls (RR 2.17, 95%CI 0.86-5.45, I2=92%, 5 RCTs, very low QoE).ConclusionsHydroxychloroquine was not efficacious as early treatment for COVID-19 infections in RCTs with low to very low quality of evidence for all outcomes. More RCTs are needed to elucidate the efficacy of hydroxychloroquine as early treatment intervention.

Applications of auditory evoked potentials in tinnitus: a review

Background and Aim: Subjective tinnitus is a phantom auditory perception caused by different factors and affects the patient’s quality of life. The tinnitus pathophysiology is not fully unders­tood; therefore, there is no effective treatment for tinnitus. Along with other methods, auditory evo­ked potentials (AEPs) may be helpful in unders­tanding this condition and the involved struc­tures. This study aimed to review the applications of AEPs in tinnitus studies. Recent Findings: The studies investigating tinnitus were categorized into three groups of tinnitus pathophysiology, pre- or post-treatment/intervention evaluation of tinnitus, and objective diagnosis of tinnitus. Contradictory and unrep­eatable findings were observed in each group. Conclusion: Discrepancies in the results of AEPs studies can be due to between-group and within-group differences, lack of proper match­ing in terms of tinnitus etiology and hearing loss, and difference in neurophysiologic models of tinnitus.

Impact of Comorbid Alcohol Use Disorder on Health-Related Quality of Life Among Patients With Depressive Symptoms

Background and Aim: In psychiatric clinical practice, comorbidity of depression and alcohol use disorder (AUD) is common. Both disorders have a negative impact on health-related quality of life (HRQoL) in general population. However, research on the impact of comorbid AUD on HRQoL among clinically depressed patients is limited. The purpose of this study was to explore the impact of a psychosocial treatment intervention on HRQoL for depressive patients in specialized psychiatric care with a special focus on the impact of AUD on HRQoL.Material and Methods: Subjects were 242 patients of the Ostrobothnia Depression Study (ClinicalTrials.gov Identifier NCT02520271). Patients referred to specialized psychiatric care who scored at least 17 points on the Beck Depression Inventory at baseline and who had no psychotic disorders were included in the ODS. The treatment intervention in ODS comprised behavioral activation for all but began with motivational interviewing for those with AUD. HRQoL was assessed regularly during 24-month follow-up by the 15D instrument. In the present study, HRQoL of ODS patients with or without AUD was compared and the factors explaining 15D score analyzed with a linear mixed model. In order to specify the impact of clinical depression on HRQoL during the early phase of treatment intervention, a general population sample of the Finnish Health 2011 Survey was used as an additional reference group.Results: HRQoL improved among all ODS study sample patients regardless of comorbid AUD during the first year of follow-up. During 12–24 months of follow-up the difference between groups was seen as HRQoL continued to improve only among the non-AUD patients. A combination of male gender, anxiety disorder, and AUD was associated with the poorest HRQoL in this sample. In combined sample analyses with the reference group, clinical depression had an impact on HRQoL in short-term follow-up regardless of the treatment intervention.Conclusions: This study suggests that, in terms of improvement in HRQoL, the heterogenous group of depressive patients in specialized psychiatric care can be successfully treated with behavioral activation in combination with motivational interviewing for those with AUD.Clinical Trial Registration:ClinicalTrials.gov Identifier: NCT02520271. Ostrobothnia Depression Study (ODS). A Naturalistic Follow-up Study on Depression and Related Substance Use Disorders. (2015). Available online at: https://clinicaltrials.gov/ct2/show/NCT02520271.

Using electrocochleography to detect sensory and neural damages in a gerbil model

Hearing is one of the five sensory organs that allows us to interact with society and our environment. However, one in eight Americans suffers from sensorineural hearing loss that is great enough to adversely impact their daily life. There is an urgent need to identify what part/degree of the auditory pathway (sensory or neural) is compromised so that appropriate treatment/intervention can be implemented. Single- or two-tone evoked potentials, the electrocochleography (eCochG), were measured along the auditory pathway, i.e., at the round window and remotely at the vertex, with simultaneous recordings of ear canal distortion product otoacoustic emissions. Sensory (cochlear) and neural components in the (remote-) eCochG responses showed distinct level- and frequency-dependent features allowing to be differentiated from each other. Specifically, the distortion products in the (remote-)eCochGs can precisely localize the sensory damage showing that they are effective to determine the sensory or neural damage along the auditory pathway.

Metabolic and Lipoprotein Profiling of Pancreatic Ductal Adenocarcinoma Patients of African Ancestry

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a characteristic dysregulated metabolism. Abnormal clinicopathological features linked to defective metabolic and inflammatory response pathways can induce PDAC development and progression. In this study, we investigated the metabolites and lipoproteins profiles of PDAC patients of African ancestry. Nuclear Magnetic Resonance (NMR) spectroscopy was conducted on serum obtained from consenting individuals (34 PDAC, 6 Chronic Pancreatitis, and 6 healthy participants). Seventy-five signals were quantified from each NMR spectrum. The Liposcale test was used for lipoprotein characterization. Spearman’s correlation and Kapan Meier tests were conducted for correlation and survival analyses respectively. In our patient cohort, the results demonstrated that levels of metabolites involved in the glycolytic pathway increased with the tumour stage. Raised ethanol and 3-hydroxybutyrate were independently correlated with a shorter patient survival time, irrespective of tumour stage. Furthermore, increased levels of bilirubin resulted in an abnormal lipoprotein profile in PDAC patients. Additionally, we observed that the levels of a panel of metabolites (such as glucose, lactate) and lipoproteins correlated with those of inflammatory markers. Taken together, the metabolic phenotype can help distinguish PDAC severity and be used in predicting patient survival and in informing treatment intervention.

Gut Microbiota Shifts Favorably with Delivery of Handwashing with Soap and Water Treatment Intervention in a Prospective Cohort (CHoBI7 Trial)

Cholera can result in the expulsion of important microbiota from the gut and result in death if left untreated. The disease transmits mainly via drinking water carrying Vibrio cholerae; and household contacts (HHC) of cholera patients are at elevated risk during the first week of infection. The gut microbiota profiles of HHC-children of cholera patients at Dhaka city slums were investigated before (day 0) and after (day 8) delivery of chlorinated water as part of the cholera-hospital-based intervention for 7 days (CHoBI7), a randomized controlled trial. Results of sequencing and analysis of bacterial community DNA revealed the predominance of two bacterial phyla: Bacteroidetes and Firmicutes at day 0 with a relative abundance of 62 ± 6 (mean ± SEM %) and 32 ± 7, respectively. The pattern reversed at day 8 with a decreased relative abundance of Bacteroidetes (39 ± 12) and an increased abundance of Firmicutes (49 ± 12). Of 65 bacterial families confirmed at day 0, six belonging to Proteobacteria including Vibrionaceae disappeared at day 8. Interestingly, the relative abundance of four Firmicutes families– Lachnospiraceae, Bifidobacteriaceae, Clostridiaceae, and Ruminococcaceae was increased in all five study children at day 8. The observed exclusion of pathogenic Proteobacteria and enhancement of beneficial Firmicutes in the gut of children delivered with chlorinated water as part of WASH intervention reflect a great promise of the CHoBI7 program in preventing cholera and improving child health.