Efficacy and safety of hydroxychloroquine/chloroquine against SARS-CoV-2 infection: A systematic review and meta-analysis

IntroductionHydroxychloroquine (HCQ)/Chloroquine (CQ) has been evaluated for treatment and prophylaxis against SARS-CoV-2 infection in various studies with conflicting results. We performed a systematic review to synthesize the currently available evidence over the efficacy and safety of HCQ/CQ therapy alone against SARS-CoV-2 infection.MethodsWe searched Embase, PubMed, Web of Science, and Cochrane central for randomized controlled trials (RCTs) and prospective cohort studies published until October 15, 2020 and assessing the efficacy of HCQ alone against SARS-CoV-2 infection. We included studies evaluating HCQ/CQ alone as intervention and placebo/standard care as a control group. Retrospective studies and studies using other drugs (namely azithromycin, corticosteroids, immunomodulators, etc.) we excluded. Thirteen RCTs and three prospective cohort studies were included in this review. We pooled data using a random-effect model.ResultsPooled data from 12 studies (9917 participants) showed that HCQs increase mortality as compared to placebo/standard of care (RR 1.10; 95% CI:1.00–1.20). Hydroxychloroquine did not reduce the need for hospitalization in out-patients (RR 0.57; 95% CI 0.31–1.02). HCQ group has a significantly higher rate of any adverse event (RR 2.68; 95% CI 1.55–4.64), as compared to the control group. Also, using HCQ for prophylaxis against SARS-CoV-2 infection did not reduce the risk of acquiring SARS-CoV-2 infection (RR 1.04; 95% CI 0.58–1.88).ConclusionsHCQ therapy for COVID-19 is associated with an increase in mortality and other adverse events. The negative effects are more pronounced in hospitalized patients. Therefore, with the available evidence, HCQ should not be used in prophylaxis or treatment of patients with COVID-19.     

Outcome of humeral shaft fractures treated by functional cast brace

Background:Functional brace application for isolated humeral shaft fracture persistently yields good results. Nonunion though uncommon involves usually the proximal third shaft fractures. Instead of polyethylene bivalve functional brace four plaster sleeves wrapped and molded with little more proximal extension expected to prevent nonunion of proximal third fractures. Periodic compressibility of the cast is likely to yield a better result. This can be applied on the 1^st day of the presentation as an outpatient basis. Comprehensive objective scoring system befitting for fracture humeral shaft is a need.Results:The results were assessed using 100 point scoring system where union allotted 30 points and 60 points allotted for angulations (10), elbow motion (10), shoulder abduction (10), shortening (5), rotation (5), absence of infection (10), absence of nerve palsy during treatment (10). Remaining 10 points were allotted for five items with two points each. They were the absence of skin sore, absence of vascular problem, absence of reflex sympathetic dystrophy (RSD), recovery of paralyzed nerve during injury and recovery of paralyzed nerve during treatment. Results were considered excellent with 90 and above, good with 80–89, fair with 70–79 and poor below 70 point. Results at 6 months were excellent in 43.94% (n = 29), good in 42.42% (n = 28), fair in 9.1% (n = 6), poor in 4.55% (n = 3). Union took place in 98.48% (n = 65) with an average of 10.3 weeks (range 6–16 weeks). 87.5% (n = 7) paralyzed radial nerve recovered. All wounds healed. Four patients had transient skin problem. One patient with mid shaft fracture had nonunion due to the muscle interposition.Conclusion:Modified functional cast brace is one of the options in treatment for humeral shaft fractures as it can be applied on the 1^st day of the presentation in most of the situations. Simple objective scoring system was useful particularly in uneducated patients.     

Conduction characteristics at the crista terminalis during onset of pulmonary vein atrial fibrillation

INTRODUCTION: Focal atrial fibrillation (AF) may initiate with an irregular rapid burst of atrial ectopic (AE) activity from a pulmonary vein (PV) focus, but how AF is maintained it is not known. The crista terminalis (CT) is an important line of block in atrial flutter (AFL), but its role in AF has not been determined. The aim of this study was to examine the conduction properties of the CT during onset of AF. METHODS AND RESULTS: In 10 patients (mean age 38 +/- 8 years), we analyzed conduction across the CT during onset of focal AF from an arrhythmogenic PV and during pacing from the same PV at cycle lengths of 700 and 300 ms. A 20-pole catheter was positioned on the CT using intracardiac echocardiography. In 10 control patients with no history of AF, we analyzed conduction across the CT during pacing from the distal coronary sinus at 700 and 300 ms. In all 10 AF patients, AF was initiated with 1 to 9 AE beats (median 5) from a PV. During sinus rhythm, there were no split components (SC) recorded on the CT. During PV AE activity, discrete SC were recorded on the CT in all patients over 6.3 +/- 0.9 bipoles (3.7 +/- 0.3 cm). Maximal splitting of SC was 66 +/- 31 ms (37-139). There was an inverse relationship between AE coupling intervals and the degree of splitting between SC in all patients. Degeneration to AF was preceded by progressive decrement across the CT. SC were recorded during PV pacing at 700 and 300 ms (maximal distance between SC of 24 +/- 3 ms and 43 +/- 5 ms, respectively, P < 0.001). Maximum SC at CT in controls was 13 +/- 8 ms at 700 ms (P = 0.06 vs AF patients) and 16 +/- 9 ms at 300 ms (P < 0.01 vs AF patients). CONCLUSION: (1) These observations provide evidence of anisotropic, decremental conduction across the CT during onset of focal AF and during pacing from the same PV. A line of functional conduction block develops along this anatomic structure (CT). Whether this line of block acts as an initiator of AF or simply contributes passively to nonuniform fibrillatory conduction is unknown. (2) In some patients with focal AF, development of conduction block along the CT may provide a substrate for typical AFL.     

Functional Impression Technique for an Ocular Prosthesis

The loss of an eye is the most devastating, psychologically damaging experience for a patient. All hope to bring such patients back to their accustomed and comfortable life-style rests on a cosmetically acceptable prosthesis. An intra-orbital ocular prosthesis serves the purpose in those defects where the orbital margins are intact. Though the stock eye may match the natural eye’s iris and sclera in color, the fit of the prosthesis to the tissue bed may not be as good as desired. Herein, a functional ocular impression technique is presented to achieve a better fit of the prosthesis to the defect area. This technique aims to combine cosmetic excellence with comfort for greater benefit to the patient.     

Evaluation of the efficacy of a prosthodontic stent in determining the position of dental implants

Purpose: To evaluate the efficacy of a dual purpose (diagnostic and surgical) acrylic resin stent with gutta percha marker used in conjunction with 3D imaging in determination of the position and inclination of dental implants. Materials and Methods: This study was performed as a case control study. A total of 41 implants, of which 20 had been placed without the use of stents and 3D imaging (control group) and 21 were placed using stents and 3D imaging (study group), were studied. A diagnostic and surgical stent with radio‐opaque indicator (gutta percha) was fabricated to determine the planned prosthetic position and inclination of the implant. Computed tomography images were obtained and were analyzed using Denta Scan software. The position of the implant was analyzed in mesiodistal and buccolingual dimensions in terms of both position and angulation. SPSS v15.0 was used for statistical analysis (p < 0.05 was considered statistically significant). Results: The study group demonstrated an overall 98.9% efficacy of the test technique being used in the study. On qualitative assessment, the results obtained were within the defined ideal threshold level for four of five parameters (distance from buccal and lingual cortical plate, inter‐implant distance, and buccolingual angulation of the implant relative to underlying alveolar bone). For mesiodistal distance from adjacent teeth, the observation was not above threshold value for only one case. For the control group, the overall efficacy was 66.9%. Conclusion: The technique of combined use of a prosthodontic stent and 3D imaging is an efficacious and better technique in achieving an ideal position of dental implants as compared to conventional techniques using periapical and panoramic radiographs and a cast.     

Copper mediated one-pot synthesis of quinazolinones and exploration of piperazine linked quinazoline derivatives as anti-mycobacterial agents

A facile method was developed for the synthesis of quinazolinone derivatives in a one-pot condensation reaction via in situ amine generation using ammonia as the amine source and with the formation of four new C–N bonds in good to excellent yields. With the optimised method, we synthesized a library of piperazine linked quinazoline derivatives and the synthesized compounds were evaluated for their inhibitory activity against Mycobacterium tuberculosis. The compounds 8b, 8e, 8f, 8m, 8n and 8v showed potent anti-mycobacterial activity with MIC values of 2–16 μg mL⁻¹. All the synthesized compounds follow Lipinski''s rules for drug likeness.

A facile method was developed for the synthesis of quinazolinone derivatives in a one-pot condensation reaction via in situ amine generation using ammonia as the amine source and with the formation of four new C–N bonds in good to excellent yields.