Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

Non-invasive assessment of pollutant particles in the lower airway of children and adults

Epidemiological studies in children suggest that inhalation of carbonaceous particulate matter (PM) adversely affects children's respiratory health. However, the relationship between markers of PM exposure and the quantity of particles entering the paediatric airway is unclear. The hypothesis was that, the carbon in alveolar macrophages (AM) reflects individual exposure of healthy children to PM. The aim was to quantify carbon in AM in extreme (biomass smoke) and with fossil fuel exposure. For fossil fuel exposure the aim was also to establish the relationship between median carbon loading per AM per child and: i) markers of exposures at the home address and ii) lung function iii) markers of airway inflammation. Healthy children were recruited from schools. Exercise parameters recorded. Environmental smoke exposure was excluded by salivary cotinine. AM were sampled by induced sputum. Median carbon area was determined by image analysis of digitized light microscopic images of AM. The median area of AM carbon was higher in Ethiopian women compared with UK adults, (p = 0.0002). Median carbon area in Ethiopian children was higher than UK children (p = 0.0002). In fossil-fuel exposure group, a weak, but significantly positive, association was found between median carbon area and modelled primary PM10 (p = 0.022), and a stronger inverse association between median carbon area and FEV1% predicted (p = 0.004), and FEF25-75% predicted (p = 0.004). There was no significant association between median carbon area and exercise variables and markers of airway inflammation

Genotypic characterization of multi-drug resistant coliform bacteria: Insights into their mechanisms of antibiotic resistance using Whole Genome Sequencing

Anthropogenically polluted water is a potential reservoir for pathogenic microorganisms and micro-contaminants like antibiotics. Due to the selective pressure of antibiotics, resident bacteria tend to acquire resistance mechanisms through mutations, genome rearrangements and horizontal gene transfer. (Darvinism: Survival of the fittest!). This study aimed to isolate and characterize multi-drug resistant coliform bacteria from natural water bodies of Pune city and to analyse whole genome sequences for identification of genomic alterations possibly responsible for multi-drug resistance (MDR). The isolates were identified by next generation sequencing. Sequence type of isolates was determined by Multilocus sequence typing (MLST). Genes responsible for antibiotic resistance were identified using Comprehensive Antibiotic Resistance Database (CARD). The isolates were found resistant to third and fourth generation cephalosporins and carbapenems which is very alarming as these are the antibiotics of last resort. The mechanisms of resistance developed by isolates were efflux pump mediated drug resistance and β- lactamase production. Mutation rate was found higher when set of genes responsible for efflux pump mediated drug resistance (mdt A, mdt B, mdt C, mex J, mex K, opr N) was analysed. Mutation leading to change in single amino acid (Arg-235 to Lys) was detected in Pseudomonas aeruginosa ST- 635 for the gene blaPDC-3 . Escherichia coli ST-410 and ST- 617 were found single amino acid variants for the gene blaCMY- 47 (Pro-121 to Ser). Mutations observed in CMY-47 and PDC-3 are indicative of rapid evolution of AmpC β- lactamases. Indiscriminate use of antibiotics has resulted into emergence and dissemination of MDR leading to antibiotic- driven adaptive bacterial evolution

Spherical agglomeration of mefenamic acid and nabumetone to improve micromeritics and solubility: A technical note

Spherical agglomeration techniques were developed for improving the flow and compressibility characteristics of microcrystalline mefenamic acid and nabumetone. The process involved agglomerating microcrystals using agglomerating solvents. Temperature and speed of agitation were optimized to obtain spherical agglomerates in a desired range, which was found to be essential to enhance compressibility. Incorporation of polymer HPMC during agglomeration significantly enhanced the dissolution rate of mefenamic acid while incorporation of solubilizing agent lecithin improved the solubility of nabumetone. Thus, spherical agglomeration is an important technique for improving direct compressibility of pharmaceutical powders and is especially useful when the drug dosage is high

Global impact of COVID-19 on stroke care.

BACKGROUND: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide. AIMS: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior). METHODS: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers. RESULTS: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, -19.7 to -18.7), 11.5% (95%CI, -12.6 to -10.6), and 12.7% (95%CI, -13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (-20.5%) had greater declines in mechanical thrombectomy volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p \u3c 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions. CONCLUSION: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes