Ketamine as adjunctive or monotherapy for post-intubation sedation in patients with trauma on mechanical ventilation: A rapid review.

Background: The effectiveness of ketamine as adjunctive or monotherapy for post-intubation sedation in adults with trauma on mechanical ventilation is unclear. Methods: A rapid review of systematic reviews of randomized controlled trials, then randomized controlled trials or observational studies was conducted searching three electronic databases (PubMed, Embase, Cochrane Library) and one clinical trial registry on June 1, 2022. We used a prespecified protocol following Cochrane rapid review methods. Results: We identified eight systematic reviews of randomized controlled trials and observational studies. Among the included reviews, only the most relevant, up to date, highest quality-assessed reviews and reviews that reported on critical outcomes were considered. Adjunctive ketamine showed a morphine sparing effect (MD -13.19 µmg kg-1 h-1, 95 % CI -22.10 to -4.28, moderate certainty of evidence, 6 RCTs), but no to little effect on midazolam sparing effect (MD 0.75 µmg kg-1 h-1, 95 % CI -1.11 to 2.61, low certainty of evidence, 6 RCTs) or duration of mechanical ventilation in days (MD -0.17 days, 95 % CI -3.03 to 2.69, moderate certainty of evidence, 3 RCTs).Adjunctive ketamine therapy may reduce mortality (OR 0.88, 95 % CI 0.54 to 1.43, P = 0.60, very low certainty of evidence, 5 RCTs, n = 3076 patients) resulting in 30 fewer deaths per 1000, ranging from 132 fewer to 87 more, but the evidence is very uncertain. Ketamine results in little to no difference in length of ICU stay (MD 0.04 days, 95 % CI -0.12 to 0.20, high certainty of evidence, 5 RCTs n = 390 patients) or length of hospital stay (MD -0.53 days, 95 % CI -1.36 to 0.30, high certainty of evidence, 5 RCTs, n = 277 patients).Monotherapy may have a positive effect on respiratory and haemodynamic outcomes, however the evidence is very uncertain. Conclusion: Adjunctive ketamine for post-intubation analgosedation results in a moderate meaningful net benefit but there is uncertainty for benefit and harms as monotherapy.

Signal of harm in morphine use in adults with acute pulmonary oedema: A rapid systematic review.

BACKGROUND: Heart failure affects nearly 65 million people globally, resulting in recurrent hospital admissions and substantial healthcare expenditure. The use of morphine in the management of acute pulmonary oedema remains controversial, with conflicting guidance and significant variation in practice. Synthesised evidence is needed to inform standard treatment guidelines and clinical practice. OBJECTIVE: To determine whether morphine should be used in the treatment of acute pulmonary oedema (APE) in adults. METHODS: A rapid review of systematic reviews of randomised controlled trials or observational studies, and then randomised controlled trials, was conducted searching three electronic databases (PubMed, Embase, Cochrane Library) and one clinical trial registry on 12 February 2022. We used a prespecified protocol following Cochrane rapid review methods and aligned to the National Standard Treatment Guidelines and Essential Medicines List methodology. We first considered relevant high-quality systematic reviews of randomised controlled trials or observational studies, then (if required) randomised controlled trials to inform time-sensitive or urgent evidence requests, clinical practice, policy, or standard treatment guidelines. RESULTS: We identified four systematic reviews of observational studies. The two most relevant, up-to-date, and highest-quality reviews were used to inform evidence for critical outcomes. Morphine may increase in-hospital mortality (odds ratio (OR) 1.78; 95% confidence interval (CI) 1.01 - 3.13; low certainty of evidence; six observational studies, n=151 735 participants), resulting in 15 more per 1 000 hospital deaths, ranging from 0 to 40 more hospital deaths. Morphine may result in a large increase in invasive mechanical ventilation (OR 2.72; 95% CI 1.09 - 6.80; low certainty of evidence; four observational studies, n=167 847 participants), resulting in 45 more per 1 000 ventilations, ranging from 2 more to 136 more. Adverse events and hospital length of stay were not measured across reviews or trials. CONCLUSION: Based on the most recent, relevant and best-available quality evidence, morphine use in adults with APE may increase in-hospital and all-cause mortality and may result in a large increase in the need for invasive mechanical ventilation compared to not using morphine. Recommending against the use of morphine in pulmonary oedema may improve patient outcomes. Disinvesting in morphine for this indication may result in cost savings, noting the possible accrued benefits of fewer patients requiring invasive ventilation and management of morphine-related side-effects.

Fit testing and comfort evaluation of prophylactic dressing use for healthcare workers under N95/P2 respirators in one health service district in Australia.

BACKGROUND: This study evaluated the use of prophylactic dressings (silicone foam, silicone tape, hydrocolloid) under N95/P2 respirators to determine which dressings fit successfully. AIM: The aim was to develop a health service protocol for one state in Australia. METHODS: Data were collected during August and September 2021 as part of the Respiratory Protection Programme on 600 health workers using three types of prophylactic dressings. Five different types of respirators were used. Participant healthcare workers rated comfort on a four-point Likert scale. RESULTS: Successful fit was achieved by 63.6% of the respirator-dressing combinations. The best-performing respirator-dressing combination was the Trident® respirator with dressing Mepilex® Lite silicone foam (90.2% pass rate). High pass rates were found in the Trident® respirator with Mepilex® Border Lite with SofSicure silicone tape (79.1%); the 3M™ 1860 respirator with Mepilex® Border Lite with SofSicure silicone tape (74%); and the BSN orange duckbill respirator with Mepilex® Lite silicone foam (69.8%). The poorest-performing combination was the BYD™ respirator with Mepilex® Border Lite with SofSicure silicone tape (25.9% pass rate). Uncorrected chi-squared tests for association revealed significant associations between dressing type and outcome (P=0.004) and respirator type and outcome (P<0.001). Most respondents (82%) found the dressing combination markedly comfortable. CONCLUSIONS: When using prophylactic dressings under N95/P2 respirators, it is necessary to perform a fit test. In this study Trident® respirators had the highest probability of successful fit, while BYD™ respirators had the lowest. Combining Trident® respirators with Mepilex® Lite dressing was optimal. Most participants reported greater comfort with the dressings under the respirators.

Meta-analytic magic, ivermectin, and socially responsible reporting.

Some clinicians prescribe ivermectin for COVID-19 despite a lack of support from any credible South African professional body. They argue that when faced by clinical urgency, weak signals of efficacy should trigger action if harm is unlikely. Several recent reviews found an apparent mortality benefit by including studies at high risk of bias and with active rather than placebo controls. If these studies are discounted, the pooled mortality effect is no longer statistically significant, and evidence of benefit is very weak. Relying on this evidence could cause clinical harm if used to justify vaccine hesitancy. Clinicians remain responsible for ensuring that guidance they follow is both legitimate and reliable. In the ivermectin debate, evidence-based medicine (EBM) principles have largely been ignored under the guise thatin a pandemic the 'rules are different', probably to the detriment of vulnerable patients and certainly to the detriment of the profession's image. Medical schools and professional interest groups are responsible for transforming EBM from a taught but seldom-used tool into a process of lifelong learning, promoting a consistent call for evidence-based and unconflicted debate integral to clinical practice.

Combination of Imaging Features and Clinical Biomarkers Predicts Positive Pathology and Microbiology Findings Suggestive of Spondylodiscitis in Patients Undergoing Image-Guided Percutaneous Biopsy.

BACKGROUND AND PURPOSE: Pathology and microbiology results for suspected spondylodiscitis on MR imaging are often negative in up to 70% of cases. We aimed to predict whether MR imaging features will add diagnostic value when combined with clinical biomarkers to predict positive findings of spondylodiscitis on pathology and/or microbiology from percutaneous biopsy. MATERIALS AND METHODS: In this retrospective single-center institutional review board-approved study, patients with radiologically suspected spondylodiscitis and having undergone percutaneous biopsies were assessed. Demographic characteristics, laboratory values, and tissue and blood cultures were collected. Pathology and microbiology results were used as end points. Three independent observers provided MR imaging-based scoring for typical MR imaging features for spondylodiscitis. Multivariate logistic regression and receiver operating characteristic analysis were performed to determine an optimal combination of imaging and clinical biomarkers in predicting positive findings on pathology and/or microbiology from percutaneous biopsy suggestive of spondylodiscitis. RESULTS: Our patient cohort consisted of 72 patients, of whom 33.3% (24/72) had spondylodiscitis. The mean age was 63 ± 16 years with a male/female ratio of 41:31. Logistic regression revealed a combination with an area under the curve of 0.72 for pathology and 0.68 for pathology and/or microbiology. Epidural enhancement on MR imaging improved predictive performance to 0.87 for pathology and 0.78 for pathology and/or microbiology. CONCLUSIONS: Our findings demonstrate that epidural enhancement on MR imaging added diagnostic value when combined with clinical biomarkers to help predict which patients undergoing percutaneous biopsy will have positive findings for spondylodiscitis on pathology and/or microbiology.

Bone health among older persons in medical clinic: A clinical audit.

Osteoporosis is commonly underdiagnosed and undertreated. We performed a clinical audit to assess the risk factors and clinical care for osteoporosis among older persons who attended medical clinic during a 4-week period in August 2013. There was a total of 128 patients with a mean age of 73.1±5.8 years, and 20.3%. had a history of fall. Fracture Risk Assessment Tool (FRAX) scores assessment showed 14.2% and 68.8% had a 10-year risk of major osteoporotic and hip fractures respectively. Only 6.3% underwent Dual-energy X-ray absorptiometry (DXA) and 73.4% did not receive any preventive treatment for osteoporosis. Older persons attending medical clinic at high risk of osteoporosis fractures did not receive appropriate screening and treatment. There is a need to improve the suboptimal care for bone health among older persons.

Essential medicine selection during the COVID-19 pandemic: Enabling access in uncharted territory.

The COVID-19 pandemic requires urgent decisions regarding treatment policy in the face of rapidly evolving evidence. In response, the South African Essential Medicines List Committee established a subcommittee to systematically review and appraise emerging evidence, within very short timelines, in order to inform the National Department of Health COVID-19 treatment guidelines. To date, the subcommittee has reviewed 14 potential treatments, and made recommendations based on local context, feasibility, resource requirements and equity. Here we describe the rapid review and evidence-to-decision process, using remdesivir and dexamethasone as examples. Our experience is that conducting rapid reviews is a practical and efficient way to address medicine policy questions under pandemic conditions.

Thrombotic thrombocytopenic purpura-like syndrome associated with arcanobacterium pyogenes endocarditis in a post-transplant patient: A case report.

Systemic Arcanobacterium pyogenes is a rare bacterial infection in humans.1The diagnosis of thrombotic thrombocytopenic purpura (TTP)-like syndrome and infective endocarditis (IE) is often elusive. We report a case of TTP-like syndrome associated with A. pyogenes endocarditis in a post-allogenic transplant patient.

Impact of continuous low-dose antibiotic prophylaxis on growth in children with vesicoureteral reflux.

BACKGROUND: Continuous antibiotic prophylaxis (CAP) is a mainstay of treatment for children with vesicoureteral reflux (VUR). There has been an increasing focus on the effect of antibiotics on gut microbiota and subsequent repercussions on growth. Continuous antibiotic prophylaxis is generally considered safe; however, its impact on growth in children with VUR remains unknown. OBJECTIVE: This objective of this study was to determine whether CAP altered height, weight, or body mass index (BMI) in children with VUR. STUDY DESIGN: Children diagnosed with primary VUR were identified. Demographics including weight and height percentiles, BMI and BMI percentiles, age, gender, antibiotic class, prior antibiotic use, urinary tract infection history, and breakthrough infections were tested in univariate and multivariate analyses. Primary outcome was change in BMI as well as weight, height, and BMI percentiles. RESULTS: One hundred eighty patients (146 girls, 34 boys) were prescribed CAP at mean age of 29.2 ± 26.2 months. Mean follow-up on CAP was 4.1 ± 3.3 years, with median follow-up of 3.08 years. Mean increase in weight percentile was 1.49 (2.02 males, 1.37 females; P = 0.46). Mean decrease in height percentile was -4.44 (-2.18 males, -4.95 females; P = 0.51). Age at diagnosis (P = 0.004) and history of prior treatment courses of antibiotics (P = 0.007) were associated with a significant BMI increase (Fig. 1). Body mass index percentile increased from 58.4 to 66.5; however, this increase was only significant in children aged above 1 year (P < 0.0001). Of note, children above 1 year of age were significantly more likely to have a history of prior treatment courses of antibiotics (58% vs 32%; P < 0.0001), and when controlling for prior antibiotic use, the increase in BMI percentile in those over 1 year of age did not reach significance. DISCUSSION: The use of antibiotics has been associated with alterations in pediatric growth parameters in both animal models and clinical studies. However, little information exists on the impact of prophylactic-dosed antibiotics on growth. While this study is limited by the retrospective analysis and small sample size, it was found that the use of CAP did impact growth parameters, with a stronger effect seen in children who had received prior treatment courses of antibiotics before the infection leading to the initiation of CAP. CONCLUSION: Continuous antibiotic prophylaxis was correlated with significant increase in BMI in children with prior antibiotic usage and a significant increase in BMI percentile in children aged above 1 year. Continuous antibiotic prophylaxis was also associated with decreased height percentiles, particularly in patients aged less than 1 year, though it did not reach statistical significance. Further analysis is needed to investigate whether these effects on weight, height, and BMI are persistent and clinically significant.

Heart Failure and Frailty in the Community-Living Elderly Population: What the UFO Study Will Tell Us.

Heart failure and frailty are clinical syndromes that present with overlapping phenotypic characteristics. Importantly, their co-presence is associated with increased mortality and morbidity. While mechanical and electrical device therapies for heart failure are vital for select patients with advanced stage disease, the majority of patients and especially those with undiagnosed heart failure would benefit from early disease detection and prompt initiation of guideline-directed medical therapies. In this article, we review the problematic interactions between heart failure and frailty, introduce a focused cardiac screening program for community-living elderly initiated by a mobile communication device app leading to the Undiagnosed heart Failure in frail Older individuals (UFO) study, and discuss how the knowledge of pre-frailty and frailty status could be exploited for the detection of previously undiagnosed heart failure or advanced cardiac disease. The widespread use of mobile devices coupled with increasing availability of novel, effective medical and minimally invasive therapies have incentivized new approaches to heart failure case finding and disease management.

FOLFOX and intensified split-course chemoradiation as initial treatment for rectal cancer with synchronous metastases.

BACKGROUND: Optimal initial management of rectal carcinoma with synchronous metastases (RCSM) is controversial - both for patients being treated with curative and palliative intent. This study aims to evaluate the use of an upfront treatment strategy combining FOLFOX chemotherapy with split-course pelvic chemoradiation (FOLFOX + CRT) for patients with RCSM. MATERIAL AND METHODS: An analysis of all patients who commenced treatment with FOLFOX + CRT at our institutions between January 2009 and June 2014 was performed. The regimen consisted of a total of 12 weeks of treatment with split-course pelvic chemoradiation (50.4Gy with concurrent oxaliplatin and 5-FU) alternating with FOLFOX chemotherapy. Restaging imaging was performed following treatment, with subsequent management as per local standard of care. RESULTS: 78 patients (15 with resectable liver-only metastases) were identified. 77 (99%) completed at least 45Gy of radiation and 87% completed ≥75% of planned dose intensity of both oxaliplatin and 5FU. Two (2.6%) patients died within 30 days of treatment. Rates of radiological complete or partial response for local and metastatic disease were 90% and 66%, respectively. 24% patients had radiological disease progression of metastatic disease. Median overall survival for patients with unresectable metastatic disease at baseline was 23 months (95%CI: 19-28). 12 patients underwent radical surgery to both the rectum and liver and had an estimated 3-year overall survival rate of 62% (95%CI: 37-100). For those patients who did not proceed to rectal surgery, only 7% required palliative re-irradiation or surgery at a later date and all >20months from initial treatment. CONCLUSIONS: In patients with unresectable metastatic disease, FOLFOX + CRT provides durable pelvic control for the majority without the need for additional local treatment. For patients with an advanced primary tumor and synchronous resectable liver-only metastases, FOLFOX + CRT can be considered a feasible and tolerable upfront treatment option.

The influence of intensive care unit-acquired central line-associated bloodstream infection on in-hospital mortality: A single-center risk-adjusted analysis.

OBJECTIVE: To explore the risk-adjusted association between intensive care unit (ICU)-acquired central line-associated bloodstream infection (CLABSI) and in-hospital mortality. DESIGN: Retrospective observational study. SETTING: Forty-five-bed adult ICU. PATIENTS: All non-extracorporeal membrane oxygenation ICU admissions between July 1, 2008, and April 30, 2014, requiring a central venous catheter (CVC), with a length of stay > 48 hours, were included. METHODS: Data were extracted from our infection prevention and ICU databases. A multivariable logistic regression model was constructed to identify independent risk factors for ICU-acquired CLABSI. The propensity toward developing CLABSI was then included in a logistic regression of in-hospital mortality. RESULTS: Six thousand three hundred fifty-three admissions were included. Forty-six cases of ICU-acquired CLABSI were identified. The overall CLABSI rate was 1.12 per 1,000 ICU CVC-days. Significant independent risk factors for ICU-acquired CLABSI included: double lumen catheter insertion (odds ratio [OR], 2.59; 95% confidence interval [CI], 1.16-5.77), CVC exposure > 7 days (OR, 2.07; 95% CI, 1.06-4.04), and CVC insertion before 2011 (OR, 2.20; 95% CI, 1.22-3.97). ICU-acquired CLABSI was crudely associated with greater in-hospital mortality, although this was attenuated once the propensity to develop CLABSI was adjusted for (OR, 1.20; 95% CI, 0.54-2.68). CONCLUSIONS: A greater propensity toward ICU-acquired CLABSI was independently associated with higher in-hospital mortality, although line infection itself was not. The requirement for prolonged specialized central venous access appears to be a key risk factor for ICU-acquired CLABSI, and likely informs mortality as a marker of persistent organ dysfunction.

Antiphospholipid syndrome in Sarawak: real world experience in a developing country.

We performed a cross-sectional study of all antiphospholipid syndrome (APS) patients during an 8-year period (2006-2013) to describe the clinical features, serology profiles, treatment regimes, and outcomes in our center. There were a total of 59 patients in our study with the female to male ratio of 9:1. They have a mean age of 41.6 ± 12.1 years and a mean duration of illness of 38.4 ± 68.5 months. The majority of patients presented with vascular thrombosis (69.5 %) with equal arterial and venous involvements. Twenty-six patients (44.1 %) presented with obstetric complications with recurrent abortions (32.2 %) as the main manifestation. Most patients were on daily warfarin doses of 2-6 mg (91.0 %) with target INR of 2-3. There was neither recurrent thrombosis nor bleeding complications documented. There were 80 % live births following treatment in our patients.

Phase II trial evaluating the feasibility of interdigitating folfox with chemoradiotherapy in locally advanced and metastatic rectal cancer.

BACKGROUND: Patients (pts) with metastatic rectal cancer and symptomatic primary, require local and systemic control. Chemotherapy used during chemoradiotherapy (CRT) is adequate for radiosensitisation, but suboptimal for systemic control. The aim of this phase II study was to assess tolerability, local/systemic benefits, of a novel regimen delivering interdigitating intensive chemotherapy with radical CRT. METHODS: Eligible pts had untreated synchronous symptomatic primary/metastatic rectal cancer. A total of 12 weeks of treatment with split-course pelvic CRT (total 50.4 Gy with concurrent oxaliplatin and 5-FU infusion) alternating with FOLFOX chemotherapy. All pts staged with CT, MRI and FDG-PET pre and post treatment. RESULTS: Twenty-six pts were treated. Rectal primary MRI stage: T3 81% and T4 15%. Liver metastases in 81%. Twenty-four pts (92%) completed the 12-week regimen. All patients received planned RT dose, and for both agents over 88% of patients achieved a relative dose intensity of >75%. Grade 3 toxicities: neutropenia 23%, diarrhoea 15%, and radiation skin reaction 12%. Grade 4 toxicity: neutropenia 15%. FDG-PET metabolic response rate for rectal primary 96%, and for metastatic disease 60%. CONCLUSIONS: Delivery of interdigitating chemotherapy with radical CRT was feasible to treat both primary and metastatic rectal cancer. High completion and response rates were encouraging.

Role of (chemo)-radiotherapy in resectable gastric cancer.

The prognosis of patients with locally advanced gastric cancer remains poor, despite radical surgical resection. Adjuvant therapy has been shown to improve survival and, in Western countries, is delivered either postoperatively (chemoradiotherapy) or perioperatively (chemotherapy). Debate continues as to which of these represents the optimal strategy. High-dose gastric irradiation comes at the expense of significant toxicity, and increasing efforts have focused on attempts to reduce toxicity and normal tissue doses. The development of advancing radiotherapy technologies now allows improved target delineation and coverage. However, gastric irradiation remains technically challenging and requires an understanding of postoperative surgical anatomy, patterns of failure and lymph node drainage, as well as an appreciation of the uncertainties around organ motion and filling. Ongoing trials are examining the optimal strategy in which to incorporate (chemo)-radiotherapy, as well as the addition of targeted therapies, in gastric cancer. This overview discusses the current role and evidence for (chemo)-radiotherapy, as well as the technical challenges encountered in the radiotherapeutic management of resectable gastric cancer.

Definitive chemoradiotherapy for oesophageal cancer -- a promising start on an exciting journey.

Despite many advances in the management of oesophageal cancer, survival rates remain poor. Currently there is no clear consensus on the optimum management modality for localised disease. Surgery alone or combined with neoadjuvant chemotherapy or chemoradiotherapy and definitive chemoradiotherapy are all treatment options used for treating selected patient groups throughout the world. This overview discusses the evidence for definitive chemoradiotherapy, its role for certain patient groups and compared with other treatment options and how it has evolved with emerging technologies over recent decades. It highlights some key areas of research for future trials, including more precise treatment delivery, treatment intensification and a possible randomised controlled trial comparing radiation and surgical-based treatment.