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.

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.

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.

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.

Augmentation of thrombin generation in neonates undergoing cardiopulmonary bypass.

INTRODUCTION: Factor concentrates are currently available and becoming increasingly used off-label for treatment of bleeding. We compared recombinant activated factor VII (rFVIIa) with three-factor prothrombin complex concentrate (3F-PCC) for the ability to augment thrombin generation (TG) in neonatal plasma after cardiopulmonary bypass (CPB). First, we used a computer-simulated coagulation model to assess the impact of rFVIIa and 3F-PCC, and then performed similar measurements ex vivo using plasma from neonates undergoing CPB. METHODS: Simulated TG was computed according to the coagulation factor levels from umbilical cord plasma and the therapeutic levels of rFVIIa, 3F-PCC, or both. Subsequently, 11 neonates undergoing cardiac surgery were enrolled. Two blood samples were obtained from each neonate: pre-CPB and post-CPB after platelet and cryoprecipitate transfusion. The post-CPB products sample was divided into control (no treatment), control plus rFVIIa (60 nM), and control plus 3F-PCC (0.3 IU ml(-1)) aliquots. Three parameters of TG were measured ex vivo. RESULTS: The computer-simulated post-CPB model demonstrated that rFVIIa failed to substantially improve lag time, TG rate and peak thrombin without supplementing prothrombin. Ex vivo data showed that addition of rFVIIa post-CPB significantly shortened lag time; however, rate and peak were not statistically significantly improved. Conversely, 3F-PCC improved all TG parameters in parallel with increased prothrombin levels in both simulated and ex vivo post-CPB samples. CONCLUSIONS: Our data highlight the importance of prothrombin replacement in restoring TG. Despite a low content of FVII, 3F-PCC exerts potent procoagulant activity compared with rFVIIa ex vivo. Further clinical evaluation regarding the efficacy and safety of 3F-PCC is warranted.

The Victorian Lung Cancer Registry pilot: improving the quality of lung cancer care through the use of a disease quality registry.

BACKGROUND: Lung cancer remains a major disease burden in Victoria (Australia) and requires a complex and multidisciplinary approach to ensure optimal care and outcomes. To date, no uniform mechanism is available to capture standardized population-based outcomes and thereby provide benchmarking. The establishment of such a data platform is, therefore, a primary requisite to enable description of process and outcome in lung cancer care and to drive improvement in the quality of care provided to individuals with lung cancer. MATERIALS AND METHODS: A disease quality registry pilot has been established to capture prospective data on all adult patients with clinical or tissue diagnoses of small cell and non-small cell lung cancer. Steering and management committees provide clinical governance and supervise quality indicator selection. Quality indicators were selected following extensive literature review and evaluation of established clinical practice guidelines. A minimum dataset has been established and training and data capture by data collectors is facilitated using a web-based portal. Case ascertainment is established by regular institutional reporting of ICD-10 discharge coding. Recruitment is optimized by provision of opt-out consent. RESULTS: The collection of a standardized minimum data set optimizes capacity for harmonized population-based data capture. Data collection has commenced in a variety of settings reflecting metropolitan and rural, and public, and private health care institutions. The data set provides scope for the construction of a risk-adjusted model for outcomes. A data access policy and a mechanism for escalation policy for outcome outliers has been established. CONCLUSIONS: The Victorian Lung Cancer Registry provides a unique capacity to provide and confirm quality assessment in lung cancer and to drive improvement in quality of care across multidisciplinary stakeholders.

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.

Effects of in utero antiretroviral exposure on mitochondrial DNA levels, mitochondrial function and oxidative stress.

OBJECTIVES: HIV and antiretroviral (ART) exposure in utero may have deleterious effects on the infant, but uncertainty still exists. The objective of this study was to evaluate aspects of mitochondrial DNA (mtDNA) content, mitochondrial function and oxidative stress simultaneously in placenta, umbilical cord blood and infant blood in HIV/ART-exposed infants compared with uninfected controls. METHODS: HIV-1-infected pregnant women and HIV-1-uninfected healthy pregnant controls were enrolled in the study prospectively. Placenta and umbilical cord blood were obtained at delivery and infant blood was obtained within 48 h of delivery. mtDNA content was determined for each specimen. Nuclear [subunit IV of cytochrome c-oxidase (COX IV)]- and mitochondrial (COX II)-encoded polypeptides of the oxidative phosphorylation enzyme cytochrome c-oxidase were quantified in cord and infant blood. Placental mitochondria malondialdehyde (MDA) concentrations were measured as a marker of oxidative stress. RESULTS: Twenty HIV-positive/HIV-exposed and 26 control mother-infant pairs were enrolled in the study. All HIV-infected women and their infants received ART. Placental MDA concentration and mtDNA content in placenta and cord blood were similar between groups. The cord blood COX II:IV ratio was lower in the HIV-positive group than in the controls, whereas the infant peripheral blood mtDNA content was higher in the HIV-exposed infants, but the infant peripheral blood COX II:IV ratio was similar. No infant had clinical evidence of mitochondrial disease or acquired HIV infection. In multivariable regression analyses, the significant findings in cord and infant blood were both most associated with HIV/ART exposure. CONCLUSIONS: HIV-exposed infants showed reduced umbilical cord blood mitochondrial enzyme expression with increased infant peripheral blood mitochondrial DNA levels, the latter possibly reflecting a compensatory mechanism to overcome HIV/ART-associated mitochondrial toxicity.

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.

FDG-PET metabolic response predicts outcomes in anal cancer managed with chemoradiotherapy.

BACKGROUND: The aim was to investigate the correlation between (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) metabolic response to chemoradiotherapy and clinical outcomes in squamous cell carcinoma (SCC) of the anus. METHODS: A total of 48 patients with biopsy-proven anal SCC underwent FDG-PET scans at baseline and post chemoradiotherapy (54 Gy, concurrent 5-FU/mitomycin). Kaplan-Meier analysis was used to determine survival outcomes according to FDG-PET metabolic response. RESULTS: In all, 79% patients (n=38) had a complete metabolic response (CMR) at all sites of disease, 15% (n=7) had a CMR in regional nodes but only partial response in the primary tumour (overall partial metabolic response (PMR)) and 6% (n=3) had progressive distant disease despite CMR locoregionally (overall no response (NR)). The 2-year progression-free survival (PFS) was 95% for patients with a CMR, 71% for PMR and 0% for NR (P<0.0001). The 5-year overall survival (OS) was 88% in CMR, 69% in PMR and 0% in NR (P<0.0001). Cox proportional hazards regression analyses for PFS and OS found significant associations for incomplete (PMR+NR) vs complete FDG-PET response to treatment only, (HR 4.1 (95% CI: 1.5-11.5, P=0.013) and 6.7 (95% CI: 2.1-21.6, P=0.002), respectively). CONCLUSION: FDG-PET metabolic response to chemoradiotherapy in anal cancer is significantly associated with PFS and OS, and in this cohort incomplete FDG-PET response was a stronger predictor than T or N stage.

Phase I trial of docetaxel, cisplatin and concurrent radical radiotherapy in locally advanced oesophageal cancer.

BACKGROUND: Locally advanced oesophageal cancer (LAEC) is associated with poor survival and more effective treatments are needed. The aim of this phase I trial was to assess the maximum tolerated dose (MTD) of a novel weekly docetaxel and cisplatin regimen concurrent with radical radiotherapy. METHODS: Patients with unresectable, non-metastatic LAEC were eligible. Treatment comprised docetaxel 15-30 mg m(-2) per week and cisplatin 15-30 mg m(-2) per week in six planned dose levels (DLs) in 3-6 patient cohorts with 50 Gy radiotherapy in 25 fractions. Maximum tolerated dose was based on defined dose-limiting toxicities (DLTs) during therapy and 2 weeks post therapy. RESULTS: A total of 24 patients were enrolled. There were two DLTs: grade 3 fever in DL1 (docetaxel 15 mg m(-2), cisplatin 15 mg m(-2)) and grade 3 nausea in DL2 (20 mg m(-2), 15 mg m(-2)). These DLs were each expanded to six patients without further DLTs. The most common acute toxicity was grade 3 radiation oesophagitis (37.5%). There were no grade 4 toxicities, and haematologic toxicity was minimal. Cisplatin and docetaxel dose intensity was 100% at the highest dose level (DL6). A MTD was not reached in this trial. Tumour overall response rate was 50% (33% complete, 17% partial). CONCLUSION: Cisplatin and docetaxel each 30 mg m(-2) per week concurrent with 50 Gy radiotherapy is recommended for use in phase II clinical trials in oesophageal cancer.

Fabrication and characterization of RF nanoantenna on a nanoliter-scale 3D microcontainer.

We report the design and fabrication of a nanoantenna structure on the surface of a 3D nanoliter-scale container for the development of communicable nanoliter-scale chemical delivery systems. The porous container was self-assembled, after which the nanoantenna was fabricated on the top of the microcontainer using focused ion beam (FIB) ion-induced metal deposition. The nanoantenna was structured as a rectangular metal coil composed of platinum (Pt) nanowires (70 nm in width). The response of the nanoantenna structure was simulated using finite element software and showed a strong resonant feature at 10.8 GHz, which was confirmed by high frequency measurements.

Chemoradiotherapy in the management of primary squamous-cell carcinoma of the rectum.

AIM: To assess the efficacy of chemoradiotherapy in the management of primary squamous-cell carcinoma of the rectum. METHOD: Nine patients with primary squamous-cell carcinoma of the rectum were treated with chemoradiotherapy from 1985 to 2007. All patients were female, with a mean age of 54 years (range 41-72 years). The mean distance of the tumour from the anal verge was 6 cm (range 4-10 cm). Seven patients were treated with curative intent (two postoperative, three preoperative, two chemoradiotherapy alone). Clinical stages for the curative group were T1N0M0 (1), T3N0M0 (3), T3N1M0 (1) and T4N0M0 (2). Chemoradiotherapy consisted of pelvic radiation 45-54 Gy in 1.8 Gy/fraction and concurrent 5-fluorouracil and mitomycin C. The mean follow-up duration for the curative group was 39 months (range 15-120 months). RESULTS: All seven patients treated with curative intent achieved local control. A complete pathological response was seen in all patients after preoperative chemoradiotherapy. Two patients did not have surgery and remained free of disease. One patient with gross residual disease after surgery achieved local control. 18-Fluorodeoxyglucose (FDG) avidity was detected in all patients who had FDG-PET scans. Both primary and metastatic tumours demonstrated FDG-avidity. CONCLUSION: Primary squamous-cell carcinoma of the rectum appears to be very sensitive to chemoradiotherapy. The high complete response rate suggests that chemoradiotherapy alone with salvage surgery for local failure should be further explored. FDG-PET scan may have a role to play in the management of this disease.

Homocysteine status and cardiovascular risk factors in patients with psoriasis: a case-control study.

BACKGROUND: Psoriasis is a hyperproliferative, cutaneous disorder with the potential to lower levels of folate. This may result in raised levels of homocysteine, an independent risk factor for the development of cardiovascular disease. OBJECTIVE: A study was conducted to compare levels of red-cell folate (RCF) and homocysteine in patients with psoriasis and in healthy controls. Levels of homocysteine were also examined in the context of other major cardiovascular risk factors. METHODS: In total, 20 patients with psoriasis and 20 controls had their RCF, homo-cysteine and other conventional cardiovascular risk factors assessed. RESULTS: Patients with psoriasis had a trend towards lower levels of RCF. Significantly raised levels of homocysteine were found in patients with psoriasis compared with controls (P = 0.007). There was no correlation between homocysteine levels, RCF levels or disease activity as measured by the Psoriasis Area and Severity Index. Patients with psoriasis had higher body mass index (P < 0.004) and higher systolic blood pressure (P < 0.001) than controls. This may contribute to the excess cardiovascular mortality observed in patients with psoriasis.

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.

What can paper-based clinical information systems tell us about the design of computerized clinical information systems (CIS) in the ICU?

BACKGROUND: Screen designs in computerized clinical information systems (CIS) have been modeled on their paper predecessors. However, limited understanding about how paper forms support clinical work means that we risk repeating old mistakes and creating new opportunities for error and inefficiency as illustrated by problems associated with computerized provider order entry systems. PURPOSE: This study was designed to elucidate principles underlying a successful ICU paper-based CIS. The research was guided by two exploratory hypotheses: (1) paper-based artefacts (charts, notes, equipment, order forms) are used differently by nurses, doctors and other healthcare professionals in different (formal and informal) conversation contexts and (2) different artefacts support different decision processes that are distributed across role-based conversations. METHOD: All conversations undertaken at the bedsides of five patients were recorded with any supporting artefacts for five days per patient. Data was coded according to conversational role-holders, clinical decision process, conversational context and artefacts. 2133 data points were analyzed using Poisson logistic regression analyses. RESULTS: Results show significant interactions between artefacts used during different professional conversations in different contexts (chi(2)((df=16))=55.8, p<0.0001). The interaction between artefacts used during different professional conversations for different clinical decision processes was not statistically significant although all two-way interactions were statistically significant. CONCLUSIONS: Paper-based CIS have evolved to support complex interdisciplinary decision processes. The translation of two design principles - support interdisciplinary perspectives and integrate decision processes - from paper to computerized CIS may minimize the risks associated with computerization.