The Dedicated Imaging Post-Prostatectomy for Enhanced Radiotherapy outcomes (DIPPER) trial protocol: a multicentre, randomised trial of salvage radiotherapy versus surveillance for low-risk biochemical recurrence after radical prostatectomy.

BACKGROUND: Salvage radiation therapy (SRT) and surveillance for low-risk prostate-specific antigen (PSA) recurrence have competing risks and benefits. The efficacy of early SRT to the prostate bed with or without pelvic lymph nodes compared to surveillance in patients with PSA recurrence after radical prostatectomy and no identifiable recurrent disease evident on prostate specific membrane antigen-positron emission tomography/computer tomography (PSMA-PET/CT) is unknown. STUDY DESIGN: The Dedicated Imaging Post-Prostatectomy for Enhanced Radiotherapy outcomes (DIPPER) is an open-label, multicentre, randomised Phase II trial. ENDPOINTS: The primary endpoint is 3-year event-free survival, with events comprising one of PSA recurrence (PSA ≥0.2 ng/mL higher than baseline), radiological evidence of metastatic disease, or initiation of systemic or other salvage treatments. Secondary endpoints include patient-reported outcomes, treatment patterns, participant perceptions, and cost-effectiveness. ELIGIBILITY CRITERIA: Eligible participants have PSA recurrence of prostate cancer after radical prostatectomy, defined by serum PSA level of 0.2-0.5 ng/mL, deemed low risk according to modified European Association of Urology biochemical recurrence risk criteria (International Society for Urological Pathology Grade Group ≤2, PSA doubling time >12 months), with no definite/probable recurrent prostate cancer on PSMA-PET/CT. PATIENTS AND METHODS: A total of 100 participants will be recruited from five Australian centres and randomised 1:1 to SRT or surveillance. Participants will undergo 6-monthly clinical evaluation for up to 36 months. Androgen-deprivation therapy is not permissible. Enrolment commenced May 2023. TRIAL REGISTRATION: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN: ACTRN12622001478707).

A network pharmacology approach to explore pharmacological mechanisms of Asparagus racemosus for ameliorative effect in epilepsy and comorbid progressive memory dysfunction.

Background: Network pharmacology approach has been observed a powerful tool to predict underlying complex pharmacological mechanism of herbs. Asparagus racemosus has been reported to show ameliorative effects in treating epilepsy and comorbid memory dysfunction but mechanism of this amelioration is elusive. Hence a network pharmacology approach was employed to investigate the plausible mechanism of A. recemosus. Methodology: : Bioactive compounds of A. racemosus were extracted based on the TCMSP, PCIDB, and BATMAN-TCM database. The potential targets of bioactive compounds were collected using target fishing. Epilepsy and comorbid dementia genes were collected from DISGENET. A PPI network among these targets was constructed using the intersecting key targets between herb targets and disease targets. Besides, DAVID bioinformatics resource was utilized for the pathway enrichment analysis on GO and KEGG. Ultimately, phytochemical compound-target genes-Pathways network has been assembled utilizing Cytoscape to decipher the mechanism of the herb. Results: The network analysis revealed that 5 targets (CASP3, TNF, VEGFA, PTGS2 and CNR1) might be the key therapeutic targets of asparagus on Epilepsy comorbid Alzheimer's disease. Based on high connectivity, four hub compounds with the highest connectivity were noted and it includes Shatavarin V, Sarsasapogenin, Shatavarin IX, and Shatavarin VI. A total of 19 KEGG terms were enriched as the potential pathways of A. racemosus in Epilepsy comorbid Alzheimer's disease. Conclusion: This study envisaged the pharmacological and molecular mechanism of A. racemosus against epilepsy comorbid Alzheimer's disease and put forward a strategy to uncover the mechanisms of Traditional Indian Medicine based on network pharmacology. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-023-00169-x.

Transforming blood pressure control in primary care through a novel remote decision support strategy based on wearable blood pressure monitoring: The NEXTGEN-BP randomized trial protocol.

BACKGROUND: Despite high blood pressure being the leading preventable risk factor for death, only 1 in 3 patients achieve target blood pressure control. Key contributors to this problem are clinical inertia and uncertainties in relying on clinic blood pressure measurements to make treatment decisions. METHODS: The NEXTGEN-BP open-label, multicenter, randomized controlled trial will investigate the efficacy, safety, acceptability and cost-effectiveness of a wearable blood pressure monitor-based care strategy for the treatment of hypertension, compared to usual care, in lowering clinic blood pressure over 12 months. NEXTGEN-BP will enroll 600 adults with high blood pressure, treated with 0 to 2 antihypertensive medications. Participants attending primary care practices in Australia will be randomized 1:1 to the intervention of a wearable-based remote care strategy or to usual care. Participants in the intervention arm will undergo continuous blood pressure monitoring using a wrist-wearable cuffless device (Aktiia, Switzerland) and participate in 2 telehealth consultations with their primary care practitioner (general practitioner [GP]) at months 1 and 2. Antihypertensive medication will be up-titrated by the primary care practitioner at the time of telehealth consults should the percentage of daytime blood pressure at target over the past week be <90%, if clinically tolerated. Participants in the usual care arm will have primary care consultations according to usual practice. The primary outcome is the difference between intervention and control in change in clinic systolic blood pressure from baseline to 12 months. Secondary outcomes will be assessed at month 3 and month 12, and include acceptability to patients and practitioners, cost-effectiveness, safety, medication adherence and patient engagement. CONCLUSIONS: NEXTGEN-BP will provide evidence for the effectiveness and safety of a new paradigm of wearable cuffless monitoring in the management of high blood pressure in primary care. TRIAL REGISTRATION: ACTRN12622001583730.

Self-ingestion of vasmol dye.

Vasmol, a commonly used hair dye, is becoming apparent as one of the major causes of suicidal poisoning in India. The toxic components in the dye include paraphenylenediamine, sodium ethylenediaminetetraacetic acid, resorcinol, and propylene glycol. Acute poisoning by consumption of dye leads to characteristic angioedema of the cervicofacial region along with multiorgan dysfunction. Early intervention with tracheostomy can be lifesaving in such cases and helps in preventing the morbidity and mortality associated with it.

A Randomized Trial of Nafamostat for Covid-19.

BACKGROUND: Nafamostat mesylate is a potent in vitro antiviral agent that inhibits the host transmembrane protease serine 2 enzyme used by severe acute respiratory syndrome coronavirus 2 for cell entry. METHODS: This open-label, pragmatic, randomized clinical trial in Australia, New Zealand, and Nepal included noncritically ill hospitalized patients with coronavirus disease 2019 (Covid-19). Participants were randomly assigned to usual care or usual care plus nafamostat. The primary end point was death (any cause) or receipt of new invasive or noninvasive ventilation or vasopressor support within 28 days after randomization. Analysis was with a Bayesian logistic model in which an adjusted odds ratio <1.0 indicates improved outcomes with nafamostat. Enrollment was closed due to falling numbers of eligible patients. RESULTS: We screened 647 patients in 21 hospitals (15 in Australia, 4 in New Zealand, and 2 in Nepal) and enrolled 160 participants from May 2021 to August 2022. In the intention-to-treat population, the primary end point occurred in 8 (11%) of 73 patients with usual care and 4 (5%) of 82 with nafamostat. The median adjusted odds ratio for the primary end point for nafamostat was 0.40 (95% credible interval, 0.12 to 1.34) with a posterior probability of effectiveness (adjusted odds ratio <1.0) of 93%. For usual care compared with nafamostat, hyperkalemia occurred in 1 (1%) of 67 and 7 (9%) of 78 participants, respectively, and clinically relevant bleeding occurred in 1 (1%) of 73 and 7 (8%) of 82 participants. CONCLUSIONS: Among hospitalized patients with Covid-19, there was a 93% posterior probability that nafamostat reduced the odds of death or organ support. Prespecified stopping criteria were not met, precluding definitive conclusions. Hyperkalemia and bleeding were more common with nafamostat. (Funded by ASCOT and others; ClinicalTrials.gov number, NCT04483960.)

Concomitant disseminated tuberculosis and lepromatous leprosy in a previously healthy male.

Tuberculosis (TB) and leprosy are two chronic mycobacterial infections caused by intracellular Gram-positive aerobic acid-fast bacilli. Both have highly variable presentations depending on immunological milieu of the host and account for significant disease morbidity. The burden of these age-old infections of humanity still remains high in India. Regardless of the same geographical endemicity of the two, coinfections are sparsely reported. Indeed, studies have revealed an antagonism between them. Of the few coinfections reported in the past, majority were diagnosed over a temporal sequence, with one occurring after the other, and most of these were localized forms of TB associated with leprosy. Only a single case of disseminated TB and lepromatous leprosy has been reported in the medical literature till date. Here, we report another rare case of disseminated TB and lepromatous leprosy that ultimately proved fatal for the patient. The diagnosis of the two diseases was made simultaneously which is again infrequent in the reported literature.

Video Presentation of Myokymia in a Snakebite.

Patients with snakebites have highly variable presentations, and delayed diagnosis may lead to unfavorable outcomes. Here, we describe the case of a snakebite in a 23-year-old male who presented with myokymias. On management with mechanical ventilation and anti-snake venom, the patient improved and was discharged. The presence of myokymias may be an early clue to diagnosis and the need for mechanical ventilation in a patient with a snakebite.

An electronic decision support-based complex intervention to improve management of cardiovascular risk in primary health care: a cluster randomised trial (INTEGRATE).

OBJECTIVES: To determine whether a multifaceted primary health care intervention better controlled cardiovascular disease (CVD) risk factors in patients with high risk of CVD than usual care. DESIGN, SETTING: Parallel arm, cluster randomised trial in 71 Australian general practices, 5 December 2016 - 13 September 2019. PARTICIPANTS: General practices that predominantly used an electronic medical record system compatible with the HealthTracker electronic decision support tool, and willing to implement all components of the INTEGRATE intervention. INTERVENTION: Electronic point-of-care decision support for general practices; combination cardiovascular medications (polypills); and a pharmacy-based medication adherence program. MAIN OUTCOME MEASURES: Proportion of patients with high CVD risk not on an optimal preventive medication regimen at baseline who had achieved both blood pressure and low-density lipoprotein (LDL) cholesterol goals at study end. RESULTS: After a median 15 months' follow-up, primary outcome data were available for 4477 of 7165 patients in the primary outcome cohort (62%). The proportion of patients who achieved both treatment targets was similar in the intervention (423 of 2156; 19.6%) and control groups (466 of 2321; 20.1%; relative risk, 1.06; 95% CI, 0.85-1.32). Further, no statistically significant differences were found for a number of secondary outcomes, including risk factor screening, preventive medication prescribing, and risk factor levels. Use of intervention components was low; it was highest for HealthTracker, used at least once for 347 of 3236 undertreated patients with high CVD risk (10.7%). CONCLUSIONS: Despite evidence for the efficacy of its individual components, the INTEGRATE intervention was not broadly implemented and did not improve CVD risk management in participating Australian general practices. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12616000233426 (prospective).

Reversible Myelosuppresion With Prolonged Usage of Linezolid in Treatment of Methicillin-Resistant Staphylococcus aureus.

Bone marrow suppression has a wide variety of causes. One of the overlooked causes is linezolid, a drug that is now being extensively used in the management of not only soft tissue infections but also hospital-acquired infections. Methicillin-resistant Staphylococcus aureus (MRSA) is widely being treated with linezolid. It becomes imperative that we comprehensively understand the hematological adverse effect profile of this drug. A reversible myelosuppression is seen with its extended use, though a number of risk factors like renal impairment are usually present. A prompt diagnosis can help us to timely discontinue the drug. We report one such case of an elderly patient with septic arthritis of the knee who developed pancytopenia after 32 days of linezolid therapy. Withdrawal of the drug led to a complete recovery of the blood counts in 21 days.

A Case of Methyl Ethyl Ketone Peroxide Ingestion Complicated by Rhabdomyolysis.

Methyl ethyl ketone peroxide (MEKP) is a colorless-to-faintly-yellow liquid that is used as a cross-linking to harden plastics or resins in various industries. It is also an ingredient of paints, varnishes, and paint removers. Because of the high reactivity of MEKP, it is available only as a 40% to 60% solution in dimethyl phthalate or other phthalates. Post-ingestion, the spectrum of complications is vast, ranging from corrosive injury in the oral cavity and gastrointestinal tract to fulminant hepatic toxicity, sepsis, multi-organ failure, and disseminated intravascular coagulation. We report the case of a 40-year-old, self-employed, male worker in a lamination workshop, who presented with accidental ingestion of MEKP from an unlabeled container. He subsequently developed a multitude of complications, most noteworthy being rhabdomyolysis and in turn acute kidney injury. The patient was managed in the intensive care unit with supportive management and hemodialysis sessions; however, the patient succumbed to his illness, despite aggressive measures.

An integrated general practice and pharmacy-based intervention to promote the use of appropriate preventive medications among individuals at high cardiovascular disease risk: protocol for a cluster randomized controlled trial.

BACKGROUND: Cardiovascular diseases (CVD) are responsible for significant morbidity, premature mortality, and economic burden. Despite established evidence that supports the use of preventive medications among patients at high CVD risk, treatment gaps remain. Building on prior evidence and a theoretical framework, a complex intervention has been designed to address these gaps among high-risk, under-treated patients in the Australian primary care setting. This intervention comprises a general practice quality improvement tool incorporating clinical decision support and audit/feedback capabilities; availability of a range of CVD polypills (fixed-dose combinations of two blood pressure lowering agents, a statin ± aspirin) for prescription when appropriate; and access to a pharmacy-based program to support long-term medication adherence and lifestyle modification. METHODS: Following a systematic development process, the intervention will be evaluated in a pragmatic cluster randomized controlled trial including 70 general practices for a median period of 18 months. The 35 general practices in the intervention group will work with a nominated partner pharmacy, whereas those in the control group will provide usual care without access to the intervention tools. The primary outcome is the proportion of patients at high CVD risk who were inadequately treated at baseline who achieve target blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels at the study end. The outcomes will be analyzed using data from electronic medical records, utilizing a validated extraction tool. Detailed process and economic evaluations will also be performed. DISCUSSION: The study intends to establish evidence about an intervention that combines technological innovation with team collaboration between patients, pharmacists, and general practitioners (GPs) for CVD prevention. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616000233426.

The medical schools outcomes database project: Australian medical student characteristics.

BACKGROUND: Global medical workforce requirements highlight the need for effective workforce planning, with the overall aims being to alleviate doctor shortages and prevent maldistribution. The Medical Schools Outcomes Database and Longitudinal Tracking (MSOD) Project provides a foundation for evaluating outcomes of medical education programs against specified workforce objectives (including rural and areas of workforce needs), assisting in medical workforce planning, and provision of a national research resource. This paper describes the methodology and baseline results for the MSOD project. METHODS: The MSOD Project is a prospective longitudinal multiple-cohort study. The project invites all commencing and completing Australian medical students to complete short questionnaires. Participants are then asked to participate in four follow-up surveys at 1, 3, 5 and 8 years after graduation. RESULTS: Since 2005, 30,635 responses for medical students (22,126 commencing students and 8,509 completing students) in Australia have been collected. To date, overall eligible cohort response rates are 91% for commencing students, and 83% for completing students. Eighty three percent of completing medical student respondents had also completed a commencing questionnaire.Approximately 80% of medical students at Australian medical schools are Australian citizens. Australian medical schools have only small proportions of Indigenous students. One third of medical students speak a language other than English at home.The top three vocational choices for commencing medical students were surgery, paediatrics and child health and general practice. The top three vocational choices for completing students were surgery, adult medicine/ physician, and general practice. Overall, 75.7% of medical students changed their first career preference from commencement to exit from medical school.Most commencing and completing medical students wish to have their future medical practice in capital cities or in major urban centers. Only 8.1% of commencing students and 4.6% of completing students stated an intention to have their future medical practice in smaller towns and small communities. CONCLUSIONS: The MSOD longitudinal project is now an established national resource that is beginning to generate significant research outputs, along with providing key information for workforce planning and policy makers. The project has now expanded to enrol New Zealand medical students.