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Background There is a high burden of skin and soft tissue infections (SSTI) – including cellulitis – among Aboriginal and Torres Strait Islander peoples living in remote communities. In tropical environments, such as the Torres Strait, cellulitis accounts for 37% of potentially preventable hospitalisations. This study aimed to evaluate the safety, effectiveness and community acceptance of outpatient antibiotic treatment for the management of skin infections in the Torres Strait. Methods This was a 12-month prospective, observational study commencing in January 2019 involving 295 adults with a skin infection across the Torres Strait. Results Most (276/295 (94%)) participants were treated successfully in the community. Of 295 enrolled patients, 151 of 295 (51%) had cellulitis, 59 of 295 (20%) had a skin abscess and 85 of 295 (28%) had a wound infection. Of the 77 of 278 (27%) infections accompanied by systemic features, 63 of 77 (82%) were managed in the community. Staphylococcus aureus was the most frequent isolate, at 165 of 261 (63%); 56 of 165 (33%) were methicillin resistant. In the 276 community-managed cases, oral trimethoprim/sulfamethoxazole was initially used in 159 (57%), oral flucloxacillin in 75 (27%) and intravenous cefazolin plus oral probenecid in 32 (13%). The clinical course was complicated in eight of 232 (3%) patients who had complete follow-up data: seven patients required hospitalisation after initial treatment in the community and one had an antibiotic side-effect. All 232 patients with complete follow-up data were content with the care they received. Conclusions Outpatient management of skin infection in the Torres Strait is effective, safe and appreciated by patients.

This practitioner-oriented article represents a strand of research by the author into the practice of developing financially quantified value propositions for customers, which is the focus of this article. There is an appendix that spells out other meanings of the word ‘value’. The data used were gathered over a 5-year period from attendance and keynote addresses on the topic of value. In total, twelve conferences and 1,200 marketing practitioners were asked about their value propositions (defined in this article) via audience response systems in order to guarantee honest answers. The results indicate that fewer than 3% have financially quantified value propositions. This compares with a verbal estimate from McKinsey of 5%. The main conclusion, while only indicative, is that it is a very low percentage of UK companies. A review of the literature on value propositions failed to reveal any kind of quantitative process for developing financially quantified value propositions, so the author developed such a process and tested it on 20 organizations, global and local in order to refine it. This article sets out the results of this work and is summarized here as a six-step process. It is important to point out that the author of this article is deeply involved in the growing community of academics and practitioners who are striving to convince organizations that it is not only about creating value for customers, but also about creating value for employees, for all stakeholders and, of course for the Planet. All of this, however, is contingent upon creating value for customers, the major issue spelled out in this article.

The reduced prevalence of insulin resistance and type 2 diabetes (T2D) in countries with endemic parasitic worm infections suggests a protective role for worms against metabolic disorders, however clinical evidence has been non-existent. This 2-year randomized controlled trial of hookworm infection in 40 people at risk of T2D involved treatment with either 20 or 40Necator americanusthird-stage larvae (L3) or Placebo. Primary outcome was safety, with homeostatic model assessment of insulin resistance (HOMA-IR), fasting blood glucose (FBG), and body mass being the key metabolic outcomes. Adverse events were more frequent in hookworm-treated participants, where 44% experienced transient gastrointestinal symptoms. FBG and HOMA-IR were significantly lowered in both hookworm-treated groups at 1-year, and body mass was significantly lowered after L3-20 treatment at 2-years. Overall, hookworm infection was well tolerated in people at risk of T2D, and were associated with improved insulin resistance, warranting further exploration of the benefits of hookworms on metabolic health.

With legislation around the world placing more emphasis on corporate governance and control procedures and with the increasing potential penalties on individual directors, the need for an objective and well-structured review and approval process is becoming greater and spells out the consequences for stakeholder value if this goal is not achieved. This paper makes the case for the supremacy of shareholder value added as the principal goal of corporate strategy. It also spells out a methodology for assessing risk and adjusting corporate strategy accordingly. This methodology is probabilistic rather than mathematical, hence the William Bruce Cameron quotation above.

BACKGROUND No consensus germline testing guidelines currently exist for glioma patients. Hence such testing is not routinely performed. The prevalence and type of germline pathogenic variants in these brain tumors remains unknown. DESIGN/ METHODS A retrospective review of patients treated at Baylor College of Medicine with paired tumor/normal sequencing using the Tempus xT tumor/normal matched approach from August 2018- April 2022 was performed. Corresponding clinical data was collected for these patients. RESULTS We identified 152 glioma patients of which 15 (9.8%) had pathogenic germline variants. Pathogenic germline variants were seen in 11/84 (13.1%) of Glioblastoma, IDH wildtype, 3/42 (7.1%) of Astrocytoma, IDH mutant and 1/26 (3.8%) of Oligodendroglioma, IDH mutant and 1p/19q co-deleted patients. Pathogenic variants in BRCA2, MUTYH and CHEK2 were seen more commonly (3/15 or 20% each). BRCA1 variants were seen in 2/15 (13%) patients, with variants in NF1, ATM, MSH2, and MSH3 occurring in one patient (7%) each. Second hit somatic variants were seen in 3/15 patients (20%). A second somatic hit was seen in NF1, MUTYH and MSH2 in one patient (7%) each. Referral to genetics was performed in 6/15 (40%) patients with pathogenic germline variants. Median overall survival was 1.6 years for glioblastoma, IDH wildtype patients with a pathogenic germline variant compared to 1.79 years for glioblastoma, IDH wildtype patients without it (p = 0.67). CONCLUSIONS Although not routinely performed in glioma patients, pathogenic germline variants occurred in ~10% of our patients. Only 40% of these patients were referred to genetics. These findings suggest a possible overlooked opportunity for determination of hereditary cancer syndromes with impact on surveillance as well as potential broader treatment options. Further research to confirm the occurrence and types of pathogenic germline variants in patients with IDH wildtype compared to IDH mutant tumors is necessary.

Acute poststreptococcal glomerulonephritis (APSGN) is an immune complex-induced glomerulonephritis that develops as a sequela of streptococcal infections. This article provides guidelines for the surveillance of APSGN due to group A Streptococcus (Strep A). The primary objectives of APSGN surveillance are to monitor trends in age- and sex-specific incidence, describe the demographic and clinical characteristics of patients with APSGN, document accompanying risk factors, then monitor trends in frequency of complications, illness duration, hospitalization rates, and mortality. This document provides surveillance case definitions for APSGN, including clinical and subclinical APSGN based on clinical and laboratory evidence. It also details case classifications that can be used to differentiate between confirmed and probable cases, and it discusses the current investigations used to provide evidence of antecedent Strep A infection. The type of surveillance recommended depends on the burden of APSGN in the community and the objectives of surveillance. Strategies for minimal surveillance and enhanced surveillance of APSGN are provided. Furthermore, a discussion covers the surveillance population and additional APSGN-specific surveillance considerations such as contact testing, active follow up of cases and contacts, frequency of reporting, surveillance visits, period of surveillance, and community engagement. Finally, the document presents core data elements to be collected on case report forms, along with guidance for documenting the course and severity of APSGN.

BackgroundBetween 1964 and 1996, the 10-year survival of patients having valve replacement surgery for rheumatic heart disease (RHD) in the Northern Territory, Australia, was 68%. As medical care has evolved since then, this study aimed to determine whether there has been a corresponding improvement in survival.MethodsA retrospective study of Aboriginal patients with RHD in the Northern Territory, Australia, having their first valve surgery between 1997 and 2016. Survival was examined using Kaplan-Meier and Cox regression analysis.FindingsThe cohort included 281 adults and 61 children. The median (IQR) age at first surgery was 31 (18–42) years; 173/342 (51%) had a valve replacement, 113/342 (33%) had a valve repair and 56/342 (16%) had a commissurotomy. There were 93/342 (27%) deaths during a median (IQR) follow-up of 8 (4–12) years. The overall 10-year survival was 70% (95% CI: 64% to 76%). It was 62% (95% CI: 53% to 70%) in those having valve replacement. There were 204/281 (73%) adults with at least 1 preoperative comorbidity. Preoperative comorbidity was associated with earlier death, the risk of death increasing with each comorbidity (HR: 1.3 (95% CI: 1.2 to 1.5), p50 mm Hg before surgery (HR 1.9 (95% CI: 1.2 to 3.1) p=0.007) were independently associated with death.InterpretationSurvival after valve replacement for RHD in this region of Australia has not improved. Although the patients were young, many had multiple comorbidities, which influenced long-term outcomes. The increasing prevalence of complex comorbidity in the region is a barrier to achieving optimal health outcomes.

Although surgery has been shown to provide a survival benefit in patients with glioblastoma multiforme (GBM), tumor location and geometry may restrict maximal resection. Additionally, the margin of resection cavity contains infiltrating tumor cells that result in recurrence and therapy resistance. Laser interstitial thermal therapy (LITT) is a treatment modality that uses thermal energy to destroy tumor cells. LITT is useful for tumors that are not appropriate for conventional surgical resection. Our laboratory has developed a LITT model to study LITT in a genetically engineered mouse model of GBM. The combination of heat activated nanoparticles and LITT represents an opportunity to target the infiltrating tumor margin, extending the treatment penumbra. We hypothesized that heat-activated liposomes containing doxorubicin (ThermoDox, Celsion) would demonstrate infiltration into the brain parenchyma after treatment with LITT. We treated tumor-bearing mice with LITT or sham (laser fiber implanted but not activated) after either ThermoDox (5mg/kg) or PBS infusion, 30 minutes before performing LITT or sham treatment. We euthanized these mice 1 hour after LITT or sham treatment, harvested brains, and performed immunofluorescence to identify doxorubicin in parenchymal cells. Doxorubicin was identified in 100% of mice treated with LITT following ThermoDox administration which is in contrast with groups treated with LITT and PBS, sham and ThermoDox, and sham and PBS. Here, we show that heat-activated nanoparticles are disrupted through hyperthermia followed by the release of doxorubicin only in the presence of hyperthermia, which paves way for the clinical use of ThermoDox as adjunct chemotherapy following LITT in treatment-resistant GBM treatment.