Bedaquiline as Treatment for Disseminated Nontuberculous Mycobacteria Infection in 2 Patients Co-Infected with HIV.

Nontuberculous mycobacteria can cause disseminated infections in immunocompromised patients and are challenging to treat because of antimicrobial resistance and adverse effects of prolonged multidrug treatment. We report successful treatment with bedaquiline, a novel antimycobacterial drug, as part of combination therapy for 2 patients with disseminated nontuberculous mycobacteria co-infected with HIV

Treating anxiety and depression in older adults: Randomised controlled trial comparing guided V. Self-guided internet-delivered cognitive-behavioural therapy

© 2016 The Royal College of Psychiatrists. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. Background Symptoms of anxiety and depression are prevalent in older adults. Aims To compare clinician-guided and self-guided versions of a transdiagnostic internet-delivered cognitive-behavioural therapy (iCBT) intervention for adults aged 60 years and above. Method Adults (n=433) with symptoms of anxiety and depression were randomly allocated to: (1) clinician-guided treatment (n=153); (2) initial clinician interview followed by self-guided treatment (n=140); or (3) self-guided treatment without interview (n=140). Results Large reductions (d ≥1.00) in symptoms of depression and anxiety were observed across groups, and sustained at follow-up. No differences were observed in clinical outcomes or satisfaction ratings. Age did not affect outcomes. Conclusions Carefully developed iCBT interventions may significantly reduce symptoms of anxiety and depression in older adults when delivered in either clinician-guided or self-guided formats

Quantifying abundance and distribution of native and invasive oysters in an urbanised estuary

Human activities have modified the chemical, physical and biological attributes of many of the world’s estuaries. Natural foreshores have been replaced by artificial habitats and non-indigenous species have been introduced by shipping, aquaculture, and as ornamental pets. In south east Australia, the native Sydney rock oyster Saccostrea glomerata is threatened by pollution, disease and competition from the invasive Pacific oyster Crassostrea gigas. This study assessed the abundance (as number m-2), size, and distribution of both invasive and native oyster species at 32 sites in the heavily urbanised Port Jackson Estuary, Australia. We tested the hypotheses that there would be: (1) a difference in the proportion of C. gigas and S. glomerata among locations; (2) a greater proportion of C. gigas on artificial compared to natural substrates; (3) a greater numbers of all oysters, with differing size characteristics, on artificial compared to natural substrates; and (4) that the abundance and size of all oysters would vary among locations along an environmental gradient. Environmental variables included distance from the estuary mouth and salinity. We found the abundance and size of all oysters differed among locations; smaller oysters occurred at greater abundances near the mouth of the estuary. Abundance was also higher on artificial, than on natural substrate. Habitat type, however, had no effect on which species of oyster was present. In contrast, distance from the estuary mouth strongly influenced the relative proportion of the two species. The invasive C. gigas comprised 16% of the oysters sampled, and up to 85% at some of the upper estuary sites. As predicted, C. gigas was more abundant at locations in the bay ends and upper channel of the estuary; it was also larger in size than the native S. glomerata. This is the first assessment of oyster distribution in Port Jackson and provides a solid base for monitoring changes in the estuarine distribution of a globally invasive pest

The pain course: A randomised controlled trial examining an internet-delivered pain management program when provided with different levels of clinician support

© 2015 International Association for the Study of Pain. The present study evaluated an internet-delivered pain management program, the Pain Course, when provided with different levels of clinician support. Participants (n5490) were randomised to 1 of 4 groups: (1) Regular Contact (n5143), (2) Optional Contact (n5 141), (3) No Contact (n 5 131), and (4) a treatment-As-usual Waitlist Control Group (n 5 75). The treatment program was based on the principles of cognitive behaviour therapy and comprised 5 internet-delivered lessons provided over 8 weeks. The 3 Treatment Groups reported significant improvements (between-group Cohen's d; avg. reduction) in disability (ds ≤ 0.50; avg. reduction ≤ 18%), anxiety (ds≤0.44; avg. reduction≤32%), depression (ds≤0.73; avg. reduction≤36%), and average pain (ds≤0.30; avg. reduction ≤ 12%) immediately posttreatment, which were sustained at or further improved to 3-month follow-up. High treatment completion rates and levels of satisfaction were reported, and no marked or consistent differences were observed between the Treatment Groups. The mean clinician time per participant was 67.69 minutes (SD533.50), 12.85 minutes (SD524.61), and 5.44 minutes (SD 5 12.38) for those receiving regular contact, the option of contact, and no clinical contact, respectively. These results highlight the very significant public health potential of carefully designed and administered internet-delivered pain management programs and indicate that these programs can be successfully administered with several levels of clinical support

Testing for sexually transmitted infections in general practice: cross-sectional study

Background: Primary care is an important provider of sexual health care in England. We sought to explore the extent of testing for chlamydia and HIV in general practice and its relation to associated measures of sexual health in two contrasting geographical settings.Methods: We analysed chlamydia and HIV testing data from 64 general practices and one genitourinary medicine (GUM) clinic in Brent (from mid-2003 to mid-2006) and 143 general practices and two GUM clinics in Avon (2004). We examined associations between practice testing status, practice characteristics and hypothesised markers of population need (area level teenage conception rates and Index of Multiple Deprivation, IMD scores).Results: No HIV or chlamydia testing was done in 19% (12/64) of general practices in Brent, compared to 2.1% (3/143) in Avon. In Brent, the mean age of general practitioners (GPs) in Brent practices that tested for chlamydia or HIV was lower than in those that had not conducted testing. Practices where no HIV testing was done had slightly higher local teenage conception rates (median 23.5 vs. 17.4/1000 women aged 15-44, p = 0.07) and served more deprived areas (median IMD score 27.1 vs. 21.8, p = 0.05). Mean yearly chlamydia and HIV testing rates, in practices that did test were 33.2 and 0.6 (per 1000 patients aged 15-44 years) in Brent, and 34.1 and 10.3 in Avon, respectively. In Brent practices only 20% of chlamydia tests were conducted in patients aged under 25 years, compared with 39% in Avon.Conclusions: There are substantial geographical differences in the intensity of chlamydia and HIV testing in general practice. Interventions to facilitate sexually transmitted infection and HIV testing in general practice are needed to improve access to effective sexual health care. The use of routinely-collected laboratory, practice-level and demographic data for monitoring sexual health service provision and informing service planning should be more widely evaluated

Hypertensive crisis associated with high dose soy isoflavone supplementation in a post-menopausal woman: a case report [ISRCTN98074661]

BACKGROUND: Isoflavones are gaining popularity as alternatives to hormone replacement therapy. However, few guidelines exist to inform the public as to an appropriate dose. This case involves a postmenopausal woman who experienced a hypertensive crisis while consuming a high-dose isoflavone supplement as part of a research protocol. CASE PRESENTATION: The participant was part of a placebo-controlled crossover trial to investigate the potential synergism of the antioxidant activity of soy isoflavones and vitamin C. Upon entry into the study, this healthy, well-nourished, normotensive postmenopausal woman (51 years old), consumed the first of four randomly assigned treatments (500 mg vitamin C plus 5 mg/kg body weight soy isoflavones). During this treatment, the participant's systolic blood pressure spiked to a recorded 226/117 mmHg, necessitating medical intervention and discontinuation of study participation. Two plausible mechanisms for this hypertensive crisis are discussed. CONCLUSION: Due to the availability and increasing popularity of soy supplements, practitioners should be aware of the potential side effects associated with their use. Practitioners counseling clients who are consuming soy isoflavone supplements should advise them that elevated blood pressure may be a potential side-effect to consider and monitor

Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology Guideline

PURPOSE: To develop recommendations about endocrine therapy for women with hormone receptor (HR) -positive metastatic breast cancer (MBC). METHODS: The American Society of Clinical Oncology convened an Expert Panel to conduct a systematic review of evidence from 2008 through 2015 to create recommendations informed by that evidence. Outcomes of interest included sequencing of hormonal agents, hormonal agents compared with chemotherapy, targeted biologic therapy, and treatment of premenopausal women. This guideline puts forth recommendations for endocrine therapy as treatment for women with HR-positive MBC. RECOMMENDATIONS: Sequential hormone therapy is the preferential treatment for most women with HR-positive MBC. Except in cases of immediately life-threatening disease, hormone therapy, alone or in combination, should be used as initial treatment. Patients whose tumors express any level of hormone receptors should be offered hormone therapy. Treatment recommendations should be based on type of adjuvant treatment, disease-free interval, and organ function. Tumor markers should not be the sole criteria for determining tumor progression; use of additional biomarkers remains experimental. Assessment of menopausal status is critical; ovarian suppression or ablation should be included in premenopausal women. For postmenopausal women, aromatase inhibitors (AIs) are the preferred first-line endocrine therapy, with or without the cyclin-dependent kinase inhibitor palbociclib. As second-line therapy, fulvestrant should be administered at 500 mg with a loading schedule and may be administered with palbociclib. The mammalian target of rapamycin inhibitor everolimus may be administered with exemestane to postmenopausal women with MBC whose disease progresses while receiving nonsteroidal AIs. Among patients with HR-positive, human epidermal growth factor receptor 2-positive MBC, human epidermal growth factor receptor 2-targeted therapy plus an AI can be effective for those who are not chemotherapy candidates

Anti-inflammatory therapy with nebulised dornase alfa in patients with severe COVID-19 pneumonia A Randomised Clinical Trial

BACKGROUND: SARS-CoV2 infection causes severe, life-threatening pneumonia. Hyper-inflammation, coagulopathy and lymphopenia are associated with pathology and poor outcomes in these patients. Cell-free (cf) DNA is prominent in COVID-19 patients, amplifies inflammation and promotes coagulopathy and immune dysfunction. We hypothesized that cf-DNA clearance by nebulised dornase alfa may reduce inflammation and improve disease outcomes. Here, we evaluated the efficacy of nebulized dornase alfa in patients hospitalised with severe COVID-19 pneumonia. METHODS: In this randomised controlled single-centre phase 2 proof-of-concept trial, we recruited adult patients admitted to hospital that exhibited stable oxygen saturation (≥94%) on supplementary oxygen and a C-reactive protein (CRP) level ≥30mg/L post dexamethasone treatment. Participants were randomized at a 3:1 ratio to receive twice-daily nebulised dornase alfa in addition to best available care (BAC) or BAC alone for seven days or until hospital discharge. A 2:1 ratio of historical controls to treated individuals (HC, 2:1) were included as the primary endpoint comparators. The primary outcome was a reduction in systemic inflammation measured by blood CRP levels over 7 days post-randomisation, or to discharge if sooner. Secondary and exploratory outcomes included time to discharge, time on oxygen, D-dimer levels, lymphocyte counts and levels of circulating cf-DNA. RESULTS: We screened 75 patients and enrolled 39 participants out of which 30 in dornase alfa arm, and 9 in BAC group. We also matched the recruited patients in the treated group (N=30) to historical controls in the BAC group (N=60). For the the primary outcome, 30 patients in the dornase alfa were compared to 69 patients in the BAC group. Dornase alfa treatment reduced CRP by 33% compared to the BAC group at 7-days (P=0.01). The dornase alfa group least squares mean CRP was 23.23 mg/L (95% CI 17.71 to 30.46) and the BAC group 34.82 mg/L (95% CI 28.55 to 42.47). A significant difference was also observed when only randomised participants were compared. Furthermore, compared to the BAC group, the chance of live discharge was increased by 63% in the dornase alfa group (HR 1.63, 95% CI 1.01 to 2.61, P=0.03), lymphocyte counts were improved (least-square mean: 1.08 vs 0.87, P=0.02) and markers of coagulopathy such as D-dimer were diminished (least-square mean: 570.78 vs 1656.96μg/mL, P=0.004). Moreover, the dornase alfa group exhibited lower circulating cf-DNA levels that correlated with CRP changes over the course of treatment. No differences were recorded in the rates and length of stay in the ICU or the time on oxygen between the groups. Dornase alfa was well-tolerated with no serious adverse events reported. CONCLUSION: In this proof-of-concept study in patients with severe COVID-19 pneumonia, treatment with nebulised dornase alfa resulted in a significant reduction in inflammation, markers of immune pathology and time to discharge. The effectiveness of dornase alfa in patients with acute respiratory infection and inflammation should be investigated further in larger trials

Clinical management and research priorities for high-risk prostate cancer in the UK:meeting report of a multidisciplinary panel in conjunction with the NCRI Prostate Cancer Clinical Studies Localised Subgroup

The management of high-risk prostate cancer has become increasingly sophisticated, with refinements in radical therapy and the inclusion of adjuvant local and systemic therapies. Despite this, high-risk prostate cancer continues to have significant treatment failure rates, with progression to metastasis, castrate resistance and ultimately disease-specific death. In an effort to discuss the challenges in this field, the UK National Clinical Research Institute’s Prostate Cancer Clinical Studies localised subgroup convened a multidisciplinary national meeting in the autumn of 2014. The remit of the meeting was to debate and reach a consensus on the key clinical and research challenges in high-risk prostate cancer and to identify themes that the UK would be best placed to pursue to help improve outcomes. This report presents the outcome of those discussions and the key recommendations for future research in this highly heterogeneous disease entity