Sodium channel-inhibiting drugs and cancer-specific survival: a population-based study of electronic primary care data.

OBJECTIVES: Antiepileptic and antiarrhythmic drugs inhibit voltage-gated sodium (Na+) channels (VGSCs), and preclinical studies show that these medications reduce tumour growth, invasion and metastasis. We investigated the association between VGSC inhibitor use and survival in patients with breast, bowel and prostate cancer. DESIGN: Retrospective cohort study. SETTING: Individual electronic primary healthcare records extracted from the Clinical Practice Research Datalink. PARTICIPANTS: Records for 132 996 patients with a diagnosis of breast, bowel or prostate cancer. OUTCOME MEASURES: Adjusted Cox proportional hazards regression was used to analyse cancer-specific survival associated with exposure to VGSC inhibitors. Exposure to non-VGSC-inhibiting antiepileptic medication and other non-VGSC blockers were also considered. Drug exposure was treated as a time-varying covariate to account for immortal time bias. RESULTS: During 1 002 225 person-years of follow-up, there were 42 037 cancer-specific deaths. 53 724 (40.4%) patients with cancer had at least one prescription for a VGSC inhibitor of interest. Increased risk of cancer-specific mortality was associated with exposure to this group of drugs (HR 1.59, 95% CI 1.56 to 1.63, p<0.001). This applied to VGSC-inhibiting tricyclic antidepressants (HR 1.61, 95% CI 1.50 to 1.65, p<0.001), local anaesthetics (HR 1.49, 95% CI 1.43 to 1.55, p<0.001) and anticonvulsants (HR 1.40, 95% CI 1.34 to 1.48, p<0.001) and persisted in sensitivity analyses. In contrast, exposure to VGSC-inhibiting class 1c and 1d antiarrhythmics was associated with significantly improved cancer-specific survival (HR 0.75, 95% CI 0.64 to 0.88, p<0.001 and HR 0.54, 95% CI 0.33 to 0.88, p=0.01, respectively). CONCLUSIONS: Association between VGSC inhibitor use and mortality in patients with cancer varies according to indication. Exposure to VGSC-inhibiting antiarrhythmics, but not anticonvulsants, supports findings from preclinical data, with improved survival. However, additional confounding factors may underlie these associations, highlighting the need for further study.

Human T-cell leukaemia virus type 1 and Adult T-cell leukaemia/lymphoma in Queensland, Australia: a retrospective cross-sectional study.

OBJECTIVES: Human T-cell leukaemia virus type 1 (HTLV-1), an STI, is reported to be highly prevalent in Indigenous communities in Central Australia. HTLV-1 is an incurable, chronic infection which can cause Adult T-cell leukaemia/lymphoma (ATL). ATL is associated with high morbidity and mortality, with limited treatment options. We studied the prevalence of HTLV-1 and ATL in the state of Queensland, Australia. METHODS: Serum samples stored at healthcare services in Brisbane, Townsville and Cairns and at haemodialysis units in Brisbane (2018-2019) were screened for HTLV-1/2 antibodies using the Abbott ARCHITECT chemiluminescent microparticle immunoassay (CMIA) for antibodies against gp46-I, gp46-II and GD21 (Abbott CMIA, ARCHITECT). Reactive samples were confirmed through Western blot. Pooled Australian National Cancer Registry surveillance data reporting on cases coded for ATL (2004-2015) were analysed. RESULTS: Two out of 2000 hospital and health services samples were confirmed HTLV-1-positive (0.1%, 95% CI 0.02% to 0.4%), both in older women, one Indigenous and one non-Indigenous. All 540 haemodialysis samples tested negative for HTLV. All samples were HTLV-2-negative. Ten out of 42 (24.8%) reported cases of ATL in Australia were from Queensland (crude incidence rate 0.025/100 000; 95% CI 0.011 to 0.045); most cases were seen in adult men of non-Indigenous origin. Nineteen deaths due to ATL were recorded in Australia. CONCLUSION: We confirm that HTLV-1 and ATL were detected in Queensland in Indigenous and non-Indigenous people. These results highlight the need for HTLV-1 prevalence studies in populations at risk of STIs to allow the implementation of focused public health sexual and mother-to-child transmission prevention strategies.

Efficacy of Corticosteroid Therapy for HTLV-1-Associated Myelopathy: A Randomized Controlled Trial (HAMLET-P).

Corticosteroids are most commonly used to treat HTLV-1-associated myelopathy (HAM); however, their clinical efficacy has not been tested in randomized clinical trials. This randomized controlled trial included 8 and 30 HAM patients with rapidly and slowly progressing walking disabilities, respectively. Rapid progressors were assigned (1:1) to receive or not receive a 3-day course of intravenous methylprednisolone in addition to oral prednisolone therapy. Meanwhile, slow progressors were assigned (1:1) to receive oral prednisolone or placebo. The primary outcomes were a composite of ≥1-grade improvement in the Osame Motor Disability Score or ≥30% improvement in the 10 m walking time (10 mWT) at week 2 for rapid progressors and changes from baseline in 10 mWT at week 24 for slow progressors. In the rapid progressor trial, all four patients with but only one of four without intravenous methylprednisolone achieved the primary outcome (p = 0.14). In the slow progressor trial, the median changes in 10 mWT were -13.8% (95% CI: -20.1--7.1; p < 0.001) and -6.0% (95% CI: -12.8-1.3; p = 0.10) with prednisolone and placebo, respectively (p for between-group difference = 0.12). Whereas statistical significance was not reached for the primary endpoints, the overall data indicated the benefit of corticosteroid therapy. (Registration number: UMIN000023798, UMIN000024085).

HTLV-1 Disease.

The years 2020 and 2021 will remain memorable years for many reasons [...].

Management of HAM/TSP: Systematic Review and Consensus-based Recommendations 2019.

PURPOSE OF REVIEW: To provide an evidence-based approach to the use of therapies that are prescribed to improve the natural history of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)-a rare disease. RECENT FINDINGS: All 41 articles on the clinical outcome of disease-modifying therapy for HAM/TSP were included in a systematic review by members of the International Retrovirology Association; we report here the consensus assessment and recommendations. The quality of available evidence is low, based for the most part on observational studies, with only 1 double-masked placebo-controlled randomized trial. SUMMARY: There is evidence to support the use of both high-dose pulsed methyl prednisolone for induction and low-dose (5 mg) oral prednisolone as maintenance therapy for progressive disease. There is no evidence to support the use of antiretroviral therapy. There is insufficient evidence to support the use of interferon-α as a first-line therapy.

Journeys to HIV testing and diagnosis among adults aged 50+ years in England: A qualitative interview study.

OBJECTIVES: In England, older adults (aged ≥50 years) are at greater risk of being diagnosed with advanced stage HIV infection than younger adults. We explored journeys to testing and diagnosis among older adults, examining factors associated with late HIV diagnosis in this age group. METHODS: Semi-structured qualitative interviews were performed with 12 adults diagnosed with HIV at age 50+ years and 12 health care professionals working in sexual health/HIV services. Data were analysed thematically, using the Model of Pathways to Treatment as a framework for analysis. RESULTS: Older adults were often found to experience non-linear and complex diagnostic journeys. Pathways to diagnosis were affected by 6 factors: (i) the non-specific nature of HIV symptoms and their misattribution as being age-related; (ii) symptom severity, impact, and visibility; (iii) HIV health literacy; (iv) perceptions of HIV risk; (v) geographical location; and (vi) assessment in non-specialist settings. CONCLUSIONS: Older adults appear to encounter additional barriers to HIV testing compared with younger people, particularly when they are not part of a group targeted in HIV prevention and testing campaigns. To diagnose HIV more promptly in adults aged 50+ years, HIV knowledge and risk perception must increase in both older people and health care professionals. Health care professionals need to look beyond the 'high risk' groups that are most affected by HIV and consider HIV more readily in the diagnostic process.

Creation and validation of a bladder dysfunction symptom score for HTLV-1-associated myelopathy/tropical spastic paraparesis.

BACKGROUND: Urinary dysfunction is one of the main features of human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, a comprehensive assessment of the severity is difficult because a standardized assessment measure is unavailable. Therefore, this study aimed to develop a novel symptom score for the assessment of urinary dysfunction in HAM/TSP. We interviewed 449 patients with HAM/TSP using four internationally validated questionnaires for assessment of urinary symptoms (27 question items in total): the International Prostate Symptom Score; the International Consultation on Incontinence Questionnaire-Short Form; the Overactive Bladder Symptom Score; and the Nocturia Quality-of-Life questionnaire. We developed a symptom score based on the data of 322 patients who did not use urinary catheters by selecting question items from questionnaires focused on descriptive statistics, correlation analysis, and exploratory factor analysis. The score distribution, reliability, and validity of the developed score were evaluated. RESULTS: First, 16 questions related to quality of life, situations, or subjective assessment were omitted from the 27 questions. Exploratory factor analysis revealed that the remaining 11 questions pertained to three factors: frequent urination, urinary incontinence, and voiding symptoms. Three questions, which had similar questions with larger factor loading, were deleted. Finally, we selected eight question items for inclusion in the novel score. The score distribution exhibited no ceiling or floor effect. The Cronbach's alpha (0.737) demonstrated reliable internal consistency. The new score comprised two subscales with acceptable factorial validity (inter-factor correlation coefficient, 0.322): storage symptoms (frequent urination plus urinary incontinence) and voiding symptoms. The correlation between each item and the subscales suggested acceptable construct validity. CONCLUSIONS: We developed a novel score, the HAM/TSP-Bladder Dysfunction Symptom Score, and demonstrated its reliability and validity. The applicability of this score to patients using catheters should be examined in future research.

Human T leukaemia Type 1 and COVID-19.

In the absence of clinical data on Human T leukaemia Type 1 and COVID-19 infection, we are providing guidance to clinicians who look after people living with HTLV-1.

Flow cytometric methodology for the detection of de novo human T-cell leukemia virus -1 infection in vitro: A tool to study novel infection inhibitors.

Methodology to detect and study de novo human T-cell leukemia virus (HTLV)-1 infection is required to further our knowledge of the viruses' mechanisms of infection and to study potential therapeutic interventions. Whilst methodology currently exists, utilisation of an anti-Tax antibody to detect de novo Tax expression in permissive cells labelled with cell tracker allowing for the detection by flow cytometry of new infection after co-culture with donor cell lines productively infected with HTLV-1 is an alternative strategy. Using this methodology, we have been able to detect de novo infection of the T cell line HUT78 following co-culture with the productively infected HTLV-1 donor cell line MT-2 and to confirm that infection can be effectively blocked with well characterised infection inhibitors. This methodology will benefit experimental studies examining HTLV infection in vitro and may aid identification of therapeutic agents that block this process.

HIV testing amongst older sexual health clinic attendees in England: an epidemiological study.

Older adults with HIV are at increased risk of late diagnosis. We aimed to explore the association between age and HIV testing rates in sexual health clinics in England using Public Health England data for 2009-2014. We investigated associations between attendee age and likelihood of HIV test offer, acceptance, and coverage. For each year, increasing age was associated with reduced likelihood of test offer (Rs -0.797 to -0.958, p < 0·01). Offer rates were highest for men who have sex with men (MSM), and lowest for heterosexual females (HSFs). HSFs had the greatest decline in offer rates with age (from 86.2% for age 25-29 to 52.1% for age 70+ in 2014). Odds ratios for test offer in 2014 for attendees aged 15-49 compared with attendees aged 50+ were 1.94 (95%CI: 1.88, 2.00) for heterosexual males (HSMs), 1.86 (95%CI: 1.81, 1.91) for HSFs, and 1.54 (95%CI: 1.45, 1.64) for MSM. Overall, there was no significant association between age and test acceptance in any year (Rs -0.070 to -0.547; p > 0·05). The strongest determinant of acceptance was sexual orientation; for attendees aged 50+, compared with HSMs, acceptance was higher for MSM (OR: 1.10; 95%CI: 1.06, 1.13) and lower for HSFs (OR: 0.30; 95%CI: 0.30, 0.31).

Sex effects on the association between sarcopenia EWGSOP and osteoporosis in outpatient older adults: data from the SARCOS study

ABSTRACT Objective: The objective was to evaluate the association between sarcopenia (EWGSOP) and osteoporosis in older adults. Subjects and methods: This is a cross sectional analysis of a baseline evaluation of the SARCopenia and OSteoporosis in Older Adults with Cardiovascular Diseases Study (SARCOS). Three hundred and thirty-two subjects over 65 years of age were evaluated. Sarcopenia was determined by EWGSOP flowchart and Osteoporosis was established by WHO's criteria. Physical function, comorbidities and medications were evaluated. Results: Women were older (79.8 ± 7.2 years) than men (78.21 ± 6.7 years) (p = 0.042). Osteoporosis occurred in 24.8% of men, and in 42.7% of women (p < 0.001); sarcopenia occurred in 25.5% of men and in 17.7%, of women (p = 0.103). Osteoporosis was diagnosed in 68% of sarcopenic women, however only 20.7% (p = 0.009) of women with osteoporosis had sarcopenia; in older men, 44.7% of individuals with sarcopenia presented osteoporosis and 42.9% (p = 0.013) of men with osteoporosis showed sarcopenia. In an adjusted logistic regression analyses for sarcopenia, osteoporosis presented a statistically significant association with sarcopenia in men [OR: 2.930 (95% CI: 1.044-8.237; p = 0.041)] but not in women [OR: 2.081 (0.787-5.5; p = 0.142)]; in the adjusted logistic regression analyses for osteoporosis, a statistically significant association occurred in men [OR: 2.984 (95% CI: 1.144-7.809; p = 0.025)], but not in women [OR: 2.093 (0.962-3.714; p = 0.137)]. Conclusion: According to sex, there are significant differences in the association between sarcopenia EWGSOP and osteoporosis in outpatient older adults. It is strong and significant in males; in females, despite showing a positive trend, it was not statistically significant.

Fragilidade é um preditor independente de morte precoce em idosos ambulatoriais com doenças cardiovasculares no Estudo SARCOS / Frailty is an independen t predictor of early death in elderly outpatients with cardiovascular disease in the SARCOS Study

Introdução: A fragilidade caracteriza-se pela perda da capacidade biológica e física de responder adequadamente ao estresse orgânico devido aos danos a diversos sistemas associados ao processo de envelhecimento. Entre os indivíduos com doenças cardiovasculares, a frequência da fragilidade é três vezes maior. Métodos: SARCOS é um estudo epidemiológico de coorte para avaliar a síndrome de vulnerabilidade com hospitalização e mortalidade em idosos ambulatoriais com doença cardiovascular (DCV). A fragilidade foi diagnosticada na presença de três ou mais dos seguintes critérios: perda de peso > 5%, velocidade de marcha reduzida, fraqueza muscular pela força de preensão, exaustão e perda de energia (levantar e sentar da cadeira cinco vezes). Resultados: Dos 169 pacientes avaliados, a fragilidade ocorreu em 19,5% (n=33). A média de idade foi de 78,3 ± 7,1 anos. A taxa mortalidade aos seis meses foi de 3% (n=5), sendo que 80% (n=4) eram frágeis e 20% (n=1) pré-frágeis (p=0,007). Na análise de regressão logística, a fragilidade mostrou ser um forte preditor de morte aos seis meses, com aumento de risco de 18 vezes quando comparado aos fortes (p=0,010), enquanto que entre as DCVs, a insuficiência cardíaca apresentou aumento de risco de quatro vezes (p=0,061). No modelo de interação entre a fragilidade e as DCVs, não houve diferença significativa da fragilidade em relação ao risco de morte. Conclusão: A fragilidade é um importante fator de risco de morte precoce em idosos ambulatoriais, independente e superior às doenças cardiovasculares crônicas mais frequentes que acometem essa população. A síndrome da fragilidade não apresenta sinergia com doenças cardiovasculares crônicas em relação ao risco de morte

Introduction: Frailty is characterized by the loss of the biological and physical capacity to respond adequately to organic stress as a result of damage to various systems associated with aging. The frequency of frailty is three times higher among individuals with cardiovascular disease. Methods: SARCOS is an epidemiological cohort study to evaluate vulnerability syndrome with hospitalization and mortality in elderly patients with cardiovascular disease (CVD). Frailty was diagnosed when three or more of the following criteria were present: Weight loss > 5%, slow walking speed, muscle weakness by the hand-grip test, exhaustion, and loss of energy (by the five times sit-to-stand test). Results: Of the 169 patients evaluated, frailty was present in 19.5%(n = 33). The mean age was 78.3 ± 7.1 years. The mortality rate at six months was 3% (n = 5), with 80% (n = 4) being frail and 20% (n = 1) pre-frail (p = 0.007). In the logistic regression analysis, frailty was shown to be a strong predictor of death at six months, with an 18-fold increase in risk when compared to strong individuals (p = 0.010), whereas among those with CVD, the heart failure presented a 4-fold increase in risk (p = 0.061). In the interaction model between frailty and CVD, there were no significant differences in frailty in relation to the risk of death. Conclusion: Frailty is an important risk factor for early death among outpatients, independent of, and higher than the most frequent chronic cardiovascular diseases that affect this population. Frailty syndrome was not correlated with chronic cardiovascular diseases, in relation to the risk of death

Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data.

BACKGROUND: The prevalence of HIV-1 resistance to antiretroviral therapies (ART) has declined in high-income countries over recent years, but drug resistance remains a substantial concern in many low and middle-income countries. The Q151M and T69 insertion (T69i) resistance mutations in the viral reverse transcriptase gene can reduce susceptibility to all nucleoside/tide analogue reverse transcriptase inhibitors, motivating the present study to investigate the risk factors and outcomes associated with these mutations. METHODS: We considered all data in the UK HIV Drug Resistance Database for blood samples obtained in the period 1997-2014. Where available, treatment history and patient outcomes were obtained through linkage to the UK Collaborative HIV Cohort study. A matched case-control approach was used to assess risk factors associated with the appearance of each of the mutations in ART-experienced patients, and survival analysis was used to investigate factors associated with viral suppression. A further analysis using matched controls was performed to investigate the impact of each mutation on survival. RESULTS: A total of 180 patients with Q151M mutation and 85 with T69i mutation were identified, almost entirely from before 2006. Occurrence of both the Q151M and T69i mutations was strongly associated with cumulative period of virological failure while on ART, and for Q151M there was a particular positive association with use of stavudine and negative association with use of boosted-protease inhibitors. Subsequent viral suppression was negatively associated with viral load at sequencing for both mutations, and for Q151M we found a negative association with didanosine use but a positive association with boosted-protease inhibitor use. The results obtained in these analyses were also consistent with potentially large associations with other drugs. Analyses were inconclusive regarding associations between the mutations and mortality, but mortality was high for patients with low CD4 at detection. CONCLUSIONS: The Q151M and T69i resistance mutations are now very rare in the UK. Our results suggest that good outcomes are possible for people with these mutations. However, in this historic sample, viral load and CD4 at detection were important factors in determining prognosis.

Highlights from the HTLV-1 symposium at the 2017 Australasian HIV and AIDS Conference held jointly with the 2017 Australasian Sexual Health Conference, November 2017, Canberra, Australia.

We are pleased to report on the inaugural HTLV-1 symposium at the 2017 Australasian HIV and AIDS Conference joint with 2017 Australasian Sexual Health Conference in Canberra, Australia. Our understanding of HTLV-1 epidemiology, pathogenesis, laboratory diagnostics and treatment options for HTLV-1 diseases has advanced tremendously over the last 40 years. However, the awareness of healthcare providers and the general population about HTLV-1, and the effective promotion and implementation of HTLV-1 transmission-prevention strategies, lag behind current knowledge. Here we present a summary of the symposium, plenary and poster presentations on HTLV-1.

Posterior reversible encephalopathy syndrome in HIV-positive patients: a case report and literature review.

We are reporting the case of a woman who was admitted acutely to our intensive care unit without any collateral history. She was diagnosed with posterior reversible encephalopathy syndrome (PRES) as a consequence of poor adherence to anti-hypertensive, anti-diabetic and anti-retroviral medications. PRES is a rare condition, which may cause cortical blindness; contrary to its name it is not always reversible. Rapid diagnosis and aggressive management of underlying causes facilitate reversibility of PRES. We also summarise the literature on patients with HIV and PRES.

Sex effects on the association between sarcopenia EWGSOP and osteoporosis in outpatient older adults: data from the SARCOS study.

OBJECTIVE: The objective was to evaluate the association between sarcopenia (EWGSOP) and osteoporosis in older adults. SUBJECTS AND METHODS: This is a cross sectional analysis of a baseline evaluation of the SARCopenia and OSteoporosis in Older Adults with Cardiovascular Diseases Study (SARCOS). Three hundred and thirty-two subjects over 65 years of age were evaluated. Sarcopenia was determined by EWGSOP flowchart and Osteoporosis was established by WHO's criteria. Physical function, comorbidities and medications were evaluated. RESULTS: Women were older (79.8 ± 7.2 years) than men (78.21 ± 6.7 years) (p = 0.042). Osteoporosis occurred in 24.8% of men, and in 42.7% of women (p < 0.001); sarcopenia occurred in 25.5% of men and in 17.7%, of women (p = 0.103). Osteoporosis was diagnosed in 68% of sarcopenic women, however only 20.7% (p = 0.009) of women with osteoporosis had sarcopenia; in older men, 44.7% of individuals with sarcopenia presented osteoporosis and 42.9% (p = 0.013) of men with osteoporosis showed sarcopenia. In an adjusted logistic regression analyses for sarcopenia, osteoporosis presented a statistically significant association with sarcopenia in men [OR: 2.930 (95% CI: 1.044-8.237; p = 0.041)] but not in women [OR: 2.081 (0.787-5.5; p = 0.142)]; in the adjusted logistic regression analyses for osteoporosis, a statistically significant association occurred in men [OR: 2.984 (95% CI: 1.144-7.809; p = 0.025)], but not in women [OR: 2.093 (0.962-3.714; p = 0.137)]. CONCLUSION: According to sex, there are significant differences in the association between sarcopenia EWGSOP and osteoporosis in outpatient older adults. It is strong and significant in males; in females, despite showing a positive trend, it was not statistically significant.