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IntroductionDuring treatment with protease inhibitor monotherapy, the number of antiretrovirals with therapeutic concentrations in the cerebrospinal fluid (CSF) is lower, compared to standard triple therapy. However, the clinical consequences are unclear.MethodsA total of 273 patients with HIV RNA <50 copies/mL for over 24 weeks on current antiretrovirals randomized to darunavir/ritonavir (DRV/r) 800/100 mg once‐daily, either as monotherapy (n=137) or with 2NRTIs (n=136). Neurocognitive function was evaluated in all patients by the Hopkins Verbal Learning Tests, the Colour Trail Tests and the Grooved Pegboard Test at screening, baseline and at Week 48. A global neurocognitive score (NPZ‐5) was derived by averaging the standardized results of the five domains. In a central nervous system (CNS) sub‐study (n=70), HIV RNA levels in the CNS were evaluated at baseline and Week 48. Clinical adverse events related to the CNS were collected at each visit.ResultsPatients were 83% male and 88% White, with median age 43 years. There were more patients with nadir CD4 count below 200 cells/µL in the DRV/r monotherapy arm (41/137, 30%) than the triple therapy arm (30/136, 22%). At Week 48, there was no difference between the treatment arms for the five combined domains of the neurocognitive score. At Week 48, the percentage of patients with an abnormal neurocognitive score among the five domains was 12.2% for DRV/r monotherapy and 14.9% for triple therapy. However, one patient on DRV/r monotherapy with a CD4 nadir of 17 cells/µL was hospitalized with HIV encephalomyelitis at Week 24, with HIV RNA 2500 copies/mL in the CSF and 125 copies/mL in the plasma. Symptoms resolved after intensification with high dose zidovudine. A second patient on DRV/r monotherapy with CD4 nadir of 166 cells/µL had a rise in HIV RNA in CSF from <40 copies/mL at baseline to 654 copies/mL at Week 48, with concurrent plasma HIV RNA of 77 copies/mL.ConclusionsIn this study for patients with HIV RNA <50 copies/mL at baseline, there was no difference in neurocognitive function between the treatment arms. However two patients on PI monotherapy with CD4 nadir <200 cells/µL developed viraemia in both CSF and plasma, with one symptomatic case. DRV/r monotherapy should be used with caution in patients with nadir CD4 counts below 200 cells/µL.

The impact of losing a limb in military service extends well beyond initial recovery and rehabilitation, with long-term consequences and challenges requiring healthcare commitments across the life-course. This paper presents a systematic review of the current state of knowledge regarding the long-term impact of ageing and limb-loss in military veterans. Key databases were systematically searched including: ASSIA, CINAHL, Cochrane Library, Medline, Web of Science, PsycArticles/PsychInfo, ProQuest Psychology and ProQuest Sociology Journals, and SPORTSDiscus. Empirical studies which focused on the long-term impact of limb-loss and/or healthcare requirements in veterans were included. The search process revealed 30 papers relevant for inclusion. These papers focused broadly on four themes: 1) long-term health outcomes, prosthetics use, and quality of life; 2) long-term psycho-social adaptation and coping with limb-loss; 3) disability and identity, and; 4) estimating the long-term costs of care and prosthetic provision. Findings present a compelling case for ensuring the long-term care needs and costs of rehabilitation for older limbless veterans are met. A dearth of information on the lived experience of limb-loss, and the needs of veterans' families calls for further research to address these important issues.

How can we understand older people as real human beings, value their wisdom, and appreciate that their norms and purposes both matter in themselves and are affected by those of others? Using a life-course approach, Valuing older people argues that the complexity and potential creativity of later life demand a humanistic vision of older people and ageing. It acknowledges the diversity of experiences of older age and presents a range of contexts and methodologies through which they can be understood. Ageing is a process of creating meaning carried out by older people, and is significant for those around them. This book, therefore, considers the impact of social norms and political and economic structures on older people's capacities to age in creative ways. What real obstacles are there to older people's construction of meaningful lives? What is being achieved when they feel they are ageing well? This collection, aimed at students, researchers, practitioners and policy-makers, offers a lively and constructive response to contemporary challenges involving ageing and how to understand it