What happens before, during and after crisis for someone with dementia living at home: A systematic review.

BACKGROUND: People living with dementia often experience crisis. Home treatment of crisis is an alternative to hospital admission that can have better outcomes. This systematic review is about people with dementia living at home and in crisis. It identifies modifiable factors in the crisis process that may facilitate crisis resolution. METHODS: The protocol is registered on PROSPERO. A systematic search of MEDLINE, EMBASE, CINAHL, AHMED, PsycINFO, Cochrane Library and references of retrieved publications, identified empirical research in English language and date range January 2000 to February 2019. Two researchers independently screened abstracts, selected publications and extracted data using a framework based on published guidelines. This is a report of the analysis and narrative synthesis. RESULTS: The search identified 2755 titles and abstracts, 76 were selected for full-text examination and 13 agreed for inclusion. The included studies evidence that: for a person with dementia, crisis is a process that begins with a problem judged to put them or others at risk of harm. It leads to decision and action to treat this risk, thus resolve the crisis. Such crisis can be predicted or unpredicted and progress quickly or slowly. Medical treatment, community resources and psychosocial support of personal resources, decision making, relationships and social networks, are all modifiable factors that can treat the risk of harm during crisis. Carers' and professionals' knowledge and skills in dementia care are likely to play a key role in crisis resolution in the home. CONCLUSION: There has been limited investigation of the process and management of crisis at home for people living with dementia. The results of this review provide a foundation for future research. There is no consensus on critical components of home treatment to facilitate crisis resolution. However, education in dementia care for carers and professionals is likely to prove essential to successful home treatment.

Crisis management for people with dementia at home: Mixed-methods case study research to identify critical factors for successful home treatment.

Best practice in dementia care is support in the home. Yet, crisis is common and can often result in hospital admission with adverse consequences. The objective of this mixed-methods case study research was to identify the critical factors for resolving crisis for a person with dementia living at home. The research was an in-depth investigation of what happens during crisis for people with dementia and how it is managed by a Home Treatment Crisis Team to resolution and outcome at 6 weeks and 6 months. The methods were; observation of crisis management for 15 patients with dementia (max three observations per patient, total 41), interviews with patients with dementia (n = 5), carers (n = 13) and professionals (n = 14, range one to six interviews per person, total 29), focus group (nine professionals), and extraction of demographics and medical history from medical records. Analysis focused on the identification of factors important for crisis resolution and avoidance of hospital admission. Critical factors for the Home Treatment Crisis Team to enable successful crisis resolution were: immediate action to reduce risk of harm, expertise in dementia care and carer education, communication skills to establish trust and promote benefits of home treatment, shared decision-making, medication management, addressing the needs of carers independently of the person with dementia and, local availability of respite and other community services. The Home Treatment Crisis Team integrated the seven factors to deploy a biopsychosocial systems approach with embedded respect for personhood. This approach enabled crisis resolution for a person with dementia by creating a system of services, treatments, resources and relationships, 'Safe Dementia Space', in the community with avoidance of hospital admission in more than 80% of referrals. The identified critical factors for crisis resolution are important considerations in the design and delivery of home treatment services for people with dementia.

Do Wellness Tourists Get Well? An Observational Study of Multiple Dimensions of Health and Well-Being After a Week-Long Retreat.

BACKGROUND: Wellness retreats use many complementary and alternative therapies within a holistic residential setting, yet few studies have evaluated the effect of retreat experiences on multiple dimensions of health and well-being, and no published studies have reported health outcomes in wellness tourists. OBJECTIVES: To assess the effect of a week-long wellness-retreat experience in wellness tourists. DESIGN: A longitudinal observational study with outcomes assessed upon arrival and departure and 6 weeks after the retreat. SETTING: A rural health retreat in Queensland, Australia. INTERVENTIONS: A holistic, 1-week, residential, retreat experience that included many educational, therapeutic, and leisure activities and an organic, mostly plant-based diet. OUTCOME MEASURES: Multiple outcome measures were performed upon arrival and departure and 6 weeks after the retreat. These included anthropometric measures, urinary pesticide metabolites, a food and health symptom questionnaire, the Five Factor Wellness Inventory, the General Self Efficacy questionnaire, the Pittsburgh Insomnia Rating Scale, the Depression Anxiety Stress Scale, the Profile of Mood States, and the Cogstate cognitive function test battery. RESULTS: Statistically significant improvements (p < 0.05) were seen in almost all measures (n = 37) after 1 week and were sustained at 6 weeks (n = 17). There were statistically significant improvements (p < 0.001) in all anthropometric measures after 1 week, with reductions in abdominal girth (2.7 cm), weight (1.6 kg), and average systolic and diastolic pressure (-16.1 mmHg and -9.3 mmHg, respectively). Statistically significant improvements (p < 0.05) were also seen in psychological and health symptom measures. Urinary pesticide metabolites were detected in pooled urine samples before the retreat and were undetectable after the retreat. CONCLUSION: Retreat experiences can lead to substantial improvements in multiple dimensions of health and well-being that are maintained for 6 weeks. Further research that includes objective biomarkers and economic measures in different populations is required to determine the mechanisms of these effects and assess the value and relevance of retreat experiences to clinicians and health insurers.

Cassette deletion in multiple shRNA lentiviral vectors for HIV-1 and its impact on treatment success.

BACKGROUND: Multiple short hairpin RNA (shRNA) gene therapy strategies are currently being investigated for treating viral diseases such as HIV-1. It is important to use several different shRNAs to prevent the emergence of treatment-resistant strains. However, there is evidence that repeated expression cassettes delivered via lentiviral vectors may be subject to recombination-mediated repeat deletion of 1 or more cassettes. RESULTS: The aim of this study was to determine the frequency of deletion for 2 to 6 repeated shRNA cassettes and mathematically model the outcomes of different frequencies of deletion in gene therapy scenarios. We created 500+ clonal cell lines and found deletion frequencies ranging from 2 to 36% for most combinations. While the central positions were the most frequently deleted, there was no obvious correlation between the frequency or extent of deletion and the number of cassettes per combination. We modeled the progression of infection using combinations of 6 shRNAs with varying degrees of deletion. Our in silico modeling indicated that if at least half of the transduced cells retained 4 or more shRNAs, the percentage of cells harboring multiple-shRNA resistant viral strains could be suppressed to < 0.1% after 13 years. This scenario afforded a similar protection to all transduced cells containing the full complement of 6 shRNAs. CONCLUSION: Deletion of repeated expression cassettes within lentiviral vectors of up to 6 shRNAs can be significant. However, our modeling showed that the deletion frequencies observed here for 6x shRNA combinations was low enough that the in vivo suppression of replication and escape mutants will likely still be effective.

Long-term survival and concomitant gene expression of ribozyme-transduced CD4+ T-lymphocytes in HIV-infected patients.

BACKGROUND: An anti-HIV-1 tat ribozyme, termed Rz2, has been shown to inhibit HIV-1 infection/replication and to decrease HIV-1-induced pathogenicity in T-lymphocyte cell lines and normal peripheral blood T-lymphocytes. We report here the results of a phase I gene transfer clinical trial using Rz2. METHODS: Apheresis was used to obtain a peripheral blood cell population from each of four HIV-negative donors. After enrichment for CD4+ T-lymphocytes, ex vivo expansion and genetic manipulation (approximately equal aliquots of the cells were transduced with the ribozyme-containing (RRz2) and the control (LNL6) retroviral vector), these cells were infused into the corresponding HIV-1-positive twin recipient. Marking was assessed over an initial 24-week period and in total over an approximate 4-year period. RESULTS: The gene transfer procedure was shown to be safe, and technically feasible. Both RRz2- and LNL6-gene-containing peripheral blood mononuclear cells (PBMC) were detected at all time points examined to 4 years. There was concomitant gene construct expression in the absence of the need for ex vivo peripheral blood cell stimulation and there was no evidence of immune elimination of the neoR T-lymphocytes nor of silencing of the Moloney murine leukemia virus long terminal repeat. CONCLUSIONS: The proof of principle results reported here demonstrate safety and feasibility of this type of gene transfer approach. While not specifically tested, T-lymphocytes containing an anti-HIV gene construct may impact on HIV-1 viral load and CD4+ T-lymphocyte count, potentially representing a new therapeutic modality for HIV-1 infection.