A Systematic Review of the Current Evidence from Randomised Controlled Trials on the Impact of Medication Optimisation or Pharmacological Interventions on Quantitative Measures of Cognitive Function in Geriatric Patients.

BACKGROUND: Cognitive decline is common in older people. Numerous studies point to the detrimental impact of polypharmacy and inappropriate medication on older people's cognitive function. Here we aim to systematically review evidence on the impact of medication optimisation and drug interventions on cognitive function in older adults. METHODS: A systematic review was performed using MEDLINE and Web of Science on May 2021. Only randomised controlled trials (RCTs) addressing the impact of medication optimisation or pharmacological interventions on quantitative measures of cognitive function in older adults (aged > 65 years) were included. Single-drug interventions (e.g., on drugs for dementia) were excluded. The quality of the studies was assessed by using the Jadad score. RESULTS: Thirteen studies met the inclusion criteria. In five studies a positive impact of the intervention on metric measures of cognitive function was observed. Only one study showed a significant improvement of cognitive function by medication optimisation. The remaining four positive studies tested methylphenidate, selective oestrogen receptor modulators, folic acid and antipsychotics. The mean Jadad score was low (2.7). CONCLUSION: This systematic review identified a small number of heterogenous RCTs investigating the impact of medication optimisation or pharmacological interventions on cognitive function. Five trials showed a positive impact on at least one aspect of cognitive function, with comprehensive medication optimisation not being more successful than focused drug interventions. More prospective trials are needed to specifically assess ways of limiting the negative impact of certain medication in particular and polypharmacy in general on cognitive function in older patients.

Factors associated with shorter length of admission among people with dementia in England and Wales: retrospective cohort study.

OBJECTIVES: To identify aspects of the organisation and delivery of acute inpatient services for people with dementia that are associated with shorter length of hospital stay. DESIGN AND SETTING: Retrospective cohort study of patients admitted to 200 general hospitals in England and Wales. PARTICIPANTS: 10 106 people with dementia who took part in the third round of National Audit of Dementia. MAIN OUTCOME MEASURE: Length of admission to hospital. RESULTS: The median length of stay was 12 days (IQR=6-23 days). People with dementia spent less time in hospital when discharge planning was initiated within 24 hours of admission (estimated effect -0.24, 95% CI: -0.29 to -0.18, p<0.001). People from ethnic minorities had shorter length of stay (difference -0.066, 95% CI: -0.13 to -0.002, p=0.043). Patients with documented evidence of discussions having taken place between their carers and medical staff spent longer in hospital (difference 0.26, 95% CI: 0.21 to 0.32, p<0.001). These associations held true in a subsample of 669 patients admitted with hip fracture and data from 74 hospitals with above average carer-rated quality of care. CONCLUSIONS: The way that services for inpatients with dementia are delivered can influence how long they spend in hospital. Initiating discharge planning within the first 24 hours of admission may help reduce the amount of time that people with dementia spend in hospital.

STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk): a Delphi study by the EuGMS Task and Finish Group on Fall-Risk-Increasing Drugs.

BACKGROUND: Healthcare professionals are often reluctant to deprescribe fall-risk-increasing drugs (FRIDs). Lack of knowledge and skills form a significant barrier and furthermore, there is no consensus on which medications are considered as FRIDs despite several systematic reviews. To support clinicians in the management of FRIDs and to facilitate the deprescribing process, STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk) and a deprescribing tool were developed by a European expert group. METHODS: STOPPFall was created by two facilitators based on evidence from recent meta-analyses and national fall prevention guidelines in Europe. Twenty-four panellists chose their level of agreement on a Likert scale with the items in the STOPPFall in three Delphi panel rounds. A threshold of 70% was selected for consensus a priori. The panellists were asked whether some agents are more fall-risk-increasing than others within the same pharmacological class. In an additional questionnaire, panellists were asked in which cases deprescribing of FRIDs should be considered and how it should be performed. RESULTS: The panellists agreed on 14 medication classes to be included in the STOPPFall. They were mostly psychotropic medications. The panellists indicated 18 differences between pharmacological subclasses with regard to fall-risk-increasing properties. Practical deprescribing guidance was developed for STOPPFall medication classes. CONCLUSION: STOPPFall was created using an expert Delphi consensus process and combined with a practical deprescribing tool designed to optimise medication review. The effectiveness of these tools in falls prevention should be further evaluated in intervention studies.

Current evidence on the impact of medication optimization or pharmacological interventions on frailty or aspects of frailty: a systematic review of randomized controlled trials.

BACKGROUND: Frailty and adverse drug effects are linked in the fact that polypharmacy is correlated with the severity of frailty; however, a causal relation has not been proven in older people with clinically manifest frailty. METHODS: A literature search was performed in Medline to detect prospective randomized controlled trials (RCTs) testing the effects of pharmacological interventions or medication optimization in older frail adults on comprehensive frailty scores or partial aspects of frailty that were published from January 1998 to October 2019. RESULTS: Twenty-five studies were identified, 4 on comprehensive frailty scores and 21 on aspects of frailty. Two trials on comprehensive frailty scores showed positive results on frailty although the contribution of medication review in a multidimensional approach was unclear. In the studies on aspects related to frailty, ten individual drug interventions showed improvement in physical performance, muscle strength or body composition utilizing alfacalcidol, teriparatide, piroxicam, testosterone, recombinant human chorionic gonadotropin, or capromorelin. There were no studies examining negative effects of drugs on frailty. CONCLUSION: So far, data on a causal relationship between drugs and frailty are inconclusive or related to single-drug interventions on partial aspects of frailty. There is a clear need for RCTs on this topic that should be based on a comprehensive, internationally consistent and thus reproducible concept of frailty assessment.

Substance misuse in later life: challenges for primary care: a review of policy and evidence.

BACKGROUND: Substance misuse in older people represents a growing clinical and public health problem within primary care. AIM: The aim of article is to explore policy and research evidence for informing best practice in the assessment, treatment effectiveness, treatment implementation and approaches to recovery for older people with substance misuse in primary care. METHODS: Relevant search terms were used to examine the databases MEDLINE, EMBASE, CINAHL and PsychINFO up to January 2016. RESULTS: An age-sensitive approach is required to overcome barriers to assessment. Training is essential for developing relevant knowledge, skills and attitudes. Clinical audit be used to develop care pathways, particularly for older people with dual diagnosis. There is also a need to develop closer links between primary care and the secondary care specialties, as well as added value in working with carers and voluntary agencies. DISCUSSION: Further research is needed to inform more effective approaches to treatment. Adequate funding for workforce development and quality improvement in service development are also essential to improve health outcomes and quality of life in older people with substance misuse.

Alcohol and age.

Alcohol consumption constitutes a substantial burden of disease. Older people are being admitted to hospital for alcohol problems in increasing numbers. A recent systematic review reports cautious supportive evidence for primary prevention interventions in reducing excessive alcohol consumption in older drinkers, but does not focus on treatment of dependent drinkers. The evidence base for treatment interventions for dependent drinkers is comparatively limited, but it is growing. In addition to brief interventions, specialist outpatient treatment and inpatient treatment have been evaluated.The responses of older people to treatment are promising: they want to abstain, they have the capacity to change, they respond well to brief advice and motivational enhancement therapy, they achieve improvements at least as comparable to younger counterparts-and sometimes better-and they do have the prospect of long-term recovery.There is a need to develop services tailored to the needs of older substance misusers. Education of the workforce, including medical students and other health care professionals, is the key. Collaboration and coordination of services, training, research and policy are essential.There are very few designated services for older substance misusers in the UK and only 7% of older people who need treatment for alcohol problems access them. There is a massive gap in the whole gamut of research from basic to clinical research in this vulnerable patient population: this has to be developed if management is to be effective and up to date.

Improving palliative care in selected settings in England using quality indicators: a realist evaluation.

BACKGROUND: There is a gap between readily available evidence of best practice and its use in everyday palliative care. The IMPACT study evaluated the potential of facilitated use of Quality Indicators as tools to improve palliative care in different settings in England. METHODS: 1) Modelling palliative care services and selecting a set of Quality Indicators to form the core of an intervention, 2) Case studies of intervention using the Quality Indicator set supported by an expert in service change in selected settings (general practice, community palliative care teams, care homes, hospital wards, in-patient hospices) with a before-and-after evaluation, and 3) realist evaluation of processes and outcomes across settings. Participants in each setting were supported to identify no more than three Quality Indicators to work on over an eight-month period in 2013/2014. RESULTS: General practices could not be recruited to the study. Care homes were recruited but not retained. Hospital wards were recruited and retained, and using the Quality Indicator (QI) set achieved some of their desired changes. Hospices and community palliative care teams were able to use the QI set to achieve almost all their desired changes, and develop plans for quality improvements. Improvements included: increasing the utility of electronic medical records, writing a manual for end of life care, establishing working relationships with a hospice; standardising information transfer between settings, holding regular multi-disciplinary team meetings, exploration of family carers' views and experiences; developing referral criteria, and improvement of information transfer at patient discharge to home or to hospital. Realist evaluation suggested that: 1) uptake and use of QIs are determined by organisational orientation towards continuous improvement; 2) the perceived value of a QI package was not powerful enough for GPs and care homes to commit to or sustain involvement; 3) the QI set may have been to narrow in focus, or more specialist than generalist; and 4) the greater the settings' 'top-down' engagement with this change project, the more problematic was its implementation. CONCLUSIONS: Whilst use of QIs may facilitate improvements in specialist palliative care services, different QI sets may be needed for generalist care settings.

Physician-facilitated designation of proxy decision maker.

With vast improvements in healthcare in recent decades, people are living longer but often with higher rates of morbidity and chronic illnesses. This has resulted in a higher proportion of the population who may benefit from early end-of-life 'conversation and planning', but also gives healthcare professionals more time during which these discussions are relevant, as people live longer with their chronic diseases. A survey conducted by Lifshitz et al (Isr J Health Policy Res 5:6, 2016) sought to assess physician awareness and willingness to discuss designating a proxy decision-maker with patients, in order to aid end-of-life care in the event that the patient is rendered unable to make or communicate these decisions later in life. Their article suggests that proxy decision-maker designation is only one aspect of end-of-life care; a challenging area littered with ethical and moral dilemmas. Without early, open and frank discussions with patients regarding their wishes at the end of life, proxy decision-makers may be in no better position than physicians or a court appointed proxy to make decisions in the patients' best interests/benefits. This commentary also touches upon the use of health and care passports being developed or in early phases in the United Kingdom, and whether these may be utilised in the field of palliative care in Israel.

Policy issues related to educating the future Israeli medical workforce: an international perspective.

A 2014 external review of medical schools in Israel identified several issues of importance to the nation's health. This paper focuses on three inter-related policy-relevant topics: planning the physician and healthcare workforce to meet the needs of Israel's population in the 21(st) century; enhancing the coordination and efficiency of medical education across the continuum of education and training; and the financing of medical education. All three involve both education and health care delivery. The physician workforce is aging and will need to be replenished. Several physician specialties have been in short supply, and some are being addressed through incentive programs. Israel's needs for primary care clinicians are increasing due to growth and aging of the population and to the increasing prevalence of chronic conditions at all ages. Attention to the structure and content of both undergraduate and graduate medical education and to aligning incentives will be required to address current and projected workforce shortage areas. Effective workforce planning depends upon data that can inform the development of appropriate policies and on recognition of the time lag between developing such policies and seeing the results of their implementation. The preclinical and clinical phases of Israeli undergraduate medical education (medical school), the mandatory rotating internship (stáge), and graduate medical education (residency) are conducted as separate "silos" and not well coordinated. The content of basic science education should be relevant to clinical medicine and research. It should stimulate inquiry, scholarship, and lifelong learning. Clinical exposures should begin early and be as hands-on as possible. Medical students and residents should acquire specific competencies. With an increasing shift of medical care from hospitals to ambulatory settings, development of ambulatory teachers and learning environments is increasingly important. Objectives such as these will require development of new policies. Undergraduate medical education (UME) in Israel is financed primarily through universities, and they receive funds through VATAT, an education-related entity. The integration of basic science and clinical education, development of earlier, more hands-on clinical experiences, and increased ambulatory and community-based medical education will demand new funding and operating partnerships between the universities and the health care delivery system. Additional financing policies will be needed to ensure the appropriate infrastructure and support for both educators and learners. If Israel develops collaborations between various government agencies such as the Ministries of Education, Health, and Finance, the universities, hospitals, and the sick funds (HMOs), it should be able to address successfully the challenges of the 21st century for the health professions and meet its population's needs.

Quality of care for people with dementia in general hospitals: national cross-sectional audit of patient assessment.

There have been recent reports of poor quality care in the National Health Service in the UK, and older people with dementia are particularly vulnerable. This study aims to examine the quality of assessment of people with dementia admitted to hospital. Cross-sectional case-note audit of key physical and psychosocial assessments was carried out in 7,934 people with dementia who were discharged from 206 general hospitals. Most people had no record of a standardised assessment of their cognitive state (56.8%, 95% confidence interval [CI] = 55.8-58.0) or functioning (74.2%, 95% CI = 73.2-75.1). Information from carers was documented in 39.0% of cases (95% CI = 37.9-40.1). There was considerable variation across hospital sites. Key assessments were less likely when people were admitted to surgical wards. Assessments fall well below recommended standards especially with regard to social and cognitive functioning. Problems are particularly marked on surgical wards.

The PREDICT (increasing the participation of the elderly in clinical trials) study: the charter and beyond.

There is general agreement that the growth of the numbers of older people throughout the world has significant implications for both health and social care and for the prevention and treatment of disease and disability. The optimum use of pharmaceuticals and possibly nutraceuticals is, and will to a greater extent, therefore be of crucial importance. A snapshot of the current status of older people in relation to the issues discussed in this review is provided in an informative report published by Age UK.

The Stroke Oxygen Study (SO2S) - a multi-center, study to assess whether routine oxygen treatment in the first 72 hours after a stroke improves long-term outcome: study protocol for a randomized controlled trial.

BACKGROUND: Mild hypoxia is common in stroke patients and may have significant adverse effects on the ischemic brain after stroke. The use of oxygen treatment is rapidly increasing in European stroke units but is not without side effects. It impedes early mobilization, could pose an infection risk, and may encourage the formation of toxic free radicals, leading to further damage to the ischemic brain. In the Stroke Oxygen Pilot Study (2 or 3 L/min for 72 hours) neurological recovery at one week was better in the oxygen group than in controls, and after correction for difference in baseline stroke severity and prognostic factors, there was a trend to better outcome with oxygen at six months. Oxygen was as effective in mild as in severe strokes.Oxygen saturation is lower at night than during the day, and episodes of oxygen desaturation are common during sleep. Nocturnal oxygen supplementation is likely to reduce the burden of hypoxia without interfering with daytime mobilization and rehabilitation.Before wider use of oxygen supplementation becomes established it is important to obtain better evidence on which patients benefit from such treatment. METHODS: Participants will be randomized to one of three groups: the first will receive continuous oxygen for 72 hours (at a rate of 2 or 3 L/min depending on baseline oxygen saturation), the second group will receive nocturnal oxygen only (at a rate of 2 or 3 L/min depending on baseline oxygen saturation) and the third group will not receive any oxygen (control). A baseline assessment is performed at randomization and a one-week follow-up completed. Outcome data at three, six and twelve months will be obtained via a questionnaire sent to the patient by the trial center. DISCUSSION: This study will provide evidence on the effectiveness of oxygen supplementation for the treatment of stroke and whether nocturnal oxygen is a potentially beneficial therapy regimen. TRIAL REGISTRATION: This trial is registered with the ISRCTN register ID number ISRCTN52416964.

Silicon-rich mineral water as a non-invasive test of the 'aluminum hypothesis' in Alzheimer's disease.

There has been a plausible link between human exposure to aluminum and Alzheimer's disease for several decades. We contend that the only direct and ethically acceptable experimental test of the 'aluminum hypothesis', which would provide unequivocal data specific to the link, is to test the null hypothesis that a reduction in the body burden of aluminum to its lowest practical limit would have no influence upon the incidence, progression, or severity of Alzheimer's disease. Herein we are testing the hypothesis that silicon-rich mineral waters can be used as non-invasive methods to reduce the body burden of aluminum in individuals with Alzheimer's disease and a control group consisting of their carers and partners. We have shown that drinking up to 1 L of a silicon-rich mineral water each day for 12 weeks facilitated the removal of aluminum via the urine in both patient and control groups without any concomitant affect upon the urinary excretion of the essential metals, iron and copper. We have provided preliminary evidence that over 12 weeks of silicon-rich mineral water therapy the body burden of aluminum fell in individuals with Alzheimer's disease and, concomitantly, cognitive performance showed clinically relevant improvements in at least 3 out of 15 individuals. This is a first step in a much needed rigorous test of the 'aluminum hypothesis of Alzheimer's disease' and a longer term study involving many more individuals is now warranted.

Effects of mobilization and tactile stimulation on chronic upper-limb sensorimotor dysfunction after stroke.

OBJECTIVE: To explore the effects of Mobilization and Tactile Stimulation (MTS) and patterns of recovery in chronic stroke (>12mo) when upper limb (UL) "performance" has reached a clear plateau. DESIGN: Replicated single-system experimental study with 8 single cases using A-B-A design (baseline-intervention-withdrawal phases); length of baseline randomly determined; intervention phase involved 6 weeks of daily MTS to the contralesional UL. SETTING: Community setting, within participants' place of residence. PARTICIPANTS: Individual stroke survivors (N=8; male-to-female ratio, 3:1; age range, 49-76y; 4 with left hemiplegia, 4 with right hemiplegia) discharged from ongoing therapy, more than 1 year post stroke (range, 14-48mo). Clinical presentations were varied across the sample. INTERVENTIONS: Participants received up to 1 hour of daily (Monday to Friday) treatment with MTS to the UL for 6 weeks during the intervention (B) phase. MAIN OUTCOME MEASURES: Motor function (Action Research Arm Test [ARAT]) and motor impairment (Motricity Index [MI] arm section) of the UL. RESULTS: UL performance was stable during baseline for all participants. On visual analysis, improvements in motor impairment were seen in all participants, and clinically significant improvements in motor function were seen in 4 of 8 participants during the intervention phase. Latency between onset of intervention and improvement ranged from 5 to 31 days (ARAT) and from 0 to 28 days (MI). Improvements in performance were maintained on withdrawal of the intervention. Randomization tests were not significant. CONCLUSIONS: MTS appears to improve UL motor impairment and functional activity many months, even years, after stroke onset. Improvement can be immediate, but more often there is latency between the start of intervention and improvement; recovery can be distal to proximal.