Can non-pharmacological interventions reduce hospital admissions in people with dementia? A systematic review.

BACKGROUND: People with dementia who are admitted to hospital have worse outcomes than those without dementia. Identifying interventions that could reduce the risk of hospitalisation in people with dementia has the potential to positively impact on lives of people with dementia. This review aimed to investigate whether there are non-pharmacological interventions that successfully reduce hospitalisation risk, length of stay and mortality in people with dementia.
METHODS: 7 electronic databases and trial registries were searched from inception to October 2018. We included randomised controlled trials that evaluated non-pharmacological interventions in out of hospital settings and targeted people with any type of dementia. All stages of the review process were performed by two reviewers. Risk of bias was assessed using the Cochrane Risk of Bias tool. We grouped studies based on intervention: care management, counselling/self-help, enhanced GP services or memory clinics, and physiotherapy or occupational therapy. Data were pooled within intervention categories using random effects meta-analysis.
RESULTS: There was no evidence that any of the intervention categories were associated with reduced hospital admission or mortality. There was very weak evidence to suggest that care management interventions (mean difference, MD, -0.16, 95% CI -0.32, 0.01), physiotherapy/occupational therapy (MD -0.16, 95% CI -0.36, 0.03) and enhanced GP/memory clinics (MD -0.14, 95% CI -0.31, 0.03) were associated with small reductions in hospital stay. There was no evidence for an effect of counselling/self-help interventions on length of hospital stay.
CONCLUSIONS: Current evidence from randomised trials suggests no clear benefit or harm associated with any of interventions on risks of hospitalisation, duration of hospitalisation or death. Further research with the primary aim to reduce hospitalisation in people with dementia is required.

Introduction

Global dementia cases are estimated at 46.8 million people worldwide, forecast to increase to 130 million by 2050. Dementia leads to a loss of both cognitive and physical function without causing rapid mortality [1] necessitating significant levels of care for extended periods of time.[1] This care incurs cost, which, combined with the rising prevalence led the World Health Organization to announce dementia as a public health priority [2].

Whilst rarely being a direct cause of hospital admission, dementia is a significant co-morbidity, increasing the likelihood of attending hospital. This in itself increases morbidity, particularly accelerated cognitive decline, and mortality[3-5]. People with dementia also have a longer length of stay in comparison to those of the same age without dementia [3, 5, 6]. Furthermore, hospitalisation may precede institutionalisation (movement from a personal home to a care/nursing home) [4, 5, 7], which is further associated with worsening cognitive and physical performance and increased mortality [8]. This culminates in both higher in-hospital and higher post-discharge costs for people with dementia compared to others with the same condition. If unnecessary hospitalisation can be reduced appropriately [9], many of the harmful sequelae can be also be reduced, and quality of life of people with dementia will be improved.

Current pharmacological treatment is limited and is focussed around two classes of medication, acetylcholinesterase inhibitors such as donepezil and galantamine and N-Methyl-D-asartic acid (NDMA) receptor antagonists such as memantine [10]. These medications have been shown to be effective at slowing symptom progression but have negligible effect on survival and are not effective for all people with dementia [11, 12]. This makes the use of non-pharmacological interventions particularly appealing given the current limited benefits of pharmacological therapy. Non-pharmacological interventions can be thought of as anything not directly involving a medication; examples include care/case management models (healthcare workers acts as a “care/case manager” attempting to optimise a complex patient’s healthcare needs) [13], and enhancing existing community services. In the context of dementia care, non-pharmacological interventions reviews have focussed on moderating problem behaviours, improving cognition or improving general quality of life and activity levels [14]. This review aims to investigate whether there are non-pharmacological interventions that successfully reduce hospitalisation risk in people with dementia.

Methods

The review followed methods recommended by Cochrane and the Centre for Reviews and Dissemination, [15] and is reported according to PRISMA guidelines [16] (see S1 File for PRISMA checklist), no ethics approval was required for this review.

Search strategy

We searched the following electronic databases from inception to October 2018: Medline, EMBASE, PsycINFO, PsycEXTRA, CINAHL Plus, Web of Science, and Cochrane Central. We also searched trial registries—clinicaltrials.gov and the International Clinical Trials Registry Platform. No date or language restrictions were applied. Search strategies were developed for each database and included terms related to dementia, hospitalisation and study type (RCTs and systematic review/meta-analysis); an example of the full search strategy is provided in Appendix A in S1 Appendix. Reference lists of included studies and relevant reviews were screened to identify additional relevant papers.

Eligibility criteria

We included randomised controlled trials (RCTs) that evaluated non-pharmacological interventions in out of hospital settings and targeted people with any dementia diagnosis. We included studies where interventions targeted staff (e.g. nurses, GPs) and/or carers alongside people with dementia but those with interventions targeting staff or caregivers alone were excluded. Studies that included only people with mild cognitive impairment or conducted in palliative populations were excluded. Studies where people with dementia formed part of a mixed population were included if data could be extracted separately for people with dementia. Data on hospitalisation had to be available as an outcome. We contacted authors for hospitalisation data if reports indicated that these may have been collected.

Study selection

Titles and abstracts retrieved by the searches were screened independently by two reviewers. Any references considered potentially relevant were obtained as full text articles. These were assessed independently by two reviewers and reasons for exclusion recorded. Disagreements were resolved through discussion or referral to a third reviewer where necessary.

Data extraction

Data were extracted by one reviewer and checked by another for accuracy using a standardised form. Any disagreements were resolved through discussion with a third person. When a paper quoted a protocol or trial registry number, that paper or trial record was retrieved and used in addition to the included paper to gather all the data possible. In cases where the primary outcome data required clarification or important data were missing, the authors were contacted.

We extracted data on: country of study, study design, study setting, sample size, participant characteristics (age, gender, type of dementia, severity of dementia, existence of comorbidities), details of the intervention and, outcomes assessed. Data to calculate two measures of hospitalisation were extracted, dichotomous data for relative risk (RR) of hospitalisation (defined as one or more hospitalisation in the measurement period) and continuous data (mean difference and standard deviation) for difference in length of hospital stay (MD); where available emergency hospital admission was selected in preference to all admission modalities. Data to calculate a RR for mortality were also extracted (extracted data can be seen in S2 File).

Risk of bias of individual studies

The Cochrane Risk of Bias Tool was used to assess included studies for risk of bias [17]. The tool includes five domains of bias: selection bias (random sequence generation and allocation concealment), performance bias (blinding of participants and personnel), attrition bias (incomplete outcome data) and reporting bias (selective reporting). We did not assess any additional sources of bias. In each domain, the risk of bias was rated ‘high’, ‘low’ or ‘unclear’. Each study was also assigned an overall risk of bias–if studies were rated ‘high’ on at least one domain then the whole study was considered at ‘high’ risk of bias; if the study was rated ‘unclear’ on at least one domain the study was considered at ‘unclear’ risk of bias; all other studies were considered at ‘low’ risk of bias.

Synthesis of results

We grouped studies according to intervention type: care management, counselling/self-help, enhanced GP services or memory clinics, and physiotherapy or occupational therapy. We produced forest plots showing relative risks together with 95% confidence intervals (CI) for hospitalisation and mortality and for mean difference with 95% CI duration of hospitalisation. We estimated summary effect sizes using random effect meta-analysis to allow for differences in the treatment effect across studies.[18] Heterogeneity was investigated visually using forest plots and statistically using the I2 statistic.[19]

Results

The searches identified 5477 unique records, of which 17 trials [20-36] reported in a further 29 publications [37-65] fulfilled our inclusion criteria (Fig 1). A full list of excluded articles and rationale for exclusion is provided in Appendix D in S1 Appendix.

Fig 1

PRISMA flow diagram.

Table 1 describes the characteristics of included trials. All were performed in high income countries either in the United States of America (USA) or northern Europe. Five were cluster randomised trials, the most common unit of randomisation was the patient-carer dyad, with many of the studies requiring a carer for inclusion into the study. Fifteen studies provided an average mini mental state score [66]. This showed a wide range of dementia severity, from 13.8 (moderate dementia) to 24 (mild dementia), with the majority being around 18 (moderate dementia). Almost all studies excluded those with a predicted life span of <6 months and those with significant sensorial deficits. Diagnostic criteria varied; ICD 9/10 and the Diagnostic and Statistical Manual of Mental Disorders III and IV were used most frequently. There was a large amount of heterogeneity in the measurement of co-morbidities making the comparison across studies difficult. Type of dementia was recorded in nine (53%) studies. [24–26, 30, 32–36]. Eight of these included two or more types of dementia while one was restricted to participants with Alzheimer’s disease. Mean age for dementia patients ranged from 77 to 82 years across studies and both male and female dementia patients were included. Study duration ranged from three months to two years; most were one-year duration.

Table 1

Characteristics of included studies.

Broad Type of intervention	Reference and Country	Intervention Description	Age, Sex, and MMSE** Score	Study duration, 1o or 2o Outcome	Unit + No randomised	Sample size***
Care Management	Amjad 2017,	Intervention:18 months of care co-ordination by team (community worker linked to nurse and geriatric psychiatrist). This team identified needs, provided dementia education and skills, coordinating referrals and linkages to other services and care monitoring.	Age: 84	18 months	Patient	I:110
			% male: 36%			C:193
	USA* [20]		MMSE: 19.1	Secondary	303
		Control: Received the results of Johns Hopkins dementia needs assessment with recommendations for each unmet need and a brief resource guide.
	Callahan 2006,	Intervention: Patients received collaborative care management, education on communication skills; caregiver coping skills; legal and financial advice; patient exercise guidelines with a guidebook and videotape; and a caregiver guide provided by the local chapter of the Alzheimer’s Association. Care managers were geriatric nurse practitioners. Initial bimonthly meetings then once a month for a year, they identified problems and attempted behavioural solutions and referral for medication.	Age: 78	12 months	Physicians	I:84
			% male: 57			C:69
			MMSE: 18	Secondary	153
	USA* [23]
		Control: Everyone received 40–90 minutes counselling and advice from a geriatric nurse practitioner and provided written materials and access to the local Alzheimer's chapter, otherwise usual care.
	Duru 2009,	Intervention: Patients were assigned a care manager. Care managers performed structure home assessments, identified problems, initiated care plans and sent summaries to home physicians, they provided ongoing care as need and reassessed every 6 months. Additional community services were also made available such as increased respite care.	Age: 80	Either 12 or 18 months	GP clinics	I:170
			% male: 45			C:126
	USA* [24]		MMSE: NRx	Secondary
		Control: Usual care.			408
	Eloniemi-Sulkava 2009	Intervention: A family care coordinator (a public health nurse advanced 3.5-year training and specific dementia training) created a support plan. Geriatrician provided comprehensive assessments, with goal orientated support group meetings (5/year) for spouse caregivers, with individualized services co-ordinated with the care co-ordinator.	Age: 78	24 months	Patient-carer dyad	I: 63
			% male: 59			C:63
			MMSE: 13.8	Secondary
	Finland [25]				125
		Control: Usual care.
	Michalowsky 2017,	Intervention: Care management by 6 trained dementia nurses, using a computer based interventional management system. Identify unmet needs, task list generated and discussed with multidisciplinary team, treatment plan is generated from this discussion. 6 months 1 visits 1 hour every month from the nurses, following 6 months the task completion was monitored.	Age: 80	12 months	GP practice	I:252
			% male: 39			C:108
			MMSE: 22.8	Secondary	136 GP's (634 patients)
	Germany [31]
		Control: Usual care
Counselling Self-help	Bass 2015,	Intervention: Partners in Dementia Care provided coaching for patients and caregivers on how to find solutions to daily problems exacerbated by their Alzheimer's. Contacts were, at minimum, once per month over telephone or email. Each patient had two co-ordinators one for medical concerns and one for non-medical concerns	Age: 79	12 months	City	I:206
			% male: 98%			C:122
	USA* [21]		MMSE: NRx	Primary	508
		Control: Usual care, both groups received dementia education materials.
	Laakkonen 2016,	Intervention: Patients received 8 weekly sessions of a bespoke designed self-help group based on a psychosocial model. Two people trained for 10 days as group facilitators led the sessions.	Age: 77	24 months	Patient-carer dyad	I:67
			% male: 42			C:69
	Finland [29]	Control: Usual care plus a leaflet on nutrition and exercise.	MMSE: 20.8	Primary	136
	Sogaard 2014	Intervention: Individual and group based counselling sessions, plus educational courses and telephone counselling, (The DAISY intervention) over 12 months	Age: 76	36 months	Patient-career dyad	I:163
			% male: 46			C:167
	Denmark [34]	Control: Controls were followed up (3 times), and were interviewed about their current symptoms and daily life and informed about available support programs. Any problems found were referred to health services	MMSE: 24	Primary
					330
	Woods 2012,	Intervention: Patients and carers participated in joint reminiscence groups (up to 12 dyads) held weekly for 12 weeks with monthly maintenance sessions for a further 7 months. Sessions followed a treatment manual and were led by two trained volunteers, each session lasted 2 hours and rotated weekly topics.	Age: 78	10 months	Patient-carer dyad	I:196
			% male: 50			C:140
	UK [36]		MMSE: 19.3	Primary	488
		Control: Usual care.
Enhanced GP / Memory clinic	Bellantonio 2008,	Intervention: Patients received four systematic, multidisciplinary assessments conducted by a geriatrician or a geriatrics advanced practice nurse, a physical therapist, a dietician and a social worker, during the first 9 months of their residence in assisted living (at 7, 30, 120 and 320 days).	Age: 82	9 months	Patient	I:48
			% male: 37%			C:52
	USA* [22]		MMSE: 14.8	Secondary	100
		Control: Usual care.
	Kohler 2014,	Intervention: The patient was assigned to a full member GP of the Uckermark dementia network. This GP had undergone specialised training in management and diagnosis and was well connected to local specialist.	Age: 78	6–12 months	Patient	I:97
			% male: 32			C:106
	Germany [28]		MMSE: 18.9	Secondary	235
		Control: The patient was assigned to associate member GP's analogous to usual care group.
	Meeuwsen 2013,	Intervention: Post dementia care performed by a memory clinic, the Memory clinics used the Dutch Institute for Healthcare Improvement guidelines.	Age: 78	12 months	Patient-carer dyad	I:83
			% male: 47			C:77
			MMSE: 22.7	Secondary	175
	Netherlands [30]	Control: Post dementia diagnosis care performed by the general practitioner amounting to usual care, GP's used the Dutch general practice and homecare dementia guidelines.
	Schwarzkopf2011,	Intervention A: GP's received additional training in diagnosis (all groups) and treatments (intervention arms only), in addition the intervention arms had rapid access to outpatient dementia specialists and family caregiver support groups.	Age: 80	24 months	GP Practice	IA:108
			% male: 32			IB:108
	Germany [31]		MMSE: 18.7	Primary	383	C:167
		Intervention B: had access to a one on one counsellor in addition to that described for intervention A.
		Control: GP's received additional training in diagnosis, otherwise care as usual.
Physio / Occupational Therapy	Engedal 1989,	Intervention: Patients were offered participation at a day-care centre 3 days a week. The centre was staffed with two nurse aids and one occupational therapist, offering social physical and occupational activities.	Age: 80	12 months	Patient	I:38
			% male: 31			C:39
	Norway [26]		MMSE: 18	Secondary	77
		Control: Usual care.
	Graff 2008,	Intervention: Patients received 10 sessions of occupational therapy at home over 5 weeks given by well trained (>80 hours and experienced >240 hours training respectively) occupational therapists specialising in dementia.	Age: 78	3 months	Patient	I:67
			% male: 44			C:65
	Netherland [27]		MMSE: 19	Secondary	78
		Control: Usual care
	Pitkala 2013,	Intervention A: Received home visits from a dementia specialist physiotherapist using “goal orientated tailored therapy”, 1 hour twice a week.	Age: 78	24 months	Patient-carer dyad	IA:70
			% male: 43			IB:70
			MMSE: 18	Secondary	210	C:70
	Finland [32]	Intervention B: Received group based exercises, with 4-hour visits to day centres twice a week, groups of 10 with two specialised physios’. Effective exercise time of 1 hour/session.
		Control: Usual community care but were given oral and written advice from the nurses regarding exercise and nutrition.
	Voigt-Radloff 2011,	Intervention: Patients received 10 occupational therapy sessions of 1-hour duration held over 5 weeks within the home environment. This consisted of an assessment phase shared goal setting and treatment phase to reach the one or two goals set. The carer was involved in learning how to supervise, problem solving and coping strategies.	Age: 78	12 months	Patient-carer dyad	I:54
			% male: 42			C:50
	Germany [35]		MMSE: 20.4	Secondary	141
		Control: Patients received 1 hour of occupational therapy, from the same occupational therapists, and received a 10-page leaflet detailing advice about physical activity and signposted to local dementia services.

* USA = United States of America

** MMSE = Mini-mental state exam

*** I = Intervention arm; C = Control arm

x NR = Not reported

Five trials evaluated care management interventions targeting people with dementia. [20, 23–25, 31] These involved introducing the role of care manager, a nurse or community worker whose job was to co-ordinate care of dementia patients, optimising clinic appointments and pathways to improve care. Three trials compared this to usual care, two provided additional assessments and advice at the beginning of the trial to control groups. Four trials evaluated counselling or self-help interventions, providing support/self-help groups, coaching and reminiscence therapy[21, 29, 34, 36]. Control groups consisted of: usual care; usual care with additional information on dementia education or nutrition and exercise; and usual care combined with interviews investigating health needs with referrals based on the needs identified. Four trials evaluated referral to specialised services–either services where GPs had received enhanced training or to memory clinics. [22, 28, 30, 33]. Control groups received either usual care or mildly augmented usual care with the GP’s reminded of existing guidelines. Four trials provided additional physiotherapy, occupational therapy or both. [26, 27, 32, 35] Controls received usual care, a lower level of occupational therapy or advice in addition to usual care.

Hospitalisation was the primary outcome in four trials [21, 22, 24, 26]; in other studies it was included as a secondary outcome, often to inform an economic evaluation. Hospitalisation was measured through direct access to electronic records in four trials [25, 29, 32, 33], through surveys or interviews with patients or carers in nine [20, 22–24, 27, 30, 31, 35]v[36] trials, or both in two trials [21, 34]. Two trials did not report how hospitalisation was assessed [26, 28]. Seven of the seventeen included trials provided additional data after correspondence with the authors [20, 25, 29, 31–34], four of which initially presented no data on hospitalisation [20, 31, 33, 34].

Risk of bias in included studies

Fifteen trials were considered at high risk of bias overall and two at unclear risk of bias; none were at low risk of bias (Fig 2) (full risk of bias assessment can be seen in Appendix B in S1 Appendix). The main limitation in included studies was lack of blinding of participants and personnel– 12 were judged at high risk of bias and the other five at unclear risk of bias for this domain. The interventions were often pragmatic in nature and so it was not feasible to blind participants to treatment allocation. Outcome assessment was blinded in eight trials and a further seven trials did not report sufficient information to judge this domain. Only two trials were at high risk of bias for random sequence generation and allocation concealment. The available study protocols or other additional papers enabled us to rule out selective reporting bias in ten trials, however, for five trials this could not be ruled out and for two trials there was evidence of selective reporting bias.

Fig 2

Result of risk of bias assessment.

+ = Low risk of bias,– = High risk of Bias, ? = Unknown risk of bias.

Effect of interventions

There was no evidence that any of the intervention categories were associated with a decreased risk of hospital admission with RR ranging from 0.95 to 1.05 (Fig 3). There was also no evidence of reduced mortality–RRs ranged from 0.62 to 1.15 across studies (Fig 4). There was very weak evidence to suggest that care management interventions (summary MD -0.16, 95% CI -0.32, 0.01; 4 trials, I2 41.3%), physiotherapy/occupational therapy (summary MD -0.16, 95% CI -0.36, 0.03; 3 trials, I2 0%) and enhanced GP/memory clinics (summary MD -0.14, 95% CI -0.31, 0.03; 1 trial, I2 0%) were associated with small reductions in hospital stay (Fig 5). There was no evidence for an effect of counselling/self-help interventions on length of hospital stay. One trial of a care management intervention reported reduced hospitalisation in the group that received care management (RR 0.46, 95% CI 0.23 to 0.92) and reduced number of nights spent in hospital (MD -0.34, 95% CI -0.57, -0.12) (Michalowsky et al., 2017). All other trials found no difference between intervention and control groups (Figs 3 and 4).

Fig 3

Forest plot of the relative risk (RR) of hospitalisation stratified according to type of intervention.

Fig 4

Forest plot relative risk (RR) of death stratified according to type of intervention.

Fig 5

Forest plot of the mean difference (MD) of nights spent in hospital stratified according to type of intervention.

Discussion

This review evaluated whether non-pharmacological interventions can reduce hospitalisation in people with dementia. We identified 17 trials evaluating a broad range of interventions including physio/occupational therapy, enhanced GP services/memory clinics, counselling/self-help and care management. Overall there was no evidence for an effect of any of the intervention categories on hospitalisation or mortality. The consistency of the effect estimates suggests that the type of intervention is not important. There was weak evidence for a very small reduction in duration of hospital stay for care management interventions, physio/occupational therapy and enhanced GP services/memory clinics.

Only one trial, which evaluated a care management intervention, showed a beneficial effect of the intervention in reducing the risk of hospital admission and number of nights spent in hospital [31]. The publication of this study did not report on hospitalisation, and only collected these data for cost analyses–we obtained the data on hospitalisation direct from the authors. The trial included patients with mild dementia and it may be that the effect would have been different for more severe cases. Care was managed by trained dementia nurses which may have also contributed to the beneficial outcome seen with the intervention. There were a large number of withdrawals from the study (43% at 12 months) which could have biased the results.

Another trial showed an increased risk of mortality with a regular counselling and self-help intervention that included monthly phone calls to patients and caregivers, and written information and taught courses on the disease [34]. The intervention group in this study were worse off in some respects at baseline such as living alone, renting instead of owning their house and quality of life. These could have contributed to the poorer outcome at the end. Also, the control group was not without intervention and ‘structured support’ was provided at each follow up session which accommodated the patient’s and the caregiver’s frustration and uncertainty associated with a recent diagnosis by providing guidance and contact with the relevant local support programmes. This structured support may be something on its own to study in the future for a potentially beneficial effect. These findings from single trials need confirmation with further testing before any conclusions can be drawn.

Strengths and weaknesses

This review followed guidelines for the conduct and reporting of systematic reviews. [15, 16] We conducted a comprehensive, sensitive search in order to identify as many eligible studies as possible and minimise the risk of publication bias by searching trial registries and contacting authors for unpublished studies and data. Our primary outcome of interest was risk of hospitalisation. We included studies that reported data on hospitalisation, or where authors were able to provide unpublished data. Only four of the included trials reported hospitalisation as a primary outcome, and for the rest it was a secondary outcome with seven studies requiring data from authors. Where hospitalisation was not the primary outcome, this suggests that the intervention may not have been specifically designed to reduce the risk of hospitalisation and so such trials may be less likely to report an effect on this outcome. However, the only trial to find a beneficial effect of the intervention on hospitalisation was one where unpublished data were obtained direct from the authors. [31] Despite our sensitive search, it is possible that we have missed relevant studies where data on hospitalisation were not reported in the publication but were collected as part of the study.

We applied pre-defined, explicit inclusion/exclusion criteria and involved two reviewers in each stage of the review process minimising the potential for bias and errors. We used the Cochrane risk of bias tool [17] to assess included trials. This identified a number of limitations in the included trials, with none judged at low risk of bias across all domains. The main limitation was lack of blinding of participants and personnel. Given the nature of the interventions evaluated, blinding is unlikely to have been feasible in most trials and as hospitalisation and mortality are objective outcomes, the potential for introduction of bias through lack of blinding is less than had more subjective outcomes been measured. We considered the interventions too diverse for an overall summary effect estimate to be appropriate. Instead we grouped studies according to intervention category and used random effects meta-analysis to pool studies within intervention categories, we did not pre-register this analysis.

Comparison with existing literature

We are aware of one recent review that has assessed a similar topic published in 2015 [9]. Inclusion criteria were similar for both reviews except that the Phelan review did not restrict based on study design but was restricted to studies published in English. We did not apply any language or publication restrictions and used a sensitive search strategy, but we limited inclusion to randomised trials to restrict the review to the highest level of evidence. This is likely why we located 12 times as many citations in our search yet included only six from their set of 10 included studies.

The Phelan review did not formally assess the risk of bias in included studies and did not carry out any statistical synthesis across studies. Very limited information was provided on study results or design. The Phelan review included 10 studies, six of which were also included in our review. The four studies included in the Phelan review not included in our review used a non-randomised design and so did not fulfil our inclusion criteria. We included a further 11 studies not included in the Phelan review. Three studies were published after the Phelan review and so would not have been available at the time that the searches for this review were conducted. A further two did not report data on hospitalisation, we contacted authors to obtain this information whereas reporting this information was a requirement for inclusion in the Phelan review. It is unclear why the other six trials were not included in the review as they appeared to fulfil the review inclusion criteria. However, despite the differences between review methods, overall conclusions were similar with regards to hospitalisation. We also considered duration of hospital stay which was only reported for one study in the Phelan review.

A Cochrane review on case management interventions [67] included some of the studies we included as well, although the overlap is limited because of differences in the set of inclusion criteria between the reviews. They found no effect at any length of follow up (6, 12, and 18–24 months) on hospitalisation risk or mortality but there was a small negative effect of case-management interventions provided in community settings on length of hospital stay (mean difference in number of nights was 0.63 (95% CI 0.40 to 0.86; 3 studies).

Implications for practice and research

Current evidence from randomised trials suggests no clear benefit or harm associated with any of interventions on risks of hospitalisation, duration of hospitalisation or death. Until better quality evidence becomes available no change in practice based on evidence is warranted.

None of the seventeen trials explicitly targeted the common causes of hospitalisation in people with dementia, either co-morbid conditions such as heart failure or more acute problems such urinary tract infections or pneumonia [68]. Future high quality trials targeting the common causes of hospitalisation in people with dementia, testing new community based interventions are needed. Because hospitalisation is an important outcome for people with dementia this should be explored as a primary outcome of such interventions. It may be that non-pharmacological interventions have no impact on risk of hospitalisation but may affect duration of stay, for example through earlier detection and treatment. This outcome also needs exploring in future studies.

Conclusions

There is little evidence that any of the included non-pharmacological interventions can reduce the risk of hospitalisation in people with dementia. Care management provides a plausible mechanism for reducing acute admissions to hospital, by proactively managing the care of a person with dementia, they can be reviewed appropriately, and problems identified before they require hospital admission. However, the available evidence is not conclusive on this. Further research with the primary aim to reduce hospitalisation in people with dementia, with explicit attempts at reducing the most common causes of hospitalisation in this group is required.

Appendix A-E.

(DOCX)

Click here for additional data file.

PRISMA 2009 checklist.

(DOCX)

Click here for additional data file.

Data extracted.

(XLSX)

Click here for additional data file.

Do-file for analysis.

(DO)

Click here for additional data file.

30 Jul 2019

PONE-D-19-18659

Can non-pharmacological interventions reduce hospital admissions in people with dementia? A systematic review

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Reviewer #2: Yes

Reviewer #3: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The manuscript is good but not for this journal, Other journals are more appropriate

Reviewer #2: This is a timely systematic review on the use of non-pharmacological approaches to reduce the risk of people with dementia being hospitalized, or having adverse outcomes (length of stay, death) in this setting.

The rationale for the study is well outlined, and the investigators used well established systematic review methods. There are a good number of studies included in the final analysis, and the results are well discussed.

I understand that the dominant approach to systematic reviews is a focus on RCTs, but there is also a substantial literature on the experience of people with dementia in hospitals that speaks to this area. Can I suggest that the authors consider alternate approaches on lessening the impact of having dementia on hospitalization that appears in the literature, perhaps by way of examples in the Discussion?

Is there potential to determine whether the interventions may have had an effect on planned vs unplanned hospitalization?

Reviewer #3: Manuscript is originally written and very well written. It is an interesting and relevant article. I consider it a useful contribution in its field. However, there are many important points that the investigators need to clarify and revise.

1. In abstract, the investigators states “November 2019” which is in the future and not correct. In the full manuscript, the investigators then described “October 2018”.

2. This meta-analysis has not been registered online. Please add this point in the limitation.

3. Figure1, suggest to use PRISMA 2009 Flow Diagram platform

4. Figure 2, please make the colors in the standard per Cochrane; red, yellow, green

5. PRISMA checklist needs to be cited and attached.

6. Who are two independent investigators?

7. It will be better to show kappa for the selection and data extraction. Please show the data of kappa of agreement during the systematic searches. How disagreements were solved during the systematic search among two independent reviewers?

8. Random or Fixed effect was used, needs to be specified in the abstract.

9. Authors should discuss the reason of heterogeneity.

10. Because the protocol has not been registered, please make the data for this review publicly available, possibly through the Open Science Framework (osf.io). Items to include: list of excluded studies, commands for statistical analysis, spreadsheets or data used for the meta-analyses, etc. Making data publicly available will promote the reproducibility of the review and is best practices for systematic reviews and meta-analyses.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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12 Sep 2019

Response to reviewers

Our response to the reviewers is separated out by reviewer comment, each reviewer’s comments have been labelled R1-3 for reviewer one to three respectively, with each comment a decimal after that, for example R2.1 is reviewer two comment one. The reply to each comment is then below that. This has been done to make reading the reply easier for each reviewer.

R1.1: The manuscript is good but not for this journal, Other journals are more appropriate

We thank reviewer 1 for their comments and their opinion that this is a good paper. They do not explain why they feel that PLOS One is not appropriate but in our opinion, this is an editorial rather than a reviewer decision. The role of reviewers is to aid the editor by commenting on the scientific value of the work (hence whether it should or should not be accepted). The editorial team will screen all manuscripts and will not usually send out papers that they do not feel are appropriate for their journal.

R2.1: This is a timely systematic review on the use of non-pharmacological approaches to reduce the risk of people with dementia being hospitalized, or having adverse outcomes (length of stay, death) in this setting.

R2.2: The rationale for the study is well outlined, and the investigators used well established systematic review methods. There are a good number of studies included in the final analysis, and the results are well discussed.

We thank reviewer 2 for these comments on both the timeliness and methodology of this manuscript, we have taken great effort to ensure the maximum number of studies could be included, including many papers after direct contact with authors to extract unpublished data.

R2.3: I understand that the dominant approach to systematic reviews is a focus on RCTs, but there is also a substantial literature on the experience of people with dementia in hospitals that speaks to this area. Can I suggest that the authors consider alternate approaches on lessening the impact of having dementia on hospitalization that appears in the literature, perhaps by way of examples in the Discussion?

Regarding the inclusion of non-RCT data, as noted by the reviewer this is the predominant for of research including in systematic reviews, we made the decision to include only RCT’s deliberately to ensure any findings we did make were based on the most robust evidence. What this has allowed us to do is make clear statements about the availability of high-quality evidence for the very specific question of evidence of non-pharmacological interventions that reduce the risk of hospitalization. We do briefly discuss potential avenues for further research but are acutely aware that this is not the question that paper is trying to answer and do not want to overstate an opinion not grounded in the evidence we found. We would be happy to be directed towards any pertinent papers that could help inform this part of the paper, although it would be limited to potential avenues for further intervention and not, as could be interpreted by this comment, ways of lessening the impact of dementia once hospitalized.

R2.4: Is there potential to determine whether the interventions may have had an effect on planned vs unplanned hospitalization?

Within some of the studies there was a distinction made between routine outpatient procedures or planned admissions and those that were deemed emergency or unplanned admissions. Within the paper there is a preference to only using figures for emergency admission where this information is available. This has now been made clearer in the methods.

R3.1: Manuscript is originally written and very well written. It is an interesting and relevant article. I consider it a useful contribution in its field.

We thank reviewer 3 for these comments.

R3.2: In abstract, the investigators states “November 2019” which is in the future and not correct. In the full manuscript, the investigators then described “October 2018”.

This is now corrected.

R3.3: This meta-analysis has not been registered online. Please add this point in the limitation.

This has now been added see end of strengths and weakness.

R3.4: Figure1, suggest to use PRISMA 2009 Flow Diagram platform

PLOS1 make restrictions on the resolution and format of their figures. To comply with those regulations a figure was created in adobe illustrator that replicated the PRISMA 2009 flow diagram, including the same four headings with virtually identical titles in the boxes. We are happy to submit a word document figure if the editor is willing to accept it.

R3.5: Figure 2, please make the colors in the standard per Cochrane; red, yellow, green

This has been changed, as suggested.

R3.6: PRISMA checklist needs to be cited and attached.

The PRISMA checklist is included, and can be found in S1 Appendix A. It is referenced within that appendix. It is cited in text, however on review that citation is incorrect and has now been corrected.

R3.7: Who are two independent investigators?

The two independent investigators for screening and extraction were Richard Packer (1st author) and Sharea Ijaz (see Acknowledgments)

R3.8: It will be better to show kappa for the selection and data extraction. Please show the data of kappa of agreement during the systematic searches.

Many thanks for this suggestion, unfortunately it is now no longer possible to go through previous databases and calculate the exact Kappa value for agreement as suggested. There was a robust process including the use of two independent reviewers with a third to act as arbiter when consensus was not present.

R3.9: How disagreements were solved during the systematic search among two independent reviewers?

Disagreements were resolved via a third person, Penny Whiting (final author). This process is described in the data extraction section of the method.

R3.10: Random or Fixed effect was used, needs to be specified in the abstract.

The analysis was using a random effects, this is stated in the last line of the methods section of the abstract.

R3.11: Authors should discuss the reason of heterogeneity.

Many thanks for this comment, the I2 statistic is now reported within the text for the highlighted results. Within the discussion we do discuss reasons why the only article to show a statistically significant difference in hospitalization may be different from the other included trials. It formed part of the care-management grouping which was the only grouping to show an elevated I2, in effect describing causes for possible heterogeneity directly without using the statistic.

R3.12: Because the protocol has not been registered, please make the data for this review publicly available, possibly through the Open Science Framework (osf.io). Items to include: list of excluded studies, commands for statistical analysis, spreadsheets or data used for the meta-analyses, etc. Making data publicly available will promote the reproducibility of the review and is best practices for systematic reviews and meta-analyses.

This is an excellent suggestion. We have made the data used for our meta-analysis available within this submission, see S3 Data Extracted. We have also included a list of studies excluded at full text stage see S2 Appendix D. The only thing not currently included are the STATA terms used to create the forest plots. These can be included within the current appendix structure and have been added as S4 Do files for analysis. Given that all the data is available within the PLOS 1 submission framework, we would suggest that there is not a need to repeat this process on the Open Science Framework.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

27 Sep 2019

Can non-pharmacological interventions reduce hospital admissions in people with dementia? A systematic review

PONE-D-19-18659R1

Dear Dr. Richard Packer,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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With kind regards,

Wisit Cheungpasitporn, MD, FACP

University of Mississippi Medical Center

Twitter: @wisit661 Email: wcheungpasitporn@gmail.com

Academic Editor

PLOS ONE

Additional Editor Comments:

I want to commend the authors on their superb efforts to revise the manuscript according to all reviewers’ suggestions. The quality of the manuscript has improved substantially.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: (No Response)

Reviewer #3: I have no competing interests. All my concerns have been fully elucidated, missing sections and analyses have been completed. Finally, comprehension errors have been corrected.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #2: No

Reviewer #3: No

9 Oct 2019

PONE-D-19-18659R1

Can non-pharmacological interventions reduce hospital admissions in people with dementia? A systematic review

Dear Dr. Packer:

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

For any other questions or concerns, please email plosone@plos.org.

Thank you for submitting your work to PLOS ONE.

With kind regards,

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on behalf of

Dr. Wisit Cheungpasitporn

Academic Editor

PLOS ONE