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A systematic review of interventions by healthcare professionals to improve management of non-communicable diseases and communicable diseases requiring long-term care in adults who are homeless

Objective Identify, describe and appraise trials of interventions delivered by healthcare professionals to manage non-communicable diseases (NCDs) and communicable diseases that require long-term care or treatment (LT-CDs), excluding mental health and substance use disorders, in homeless adults. Design Systematic review of randomised controlled trials (RCTs), non-RCTs and controlled before–after studies. Interventions characterised using Effective Practice and Organisation of Care (EPOC) taxonomy. Quality assessed using EPOC risk of bias criteria. Data sources Database searches (MEDLINE, Embase, PsycINFO, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Applied Social Sciences Index and Abstracts (ASSIA) and Cochrane Central Register of Controlled Trials), hand searching reference lists, citation searches, grey literature and contact with study authors. Setting Community. Participants Adults (≥18 years) fulfilling European Typology of Homelessness criteria. Intervention Delivered by healthcare professionals managing NCD and LT-CDs. Outcomes Primary outcome: unscheduled healthcare utilisation. Secondary outcomes: mortality, biological markers of disease control, adherence to treatment, engagement in care, patient satisfaction, knowledge, self-efficacy, quality of life and cost-effectiveness. Results 11 studies were included (8 RCTs, 2 quasi-experimental and 1 feasibility) involving 9–520 participants (67%–94% male, median age 37–49 years). Ten from USA and one from UK. Studies included various NCDs (n=3); or focused on latent tuberculosis (n=4); HIV (n=2); hepatitis C (n=1) or type 2 diabetes (n=1). All interventions were complex with multiple components. Four described theories underpinning intervention. Three assessed unscheduled healthcare utilisation: none showed consistent reduction in hospitalisation or emergency department attendance. Six assessed adherence to specific treatments, of which four showed improved adherence to latent tuberculosis therapy. Three concerned education case management, all of which improved disease-specific knowledge. No improvements in biological markers of disease (two studies) and none assessed mortality. Conclusions Evidence for management of NCD and LT-CDs in homeless adults is sparse. Educational case-management interventions may improve knowledge and medication adherence. Large trials of theory-based interventions are needed, assessing healthcare utilisation and outcomes as well as assessment of biological outcomes and cost-effectiveness.


Conclusions: Evidence for management of physical LTCs in homeless adults is sparse.
Educational case-management interventions may improve knowledge and medication adherence. Large trials of theory-based, interventions, assessing health care utilization and outcomes as well as assessment of biological outcomes and cost-effectiveness, are needed.

Strengths and Limitations of the Study
• This is the first systematic review to focus on effects of physical long-term condition management interventions for adults who are homeless.
• A comprehensive search strategy was supplemented with hand searching, Grey literature searches and contact with study authors.
• Interventions are described using the Effective Practice and Organisation of Care (EPOC) Taxonomy • Significant heterogeneity precluded meta-analysis, so a narrative synthesis is presented along with a Harvest Plot summarising study findings.
• Evidence available for high income countries only.

INTRODUCTION
The prevalence of homelessness is increasing across high income countries. [1] The experience of homelessness is associated with increased morbidity and mortality. [2][3][4] Social exclusion and socio-economic deprivation, [5,6] adversity over the life course, [7] as well as environmental and behavioral risk factors [8] typical of homelessness, contribute to an increased prevalence of a range of physical long-term conditions (LTCs) compared to the rest of the population. [1] Outcomes of physical LTCs are poorer among people who are homeless. [9,10] Engagement with scheduled appointments, preventative health services and adherence to treatment are typically lower. [11][12][13][14] Barriers to access, conflicting priorities, physical and mental multimorbidity are thought to contribute to poorly coordinated use of healthcare services. [14] Consequently, there is a need for tailored services. [14][15][16] Healthcare delivery models for people experiencing homelessness include specialised or generalist primary care services ; [17] and integrated housing and health interventions. There is insufficient evidence of reach and effectiveness to favour one model over another. [18]The expanding role of non-medical healthcare professionals e.g. nurse and pharmacist prescribers, targeting physical LTCs, [19] offers a complementary model of healthcare for people who are homeless. Sharing clinical roles may be welcome given the increasing evidence of multimorbidity and polypharmacy. [20] Controlled evaluations of models of healthcare for people who are homeless are relatively few and optimal delivery varies between different health and social care systems. [16] There have been calls to evaluate more interventions to improve the health of people who are homeless, [21] including long-term prospective studies with economic analyses. [14] Previous systematic reviews have identified the potential benefit of tailored interventions and strategies for addressing mental health and substance misuse. [22,23] These have shown potential for monetary incentives to improve adherence for people who are homeless with latent tuberculosis, [22] and that provision of housing improved health outcomes in HIV. [23]However, to the authors' knowledge, no previous systematic reviews have focused specifically on the management of physical LTCs for people who are homeless.

Aims
This review aims to systematically identify, describe and appraise trials of interventions focusing on the management of physical LTCs, delivered by healthcare professionals for adults who are homeless. It addresses the following two research questions: against the eligibility criteria. At all levels disagreements were resolved by discussion, involving a third reviewer (RL or LY) when consensus could not be reached. Where studies included homeless participants but analysis of these participants was not presented separately, we contacted the study authors to request these data. Studies were excluded if these were not available. Using a standardised data extraction form, two reviewers (PH plus LY or LG) independently extracted data from each study eligible for inclusion. The components of each intervention were described according to the Cochrane Effective Practice and Organization of Care (EPOC) taxonomy. [27] Two reviewers independently assessed each study according to the criteria outlined in the Cochrane EPOC guidelines for assessing risk of bias (ROB) in RCTs, non-randomised controlled trials and CBA studies. [27] After grading each study a judgment of the overall risk of bias was made for each outcome, taking into account the relative importance of potential sources of bias to the outcome in question.  9 We assessed the clinical and methodological heterogeneity of the eligible studies. Few studies considered similar outcomes, and those that did had either different comparator groups, [28,29] differing methods of assessing similar outcomes (e.g. survey vs. routine data for emergency department (ED) attendance) [30,31] or concerned complex interventions, the diversity of which would limit the utility of a pooled analysis. [30,32] Consequently, a meta-analysis was deemed inappropriate and we performed a narrative synthesis of the study findings. Studies were grouped by outcome and the strength of the body of evidence for each outcome was assessed using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. [33] We constructed a Harvest Plot post hoc to display the results. Harvest plots use bars representing individual studies placed on a plot matrix to indicate whether the review intervention showed an overall positive, negative, or no consistent effect for the outcome in question. They enable data to be summarised when study designs and outcomes are diverse and heterogeneous. [34,35] We used the following criteria to decide how each study should be displayed:

Synthesis
• Height of the bar represented the number of participants in the study; • RCTs were displayed in bold with other designs in grey; • The risk of bias for the outcome of each study was indicated as low, moderate or high using a coloured dot above the bar; • Statistically significant differences were displayed as a positive effect if they favoured the intervention; negative if they favoured the comparator and neutral if not statistically significant; • Where some, but not all, findings in a group of outcomes showed a positive or negative effect, bars were hatched to indicate inconsistency.

Study Selection
The results of abstract and full-text screening are shown in the PRISMA diagram in

Study Populations
Details of the study populations are summarised in table 1. Sample sizes ranged from 9 to 520. Median age ranged from 37 to 49 years. In all of the studies the majority of participants were male (percentage male participants ranged from 67% to 94% in the intervention groups). Age and sex distributions were consistent with previous literature on homelessness. [1] Six studies, all from the USA reported details of ethnicity. [28,29,36,40,42,45] African American participants were the most prevalent in five of these. Only two studies included any detail of comorbidities. [30,36] Details of attrition are shown in Additional File 4.

Quality Assessment
Results of the EPOC Risk of Bias assessment for each of the included studies is shown in table 2. None of the included studies scored low risk for each of the criteria. These were used to inform outcome-level risk of bias assessment. These are displayed, along with justification, in Additional File 4.

Intervention Components and Theoretical Underpinnings
Each of the studies described interventions that were complex and included multiple components. These included changes to how, and where, care was delivered, the personnel delivering care, how care delivery was coordinated, and the provision of

The Impact of Interventions on Healthcare Outcomes
The overall findings of the included studies for impact on unscheduled healthcare utilization, adherence or access to care, and knowledge of selfefficacy, are illustrated in the harvest plot shown in Figure 2. The text that follows synthesized these findings under each outcome.

Primary Review Outcomes Unscheduled Healthcare Utilisation
Three studies assessed the impact of interventions on hospital admissions and emergency department (ED) attendance. [30][31][32] None focused on a specific LTC, however participants reported a range of LTCs and each intervention included identification and engagement with medical, as well as wider needs. The highest quality evidence was from two RCTs, neither of which showed any significant reduction in unscheduled healthcare utilisation. [30,32] One RCT evaluated a multidisciplinary, multicomponent intervention targeting patients in two innercity hospitals involving goal setting, discharge planning, and liaising with community services. [30] Neither hospital admissions, nor ED attendance after one year, were significantly different compared with usual care. The other RCT was a four-arm trial comparing usual care; a brief nurse-led physical health needs assessment; a guided orientation to clinical facilities with introduction to staff; and clinic orientation in combination with the physical health assessment. [32]Hospital admissions and ED attendance were assessed at 6 months post intervention in a post-hoc analysis and showed no significant difference to usual care. A third study, with a quasi-experimental design and high risk of bias, concerned a 'comprehensive health assessment' delivered to residents at transitional housing facilities. ED attendances were reportedly lower at 18 month follow-up, but not at 6 months. There was no difference in hospitalization at either follow-up point.
Taken together the available evidence does not suggest that the multidisciplinary, multifaceted interventions described reduced rates of unscheduled healthcare utilisation. The overall confidence in the estimate of effect is low.

Secondary Review Outcomes
Access to primary healthcare One RCT concerned access to primary healthcare. [32] A brief nurse-led physical health needs assessment; a guided orientation to clinical facilities with introduction to staff; and clinic orientation in combination with the physical health assessment were compared to usual care. All three intervention groups showed higher uptake of primary healthcare services after 6 months with clinic orientation alone and in combination with a physical health assessment significantly improving primary care access in adjusted analyses.

Adherence to specific treatment
Six studies (7 papers) assessed adherence to treatment or attendance at appointments. [28,29,36,40,42,43,46] Four recruited patients with latent tuberculosis undergoing directly observed therapy (DOT) [28,29,36,40], one included participants with HIV and alcohol problems, [46] and one (2 papers) concerned participants with HIV and co-morbid depression. [42,43] Of the TB studies, three were conducted by the same research group and assessed the impact of monetary incentives (cash and/or voucher) on attendance at initial TB clinic follow up [40] or on completion of DOT with isoniazid. [28,29] Clinic attendance and DOT completion rates were significantly higher with cash incentives compared with usual care or peer-health advisors. [29] There was no statistically significant difference in DOT completion between cash and voucher incentives. [28] Details of the availability to the participants of social security or other sources of financial support are not described in either study. Although the cash incentive and delivery of the intervention were similar in both studies assessing DOT completion, the completion rate in the intervention group differed widely between the two studies (44% and 89%, respectively). [28,29] The authors speculate that the location of the clinic (the higher completion rate being in an area more accessible and frequented by people who are homeless) or alterations in the follow-up protocol for non-attendees may explain the differences.
The final study concerning TB evaluated the impact of a nurse-led case management intervention on completion of latent tuberculosis treatment and tuberculosis knowledge (described below under knowledge and self-efficacy). They found odds of DOT completion were three times greater with the intervention compared with usual care. [36] An RCT concerning people with HIV and comorbid depression compared fluoxetine prescription and weekly psychiatric evaluation with signposting to local psychology services without the prescription of fluoxetine. Both arms were given a weekly cash incentive for attending. Outcomes included rate of uptake of anti-retroviral treatment (ART), and adherence to ART (assessed by unannounced pill counts) for those receiving treatment. Neither outcome was significantly different between the groups despite an improvement in depression severity and remission in the fluoxetine group. [42,43] Finally an RCT aimed at supporting antiretroviral medication adherence among HIV positive participants with a history of alcohol dependence or harmful drinking showed no change in antiretroviral adherence. [46] Findings were similar to a secondary analysis of participants who described themselves as homeless (unpublished results).
Overall, there is a moderate level of evidence for interventions improving adherence to treatment for latent TB, including a case-management educational

Knowledge and Self-efficacy
Three studies (5 papers) assessed the impact of interventions on TB, HIV, hepatitis and diabetes disease knowledge and self-efficacy. [36-38, 41, 45] Two were trials incorporating nurse-led case management (for patients with latent TB or hepatitis C, respectively) combined with a regular educational intervention focusing on self-management, self-esteem, communication skills and social support. One was an RCT focusing on DOT for latent TB and assessed the impact on TB knowledge in all participants. [36] The intervention also involved HIV education and the impact of this was evaluated in a subset judged to be 'at risk' of HIV (i.e. sexually active or known to be intravenous drug users). Two analyses using structural equation modeling showed that the nurse-led case management intervention was associated with greater improvement in TB knowledge [37] and in HIV knowledge in the 'at risk' subset. [38] The latter also showed improved self-efficacy for condom use. [38] The other evaluated a similar approach concerning Hepatitis education for participants enrolled in a Hepatitis A/B vaccination programme (only the Hepatitis C positive subset was included in this review). [45] The case-management group showed a greater improvement in Hepatitis C knowledge than the control group. However, the randomisation procedure was designed for the vaccine trial, not for the evaluation of the casemanagement intervention, and the statistical analysis was not designed to compare the intervention with control in the Hepatitis C subset alone. [45] The third study reported improved knowledge in a small (n=9) pilot study using a self-efficacy based approach for Type 2 Diabetes Mellitus. However, the small sample size meant there was insufficient power to detect any difference between groups and there was incomplete reporting of outcomes and no clear comparison is made between the intervention and comparator. [41] Taken together, there is a moderate quality of evidence showing that an educational case-management approach can improve disease specific knowledge when delivered alongside wider interventions, such as DOT or a vaccine study.
The available studies, however, do not assess the impact on behavioural outcomes or the retention of knowledge beyond the trial period.

Biological markers of disease control
Two studies (3 papers) assessed the impact of interventions on disease control outcomes. One RCT assessed the impact on HIV-1 viral load of directly observed fluoxetine in comorbid HIV and depression. There was no difference in viral suppression between intervention and comparator groups. [42][43][44] The other RCT found no difference in viral load or CD4+ count with adherence support for antiretroviral therapy in HIV infected individuals with a history of alcohol problems. [46] Cost effectiveness Only one study assessed the cost-effectiveness of the intervention.

Summary of findings
The available evidence from controlled trials of interventions by healthcare professionals managing physical LTCs in people who are homeless does not show any convincing effects on unscheduled healthcare utilisation. [30][31][32] The impact on mortality was not assessed, and evidence for the impact on biological markers of disease control is limited to a few studies on HIV, which did not show any evidence of benefit on viral load. [42,43] Patient-centred interventionsincorporating case management, education, self-management support and social support -may improve disease specific knowledge in TB, HIV, and Hepatitis C; improve completion of DOT in latent TB; and increase access to primary care in combination with clinic orientation. [32,[36][37][38]45] Cash and non-cash incentives, in the context of DOT for latent TB, may improve clinic attendance and treatment adherence; however treatment completion rates vary between different studies of similar interventions. [28,29,40] It is not clear if improvement in these intermediate outcomes impacts other clinical outcomes, or if effects are sustained beyond the course of treatment evaluated in these studies. There was only one study of cost effectiveness. The strengths of this review include a-priori methods with a robust process for study identificatuion, appraisal, data extraction and description. [24] The comprehensive search strategy included database searches supplemented by hand searching, forward citation searching, grey literature, and contact with study authors. All screening and data extraction was performed by two reviewers independently. We also described the components of each intervention using a previously defined taxonomy, [27] which is important when reviewing complex interventions such as those included. [47,48] However, many of the findings, particularly those concerning adherence to treatment, were in the context of specific conditions (e.g. latent TB), included a time-limited course of treatment, and were conducted in a single centre. All but one of the included studies was from the USA. As such the findings may not be directly applicable to other disease areas or other health and social care contexts. Limitations in the existing evidence base also meant we were unable to undertake a formal metaanalyses.
Survey data collected using telephone followup and was only obtained for 110 participants (57 intervention, 53 I: During hospital admission patients who were homeless were identified by ward teams. Nurse met completes interview including medical, mental health, drug and alcohol details, housing history, care needs and consideration of any goals on discharge.3x weekly GP led ward round reviewing goals, care plans, medial findings and discharge planning. Regular visit by homelessness nurse to provide community links including with social work and housing services. Weekly

3-4 times weekly GP ward round during admission
Initial meeting by nurse followed by liaising with relevant services.
None explicitly described. Development of service was the result of quality improvement work based in the study site which has been published and described ED attendance: no significant difference between standard or enhanced care at 12 months (adjusted mean difference -0. 8 Follow-up for reinterview was 81% at 1 month and 71% at 6 months. orientation, transported to clinic and introduced to clinic team. Orientated to services available. Usual care only following this. Group 3, (n=44), physical health assessment plus clinic orientation.
C: Usual care, comprising social-worker administered assessment of homelessness and social needs, description of services available and how to access (verbal or written) Follow-up at 1 and 6 months.
3.41 (95% CI 2.02 to 5.76)) were both significantly associated with improved primary care access. Unadjusted Chisquared estimates were significant at both 4-weeks and 6-months with usual care showing lowest rates of access. eligible participants. Potential bias from randomisation procedure for clinic orientation arm as randomised by calendar day based on attendance. I2: Peer health advisors: In addition to bus tokens and appointment, peer health advisors met participants in shelters, accompanied to appointment, helped with paperwork and orientation.

RCT
C: Usual care. Bus tokens and TB clinic appointment only.
One off payment for monetary incentive arm.
One off intervention in peer health advisor arm, as described. Included transport assistance and support in attendance.

None described
Attendance at initial TB clinic followup: Monetary incentive (84%) and peer health advisor (75%) groups more likely to attend appointment than usual care (53%) (p=<0.001 and p=0.004, respectively). Both interventions significant predictors of adherence in multivariate analysis. No separate analysis of homeless participants is provided in the published paper. Analyses were repeated on the homeless participants only using Generalised Estimating Equations as described in the original manuscript. Data were provided by the study authors and the analysis was performed by the review authors. Models were fit to analyse the overage intervention effect over time.

Adherence to Antiretroviral
Low: Objective assessment of outcomes and adjustment for baseline variables Chronic disease selfmanagement approach based on self-efficacy theory.
Self-efficacy: paper states "participants who attended the intervention had higher scores on some outcome variables, most notable in cognitive symptom management, which improved from a pre-intervention score of 1.3/5 to a post-intervention score of 2.75". Participants in comparison stated to have "similar scores" at baseline and 12 week follow-up. Hepatitis C knowledge: Measured using a modification of an 18 item tool initially developed for tuberculosis. Greater improvement in the nurse case-managed group than the standard intervention in the hepatitis C positive subset. Statistical analysis of the significance of the difference between intervention and control groups not performed for the hepatitis C positive subset.
High: Randomisation was carried out according to a protocol to assess the vaccine efficacy, not that of the casemanagement/education intervention. Futhermore, while data on the hepatitis C positive subset are presented, the study design and analysis was not focused on a comparison of intervention and control intervention in this subset of participants. As such baseline imbalances and sequence of allocation could introduce bias for the outcome of hepatitis C knowledge.

DISCUSSION
Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).

24
Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).  The prevalence of homelessness is increasing across high income countries. 1 The 91 experience of homelessness is associated with increased morbidity and 92 mortality. [2][3][4] Social exclusion and socio-economic deprivation, 5  LTCs. However, no previous systematic reviews have specifically focussed on the 110 potential impact of healthcare professional or other intervention on physical 111 LTCs for adults experiencing homelessness. This is despite calls for more 112 access to prevention and early intervention. 12 114 115 Outcomes of physical LTCs are poorer among people who are homeless. 13 14 116 Engagement with scheduled appointments, preventative health services and 117 adherence to treatment are typically lower. [15][16][17][18] Barriers to access, conflicting 118 priorities, physical and mental multimorbidity are thought to contribute to 119 poorly coordinated use of healthcare services. 18 Consequently, there is a need 120 for tailored services. [18][19][20] Healthcare delivery models for people experiencing 121 homelessness include specialised or generalist primary care services; 21 and 122 integrated housing and health interventions. There is insufficient evidence of 123 reach and effectiveness to favour one model over another. 22 The expanding role 124 of various healthcare professionals e.g. nurse and pharmacist prescribers, 125 targeting physical LTCs, 23 26 27 These have shown potential for monetary incentives to improve 138 adherence for people who are homeless with latent tuberculosis, 26 and that 139 provision of housing improved health outcomes in HIV. 27  This systematic review followed a pre-specified protocol 28  Eligibility criteria and search process are described in detail in our published 166 protocol paper, 28 and are outlined briefly below. Full details are given in 167 Additional File 1. Homelessness was defined according to the ETHOS criteria 30 . 168 Eligible studies included adult participants who met the ETHOS defined 169 homelessness criteria with one or more physical LTC or those concerning 170 physical LTC management as part of a broader intervention (e.g. access to 171 primary care). Delivery by a healthcare professional (any professional trained to 172 provide any form of health care, but excluding social workers and professionals 173 without a health-related training) was required, either alone or as part of a wider 174 team. We considered a range of pre-specified outcomes. Studies including any of 175 our primary or secondary outcomes were eligible for inclusion. Unscheduled  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  could not be reached. Where studies included homeless participants but analysis 201 of these participants was not presented separately, we contacted the study 202 authors to request these data. Studies were excluded if these were not available. 203 Using a standardised data extraction form, two reviewers (PH plus LY or LG) 204 independently extracted data from each study eligible for inclusion. The 205 components of each intervention were described according to the Cochrane 206 Few studies considered similar outcomes, and those that did had either different 219 comparator groups, 32 33 differing methods of assessing similar outcomes (e.g. 220 survey vs. routine data for emergency department (ED) attendance) 34 35 or 221 concerned complex interventions, the diversity of which would limit the utility of 222 a pooled analysis. 34 36 Consequently, a meta-analysis was deemed inappropriate 223 and we performed a narrative synthesis of the study findings.  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60   F  o  r  p  e  e  r  r  e  v  i  e  w  o  n  l  y   11 effect for the outcome in question. They enable data to be summarised when 232 study designs and outcomes are diverse and heterogeneous. 38 39 We used the 233 following criteria to decide how each study should be displayed: 234 • Height of the bar represented the number of participants in the study; 235 • RCTs were displayed in bold with other designs in grey; 236 • The risk of bias for the outcome of each study was indicated as low, 237 moderate or high using a coloured dot above the bar; 238  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  Sixteen papers were eligible for inclusion which described eleven unique 256 studies. 32-36 40-50 Ten studies were from the USA 32 1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60 o n l y 14    however participants reported a range of LTCs and each intervention included 308 identification and engagement with medical, as well as wider needs. The highest 309 quality evidence was from two RCTs, neither of which showed any significant 310 reduction in unscheduled healthcare utilisation. 34 36 One RCT evaluated a 311 multidisciplinary, multicomponent intervention targeting patients in two inner-312 city hospitals involving goal setting, discharge planning, and liaising with 313 community services. 34 Neither hospital admissions, nor ED attendance after one 314 year, were significantly different compared with usual care. The other RCT was a 315 four-arm trial comparing usual care; a brief nurse-led physical health needs 316 assessment; a guided orientation to clinical facilities with introduction to staff; 317 and clinic orientation in combination with the physical health 318  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58 1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  Six studies (7 papers) assessed adherence to treatment or attendance at 348 appointments. 32  with HIV and co-morbid depression. 46 47 Of the TB studies, three were conducted 352 by the same research group and assessed the impact of monetary incentives 353 (cash and/or voucher) on attendance at initial TB clinic follow up 44 or on 354 completion of DOT with isoniazid. 32 33 Clinic attendance and DOT completion 355 rates were significantly higher with cash incentives compared with usual care or 356 peer-health advisors. 33 There was no statistically significant difference in DOT 357 completion between cash and voucher incentives. 32 Details of the availability to 358 the participants of social security or other sources of financial support are not 359 described in either study. Although the cash incentive and delivery of the 360 intervention were similar in both studies assessing DOT completion, the 361 completion rate in the intervention group differed widely between the two 362 studies (44% and 89%, respectively). 32 33 The authors speculate that the location 363 of the clinic (the higher completion rate being in an area more accessible and 364 frequented by people who are homeless) or alterations in the follow-up protocol 365 for non-attendees may explain the differences. 366  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58 1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  on TB knowledge in all participants. 40 The intervention also involved HIV 404 education and the impact of this was evaluated in a subset judged to be 'at risk' 405 of HIV (i.e. sexually active or known to be intravenous drug users). Two analyses 406 using structural equation modeling showed that the nurse-led case management 407 intervention was associated with greater improvement in TB knowledge 41 and 408 in HIV knowledge in the 'at risk' subset. 42 The latter also showed improved self-409 efficacy for condom use. 42 The other evaluated a similar approach concerning 410 Hepatitis education for participants enrolled in a Hepatitis A/B vaccination 411 programme (only the Hepatitis C positive subset was included in this review). 49

Contact with study authors
Where data pertaining to homeless participants were not presented separately, we attempted to contact study authors to request these data. One off intervention in peer health advisor arm, as described. Included transport assistance and support in attendance.

None described
Attendance at initial TB clinic followup: Monetary incentive (84%) and peer health advisor (75%) groups more likely to attend appointment than usual care (53%) (p=<0.001 and p=0.004, respectively). Both interventions significant predictors of adherence in multivariate analysis.
Moderate: Details of randomisation not clear and blinding not possible, otherwise low risk of bias. Intervention used behavioural science theories using motivational interviewing to promote behaviour change and using principles of the Health Belief Model to support the benefit and need for therapy.

RCT
No separate analysis of homeless participants is provided in the published paper. Analyses were repeated on the homeless participants only using Generalised Estimating Equations as described in the original manuscript. Data were provided by the study authors and the analysis was performed by the review authors. Models were fit to analyse the overage intervention effect over time.
Self-efficacy: paper states ³SDUWLFLSDQWV ZKR DWWHQGHG WKH intervention had higher scores on some outcome variables, most notable in cognitive symptom management, which improved from a pre-intervention score of 1.3/5 to a post-intervention score of ´ 3DUWLFLSDQWV LQ FRPSDULVRQ VWDWHG WR KDYH ³VLPLODU VFRUHV´ DW EDVHOLQH DQG 12 week follow-up. Weekly dispensing and incentive. Weekly psychiatric evaluation.

None stated
Adherence to antiretroviral therapy: Mixed-model analysis showed no statistically significant effects of the intervention on antiretroviral therapy update (adjusted OR 1.18 (95% CI (0.83 to 1.68)). Percentage of antiretroviral adherence was similar in intervention and comparator groups.

HIV-1 viral load:
I: Cash incentive: $5 payment for keeping twice weekly appointment for directly observed isoniazid therapy. Tracking included names and addresses of family, friends and case workers. Missed appointments were followed up by letters, telephone calls, and using tracking information, following a protocol specifying a number of outreach attempts.
C: Non-cash incentive: A choice of fast-food or grocery coupons, phone cards or bus tokens with a value of $5 was offered from each kept appointment. Tracking and follow-up of missed appointment was identical to the cash incentive group.
Twice weekly attendance at TB clinic over 6 months in all participants.
Interventions were on top of this, with the same frequency and duration.
6 month follow-up None described Completion of 6 months isoniazid therapy: Completion rates were 89% with monetary incentives and 81% with non-monetary incentives (no statistically significant difference, p=0.23)

Moderate:
Randomisation/allocation procedure not clear. Method of assessment of adherence to isoniazid differed between directly observed group and usual care (former directly observed, latter assessed by percentage pick up of prescriptions). If anything, however, this would lead to underestimation of the effect size of the intervention.

Tyler 2014
Randomised quasiexperimental Hepatitis C knowledge: Measured using a modification of an 18 item tool initially developed for tuberculosis. Greater improvement in the nurse case-managed group than the standard intervention in the hepatitis C positive subset. Statistical analysis of the significance of the difference between intervention and control groups not performed for the hepatitis C positive subset.

5-6
Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

METHODS
Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.

DISCUSSION
Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).
Group 2, (n=40), clinic orientation, transported to clinic and introduced to clinic team. Orientated to services available. Usual care only following this. Group 3, (n=44), physical health assessment plus clinic orientation.
C: Usual care, comprising social-worker administered assessment of homelessness and social needs, description of services available and how to access (verbal or written) Follow-up at 1 and 6 months. combination with clinic orientation (HR 3.41 (95% CI 2.02 to 5.76)) were both significantly associated with improved primary care access. Unadjusted Chisquared estimates were significant at both 4-weeks and 6-months with usual care showing lowest rates of access. collected and complete for eligible participants. Potential bias from randomisation procedure for clinic orientation arm as randomised by calendar day based on attendance. 24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44

Homeless definition:
Either "literally homeless", staying in emergency shelter, street, car, or other shelter not designed for sleeping, or "maginally housed", staying in lowcost temporary accommodation.

Inclusion/exclusion:
Positive TST without active TB and with no TB follow-up or prevention in previous 6 months Recruitment from emergency shelters, free meal lines and low cost residential hostels. Participants were interviewed and screened with a tuberculin skin testing (TST) using Mantoux method.
Eligibility was positive TST and no TB follow-up in previous 6 months.
2158 screened. 618 positive TST. 89 refused randomisation. 199 ineligible as did not return or rsults, HIV infection, recent screening with chest xray or current isoniazid treatment. 330 randomised and attended clinic. Of these 121 prescribed isoniazid.

I1:
Monetary incentive: $5 at each twice weekly visit for directly observed isoniazid. If a dose missed, attempts to contact participant made by letter or telephone call. Any onward referrals were made by TB clinic, not research assistants following up patients. I2: Peer health adviser: Adviser provided and observed isoniazid twice weekly. Adviser accompanied participant for monthly refill appointments. If appointments missed, adviser spent an allotted amount of time looking for the participant.
C: Usual care: routine TB clinic care. Given 1 month supply of treatment and monthly drop in follow-up scheduled. Adherence monitored by TB charts. For non-attendance, standard follow-up or 3 letters or telephone calls. Treatment not directly observed. Protocol change during study due to low initial clinic attendance in usual care arm meant that the protocol was changed to offer all participants $5 at the initial visit.
Twice weekly attendance at TB clinic over 6 months in all participants. Interventions were on top of this, with the same frequency and duration.
6 month follow-up Hepatitis C knowledge: Measured using a modification of an 18 item tool initially developed for tuberculosis. Greater improvement in the nurse case-managed group than the standard intervention in the hepatitis C positive subset. Statistical analysis of the significance of the difference between intervention and control groups not performed for the hepatitis C positive subset.
High: Randomisation was carried out according to a protocol to assess the vaccine efficacy, not that of the casemanagement/education intervention. Futhermore, while data on the hepatitis C positive subset are presented, the study design and analysis was not focused on a comparison of intervention and control intervention in this subset of participants. As such baseline imbalances and sequence of allocation could introduce bias for the outcome of hepatitis C knowledge.    Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

DISCUSSION
Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).