Informal caregivers are the primary source of support for cancer patients, providing assistance with household tasks, medical care and emotional support. These responsibilities often result in high levels of emotional, physical, social and financial burden for the caregiver. The aim of this study was to perform a scoping review exploring what is known regarding the financial costs experienced by caregivers and identify gaps in the literature. Seven databases were searched for articles published between May 2008 and May 2018 related to direct and indirect costs of informal cancer care. Included articles reported on the costs incurred by cancer caregivers as a dollar value, relied on caregiver‐reported costs and were peer reviewed. A total of 19 studies met the inclusion criteria. These studies reported out of pocket costs‚ opportunity costs of informal care time and caregiver time loss from paid employment. Care time was the largest source of cancer caregiver costs, averaging $4,809 per month when valued using the proxy good method or $2,877 per month when the opportunity cost approach was used. Caregiver costs were highest when the care recipient was in the palliative phase of the disease. There was an absence of literature reporting costs for cancer caregivers in low and middle income countries and none of the included studies considered costs related to the caregivers' medical expenditures. There were many challenges when comparing the costs across studies due to variations in the type of expenses reported and the methods used to value expenses. Quantifying the financial costs associated with being an informal caregiver can facilitate the communication of the financial burden caregivers experience, potentially spurring the development of policies and programs to reduce their financial burden and better support cancer caregivers.

Osmolyte accumulation and release can protect cells from abiotic stresses. In Escherichia coli, known mechanisms mediate osmotic stress-induced accumulation of K ؉ glutamate, trehalose, or zwitterions like glycine betaine. Previous observations suggested that additional osmolyte accumulation mechanisms (OAMs) exist and their impacts may be abiotic stress specific. Derivatives of the uropathogenic strain CFT073 and the laboratory strain MG1655 lacking known OAMs were created. CFT073 grew without osmoprotectants in minimal medium with up to 0.9 M NaCl. CFT073 and its OAM-deficient derivative grew equally well in high-and low-osmolality urine pools. Urine-grown bacteria did not accumulate large amounts of known or novel osmolytes. Thus, CFT073 showed unusual osmotolerance and did not require osmolyte accumulation to grow in urine. Yeast extract and brain heart infusion stimulated growth of the OAM-deficient MG1655 derivative at high salinity. Neither known nor putative osmoprotectants did so. Glutamate and glutamine accumulated after growth with either organic mixture, and no novel osmolytes were detected. MG1655 derivatives retaining individual OAMs were created. Their abilities to mediate osmoprotection were compared at 15°C, 37°C without or with urea, and 42°C. Stress protection was not OAM specific, and variations in osmoprotectant effectiveness were similar under all conditions. Glycine betaine and dimethylsulfoniopropionate (DMSP) were the most effective. Trimethylamine-N-oxide (TMAO) was a weak osmoprotectant and a particularly effective urea protectant. The effectiveness of glycine betaine, TMAO, and proline as osmoprotectants correlated with their preferential exclusion from protein surfaces, not with their propensity to prevent protein denaturation. Thus, their effectiveness as stress protectants correlated with their ability to rehydrate the cytoplasm.

Osmosensing by transporter ProP is modulated by its cardiolipin (CL)-dependent concentration at the poles of Escherichia coli cells. Other contributors to this phenomenon were sought with the BACterial Two-Hybrid System (BACTH). The BACTH-tagged variants T18-ProP and T25-ProP retained ProP function and localization. Their interaction confirmed the ProP homo-dimerization previously established by protein crosslinking. YdhP, YjbJ and ClsA were prominent among the putative ProP interactors identified by the BACTH system. The functions of YdhP and YjbJ are unknown, although YjbJ is an abundant, osmotically induced, soluble protein. ClsA (CL Synthase A) had been shown to determine ProP localization by mediating CL synthesis. Unlike a deletion of clsA, deletion of ydhP or yjbJ had no effect on ProP localization or function. All three proteins were concentrated at the cell poles, but only ClsA localization was CL-dependent. ClsA was shown to be N-terminally processed and membrane-anchored, with dual, cytoplasmic, catalytic domains. Active site amino acid replacements (H224A plus H404A) inactivated ClsA and compromised ProP localization. YdhP and YjbJ may be ClsA effectors, and interactions of YdhP, YjbJ and ClsA with ProP may reflect their colocalization at the cell poles. Targeted CL synthesis may contribute to the polar localization of CL, ClsA and ProP.

Transporter-mediated osmolyte accumulation stimulates the growth of Escherichia coli in high-osmolality environments. YehZYXW was predicted to be an osmoregulatory transporter because (1) osmotic and stationary phase induction of yehZYXW is mediated by RpoS, (2) the Yeh proteins are homologous to the components of known osmoregulatory ABC transporters (e.g., ProU of E. coli), and (3) YehZ models based on the structures of periplasmic betaine-binding proteins suggested that YehZ retains key betaine-binding residues. The betaines choline-O-sulfate, glycine betaine, and dimethylsulfoniopropionate bound YehZ and ProX with millimolar and micromolar affinities, respectively, as determined by equilibrium dialysis and isothermal titration calorimetry. The crystal structure of the YehZ apoprotein, determined at 1.5 Å resolution (PDB ID: 4WEP ), confirmed its similarity to other betaine-binding proteins. Small and nonpolar residues in the hinge region of YehZ (e.g., Gly223) pack more closely than the corresponding residues in ProX, stabilizing the apoprotein. Betaines bound YehZ-Gly223Ser an order of magnitude more tightly than YehZ, suggesting that weak substrate binding in YehZ is at least partially due to apo state stabilization. Neither ProX nor YehZ bound proline. Assays based on osmoprotection or proline auxotrophy failed to detect YehZYXW-mediated uptake of proline, betaines, or other osmolytes. However, transport assays revealed low-affinity glycine betaine uptake, mediated by YehZYXW, that was inhibited at high salinity. Thus, YehZYXW is a betaine transporter that shares substrate specificity, but not an osmoregulatory function, with homologues like E. coli ProU. Other work suggests that yehZYXW may be an antivirulence locus whose expression promotes persistent, asymptomatic bacterial infection.

Background Informal caregivers (i.e. family and friends) provide essential support to people with chronic kidney disease (CKD). Many informal caregivers experience mental health problems such as anxiety and depression due to the caregiving role, and commonly have unmet psychological support needs. One potential solution is cognitive behavioural therapy (CBT) self-help interventions that are less reliant on extensive involvement of healthcare professionals, which may increase access. Within the intervention development phase of the MRC framework, the study’s primary objective was to examine informal caregivers’ self-help intervention preferences (e.g. delivery format, content). Secondary objectives were to describe the informal caregiver’s situation (e.g. type of care activities) and mental health (symptoms of depression, anxiety, and stress). Methods An online cross-sectional survey conducted in the United Kingdom. Informal caregivers of adults living with CKD were recruited via social media, websites, newsletters, magazine articles, a podcast episode, and paid Facebook advertisements. The survey examined: informal caregiver characteristics; care recipient characteristics; self-help intervention preferences; and informal caregiver’s mental health using the DASS-21. Data were analysed using descriptive statistics. Results Sixty-five informal caregivers participated. The majority (85%) were female, caring for a male (77%) spouse/partner (74%). Responses indicated 58% of informal caregivers were experiencing at least mild depression. In total, 48% indicated they were likely to use a CBT self-help intervention, preferring an intervention provided via internet (e.g. website) (64%), workbook (56%), or individually in-person (54%). Regarding content, interventions should cover a wide range of topics including living with CKD, support services, informal caregiver’s physical health, and diet. Overall, 48% reported a preference for a supported intervention, with support delivered in-person or via email by a trained professional at a community organisation. Conclusions Results suggest CBT self-help interventions may be an acceptable way to provide psychological support to informal caregivers, however the study is limited by the small sample size. A wide range of intervention preferences were identified indicating a need to tailor intervention content and delivery to enhance acceptability and engagement. Results will inform development of a CBT self-help intervention for informal caregivers of people with CKD.

Background Informal caregivers commonly experience mental health difficulties related to their caregiving role. e–Mental health interventions provide mental health support in a format that may be more accessible to informal caregivers. However, e–mental health interventions are seldom implemented in real-world practice. Objective This mixed methods systematic review aimed to examine factors associated with the effectiveness and implementation of e–mental health interventions for informal caregivers of adults with chronic diseases. To achieve this aim, two approaches were adopted: combinations of implementation and intervention characteristics sufficient for intervention effectiveness were explored using qualitative comparative analysis, and barriers to and facilitators of implementation of e–mental health interventions for informal caregivers were explored using thematic synthesis. Methods We identified relevant studies published from January 1, 2007, to July 6, 2022, by systematically searching 6 electronic databases and various secondary search strategies. Included studies reported on the effectiveness or implementation of e–mental health interventions for informal caregivers of adults with cancer, chronic obstructive pulmonary disease, dementia, diabetes, heart disease, or stroke. Randomized controlled trials reporting on caregivers’ mental health outcomes were included in a crisp-set qualitative comparative analysis. We assessed randomized controlled trials for bias using the Risk of Bias 2.0 tool, and we assessed how pragmatic or explanatory their trial design was using the Pragmatic Explanatory Continuum Indicator Summary 2 tool. Studies of any design reporting on implementation were included in a thematic synthesis using the Consolidated Framework for Implementation Research to identify barriers to and facilitators of implementation. Results Overall, 53 reports, representing 29 interventions, were included in the review. Most interventions (27/29, 93%) focused on informal cancer or dementia caregivers. In total, 14 reports were included in the qualitative comparative analysis, exploring conditions including the presence of peer or professional support and key persuasive design features. Low consistency and coverage prevented the determination of condition sets sufficient for intervention effectiveness. Overall, 44 reports were included in the thematic synthesis, and 152 barriers and facilitators were identified, with the majority related to the intervention and individual characteristic domains of the Consolidated Framework for Implementation Research. Implementation barriers and facilitators in the inner setting (eg, organizational culture) and outer setting (eg, external policies and resources) domains were largely unexplored. Conclusions e–Mental health interventions for informal caregivers tend to be well-designed, with several barriers to and facilitators of implementation identified related to the intervention and individual user characteristics. Future work should focus on exploring the views of stakeholders involved in implementation to determine barriers to and facilitators of implementing e–mental health interventions for informal caregivers, focusing on inner and outer setting barriers and facilitators. Trial Registration PROSPERO (International Prospective Register of Systematic Reviews) CRD42020155727; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020155727 International Registered Report Identifier (IRRID) RR2-10.1136/bmjopen-2019-035406

IntroductionInformal caregivers provide the majority of care to individuals with chronic health conditions, benefiting the care recipient and reducing use of formal care services. However, providing informal care negatively impacts the mental health of many caregivers. E-mental health interventions have emerged as a way to provide accessible mental healthcare to caregivers. Much attention has been given to reviewing the effectiveness and efficacy of such interventions, however, factors related to implementation have received less consideration. Therefore, this mixed-methods systematic review will aim to examine factors associated with the effectiveness and implementation of e-mental health interventions for caregivers.Methods and analysisEligible studies published since 1 January 2007 will be searched for in several electronic databases (CINAHL Plus with Full Text, the Cochrane Library, EMBASE, PsycINFO, PubMed and Web of Science), clinical trial registries and OpenGrey, with all screening steps conducted by two independent reviewers. Studies will be included if they focus on the implementation or effectiveness of e-mental health interventions designed for informal adult caregivers of adults with cancer, heart disease, stroke, diabetes, dementia or chronic obstructive pulmonary disease. Pragmatic randomised controlled trials quantitatively reporting on caregiver anxiety, depression, psychological distress or stress will be used for a qualitative comparative analysis to identify combinations of conditions that result in effective interventions. Qualitative and quantitative data on implementation of e-mental health interventions for caregivers will be integrated in a thematic synthesis to identify barriers and facilitators to implementation. These results will inform future development and implementation planning of e-mental health interventions for caregivers.Ethics and disseminationEthical approval is not required for this study as no primary data will be collected. Results will be disseminated in the form of a scientific publication and presentations at academic conferences and plain language summaries for various stakeholders.PROSPERO registration numberCRD42020155727.

Demands placed on informal caregivers can result in an increased likelihood of experiencing common mental health difficulties that may affect their ability to undertake the caring role. Currently, however, few evidence-based interventions have been specifically developed for informal caregivers and available interventions are difficult to access. The Improving Access to Psychological Therapies (IAPT) programme aims to improve access to evidence-based psychological therapies for all groups and may therefore present an opportunity to meet informal caregiver needs. Located within the MRC Complex Intervention Framework, a Phase II feasibility randomised controlled trial (RCT) examines key methodological, procedural and clinical uncertainties associated with running a definitive Phase III RCT of an adapted written cognitive behavioural therapy (CBT) self-help intervention for informal caregivers of stroke survivors. Recruitment was low despite different recruitment strategies being adopted, highlighting significant challenges moving towards a Phase III RCT until resolved. Difficulties with study recruitment may reflect wider challenges engaging informal caregivers in psychological interventions and may have implications for IAPT services seeking to improve access for this group. Further attempts to develop a successful recruitment protocol to progress to a Phase III RCT examining effectiveness of the adapted CBT self-help intervention should be encouraged. Key learning aims After reading this article, readers should be able to: (1) Consider key feasibility issues with regard to recruitment and attrition when running a randomised controlled trial of an adapted written cognitive behavioural therapy (CBT) self-help intervention for informal caregivers of stroke survivors. (2) Understand potential barriers experienced by an informal caregiving population to accessing psychological interventions. (3) Appreciate implications for clinical practice to enhance access to IAPT services and low-intensity CBT working with an informal caregiver population.