Non-pharmacological interventions for cognitive impairment due to systemic cancer treatment (Review)

Background

It is estimated that up to 75% of cancer survivors may experience cognitive impairment as a result of cancer treatment and given the increasing size of the cancer survivor population, the number of affected people is set to rise considerably in coming years. There is a need, therefore, to identify effective, non-pharmacological interventions for maintaining cognitive function or ameliorating cognitive impairment among people with a previous cancer diagnosis.
Objectives

To evaluate the cognitive effects, non-cognitive effects, duration and safety of non-pharmacological interventions among cancer patients targeted at maintaining cognitive function or ameliorating cognitive impairment as a result of cancer or receipt of systemic cancer treatment (i.e. chemotherapy or hormonal therapies in isolation or combination with other treatments).
Search methods

We searched the Cochrane Centre Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PUBMED, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and PsycINFO databases. We also searched registries of ongoing trials and grey literature including theses, dissertations and conference proceedings. Searches were conducted for articles published from 1980 to 29 September 2015.
Selection criteria

Randomised controlled trials (RCTs) of non-pharmacological interventions to improve cognitive impairment or to maintain cognitive functioning among survivors of adult-onset cancers who have completed systemic cancer therapy (in isolation or combination with other treatments) were eligible. Studies among individuals continuing to receive hormonal therapy were included. We excluded interventions targeted at cancer survivors with central nervous system (CNS) tumours or metastases, non-melanoma skin cancer or those who had received cranial radiation or, were from nursing or care home settings. Language restrictions were not applied.
Data collection and analysis

Author pairs independently screened, selected, extracted data and rated the risk of bias of studies. We were unable to conduct planned meta-analyses due to heterogeneity in the type of interventions and outcomes, with the exception of compensatory strategy training interventions for which we pooled data for mental and physical well-being outcomes. We report a narrative synthesis of intervention effectiveness for other outcomes.
Main results

Five RCTs describing six interventions (comprising a total of 235 participants) met the eligibility criteria for the review. Two trials of computer-assisted cognitive training interventions (n = 100), two of compensatory strategy training interventions (n = 95), one of meditation (n = 47) and one of physical activity intervention (n = 19) were identified. Each study focused on breast cancer survivors. All five studies were rated as having a high risk of bias. Data for our primary outcome of interest, cognitive function were not amenable to being pooled statistically. Cognitive training demonstrated beneficial effects on objectively assessed cognitive function (including processing speed, executive functions, cognitive flexibility, language, delayed- and immediate- memory), subjectively reported cognitive function and mental well-being. Compensatory strategy training demonstrated improvements on objectively assessed delayed-, immediate- and verbal-memory, self-reported cognitive function and spiritual quality of life (QoL). The meta-analyses of two RCTs (95 participants) did not show a beneficial effect from compensatory strategy training on physical well-being immediately (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.59 to 0.83; I2= 67%) or two months post-intervention (SMD - 0.21, 95% CI -0.89 to 0.47; I2 = 63%) or on mental well-being two months post-intervention (SMD -0.38, 95% CI -1.10 to 0.34; I2 = 67%). Lower mental well-being immediately post-intervention appeared to be observed in patients who received compensatory strategy training compared to wait-list controls (SMD -0.57, 95% CI -0.98 to -0.16; I2 = 0%). We assessed the assembled studies using GRADE for physical and mental health outcomes and this evidence was rated to be low quality and, therefore findings should be interpreted with caution. Evidence for physical activity and meditation interventions on cognitive outcomes is unclear.
Authors' conclusions

Overall, the, albeit low-quality evidence may be interpreted to suggest that non-pharmacological interventions may have the potential to reduce the risk of, or ameliorate, cognitive impairment following systemic cancer treatment. Larger, multi-site studies including an appropriate, active attentional control group, as well as consideration of functional outcomes (e.g. activities of daily living) are required in order to come to firmer conclusions about the benefits or otherwise of this intervention approach. There is also a need to conduct research into cognitive impairment among cancer patient groups other than women with breast cancer.

Sustained effectiveness of a multifaceted intervention to reduce potentially inappropriate prescribing in older patients in primary care (OPTI-SCRIPT study)

Background: Potentially inappropriate prescribing (PIP) is common in older people in primary care and can result in increased morbidity, adverse drug events and hospitalisations. We previously demonstrated the success of a multifaceted intervention in decreasing PIP in primary care in a cluster randomised controlled trial (RCT).
Objective: We sought to determine whether the improvement in PIP in the short term was sustained at 1-year follow-up.
Methods: A cluster RCT was conducted with 21 GP practices and 196 patients (aged ≥70) with PIP in Irish primary care. Intervention participants received a complex multifaceted intervention incorporating academic detailing, medicine review with web-based pharmaceutical treatment algorithms that provide recommended alternative treatment options, and tailored patient information leaflets. Control practices delivered usual care and received simple, patient-level PIP feedback. Primary outcomes were the proportion of patients with PIP and the mean number of potentially inappropriate prescriptions at 1-year follow-up. Intention-to-treat analysis using random effects regression was used.
Results: All 21 GP practices and 186 (95 %) patients were followed up. We found that at 1-year follow-up, the significant reduction in the odds of PIP exposure achieved during the intervention was sustained after its discontinuation (adjusted OR 0.28, 95 % CI 0.11 to 0.76, P = 0.01). Intervention participants had significantly lower odds of having a potentially inappropriate proton pump inhibitor compared to controls (adjusted OR 0.40, 95 % CI 0.17 to 0.94, P = 0.04).
Conclusion: The significant reduction in the odds of PIP achieved during the intervention was sustained after its discontinuation. These results indicate that improvements in prescribing quality can be maintained over time.

Development and Evaluation of a Computer-Based, Self-Management Tool for People Recently Diagnosed with Type 2 Diabetes

Aim. The purpose of this study was to develop and evaluate a computer-based, dietary, and physical activity self-management program for people recently diagnosed with type 2 diabetes. 
Methods. The computer-based program was developed in conjunction with the target group and evaluated in a 12-week randomised controlled trial (RCT). Participants were randomised to the intervention (computer-program) or control group (usual care). Primary outcomes were diabetes knowledge and goal setting (ADKnowl questionnaire, Diabetes Obstacles Questionnaire (DOQ)) measured at baseline and week 12. User feedback on the program was obtained via a questionnaire and focus groups. Results. Seventy participants completed the 12-week RCT (32 intervention, 38 control, mean age 59 (SD) years). After completion there was a significant between-group difference in the “knowledge and beliefs scale” of the DOQ. Two-thirds of the intervention group rated the program as either good or very good, 92% would recommend the program to others, and 96% agreed that the information within the program was clear and easy to understand. 
Conclusions. The computer-program resulted in a small but statistically significant improvement in diet-related knowledge and user satisfaction was high. With some further development, this computer-based educational tool may be a useful adjunct to diabetes self-management.

A process evaluation of a cluster randomised trial to reduce potentially inappropriate prescribing in older people in primary care (OPTI-SCRIPT study)

Background
The OPTI-SCRIPT cluster randomised controlled trial (RCT) found that a three-phase multifaceted intervention including academic detailing with a pharmacist, GP-led medicines reviews, supported by web-based pharmaceutical treatment algorithms, and tailored patient information leaflets, was effective in reducing potentially inappropriate prescribing (PIP) in Irish primary care. We report a process evaluation exploring the implementation of the intervention, the experiences of those participating in the study and lessons for future implementation.

Methods
The OPTI-SCRIPT trial included 21 GP practices and 196 patients. The process evaluation used mixed methods. Quantitative data were collected from all GP practices and semi-structured interviews were conducted with GPs from intervention and control groups, and a purposive sample of patients from the intervention group. All interviews were transcribed verbatim and analysed using a thematic analysis.

Results
Despite receiving a standardised academic detailing session, intervention delivery varied among GP practices. Just over 70 % of practices completed medicines review as recommended with the patient present. Only single-handed practices conducted reviews without patients present, highlighting the influence of practice characteristics and resources on variation. Medications were more likely to be completely stopped or switched to another more appropriate medication when reviews were conducted with patients present. The patient information leaflets were not used by any of the intervention practices. Both GP (32 %) and patient (40 %) recruitment rates were modest. For those who did participate, overall, the experience was positively viewed, with GPs and patients referring to the value of medication reviews to improve prescribing and reduce unnecessary medications. Lack of time in busy GP practices and remuneration were identified as organisational barriers to future implementation.

Conclusions
The OPTI-SCRIPT intervention was positively viewed by both GPs and patients, both of whom valued the study’s objectives. Patient information leaflets were not a successful component of the intervention. Academic detailing and medication reviews are important components in changing PIP, and having patients present during the review process seems to be a more effective approach for decreasing PIP.

PIPc study: development of indicators of potentially inappropriate prescribing in children (PIPc) in primary care using a modified Delphi technique

Objective There is limited evidence regarding the quality of prescribing for children in primary care. Several prescribing criteria (indicators) have been developed to assess the appropriateness of prescribing in older and middle-aged adults but few are relevant to children. The objective of this study was to develop a set of prescribing indicators that can be applied to prescribing or dispensing data sets to determine the prevalence of potentially inappropriate prescribing in children (PIPc) in primary care settings.


Design Two-round modified Delphi consensus method.


Setting Irish and UK general practice.


Participants A project steering group consisting of academic and clinical general practitioners (GPs) and pharmacists was formed to develop a list of indicators from literature review and clinical expertise. 15 experts consisting of GPs, pharmacists and paediatricians from the Republic of Ireland and the UK formed the Delphi panel.


Results 47 indicators were reviewed by the project steering group and 16 were presented to the Delphi panel. In the first round of this exercise, consensus was achieved on nine of these indicators. Of the remaining seven indicators, two were removed following review of expert panel comments and discussion of the project steering group. The second round of the Delphi process focused on the remaining five indicators, which were amended based on first round feedback. Three indicators were accepted following the second round of the Delphi process and the remaining two indicators were removed. The final list consisted of 12 indicators categorised by respiratory system (n=6), gastrointestinal system (n=2), neurological system (n=2) and dermatological system (n=2).


Conclusions The PIPc indicators are a set of prescribing criteria developed for use in children in primary care in the absence of clinical information. The utility of these criteria will be tested in further studies using prescribing databases.

Statin prescription initiation and lifestyle behaviour: a primary care cohort study

BACKGROUND: Statin prescribing and healthy lifestyles contribute to declining cardiovascular disease mortality. Recent guidelines emphasise the importance of giving lifestyle advice in association with prescribing statins but adherence to healthy lifestyle recommendations is sub-optimal. However, little is known about any change in patients' lifestyle behaviours when starting statins or of their recall of receiving advice. This study aimed to examine patients' diet and physical activity (PA) behaviours and their recall of lifestyle advice following initiation of statin prescribing in primary care.

METHOD: In 12 general practices, patients with a recent initial prescription of statin therapy, were invited to participate. Those who agreed received a food diary by post, to record food consumed over 4 consecutive days and return to the researcher. We also telephoned participants to administer brief validated questionnaires to assess typical daily diet (DINE) and PA level (Godin). Using the same methods, food diaries and questionnaires were repeated 3 months later. At both times participants were asked if they had changed their behaviour or received advice about their diet or PA.

RESULTS: Of 384 invited, 122 (32 %) participated; 109 (89.3 %) completed paired datasets; 50 (45.9 %) were male; their mean age was 64 years. 53.2 % (58/109) recalled receiving lifestyle advice. Of those who did, 69.0 % (40/58) reported having changed their diet or PA, compared to 31.4 % (16/51) of those who did not recall receiving advice. Initial mean daily saturated fat intake (12.9 % (SD3.5) of total energy) was higher than recommended; mean fibre intake (13.8 g/day (SD5.5)), fruit/vegetable consumption (2.7 portions/day (SD1.3)) and PA levels (Godin score 7.1 (SD13.9)) were low. Overall, although some individuals showed evidence of behaviour change, there were no significant changes in the proportions who reported high or medium fat intake (42.2 % v 49.5 %), low fibre (51.4 % v 55.0 %), or insufficient PA (80.7 % v 83.5 %) at 3-month follow-up.

CONCLUSION: Whilst approximately half of our cohort recalled receiving lifestyle advice associated with statin prescribing this did not translate into significant changes in diet or PA. Further research is needed to explore gaps between people's knowledge and behaviours and determine how best to provide advice that supports behaviour change.

Psychological factors associated with self-management among adolescents with Type 1 diabetes: a review

This review aims to synthesise the literature examining the psychosocial variables related to self-management (insulin adherence, non-adherence and administration, blood sugar monitoring, dietary behaviour, exercise behaviour) in adolescents with type 1 diabetes.
A systematic search of three electronic databases was carried out and, after the application of eligibility criteria, 21 articles were assessed for quality prior to data extraction. Numerous psychological factors were found to be associated with self-management; however, correlations were typically small to moderate. The strongest associations were found between social anxiety and diet (among males); greater intrinsic motivation, conscientiousness and diet; and extraversion and exercise.

An Assessment of How Nurse Practitioners Create Access to Primary Care in Canadian Residential Long-Term Care Settings

The aim of this paper is to explore the role and activities of nurse practitioners (NPs) working in long-term care (LTC) to understand concepts of access to primary care for residents. Utilizing the "FIT" framework developed by Penchanksy and Thomas, we used a directed content analysis method to analyze data from a pan-Canadian study of NPs in LTC. Individual and focus group interviews were conducted at four sites in western, central and eastern regions of Canada with 143 participants, including NPs, RNs, regulated and unregulated nursing staff, allied health professionals, physicians, administrators and directors and residents and family members. Participants emphasized how the availability and accessibility of the NP had an impact on access to primary and urgent care for residents. Understanding more about how NPs affect access in Canadian LTC will be valuable for nursing practice and healthcare planning and policy and may assist other countries in planning for the introduction of NPs in LTC settings to increase access to primary care.

An investigation of routes to cancer diagnosis in 10 international jurisdictions, as part of the International Cancer Benchmarking Partnership: survey development and implementation

Objectives This paper describes the methods used in the International Cancer Benchmarking Partnership Module 4 Survey (ICBPM4) which examines time intervals and routes to cancer diagnosis in 10 jurisdictions. We present the study design with defining and measuring time intervals, identifying patients with cancer, questionnaire development, data management and analyses.
Design and setting Recruitment of participants to the ICBPM4 survey is based on cancer registries in each jurisdiction. Questionnaires draw on previous instruments and have been through a process of cognitive testing and piloting in three jurisdictions followed by standardised translation and adaptation. Data analysis focuses on comparing differences in time intervals and routes to diagnosis in the jurisdictions.
Participants Our target is 200 patients with symptomatic breast, lung, colorectal and ovarian cancer in each jurisdiction. Patients are approached directly or via their primary care physician (PCP). Patients’ PCPs and cancer treatment specialists (CTSs) are surveyed, and ‘data rules’ are applied to combine and reconcile conflicting information. Where CTS information is unavailable, audit information is sought from treatment records and databases.
Main outcomes Reliability testing of the patient questionnaire showed that agreement was complete (κ=1) in four items and substantial (κ=0.8, 95% CI 0.333 to 1) in one item. The identification of eligible patients is sufficient to meet the targets for breast, lung and colorectal cancer. Initial patient and PCP survey response rates from the UK and Sweden are comparable with similar published surveys. Data collection was completed in early 2016 for all cancer types.
Conclusion An international questionnaire-based survey of patients with cancer, PCPs and CTSs has been developed and launched in 10 jurisdictions. ICBPM4 will help to further understand international differences in cancer survival by comparing time intervals and routes to cancer diagnosis.

GPs’ and community pharmacists’ opinions on medication management at transitions of care in Ireland

Objective. The aim of this study was to survey GPs and community pharmacists (CPs) in Ireland regarding current practices of medication management, specifically medication reconciliation, communication between health care providers and medication errors as patients transition in care.
Methods. A national cross-sectional survey was distributed electronically to 2364 GPs, 311 GP Registrars and 2382 CPs. Multivariable associations comparing GPs to CPs were generated and content analysis of free text responses was undertaken.
Results. There was an overall response rate of 17.7% (897 respondents—554 GPs/Registrars and 343 CPs). More than 90% of GPs and CPs were positive about the effects of medication reconciliation on medication safety and adherence. Sixty per cent of GPs reported having no formal system of medication reconciliation. Communication between GPs and CPs was identified as good/very good by >90% of GPs and CPs. The majority (>80%) of both groups could clearly recall prescribing errors, following a transition of care, they had witnessed in the previous 6 months. Free text content analysis corroborated the positive relationship between GPs and CPs, a frustration with secondary care communication, with many examples given of prescribing errors.
Conclusions. While there is enthusiasm for the benefits of medication reconciliation there are limited formal structures in primary care to support it. Challenges in relation to systems that support inter-professional communication and reduce medication errors are features of the primary/secondary care transition. There is a need for an improved medication management system. Future research should focus on the identified barriers in implementing medication reconciliation and systems that can improve it.

Cost-effectiveness of zoledronic acid and strontium-89 as bone protecting treatments in addition to chemotherapy in patients with metastatic castrate-refractory prostate cancer: results from the TRAPEZE trial (ISRCTN 12808747)

OBJECTIVE: To evaluate the cost-effectiveness of adding zoledronic acid or strontium-89 to standard docetaxel chemotherapy for patients with castrate-refractory prostate cancer (CRPC).

PATIENTS AND METHODS: Data on resource use and quality of life for 707 patients collected prospectively in the TRAPEZE 2 × 2 factorial randomised trial (ISRCTN 12808747) were used to assess the cost-effectiveness of i) zoledronic acid versus no zoledronic acid (ZA vs. no ZA), and ii) strontium-89 versus no strontium-89 (Sr89 vs. no Sr89). Costs were estimated from the perspective of the National Health Service in the UK and included expenditures for trial treatments, concomitant medications, and use of related hospital and primary care services. Quality-adjusted life-years (QALYs) were calculated according to patients' responses to the generic EuroQol EQ-5D-3L instrument, which evaluates health status. Results are expressed as incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves.

RESULTS: The per-patient cost for ZA was £12 667, £251 higher than the equivalent cost in the no ZA group. Patients in the ZA group had on average 0.03 QALYs more than their counterparts in no ZA group. The ICER for this comparison was £8 005. Sr89 was associated with a cost of £13 230, £1365 higher than no Sr89, and a gain of 0.08 QALYs compared to no Sr89. The ICER for Sr89 was £16 884. The probabilities of ZA and Sr89 being cost-effective were 0.64 and 0.60, respectively.

CONCLUSIONS: The addition of bone-targeting treatments to standard chemotherapy led to a small improvement in QALYs for a modest increase in cost (or cost-savings). ZA and Sr89 resulted in ICERs below conventional willingness-to-pay per QALY thresholds, suggesting that their addition to chemotherapy may represent a cost-effective use of resources.