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.

DESCRIBING SLEEP AND SEDATION PRACTICES IN THE ICU: A MULTINATIONAL SURVEY

Introduction Sleep disturbances are common in critically ill patients treated in the intensive care unit (ICU) with the potential for serious consequences and long-term effects on health outcomes and patient morbidity.
Objectives Our aim was to describe sleep management and sedation practices of adult ICUs in ten countries and to evaluate roles and responsibilities of the ICU staff in relation to key sleep and sedation decisions.
Methods A multicenter, self-administered survey sent to nurse managers of adult ICUs across 10 countries. The questionnaire comprised four domains: sleep characteristics of the critically ill; sleep and sedation practices; non-pharmacological and pharmacological interventions used to improve sleep; and the autonomy and influence of nurses on sleeping practices in the ICU.
Results Overall response rate was 66% (range 32% UK to 100% Cyprus), providing data from 522 ICUs. In all countries, the most frequent patient characteristic perceived to identify sleep was lying quietly with closed eyes (N=409, 78%) (range 92% Denmark to 36% Italy). The most commonly used sedation scale was the Richmond Agitation-Sedation Score (RASS) (N=220, 42%) (range 81% UK to 0% Denmark, Cyprus where most ICUs used the Ramsay score). In most ICUs, selection of sleep medication (N=265, 51%) and assessment of effect (N=309, 59%) was performed by physicians and nurses based on collaborative discussion. In a minority of ICUs (N=161, 31%), decisions and assessments were made by physicians alone. The most commonly used (in all countries) non-pharmacological intervention to promote sleep was reducing ICU staff noise (N=473, 91%) (range 100% Denmark, Norway to 78% Canada). Only 95 ICUs (18%) used earplugs on a frequent basis (range 0% Greece, Cyprus, Denmark to 57% Sweden). Propofol was the drug used most commonly for sedation (N=359, 69%) (range 96% Sweden to 29% Canada). Chloral hydrate was used by only 63 (12%) ICUs (range 0% Greece, Cyprus, Denmark, Italy to 56% Germany). Sedation scales were used on a routine basis by 77% of the 522 ICUs. Participants scored nursing autonomy for sleep and sedation management as moderate; median score of 5 (scale of 0 to 10), range 7 (Canada, Greece, Sweden) to 4 (Norway, Poland). Nursing influence on sleep and sedation decisions was perceived considerable; median score 8, range 9 (Denmark) to 5 (Poland).
Conclusions We found considerable across country variation in sleep promotion and sedation management practices though most have adopted a sedation scale as recommended in professional society guidelines. Most ICUs in all countries used a range of pharmacological and non-pharmacological interventions to promote sleep. Most units reported inter-professional decision-making with nurses perceived to have substantial influence on sleep/sedation decisions.

The effectiveness of a nurse practitioner-led pain management team in long-term care: A mixed methods study

BACKGROUND: Considering the high rates of pain as well as its under-management in long-term care (LTC) settings, research is needed to explore innovations in pain management that take into account limited resource realities. It has been suggested that nurse practitioners, working within an inter-professional model, could potentially address the under-management of pain in LTC.

OBJECTIVES: This study evaluated the effectiveness of implementing a nurse practitioner-led, inter-professional pain management team in LTC in improving (a) pain-related resident outcomes; (b) clinical practice behaviours (e.g., documentation of pain assessments, use of non-pharmacological and pharmacological interventions); and, (c) quality of pain medication prescribing practices.

METHODS: A mixed method design was used to evaluate a nurse practitioner-led pain management team, including both a quantitative and qualitative component. Using a controlled before-after study, six LTC homes were allocated to one of three groups: 1) a nurse practitioner-led pain team (full intervention); 2) nurse practitioner but no pain management team (partial intervention); or, 3) no nurse practitioner, no pain management team (control group). In total, 345 LTC residents were recruited to participate in the study; 139 residents for the full intervention group, 108 for the partial intervention group, and 98 residents for the control group. Data was collected in Canada from 2010 to 2012.

RESULTS: Implementing a nurse practitioner-led pain team in LTC significantly reduced residents' pain and improved functional status compared to usual care without access to a nurse practitioner. Positive changes in clinical practice behaviours (e.g., assessing pain, developing care plans related to pain management, documenting effectiveness of pain interventions) occurred over the intervention period for both the nurse practitioner-led pain team and nurse practitioner-only groups; these changes did not occur to the same extent, if at all, in the control group. Qualitative analysis highlighted the perceived benefits of LTC staff about having access to a nurse practitioner and benefits of the pain team, along with barriers to managing pain in LTC.

CONCLUSIONS: The findings from this study showed that implementing a nurse practitioner-led pain team can significantly improve resident pain and functional status as well as clinical practice behaviours of LTC staff. LTC homes should employ a nurse practitioner, ideally located onsite as opposed to an offsite consultative role, to enhance inter-professional collaboration and facilitate more consistent and timely access to pain management.

Statin withdrawal in people with dementia

Background: There are approximately 24 million people worldwide with dementia; this is likely to increase to 81 million by 2040. Dementia is a progressive condition, and usually leads to death eight to ten years after first symptoms. End-of-life care should emphasise treatments that optimise quality of life and physicians should minimise unnecessary or non-beneficial interventions. Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors; they have become the cornerstone of pharmacotherapy for the management of hypercholesterolaemia but their ability to provide benefit is unclear in the last weeks or months of life. Withdrawal of statins may improve quality of life in people with advanced dementia, as they will not be subjected to unnecessary polypharmacy or side effects. However, they may help to prevent further vascular events in people of advanced age who are at high risk of such events.

Objectives: To evaluate the effects of withdrawal or continuation of statins in people with dementia on: cognitive outcomes, adverse events, behavioural and functional outcomes, mortality, quality of life, vascular morbidity, and healthcare costs.

Search methods: We searched ALOIS (medicine.ox.ac.uk/alois/), the Cochrane Dementia and Cognitive Improvement Group Specialised Register on 11 February 2016. We also ran additional searches in MEDLINE, EMBASE, PsycINFO, CINAHL, Clinical.Trials.gov and the WHO Portal/ICTRP on 11 February 2016, to ensure that the searches were as comprehensive and as up-to-date as possible.

Selection criteria: We included all randomised, controlled clinical trials with either a placebo or 'no treatment' control group. We applied no language restrictions.

Data collection and analysis: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria, using standard methodological procedures expected by Cochrane. We found no studies suitable for inclusion therefore analysed no data.

Main results: The search strategy identified 28 unique references, all of which were excluded.

Authors' conclusions: We found no evidence to enable us to make an informed decision about statin withdrawal in dementia. Randomised controlled studies need to be conducted to assess cognitive and other effects of statins in participants with dementia, especially when the disease is advanced.

A Simultaneous Equation Approach to Estimating HIV Prevalence with Non-Ignorable Missing Responses

Estimates of HIV prevalence are important for policy in order to establish the health status of a country's population and to evaluate the effectiveness of population-based interventions and campaigns. However, participation rates in testing for surveillance conducted as part of household surveys, on which many of these estimates are based, can be low. HIV positive individuals may be less likely to participate because they fear disclosure, in which case estimates obtained using conventional approaches to deal with missing data, such as imputation-based methods, will be biased. We develop a Heckman-type simultaneous equation approach which accounts for non-ignorable selection, but unlike previous implementations, allows for spatial dependence and does not impose a homogeneous selection process on all respondents. In addition, our framework addresses the issue of separation, where for instance some factors are severely unbalanced and highly predictive of the response, which would ordinarily prevent model convergence. Estimation is carried out within a penalized likelihood framework where smoothing is achieved using a parametrization of the smoothing criterion which makes estimation more stable and efficient. We provide the software for straightforward implementation of the proposed approach, and apply our methodology to estimating national and sub-national HIV prevalence in Swaziland, Zimbabwe and Zambia.

FLIP: a targetable mediator of resistance to radiation in non-small cell lung cancer

Resistance to radiotherapy due to insufficient cancer cell death is a significant cause of treatment failure in non-small cell lung cancer (NSCLC). The endogenous caspase-8 inhibitor, FLIP, is a critical regulator of cell death that is frequently overexpressed in NSCLC and is an established inhibitor of apoptotic cell death induced via the extrinsic death receptor pathway. Apoptosis induced by ionizing radiation (IR) has been considered to be mediated predominantly via the intrinsic apoptotic pathway; however, we found that IR-induced apoptosis was significantly attenuated in NSCLC cells when caspase-8 was depleted using RNA interference (RNAi), suggesting involvement of the extrinsic apoptosis pathway. Moreover, overexpression of wild-type FLIP, but not a mutant form that cannot bind the critical death receptor adaptor protein FADD, also attenuated IR-induced apoptosis, confirming the importance of the extrinsic apoptotic pathway as a determinant of response to IR in NSCLC. Importantly, when FLIP protein levels were down-regulated by RNAi, IR-induced cell death was significantly enhanced. The clinically relevant histone deacetylase (HDAC) inhibitors vorinostat and entinostat were subsequently found to sensitize a subset of NSCLC cell lines to IR in a manner that was dependent on their ability to suppress FLIP expression and promote activation of caspase-8. Entinostat also enhanced the anti-tumor activity of IR in vivo. Therefore, FLIP down-regulation induced by HDAC inhibitors is a potential clinical strategy to radio-sensitize NSCLC and thereby improve response to radiotherapy. Overall, this study provides the first evidence that pharmacological inhibition of FLIP may improve response of NCSLC to IR.

Effectiveness of Community versus Hospital Eye Service follow-up for patients with neovascular age-related macular degeneration with quiescent disease (ECHoES): a virtual non-inferiority trial

OBJECTIVES: To compare the ability of ophthalmologists versus optometrists to correctly classify retinal lesions due to neovascular age-related macular degeneration (nAMD).

DESIGN: Randomised balanced incomplete block trial. Optometrists in the community and ophthalmologists in the Hospital Eye Service classified lesions from vignettes comprising clinical information, colour fundus photographs and optical coherence tomographic images. Participants' classifications were validated against experts' classifications (reference standard).

SETTING: Internet-based application.

PARTICIPANTS: Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care.

INTERVENTIONS: The trial emulated a conventional trial comparing optometrists' and ophthalmologists' decision-making, but vignettes, not patients, were assessed. Therefore, there were no interventions and the trial was virtual. Participants received training before assessing vignettes.

MAIN OUTCOME MEASURES: Primary outcome-correct classification of the activity status of a lesion based on a vignette, compared with a reference standard. Secondary outcomes-potentially sight-threatening errors, judgements about specific lesion components and participants' confidence in their decisions.

RESULTS: In total, 155 participants registered for the trial; 96 (48 in each group) completed all assessments and formed the analysis population. Optometrists and ophthalmologists achieved 1702/2016 (84.4%) and 1722/2016 (85.4%) correct classifications, respectively (OR 0.91, 95% CI 0.66 to 1.25; p=0.543). Optometrists' decision-making was non-inferior to ophthalmologists' with respect to the prespecified limit of 10% absolute difference (0.298 on the odds scale). Optometrists and ophthalmologists made similar numbers of sight-threatening errors (57/994 (5.7%) vs 62/994 (6.2%), OR 0.93, 95% CI 0.55 to 1.57; p=0.789). Ophthalmologists assessed lesion components as present less often than optometrists and were more confident about their classifications than optometrists.

CONCLUSIONS: Optometrists' ability to make nAMD retreatment decisions from vignettes is not inferior to ophthalmologists' ability. Shared care with optometrists monitoring quiescent nAMD lesions has the potential to reduce workload in hospitals.

TRIAL REGISTRATION NUMBER: ISRCTN07479761; pre-results registration.

A realist synthesis of educational interventions to improve nutrition care competencies and delivery by doctors and other healthcare professionals

Objective: To determine what, how, for whom, why, and in what circumstances educational interventions to improve the delivery of nutrition care by doctors and other healthcare professionals work?

Design: Realist synthesis following a published protocol and reported following Realist and Meta-narrative Evidence Synthesis: Evolving Standards (RAMESES) guidelines. A multidisciplinary team searched Medline, CINAHL, ERIC, EMBASE, PsyINFO, Sociological Abstracts, Web of Science, Google Scholar, and Science Direct for published and unpublished (grey) literature. The team identified studies with varied designs; appraised their ability to answer the review question; identified relationships between contexts, mechanisms, and outcomes (CMOs); and entered them into a spreadsheet configured for the purpose. The final synthesis identified commonalities across CMO configurations.

Results: Over half of the 46 studies from which we extracted data originated from the US. Interventions that improved the delivery of nutrition care improved skills and attitudes rather than just knowledge; provided opportunities for superiors to model nutrition care; removed barriers to nutrition care in health systems; provided participants with local, practically relevant tools and messages; and incorporated non-traditional, innovative teaching strategies. Operating in contexts where student and qualified healthcare professionals provided nutrition care in both developed and developing countries, these interventions yielded health outcomes by triggering a range of mechanisms, which included: feeling competent; feeling confident and comfortable; having greater self-efficacy; being less inhibited by barriers in healthcare systems; and feeling that nutrition care was accepted and recognised.

Conclusion: These findings show how important it is to move education for nutrition care beyond the simple acquisition of knowledge. They show how educational interventions embedded within systems of healthcare can improve patients’ health by helping health students and professionals to appreciate the importance of delivering nutrition care and feel competent to deliver it.