Pre-existing musculoskeletal pain and its association with mortality in newly diagnosed co-morbid conditions: an electronic health record cohort study.

Objective: Musculoskeletal pain is a common risk factor for co-morbid conditions and might increase the risk of poor outcomes. The objective was to determine whether patients with pre-existing musculoskeletal pain have an increased risk for mortality following a new diagnosis of a co-morbid condition. Methods: Patients aged ≥45 years with a new diagnosis of acute coronary syndrome (ACS), stroke, cancer, dementia or pneumonia recorded in a UK electronic primary care database linked to hospital and mortality records were examined. The association of mortality with musculoskeletal pain (inflammatory conditions, OA and regional pain) was determined. Results: The sample size varied from 128 649 (stroke) to 406 289 (cancer) by cohort, with 22-31% having pre-existing musculoskeletal conditions. In the ACS cohort, there was a higher rate of mortality for all musculoskeletal types. There were also higher unadjusted mortality rates in patients with inflammatory arthritis compared with those without musculoskeletal pain in the stroke, cancer and dementia cohorts and for patients with OA in the stroke and cancer cohorts. After adjustment for the number of prescribed medications and age, the increased risk of mortality remained only for patients with inflammatory arthritis in the ACS cohort (adjusted hazard ratio = 1.07; 95% CI 1.03, 1.10). Conclusion: Older adults with inflammatory arthritis and OA have increased risk of mortality when they develop a new condition, which seems to be related to the prescription of multiple medicines. Pre-existing musculoskeletal pain is an indicator of a complex patient who is at risk of poorer outcomes at the onset of new illnesses.

Estimating the direct healthcare utilization and cost of musculoskeletal pain among people with comorbidity: a retrospective electronic health record study.

OBJECTIVE: To investigate the impact of pre-existing painful musculoskeletal conditions on healthcare utilization and costs among patients with five common conditions: acute coronary syndrome (ACS), stroke, cancer, dementia and pneumonia. METHODS: Using primary and secondary care services data from electronic health records, a negative binomial regression model was used to compare resource use while a two-part model was used to compare costs across the five conditions, between those with and without a pre-existing musculoskeletal pain. RESULTS: The study included 760,792 patients (144,870 with ACS, 121,208 with stroke, 231,702 with cancer, 134,638 with dementia, and 128,374 with pneumonia) in the complete case analysis. Pre-existing musculoskeletal pain had an incident rate ratio of above one for most healthcare resources over the follow-up period and an adjusted additional mean cumulative total healthcare costs per patient of £674.59 (95%CI 570.30 to 778.87) for ACS; £613.34 (95%CI 496.87 to 729.82) for stroke; £459.26 (95%CI 376.60 to 541.91) for cancer; and £766.23 (95%CI 655.06 to 877.39) for dementia over five years after diagnosis; and £200.85 (95%CI 104.16 to 297.55) for pneumonia over one year after diagnosis compared to those without musculoskeletal pain. CONCLUSION: This study highlights that individuals with painful musculoskeletal conditions have higher healthcare utiliszation and costs than those without painful musculoskeletal conditions. Given the high occurrence of musculoskeletal pain in patients with other conditions, effective management strategies are needed to reduce the burden on healthcare resources.

Musculoskeletal pain and its impact on prognosis following acute coronary syndrome or stroke: A linked electronic health record cohort study.

OBJECTIVE: Musculoskeletal painful conditions are a risk factor for cardiovascular disease (CVD), but less is known about whether musculoskeletal pain also worsens prognosis from CVD. The objective was to determine whether patients with musculoskeletal pain have poorer prognosis following acute coronary syndrome (ACS) or stroke. METHODS: The study utilised UK electronic primary care records (CPRD Aurum) with linkage to hospital and mortality records. Patients aged ≥45 years admitted to hospital with incident ACS/stroke were categorised by healthcare use for musculoskeletal pain (inflammatory conditions, osteoarthritis [OA], and regional pain) based on primary care consultations in the prior 24 months. Outcomes included mortality, length of stay, readmission and management of index condition (ACS/stroke). RESULTS: There were 171,670 patients with incident ACS and 138,512 with stroke; 30% consulted for musculoskeletal pain prior to ACS/stroke and these patients had more comorbidity than those without musculoskeletal pain. Rates of mortality and readmission, and length of stay were higher in those with musculoskeletal pain, particularly OA and inflammatory conditions, in ACS. Readmission was also higher for patients with musculoskeletal pain in stroke. However, increased risks associated with musculoskeletal pain did not remain after adjustment for age and polypharmacy. Inflammatory conditions were associated with increased likelihood of prescriptions for dual anti-platelets (ACS only) and anti-coagulants. CONCLUSIONS: Patients with musculoskeletal pain have higher rates of poor outcome from ACS which relates to being older but also increased polypharmacy. The high rates of comorbidity including polypharmacy highlight the complexity of patients with musculoskeletal pain who have new onset ACS/stroke.

Micronutrient Deficiencies Presenting with Optic Disc Swelling Associated with or without Intracranial Hypertension: A Systematic Review.

Idiopathic intracranial hypertension (IIH) is a neurological disorder characterised by optic disc swelling secondary to raised intracranial pressure (ICP) of unknown cause. Obesity is the most established and prevalent risk factor in developed countries. As obesogenic diets are high in calories and nutrient-poor, there may be associated nutritional deficiencies that contribute to the clinical presentation of IIH. Yet none, aside from iron deficiency, are currently included in the inclusion or exclusion criteria for the diagnosis of IIH. Our primary aim was to determine which micronutrient deficiencies, aside from iron deficiency, could present with optic disc swelling associated with or without intracranial hypertension that could potentially meet current IIH diagnostic criteria. To this end, we conducted a systematic search of articles published between 1 January 1980 and 18 December 2020 reporting cases of optic disc swelling associated with micronutrient deficiencies. In total, 65 cases met the eligibility criteria from initial searches: all were case reports and case series with a high risk of bias. Our findings suggest that patients with IIH or unexplained optic disc swelling ought to be screened, investigated, and treated for associated micronutrient deficiencies in vitamin A, B1 and B12; and weight loss interventions in IIH patients ought to promote better nutrition in addition to overall calorie restriction.

A pilot study of the mistletoe and breast cancer (MAB) trial: a protocol for a randomised double-blind controlled trial.

BACKGROUND: A Cochrane review of mistletoe therapy concludes that there is some evidence that mistletoe extracts may offer benefits on measures of quality of life during chemotherapy for breast cancer, but these results need replication. Our aim is to add to this evidence base by initially testing the feasibility of a UK pilot placebo-controlled, double-blind randomised controlled trial of mistletoe therapy in patients with breast cancer undergoing chemotherapy with or without radiotherapy. METHODS/DESIGN: A mixed phase pilot placebo-controlled, double-blind randomised controlled trial of mistletoe therapy in patients with breast cancer (EudraCT number: 2018-000279-34). There will be three arms (groups) in the trial: Iscador M, Iscador P, with physiological saline as the placebo. The aim is to recruit 45 adult patients with a new diagnosis of early or locally advanced breast cancer, up to 12 weeks following definitive breast surgery whose standard treatment plan includes chemotherapy with or without radiotherapy. They will be taught to administer the mistletoe and breast cancer (MAB) therapies subcutaneously. MAB therapy will continue throughout their standard chemotherapy and radiotherapy and 1 month beyond. The main outcome of the MAB study is the feasibility of conducting such a trial within the NHS in order to inform a future fully powered investigative trial. Feasibility will be measured through recruitment, retention and patient experience using clinical research forms, patient diaries, cancer-related questionnaires and qualitative interviews conducted with both patients and oncology staff. DISCUSSION: This trial is the first of its kind in the UK. Currently, mistletoe therapy is mostly available through private practice in the UK. Completion of this feasibility study will support applications for further funding for a fully powered randomised controlled trial which will measure effectiveness and cost-effectiveness of this herbal therapy.

Enablers and barriers to treatment adherence in heterozygous familial hypercholesterolaemia: a qualitative evidence synthesis.

OBJECTIVES: Individuals with heterozygous familial hypercholesterolaemia (FH) are at high risk of developing cardiovascular disease (CVD). This risk can be substantially reduced with lifelong pharmacological and lifestyle treatment; however, research suggests adherence is poor. We synthesised the qualitative research to identify enablers and barriers to treatment adherence. DESIGN: This study conducted a thematic synthesis of qualitative studies. DATA SOURCES: MEDLINE, Embase, PsycINFO via OVID, Cochrane library and CINAHL databases and grey literature sources were searched through September 2018. ELIGIBILITY CRITERIA: We included studies conducted in individuals with FH, and their family members, which reported primary qualitative data regarding their experiences of and beliefs about their condition and its treatment. DATA EXTRACTION AND SYNTHESIS: Quality assessment was undertaken using the Critical Appraisal Skills Programme for qualitative studies. A thematic synthesis was conducted to uncover descriptive and generate analytical themes. These findings were then used to identify enablers and barriers to treatment adherence for application in clinical practice. RESULTS: 24 papers reporting the findings of 15 population samples (264 individuals with FH and 13 of their family members) across 8 countries were included. Data captured within 20 descriptive themes were considered in relation to treatment adherence and 6 analytical themes were generated: risk assessment; perceived personal control of health; disease identity; family influence; informed decision-making; and incorporating treatment into daily life. These findings were used to identify seven enablers (eg, 'commencement of treatment from a young age') and six barriers (eg, 'incorrect and/or inadequate knowledge of treatment advice') to treatment adherence. There were insufficient data to explore if the findings differed between adults and children. CONCLUSIONS: The findings reveal several enablers and barriers to treatment adherence in individuals with FH. These could be used in clinical practice to facilitate optimal adherence to lifelong treatment thereby minimising the risk of CVD in this vulnerable population. PROSPERO REGISTRATION NUMBER: CRD42018085946.

Methodological exemplar of integrating quantitative and qualitative evidence - supportive care for men with prostate cancer: what are the most important components?

AIMS: To present a methodological exemplar of integrating findings from a quantitative and qualitative review on the same topic to provide insight into components of care that contribute to supportive care that is acceptable to men with prostate cancer. BACKGROUND: Men with prostate cancer are likely to live a long time with the disease, experience side effects from treatment and therefore have ongoing supportive care needs. Quantitative and qualitative reviews have been published but the findings have yet to be integrated. DESIGN: Integration of quantitative and qualitative synthesized evidence. DATA SOURCE: Two previously published systematic reviews. REVIEW METHODS: Synthesized evidence on supportive care for men with prostate cancer was integrated from two previously published systematic reviews: a narrative quantitative review and a qualitative review with thematic synthesis. These two streams of synthesized evidence were synthesized using concurrent narrative summary. Data from both reviews were used to develop a set of propositions from which a summary of components of care that likely to contribute to supportive care acceptable to men with prostate cancer were identified. RESULTS: Nine propositions were developed which covered men's supportive care focusing on the role of health professionals. These propositions were used to compose nine components of care likely to lead to supportive care that is acceptable to men with prostate cancer. Some of these components are no/low cost such as developing a more empathic personalized approach, but more specific approaches need further investigation in randomized controlled trials, for example, online support. CONCLUSION: This methodological exemplar demonstrates the integration of quantitative and qualitative synthesized data to determine components of care likely to lead to provision of supportive care acceptable to men with prostate cancer.

Cancer Patients' Experiences of Using Mistletoe (Viscum album): A Qualitative Systematic Review and Synthesis.

OBJECTIVE: Systematic reviews of mistletoe therapy (MT) trials in cancer show promising results in improvement of patients' quality of life during chemotherapy and reduction of fatigue. However, patients' experiences of side effects and the acceptability, tolerability, and perceived benefits of MT have not been systematically reviewed. The aim of this study was to systematically review and synthesise the results of qualitative studies of cancer patients' experiences of using MT. DESIGN: A systematic search was conducted in MEDLINE, Embase, PsychLIT, CINAHL, and AMED to identify qualitative studies of MT. Articles were screened independently by two reviewers and critically appraised using the Critical Appraisal Skills Programme tool. A thematic synthesis of the findings was carried out. RESULTS: One hundred and seventy-three papers were identified; 156 were excluded at initial screening. Seventeen papers were read in full, 14 of which were excluded. Three articles about patients' experiences of MT alongside conventional treatment were included in the synthesis, either as a monotherapy (two articles) or as part of a package of anthroposophic treatment (one article). Patients reported demonstrable changes to their physical, emotional, and psychosocial well-being following MT, as well as a reduction in chemotherapy side effects. Self-reported side effects from MT were few, and the studies suggest good adherence to the therapy. Self-injection gave patients a sense of empowerment through involvement in their own treatment. CONCLUSIONS: A systematic search revealed a small number of qualitative studies of MT in cancer. These were effectively combined to provide a detailed overview of patients' experiences in order to complement the developing evidence base from trials. Given the variation in context of MT delivery across the articles, it is not possible to ascribe changes in patients' quality of life specifically to MT. The results of this review will help in the design of outcome measures that more fully capture patients' experiences. It is essential to embed qualitative research of patients' experiences of MT and other CAM therapies within future trials.

Supportive care for men with prostate cancer: why are the trials not working? A systematic review and recommendations for future trials.

Men with prostate cancer are likely to have a long illness and experience psychological distress for which supportive care may be helpful. This systematic review describes the evidence for effectiveness and cost-effectiveness of supportive care for men with prostate cancer, taking into account treatment pathway and components of interventions. MEDLINE, EMBASE, CINAHL, CENTRAL, and Psychinfo were searched from inception--July 2013 for randomized controlled trials and controlled trials. Two authors independently assessed risk of bias and extracted data. Twenty-six studies were included (2740 participants). Interventions were delivered pre and during (n = 12), short-term (n = 8), and longer term (18 months) (n = 5) after primary treatment. No interventions were delivered beyond this time. Few trials recruited ethnic minorities and none recruited men in same sex relationships. Intervention components included information, education, health professional discussion, homework, peer discussion, buddy support, cognitive behavioral therapy, cognitive restructuring, psychoeducation, Reiki and relaxation. Most interventions were delivered for 5-10 weeks. Risk of bias of trials was assessed as unclear for most domains due to lack of information. The majority of trials measuring quality of life and depression found no effect. Relatively few trials measured anxiety, coping skills and self-efficacy, and the majority found no effect. No cost data were available. Trials of supportive care for men with prostate cancer cover a range of interventions but are limited by population diversity, inconsistent measurement and reporting of outcomes, and inability to assess risk of bias. Recommendations on design and conduct of future trials are presented.

Pharmacist-led interventions to reduce unplanned admissions for older people: a systematic review and meta-analysis of randomised controlled trials.

PURPOSE: medication problems are thought to cause between 10 and 30% of all hospital admissions in older people. This systematic review aimed to evaluate the effectiveness of interventions led by hospital or community pharmacists in reducing unplanned hospital admissions for older people. METHODS: eighteen databases were searched with a customised search strategy. Relevant websites and reference lists of included trials were checked. Randomised controlled trials were included that evaluated pharmacist-led interventions compared with usual care, with unplanned admissions or readmissions as an outcome. Two authors independently extracted data and assessed methodological quality. RESULTS: twenty-seven randomised controlled trials (RCTs) were identified; seven trials were excluded. The 20 included trials comprised 16 for older people and 4 for older people with heart failure. Interventions led by hospital pharmacists (seven trials) or community pharmacists (nine trials) did not reduce unplanned admissions in the older population (risk ratios 0.97 95% CI: 0.88, 1.07; 1.07 95% CI: 0.96, 1.20). Three trials in older people with heart failure showed that interventions delivered by a hospital pharmacist reduced the relative risk of admissions. However, these trials were heterogeneous in intensity and duration of follow-up. One trial had a high risk of bias. CONCLUSIONS: evidence from three randomised controlled trials suggests that interventions led by hospital pharmacists reduce unplanned hospital admissions in older patients with heart failure, although these trials were heterogeneous. Data from 16 trials do not support the concept that interventions led by hospital or community pharmacists for the general older population reduces unplanned admissions.

Green tea and green tea catechin extracts: an overview of the clinical evidence.

BACKGROUND: Tea leaves contain varying amounts of polyphenols of which the majority are catechins. There has been a sizable amount of research on the potential effect of green tea catechins for cancer risk, cardiovascular disease risk and weight loss; all conditions that are relevant to mid-life health. The aim was to produce an overview of the evidence for green tea for these three important health conditions. METHODS: The databases Medline (& Medline in process) and Embase, were searched for systematic reviews and meta-analyses using customised search strategies performed up until April 2012. Assessment of Multiple Systematic Reviews criteria were used to assess the quality of the included reviews. Relevant data were extracted into predefined tables. The results are described and discussed narratively. RESULTS: We included eight systematic reviews and meta-analyses covering the topics of cancer risk (n=2), cardiovascular risk (n=4) and weight loss (n=2). CONCLUSIONS: The evidence for green tea and cancer risk is inadequate and inconclusive. However there is some positive evidence for risk reduction of breast, prostate, ovarian and endometrial cancers with green tea. RCTs of green tea and cardiovascular risk factors suggest that green tea may reduce low-density lipoproteins and total cholesterol, although studies are of short duration. There is no robust evidence to support a reduction in coronary artery disease risk in green tea drinkers. There are a considerable number of RCTs to suggest that green tea does reduce body weight in the short term, but this not likely to be of clinical relevance.

The safety of black cohosh (Actaea racemosa, Cimicifuga racemosa).

Black cohosh (Actaea racemosa/Cimicifuga racemosa) is a North American perennial plant that has been used for traditional medicinal purposes by the native Indian population. Its modern day application is the treatment of menopausal symptoms. Unlike conventional non-herbal medications, herbal preparations have not been systematically evaluated for their safety. However, the evidence from in vitro, animal and clinical studies all suggest that black cohosh is a safe herbal therapy for menopausal women if taken for a limited period. More research is needed to evaluate the safety of this herb over longer periods of time, and also to further investigate its mechanism of action.