Preventing male suicide through a psychosocial intervention that provides psychological support and tackles financial difficulties: a mixed method evaluation.

BACKGROUND: To help resolve high suicide rates in Bristol, North Somerset and South Gloucestershire, the charity Second Step was commissioned to roll-out the Hope service offering a psychosocial intervention for men, supporting them through acute distress and addressing financial difficulties. This study evaluated the impact of the Hope service on men at risk of suicide experiencing financial and other difficulties. METHODS: Mixed methods study using: (i) a prospective cohort study design to compare depression, suicidal ideation and financial self-efficacy scores of men aged 30-64, referred to the service between October 2018 and July 2020, at baseline and 6 months follow-up and between low and moderate to high-intensity service users; and (ii) a qualitative interview study to evaluate the acceptability and impact of the Hope service to Hope service users. RESULTS: There was a 49% reduction in depression score (mean reduction - 10.0, 95% CI - 11.7 to - 8.3) and in the proportion of service users with suicidal ideation (percent reduction - 52.5, 95% CI - 64.1% to - 40.9%) at 6 months follow-up compared to baseline. Financial self-efficacy scores increased by 26% (mean increase 2.9, 95% CI 1.8 to 3.9). Qualitative accounts illustrated how 'Hope saved my life' for several men interviewed; most respondents described being able to move forward and tackle challenges with more confidence following the Hope intervention. Professional advice to tackle financial and other difficulties such as housing helped to relieve anxiety and stress and enable practical issues to be resolved. CONCLUSIONS: The Hope service offered practical and emotional support to men who have experienced suicidal feelings, redundancy, homelessness and poverty and occupies an important space between mental health and social care provision. Hope demonstrates the value of an intervention which cuts across traditional boundaries between psychiatric care and social advice agencies to provide, what is, in effect, an integrated care service.

Unmet Medical Needs in Metastatic Lung and Digestive Neuroendocrine Neoplasms.

Unmet medical needs are not infrequent in oncology, and these needs are usually of higher magnitude in rare cancers. The field of neuroendocrine neoplasms (NENs) has evolved rapidly during the last decade, and, currently, a new WHO classification is being implemented and several treatment options are available in the metastatic setting after the results of prospective phase III clinical trials. However, several questions are still unanswered, and decisions in our daily clinical practice should be made with limited evidence. In the 2016 meeting of the advisory board of the European Neuroendocrine Tumor Society (ENETS), the main unmet medical needs in the metastatic NENs setting were deeply discussed, and several proposals to try to solve them are presented in this article, including biomarkers, imaging, and therapy.

Pharmacological interventions for treatment-resistant depression in adults.

BACKGROUND: Although antidepressants are often a first-line treatment for adults with moderate to severe depression, many people do not respond adequately to medication, and are said to have treatment-resistant depression (TRD). Little evidence exists to inform the most appropriate 'next step' treatment for these people. OBJECTIVES: To assess the effectiveness of standard pharmacological treatments for adults with TRD. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) (March 2016), CENTRAL, MEDLINE, Embase, PsycINFO and Web of Science (31 December 2018), the World Health Organization trials portal and ClinicalTrials.gov for unpublished and ongoing studies, and screened bibliographies of included studies and relevant systematic reviews without date or language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) with participants aged 18 to 74 years with unipolar depression (based on criteria from DSM-IV-TR or earlier versions, International Classification of Diseases (ICD)-10, Feighner criteria or Research Diagnostic Criteria) who had not responded to a minimum of four weeks of antidepressant treatment at a recommended dose. Interventions were: (1) increasing the dose of antidepressant monotherapy; (2) switching to a different antidepressant monotherapy; (3) augmenting treatment with another antidepressant; (4) augmenting treatment with a non-antidepressant. All were compared with continuing antidepressant monotherapy. We excluded studies of non-standard pharmacological treatments (e.g. sex hormones, vitamins, herbal medicines and food supplements). DATA COLLECTION AND ANALYSIS: Two reviewers used standard Cochrane methods to extract data, assess risk of bias, and resolve disagreements. We analysed continuous outcomes with mean difference (MD) or standardised mean difference (SMD) and 95% confidence interval (CI). For dichotomous outcomes, we calculated a relative risk (RR) and 95% CI. Where sufficient data existed, we conducted meta-analyses using random-effects models. MAIN RESULTS: We included 10 RCTs (2731 participants). Nine were conducted in outpatient settings and one in both in- and outpatients. Mean age of participants ranged from 42 - 50.2 years, and most were female. One study investigated switching to, or augmenting current antidepressant treatment with, another antidepressant (mianserin). Another augmented current antidepressant treatment with the antidepressant mirtazapine. Eight studies augmented current antidepressant treatment with a non-antidepressant (either an anxiolytic (buspirone) or an antipsychotic (cariprazine; olanzapine; quetiapine (3 studies); or ziprasidone (2 studies)). We judged most studies to be at a low or unclear risk of bias. Only one of the included studies was not industry-sponsored. There was no evidence of a difference in depression severity when current treatment was switched to mianserin (MD on Hamilton Rating Scale for Depression (HAM-D) = -1.8, 95% CI -5.22 to 1.62, low-quality evidence)) compared with continuing on antidepressant monotherapy. Nor was there evidence of a difference in numbers dropping out of treatment (RR 2.08, 95% CI 0.94 to 4.59, low-quality evidence; dropouts 38% in the mianserin switch group; 18% in the control). Augmenting current antidepressant treatment with mianserin was associated with an improvement in depression symptoms severity scores from baseline (MD on HAM-D -4.8, 95% CI -8.18 to -1.42; moderate-quality evidence). There was no evidence of a difference in numbers dropping out (RR 1.02, 95% CI 0.38 to 2.72; low-quality evidence; 19% dropouts in the mianserin-augmented group; 38% in the control). When current antidepressant treatment was augmented with mirtazapine, there was little difference in depressive symptoms (MD on Beck Depression Inventory (BDI-II) -1.7, 95% CI -4.03 to 0.63; high-quality evidence) and no evidence of a difference in dropout numbers (RR 0.50, 95% CI 0.15 to 1.62; dropouts 2% in mirtazapine-augmented group; 3% in the control). Augmentation with buspirone provided no evidence of a benefit in terms of a reduction in depressive symptoms (MD on Montgomery and Asberg Depression Rating Scale (MADRS) -0.30, 95% CI -9.48 to 8.88; low-quality evidence) or numbers of drop-outs (RR 0.60, 95% CI 0.23 to 1.53; low-quality evidence; dropouts 11% in buspirone-augmented group; 19% in the control). Severity of depressive symptoms reduced when current treatment was augmented with cariprazine (MD on MADRS -1.50, 95% CI -2.74 to -0.25; high-quality evidence), olanzapine (MD on HAM-D -7.9, 95% CI -16.76 to 0.96; low-quality evidence; MD on MADRS -12.4, 95% CI -22.44 to -2.36; low-quality evidence), quetiapine (SMD -0.32, 95% CI -0.46 to -0.18; I2 = 6%, high-quality evidence), or ziprasidone (MD on HAM-D -2.73, 95% CI -4.53 to -0.93; I2 = 0, moderate-quality evidence) compared with continuing on antidepressant monotherapy. However, a greater number of participants dropped out when antidepressant monotherapy was augmented with an antipsychotic (cariprazine RR 1.68, 95% CI 1.16 to 2.41; quetiapine RR 1.57, 95% CI: 1.14 to 2.17; ziprasidone RR 1.60, 95% CI 1.01 to 2.55) compared with antidepressant monotherapy, although estimates for olanzapine augmentation were imprecise (RR 0.33, 95% CI 0.04 to 2.69). Dropout rates ranged from 10% to 39% in the groups augmented with an antipsychotic, and from 12% to 23% in the comparison groups. The most common reasons for dropping out were side effects or adverse events. We also summarised data about response and remission rates (based on changes in depressive symptoms) for included studies, along with data on social adjustment and social functioning, quality of life, economic outcomes and adverse events. AUTHORS' CONCLUSIONS: A small body of evidence shows that augmenting current antidepressant therapy with mianserin or with an antipsychotic (cariprazine, olanzapine, quetiapine or ziprasidone) improves depressive symptoms over the short-term (8 to 12 weeks). However, this evidence is mostly of low or moderate quality due to imprecision of the estimates of effects. Improvements with antipsychotics need to be balanced against the increased likelihood of dropping out of treatment or experiencing an adverse event. Augmentation of current antidepressant therapy with a second antidepressant, mirtazapine, does not produce a clinically important benefit in reduction of depressive symptoms (high-quality evidence). The evidence regarding the effects of augmenting current antidepressant therapy with buspirone or switching current antidepressant treatment to mianserin is currently insufficient. Further trials are needed to increase the certainty of these findings and to examine long-term effects of treatment, as well as the effectiveness of other pharmacological treatment strategies.

Interventions to promote patient utilisation of cardiac rehabilitation.

BACKGROUND: International clinical practice guidelines routinely recommend that cardiac patients participate in rehabilitation programmes for comprehensive secondary prevention. However, data show that only a small proportion of these patients utilise rehabilitation. OBJECTIVES: First, to assess interventions provided to increase patient enrolment in, adherence to, and completion of cardiac rehabilitation. Second, to assess intervention costs and associated harms, as well as interventions intended to promote equitable CR utilisation in vulnerable patient subpopulations. SEARCH METHODS: Review authors performed a search on 10 July 2018, to identify studies published since publication of the previous systematic review. We searched the Cochrane Central Register of Controlled Trials (CENTRAL); the National Health Service (NHS) Centre for Reviews and Dissemination (CRD) databases (Health Technology Assessment (HTA) and Database of Abstracts of Reviews of Effects (DARE)), in the Cochrane Library (Wiley); MEDLINE (Ovid); Embase (Elsevier); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCOhost); and Conference Proceedings Citation Index - Science (CPCI-S) on Web of Science (Clarivate Analytics). We checked the reference lists of relevant systematic reviews for additional studies and also searched two clinical trial registers. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in adults with myocardial infarction, with angina, undergoing coronary artery bypass graft surgery or percutaneous coronary intervention, or with heart failure who were eligible for cardiac rehabilitation. Interventions had to aim to increase utilisation of comprehensive phase II cardiac rehabilitation. We included only studies that measured one or more of our primary outcomes. Secondary outcomes were harms and costs, and we focused on equity. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of all identified references for eligibility, and we obtained full papers of potentially relevant trials. Two review authors independently considered these trials for inclusion, assessed included studies for risk of bias, and extracted trial data independently. We resolved disagreements through consultation with a third review author. We performed random-effects meta-regression for each outcome and explored prespecified study characteristics. MAIN RESULTS: Overall, we included 26 studies with 5299 participants (29 comparisons). Participants were primarily male (64.2%). Ten (38.5%) studies included patients with heart failure. We assessed most studies as having low or unclear risk of bias. Sixteen studies (3164 participants) reported interventions to improve enrolment in cardiac rehabilitation, 11 studies (2319 participants) reported interventions to improve adherence to cardiac rehabilitation, and seven studies (1567 participants) reported interventions to increase programme completion. Researchers tested a variety of interventions to increase utilisation of cardiac rehabilitation. In many studies, this consisted of contacts made by a healthcare provider during or shortly after an acute care hospitalisation.Low-quality evidence shows an effect of interventions on increasing programme enrolment (19 comparisons; risk ratio (RR) 1.27, 95% confidence interval (CI) 1.13 to 1.42). Meta-regression revealed that the intervention deliverer (nurse or allied healthcare provider; P = 0.02) and the delivery format (face-to-face; P = 0.01) were influential in increasing enrolment. Low-quality evidence shows interventions to increase adherence were effective (nine comparisons; standardised mean difference (SMD) 0.38, 95% CI 0.20 to 0.55), particularly when they were delivered remotely, such as in home-based programs (SMD 0.56, 95% CI 0.37 to 0.76). Moderate-quality evidence shows interventions to increase programme completion were also effective (eight comparisons; RR 1.13, 95% CI 1.02 to 1.25), but those applied in multi-centre studies were less effective than those given in single-centre studies, leading to questions regarding generalisability. A moderate level of statistical heterogeneity across intervention studies reflects heterogeneity in intervention approaches. There was no evidence of small-study bias for enrolment (insufficient studies to test for this in the other outcomes).With regard to secondary outcomes, no studies reported on harms associated with the interventions. Only two studies reported costs. In terms of equity, trialists tested interventions designed to improve utilisation among women and older patients. Evidence is insufficient for quantitative assessment of whether women-tailored programmes were associated with increased utilisation, and studies that assess motivating women are needed. For older participants, again while quantitative assessment could not be undertaken, peer navigation may improve enrolment. AUTHORS' CONCLUSIONS: Interventions may increase cardiac rehabilitation enrolment, adherence and completion; however the quality of evidence was low to moderate due to heterogeneity of the interventions used, among other factors. Effects on enrolment were larger in studies targeting healthcare providers, training nurses, or allied healthcare providers to intervene face-to-face; effects on adherence were larger in studies that tested remote interventions. More research is needed, particularly to discover the best ways to increase programme completion.

Non-medical prescribing of systemic anticancer therapy in a multidisciplinary team oncology clinic.

The number of people diagnosed and living with cancer in the UK continues to rise, placing increasing demands on specialist cancer care services. The incidence and prevalence of neuroendocrine tumours (NETs) has increased. An NET remains a rare cancer requiring specialist care and the clinical nurse specialist (CNS) team is ideally placed to support these patients. Oncology clinics are becoming increasingly pressured and the need to think of innovative ways of reducing pressure while maintaining and enhancing the patient's experience is important. A new multidisciplinary team (MDT) systemic anti-cancer therapy (SACT) clinic for NET patients was developed that incorporated a CNS SACT non-medical prescriber (NMP) to improve patient experience and reduce the number of oncologist clinic reviews. Methods and analysis: the clinic was designed and a protocol developed to help ensure safe practice and support for the CNS NMP. The patient experience was prioritised and the medical team was involved in the design. All NMP SACT prescriptions were reviewed and questionnaires were given to patients after 3 months. A questionnaire was also given to all oncologists within the clinic and to the oncology pharmacist for analysis. Findings: 29 SACT NMP prescriptions for 15 patients were written. Patient and medical colleague feedback was positive. Discussion: this experience has helped to highlight the positive impact of innovative clinics that combine the expertise of both independent nurse practitioners and the medical team. This has paved the way for further clinics of this kind within the author's trust and the NET service.

Complementary and alternative medicine use during chemotherapy for neuroendocrine tumours.

Exploring the patient experience of complementary and alternative medicine (CAM) can provide insight into the needs, preferences and values of patients with an neuroendocrine tumour (NET). Use and interest in CAM after a NET diagnosis has not been investigated until now. The authors aimed to identify the types of CAM being used by patients undergoing chemotherapy and what types of CAM patients considered most beneficial. Patients were identified for clinical audit from one hospital's NET nurse chemotherapy database. A questionnaire was given to 79 patients who had completed intravenous chemotherapy during the previous 3 years. CAM use by NET patients was found to be popular and included practices to support both physical and emotional health. Massage and taking vitamin and mineral supplements were most widely used. The antioxidant effects of some high-dose supplements may impact on chemotherapy outcomes. Massage, despite its irregular use, was perceived by patients to be the most useful CAM.

Psychological therapies for treatment-resistant depression in adults.

BACKGROUND: Antidepressants are a first-line treatment for adults with moderate to severe major depression. However, many people prescribed antidepressants for depression don't respond fully to such medication, and little evidence is available to inform the most appropriate 'next step' treatment for such patients, who may be referred to as having treatment-resistant depression (TRD). National Institute for Health and Care Excellence (NICE) guidance suggests that the 'next step' for those who do not respond to antidepressants may include a change in the dose or type of antidepressant medication, the addition of another medication, or the start of psychotherapy. Different types of psychotherapies may be used for TRD; evidence on these treatments is available but has not been collated to date.Along with the sister review of pharmacological therapies for TRD, this review summarises available evidence for the effectiveness of psychotherapies for adults (18 to 74 years) with TRD with the goal of establishing the best 'next step' for this group. OBJECTIVES: To assess the effectiveness of psychotherapies for adults with TRD. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register (until May 2016), along with CENTRAL, MEDLINE, Embase, and PsycINFO via OVID (until 16 May 2017). We also searched the World Health Organization (WHO) trials portal (ICTRP) and ClinicalTrials.gov to identify unpublished and ongoing studies. There were no date or language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with participants aged 18 to 74 years diagnosed with unipolar depression that had not responded to minimum four weeks of antidepressant treatment at a recommended dose. We excluded studies of drug intolerance. Acceptable diagnoses of unipolar depression were based onthe Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) or earlier versions, International Classification of Diseases (ICD)-10, Feighner criteria, or Research Diagnostic Criteria. We included the following comparisons.1. Any psychological therapy versus antidepressant treatment alone, or another psychological therapy.2. Any psychological therapy given in addition to antidepressant medication versus antidepressant treatment alone, or a psychological therapy alone.Primary outcomes required were change in depressive symptoms and number of dropouts from study or treatment (as a measure of acceptability). DATA COLLECTION AND ANALYSIS: We extracted data, assessed risk of bias in duplicate, and resolved disagreements through discussion or consultation with a third person. We conducted random-effects meta-analyses when appropriate. We summarised continuous outcomes using mean differences (MDs) or standardised mean differences (SMDs), and dichotomous outcomes using risk ratios (RRs). MAIN RESULTS: We included six trials (n = 698; most participants were women approximately 40 years of age). All studies evaluated psychotherapy plus usual care (with antidepressants) versus usual care (with antidepressants). Three studies addressed the addition of cognitive-behavioural therapy (CBT) to usual care (n = 522), and one each evaluated intensive short-term dynamic psychotherapy (ISTDP) (n = 60), interpersonal therapy (IPT) (n = 34), or group dialectical behavioural therapy (DBT) (n = 19) as the intervention. Most studies were small (except one trial of CBT was large), and all studies were at high risk of detection bias for the main outcome of self-reported depressive symptoms.A random-effects meta-analysis of five trials (n = 575) showed that psychotherapy given in addition to usual care (vs usual care alone) produced improvement in self-reported depressive symptoms (MD -4.07 points, 95% confidence interval (CI) -7.07 to -1.07 on the Beck Depression Inventory (BDI) scale) over the short term (up to six months). Effects were similar when data from all six studies were combined for self-reported depressive symptoms (SMD -0.40, 95% CI -0.65 to -0.14; n = 635). The quality of this evidence was moderate. Similar moderate-quality evidence of benefit was seen on the Patient Health Questionnaire-9 Scale (PHQ-9) from two studies (MD -4.66, 95% CI 8.72 to -0.59; n = 482) and on the Hamilton Depression Rating Scale (HAMD) from four studies (MD -3.28, 95% CI -5.71 to -0.85; n = 193).High-quality evidence shows no differential dropout (a measure of acceptability) between intervention and comparator groups over the short term (RR 0.85, 95% CI 0.58 to 1.24; six studies; n = 698).Moderate-quality evidence for remission from six studies (RR 1.92, 95% CI 1.46 to 2.52; n = 635) and low-quality evidence for response from four studies (RR 1.80, 95% CI 1.2 to 2.7; n = 556) indicate that psychotherapy was beneficial as an adjunct to usual care over the short term.With the addition of CBT, low-quality evidence suggests lower depression scores on the BDI scale over the medium term (12 months) (RR -3.40, 95% CI -7.21 to 0.40; two studies; n = 475) and over the long term (46 months) (RR -1.90, 95% CI -3.22 to -0.58; one study; n = 248). Moderate-quality evidence for adjunctive CBT suggests no difference in acceptability (dropout) over the medium term (RR 0.98, 95% CI 0.66 to 1.47; two studies; n = 549) and lower dropout over long term (RR 0.80, 95% CI 0.66 to 0.97; one study; n = 248).Two studies reported serious adverse events (one suicide, two hospitalisations, and two exacerbations of depression) in 4.2% of the total sample, which occurred only in the usual care group (no events in the intervention group).An economic analysis (conducted as part of an included study) from the UK healthcare perspective (National Health Service (NHS)) revealed that adjunctive CBT was cost-effective over nearly four years. AUTHORS' CONCLUSIONS: Moderate-quality evidence shows that psychotherapy added to usual care (with antidepressants) is beneficial for depressive symptoms and for response and remission rates over the short term for patients with TRD. Medium- and long-term effects seem similarly beneficial, although most evidence was derived from a single large trial. Psychotherapy added to usual care seems as acceptable as usual care alone.Further evidence is needed on the effectiveness of different types of psychotherapies for patients with TRD. No evidence currently shows whether switching to a psychotherapy is more beneficial for this patient group than continuing an antidepressant medication regimen. Addressing this evidence gap is an important goal for researchers.

Prevalence of self-reported side effects in neuroendocrine tumour patients prescribed somatostatin analogues.

Somatostatin analogues (SSA) are a common treatment for some forms of neuroendocrine tumours (NETs). Patients report a variety of side effects after starting these drugs, so in most cases they require a lot of nutritional input. The authors used an online survey to invite responses from patients worldwide to determine the extent of reported side effects. Patients were asked which SSA they were taking and how they rated the severity of their side effects. They were provided with a list of 11 options to choose from, but not given any guidance or a definition of terms. The most commonly reported side effect was constipation (85%), with 8.6% of these respondents rating its severity as 10/10. The survey found that many self-reported side effects from the use of SSAs were experienced more frequently than previous clinical studies or the patient information leaflets reported. As this was an online survey, so the findings are limited in that first, this was a self-selected sample of patients and second, patients were able to respond more than once.

Psychological interventions for coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) is the most common cause of death globally, although mortality rates are falling. Psychological symptoms are prevalent for people with CHD, and many psychological treatments are offered following cardiac events or procedures with the aim of improving health and outcomes. This is an update of a Cochrane systematic review previously published in 2011. OBJECTIVES: To assess the effectiveness of psychological interventions (alone or with cardiac rehabilitation) compared with usual care (including cardiac rehabilitation where available) for people with CHD on total mortality and cardiac mortality; cardiac morbidity; and participant-reported psychological outcomes of levels of depression, anxiety, and stress; and to explore potential study-level predictors of the effectiveness of psychological interventions in this population. SEARCH METHODS: We updated the previous Cochrane Review searches by searching the following databases on 27 April 2016: CENTRAL in the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid), and CINAHL (EBSCO). SELECTION CRITERIA: We included randomised controlled trials (RCTs) of psychological interventions compared to usual care, administered by trained staff, and delivered to adults with a specific diagnosis of CHD. We selected only studies estimating the independent effect of the psychological component, and with a minimum follow-up of six months. The study population comprised of adults after: a myocardial infarction (MI), a revascularisation procedure (coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI)), and adults with angina or angiographically defined coronary artery disease (CAD). RCTs had to report at least one of the following outcomes: mortality (total- or cardiac-related); cardiac morbidity (MI, revascularisation procedures); or participant-reported levels of depression, anxiety, or stress. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts of all references for eligibility. A lead review author extracted study data, which a second review author checked. We contacted study authors to obtain missing information. MAIN RESULTS: This review included 35 studies which randomised 10,703 people with CHD (14 trials and 2577 participants added to this update). The population included mainly men (median 77.0%) and people post-MI (mean 65.7%) or after undergoing a revascularisation procedure (mean 27.4%). The mean age of participants within trials ranged from 53 to 67 years. Overall trial reporting was poor, with around a half omitting descriptions of randomisation sequence generation, allocation concealment procedures, or the blinding of outcome assessments. The length of follow-up ranged from six months to 10.7 years (median 12 months). Most studies (23/35) evaluated multifactorial interventions, which included therapies with multiple therapeutic components. Ten studies examined psychological interventions targeted at people with a confirmed psychopathology at baseline and two trials recruited people with a psychopathology or another selecting criterion (or both). Of the remaining 23 trials, nine studies recruited unselected participants from cardiac populations reporting some level of psychopathology (3.8% to 53% with depressive symptoms, 32% to 53% with anxiety), 10 studies did not report these characteristics, and only three studies excluded people with psychopathology.Moderate quality evidence showed no risk reduction for total mortality (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.77 to 1.05; participants = 7776; studies = 23) or revascularisation procedures (RR 0.94, 95% CI 0.81 to 1.11) with psychological therapies compared to usual care. Low quality evidence found no risk reduction for non-fatal MI (RR 0.82, 95% CI 0.64 to 1.05), although there was a 21% reduction in cardiac mortality (RR 0.79, 95% CI 0.63 to 0.98). There was also low or very low quality evidence that psychological interventions improved participant-reported levels of depressive symptoms (standardised mean difference (SMD) -0.27, 95% CI -0.39 to -0.15; GRADE = low), anxiety (SMD -0.24, 95% CI -0.38 to -0.09; GRADE = low), and stress (SMD -0.56, 95% CI -0.88 to -0.24; GRADE = very low).There was substantial statistical heterogeneity for all psychological outcomes but not clinical outcomes, and there was evidence of small-study bias for one clinical outcome (cardiac mortality: Egger test P = 0.04) and one psychological outcome (anxiety: Egger test P = 0.012). Meta-regression exploring a limited number of intervention characteristics found no significant predictors of intervention effects for total mortality and cardiac mortality. For depression, psychological interventions combined with adjunct pharmacology (where deemed appropriate) for an underlying psychological disorder appeared to be more effective than interventions that did not (ß = -0.51, P = 0.003). For anxiety, interventions recruiting participants with an underlying psychological disorder appeared more effective than those delivered to unselected populations (ß = -0.28, P = 0.03). AUTHORS' CONCLUSIONS: This updated Cochrane Review found that for people with CHD, there was no evidence that psychological treatments had an effect on total mortality, the risk of revascularisation procedures, or on the rate of non-fatal MI, although the rate of cardiac mortality was reduced and psychological symptoms (depression, anxiety, or stress) were alleviated; however, the GRADE assessments suggest considerable uncertainty surrounding these effects. Considerable uncertainty also remains regarding the people who would benefit most from treatment (i.e. people with or without psychological disorders at baseline) and the specific components of successful interventions. Future large-scale trials testing the effectiveness of psychological therapies are required due to the uncertainty within the evidence. Future trials would benefit from testing the impact of specific (rather than multifactorial) psychological interventions for participants with CHD, and testing the targeting of interventions on different populations (i.e. people with CHD, with or without psychopathologies).

Symptomatic and quality-of-life outcomes after treatment for clinically localised prostate cancer: a systematic review.

To conduct a systematic review of the risks of short-term outcomes after major treatments for clinically localised prostate cancer. MEDLINE, EMBASE and the Cochrane Library were searched from 2004 to January 2013. Study arms that included ≥100 men with localised prostate cancer in receipt of surgery, radiotherapy or active surveillance and reported symptomatic and quality-of-life (QoL) data from 6 to 60 months after treatment were eligible. Data were extracted by one reviewer and checked by another. In all, 64 studies (80 treatment cohorts) were included. Most were single treatment cohorts from the USA or Europe. Radiotherapy was the most common treatment (40 cohorts, including 31 brachytherapy cohorts) followed by prostatectomy (39 cohorts), with only one active surveillance cohort. Most frequently measured symptoms were urinary, followed by sexual, and bowel; QoL was assessed in only 17 cohorts. Most studies used validated measures, although poor data reporting and differences between studies meant that it was not possible to pool data. Data on the precise impact of short-term symptomatic and QoL outcomes after treatment for localised prostate cancer are of insufficient quality for clear guidance to men about the risks to these aspects of their lives. It is important that future studies focus on collecting core outcomes through validated measures and comply with reporting guidelines, so that clear and accurate information can be derived for men considering screening or treatment for prostate cancer.

Interventions to improve adherence to lipid-lowering medication.

BACKGROUND: Lipid-lowering drugs are widely underused, despite strong evidence indicating they improve cardiovascular end points. Poor patient adherence to a medication regimen can affect the success of lipid-lowering treatment. OBJECTIVES: To assess the effects of interventions aimed at improving adherence to lipid-lowering drugs, focusing on measures of adherence and clinical outcomes. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and CINAHL up to 3 February 2016, and clinical trials registers (ANZCTR and ClinicalTrials.gov) up to 27 July 2016. We applied no language restrictions. SELECTION CRITERIA: We evaluated randomised controlled trials of adherence-enhancing interventions for lipid-lowering medication in adults in an ambulatory setting with a variety of measurable outcomes, such as adherence to treatment and changes to serum lipid levels. Two teams of review authors independently selected the studies. DATA COLLECTION AND ANALYSIS: Three review authors extracted and assessed data, following criteria outlined by the Cochrane Handbook for Systematic Reviews of Interventions. We assessed the quality of the evidence using GRADEPro. MAIN RESULTS: For this updated review, we added 24 new studies meeting the eligibility criteria to the 11 studies from prior updates. We have therefore included 35 studies, randomising 925,171 participants. Seven studies including 11,204 individuals compared adherence rates of those in an intensification of a patient care intervention (e.g. electronic reminders, pharmacist-led interventions, healthcare professional education of patients) versus usual care over the short term (six months or less), and were pooled in a meta-analysis. Participants in the intervention group had better adherence than those receiving usual care (odds ratio (OR) 1.93, 95% confidence interval (CI) 1.29 to 2.88; 7 studies; 11,204 participants; moderate-quality evidence). A separate analysis also showed improvements in long-term adherence rates (more than six months) using intensification of care (OR 2.87, 95% CI 1.91 to 4.29; 3 studies; 663 participants; high-quality evidence). Analyses of the effect on total cholesterol and LDL-cholesterol levels also showed a positive effect of intensified interventions over both short- and long-term follow-up. Over the short term, total cholesterol decreased by a mean of 17.15 mg/dL (95% CI 1.17 to 33.14; 4 studies; 430 participants; low-quality evidence) and LDL-cholesterol decreased by a mean of 19.51 mg/dL (95% CI 8.51 to 30.51; 3 studies; 333 participants; moderate-quality evidence). Over the long term (more than six months) total cholesterol decreased by a mean of 17.57 mg/dL (95% CI 14.95 to 20.19; 2 studies; 127 participants; high-quality evidence). Included studies did not report usable data for health outcome indications, adverse effects or costs/resource use, so we could not pool these outcomes. We assessed each included study for bias using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. In general, the risk of bias assessment revealed a low risk of selection bias, attrition bias, and reporting bias. There was unclear risk of bias relating to blinding for most studies. AUTHORS' CONCLUSIONS: The evidence in our review demonstrates that intensification of patient care interventions improves short- and long-term medication adherence, as well as total cholesterol and LDL-cholesterol levels. Healthcare systems which can implement team-based intensification of patient care interventions may be successful in improving patient adherence rates to lipid-lowering medicines.

Promoting patient uptake and adherence in cardiac rehabilitation.

BACKGROUND: Cardiac rehabilitation is an important component of recovery from coronary events but uptake and adherence to such programs are below recommended levels. In 2010, our Cochrane review identified some evidence that interventions to increase uptake of cardiac rehabilitation can be effective but there was insufficient evidence to provide recommendations on intervention to increase adherence. In this review, we update the previously published Cochrane review. OBJECTIVES: To determine the effects, both harms and benefits, of interventions to increase patient uptake of, or adherence to, cardiac rehabilitation. SEARCH METHODS: We performed an updated search in January 2013 to identify studies published after publication of the previous systematic review. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 12, 2012), MEDLINE (Ovid), EMBASE (Ovid), CINAHL EBSCO, Conference Proceedings Citation Index - Science (CPCI-S) on Web of Science (Thomson Reuters), and National Health Service (NHS) Centre for Reviews and Dissemination (CRD) databases (Health Technology Assessment (HTA) and Database of Abstracts of Reviews of Effects (DARE)) on The Cochrane Library (Issue 4, 2012). We also checked reference lists of identified systematic reviews and randomised controlled trials (RCTs) for additional studies. We applied no language restrictions. SELECTION CRITERIA: Adults with myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, heart failure, angina, or coronary heart disease eligible for cardiac rehabilitation and RCTs or quasi-randomized trials of interventions to increase uptake or adherence to cardiac rehabilitation or any of its component parts. We only included studies reporting a primary outcome. DATA COLLECTION AND ANALYSIS: At least three authors independently screened titles and abstracts of all identified references for eligibility and obtained full papers of potentially relevant trials. At least two authors checked the selection. Three authors assessed included studies for risk of bias. MAIN RESULTS: The updated search identified seven new studies (880 participants) of interventions to improve uptake of cardiac rehabilitation and one new study (260 participants) of interventions to increase adherence. When added to the previous version of this review, we included 18 studies (2505 participants), 10 studies (1338 participants) of interventions to improve uptake of cardiac rehabilitation and eight studies (1167 participants) of interventions to increase adherence. We assessed the majority of studies as having high or unclear risk of bias. Meta-analysis was not possible due to multiple sources of heterogeneity. Eight of 10 studies demonstrated increased uptake of cardiac rehabilitation. Successful interventions to improve uptake of cardiac rehabilitation included: structured nurse- or therapist-led contacts, early appointments after discharge, motivational letters, gender-specific programs, and intermediate phase programs for older patients. Three of eight studies demonstrated improvement in adherence to cardiac rehabilitation. Successful interventions included: self monitoring of activity, action planning, and tailored counselling by cardiac rehabilitation staff. Data were limited on mortality and morbidity but did not demonstrate a difference in cardiovascular events or mortality except for one study that noted an increased rate of revascularization in the intervention group. None of the studies found a difference in health-related quality of life and there was no evidence of adverse events. No studies reported on costs or healthcare utilization. AUTHORS' CONCLUSIONS: We found only weak evidence to suggest that interventions to increase the uptake of cardiac rehabilitation are effective. Practice recommendations for increasing adherence to cardiac rehabilitation cannot be made. Interventions targeting patient-identified barriers may increase the likelihood of success. Further high-quality research is still needed. 

Efficacy of PD-1/PD-L1 immunotherapy on brain metastatic non-small-cell lung cancer and treatment-related adverse events: A systematic review.

BACKGROUND: Recent evidence suggests that PD-1/PD-L1 immunotherapy improves outcomes in patients with brain metastatic non-small cell lung cancer. METHODS: Records were searched electronically on MEDLINE, Embase and BIOSIS. Hazard ratios and their 95% confidence intervals for overall survival and progression free survival, and treatment-related adverse events data were extracted. Risk of bias was assessed in included studies using the Cochrane Collaboration's revised tool to assess risk of bias in randomized trials. RESULTS: PD-1/PD-L1 immunotherapy increased overall survival by 33% and progression free survival by 47% compared with chemotherapy. Two studies had a high risk of bias. Treatment-related adverse events were reported in 95%, 89% and 65% of patients receiving chemoimmunotherapy,chemotherapy and single agent immunotherapy, respectively. CONCLUSION: PD-1/PD-L1 inhibitors alone or in addition to chemotherapy increase overall and progression free survival when compared with chemotherapy alone. Chemoimmunotherapy and chemotherapy patients experienced the most treatment-related adverse events.

Behavioural therapies versus other psychological therapies for depression.

BACKGROUND: Behavioural therapies represent one of several categories of psychological therapies that are currently used in the treatment of depression. However, the effectiveness and acceptability of behavioural therapies for depression compared with other psychological therapies remain unclear. OBJECTIVES: 1. To examine the effects of all BT approaches compared with all other psychological therapy approaches for acute depression.2. To examine the effects of different BT approaches (behavioural therapy, behavioural activation, social skills training and relaxation training) compared with all other psychological therapy approaches for acute depression.3. To examine the effects of all BT approaches compared with different psychological therapy approaches (CBT, third wave CBT, psychodynamic, humanistic and integrative psychological therapies) for acute depression. SEARCH METHODS: We searched the Cochrane Depression Anxiety and Neurosis Group Trials Specialised Register (CCDANCTR, 31/07/2013), which includes relevant randomised controlled trials from The Cochrane Library (all years), EMBASE, (1974-), MEDLINE (1950-) and PsycINFO (1967-). We also searched CINAHL (May 2010) and PSYNDEX (June 2010) and reference lists of the included studies and relevant reviews for additional published and unpublished studies. SELECTION CRITERIA: Randomised controlled trials that compared behavioural therapies with other psychological therapies for acute depression in adults. DATA COLLECTION AND ANALYSIS: Two or more review authors independently identified studies, assessed trial quality and extracted data. We contacted study authors for additional information. MAIN RESULTS: Twenty-five trials involving 955 participants compared behavioural therapies with one or more of five other major categories of psychological therapies (cognitive-behavioural, third wave cognitive-behavioural, psychodynamic, humanistic and integrative therapies). Most studies had a small sample size and were assessed as being at unclear or high risk of bias. Compared with all other psychological therapies together, behavioural therapies showed no significant difference in response rate (18 studies, 690 participants, risk ratio (RR) 0.97, 95% confidence interval (CI) 0.86 to 1.09) or in acceptability (15 studies, 495 participants, RR of total dropout rate 1.02, 95% CI 0.65 to 1.61). Similarly, in comparison with each of the other classes of psychological therapies, low-quality evidence showed better response to cognitive-behavioural therapies than to behavioural therapies (15 studies, 544 participants, RR 0.93, 95% CI 0.83 to 1.05) and low-quality evidence of better response to behavioural therapies over psychodynamic therapies (2 studies, 110 participants, RR 1.24, 95% CI 0.84 to 1.82).When compared with integrative therapies and humanistic therapies, only one study was included in each comparison, and the analysis showed no significant difference between behavioural therapies and integrative or humanistic therapies. AUTHORS' CONCLUSIONS: We found low- to moderate-quality evidence that behavioural therapies and other psychological therapies are equally effective. The current evidence base that evaluates the relative benefits and harms of behavioural therapies is very weak. This limits our confidence in both the size of the effect and its precision for our key outcomes related to response and withdrawal. Studies recruiting larger samples with improved reporting of design and fidelity to treatment would improve the quality of evidence in this review.

'Third wave' cognitive and behavioural therapies versus treatment as usual for depression.

BACKGROUND: So-called 'third wave' cognitive and behavioural therapies represent a new generation of psychological therapies that are increasingly being used in the treatment of psychological problems. However, the effectiveness and acceptability of third-wave cognitive and behavioural therapy (CBT) approaches as treatment for acute depression remain unclear. OBJECTIVES: 1. To examine the effects of all third wave CBT approaches compared with treatment as usual/waiting list/attention placebo/psychological placebo control conditions for acute depression.2. To examine the effects of different third wave CBT approaches (ACT, compassionate mind training, functional analytic psychotherapy, dialectical behaviour therapy, MBCT, extended behavioural activation and metacognitive therapy) compared with treatment as usual/waiting list/attention placebo/psychological placebo control conditions for acute depression.3. To examine the effects of all third wave CBT approaches compared with different types of comparators (treatment as usual, no treatment, waiting list, attention placebo, psychological placebo) for acute depression. SEARCH METHODS: We searched the Cochrane Depression Anxiety and Neurosis Group Trials Specialised Register (CCDANCTR to 01/01/12), which includes relevant randomised controlled trials from The Cochrane Library (all years), EMBASE, (1974-), MEDLINE (1950-) and PsycINFO (1967-). We also searched CINAHL (May 2010) and PSYNDEX (June 2010) and reference lists of the included studies and relevant reviews for additional published and unpublished studies. An updated search of CCDANCTR restricted to search terms relevant to third wave CBT therapies was conducted in March 2013 (CCDANCTR to 01/02/13). SELECTION CRITERIA: Randomised controlled trials that compared third wave CBT therapies with control conditions for acute depression in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently identified studies, assessed trial quality and extracted data. Study authors were contacted for additional information when required. We rated the quality of evidence using GRADE methods. MAIN RESULTS: Four small studies (224 participants) were included in the review. Little information was provided about the process of allocating participants to groups. None of the studies used independent outcome assessors, and evidence suggested researcher allegiance towards the active treatments. The four studies examined a diversity of third wave CBT approaches (extended behavioural activation, acceptance and commitment therapy and competitive memory training) and control conditions. None of the studies conducted follow-up assessments. The results showed a significant difference in clinical response rates in favour of third wave CBT when compared with treatment as usual (TAU) conditions (three studies, 170 participants, risk ratio (RR) 0.51, 95% confidence interval (CI) 0.27 to 0.95; very low quality). No significant difference in treatment acceptability based on dropout rates was found between third wave CBT approaches and TAU (four studies, 224 participants, RR 1.01, 95% CI 0.08 to 12.30; very low quality). Both analyses showed substantial statistical heterogeneity. AUTHORS' CONCLUSIONS: Very low quality evidence suggests that third wave CBT approaches appear to be more effective than treatment as usual in the treatment of acute depression. The very small number of available studies and the diverse types of interventions and control comparators, together with methodological limitations, limit the ability to draw any conclusions on their effect in the short term or over a longer term. The increasing popularity of third wave CBT approaches in clinical practice underscores the importance of completing further studies of third wave CBT approaches in the treatment of acute depression, on a short- and long-term basis, to provide evidence of their effectiveness to policy-makers, clinicians and users of services.

'Third wave' cognitive and behavioural therapies versus other psychological therapies for depression.

BACKGROUND: So-called 'third wave' cognitive and behavioural therapies represents a new generation of psychological therapies that are increasingly being used in the treatment of psychological problems. However, the effectiveness and acceptability of third wave cognitive and behavioural therapy (CBT) approaches as a treatment for depression compared with other psychological therapies remain unclear. OBJECTIVES: 1. To examine the effects of all third wave CBT approaches compared with all other psychological therapy approaches for acute depression.2. To examine the effects of different third wave CBT approaches (ACT, compassionate mind training, functional analytic psychotherapy, extended behavioural activation and metacognitive therapy) compared with all other psychological therapy approaches for acute depression.3. To examine the effects of all third wave CBT approaches compared with different psychological therapy approaches (psychodynamic, behavioural, humanistic, integrative, cognitive-behavioural) for acute depression. SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Group Specialised Register (CCDANCTR to 01/01/12), which includes relevant randomised controlled trials from The Cochrane Library (all years), EMBASE (1974-), MEDLINE (1950-) and PsycINFO (1967-). We also searched CINAHL (May 2010) and PSYNDEX (June 2010) and reference lists of the included studies and relevant reviews for additional published and unpublished studies. An updated search of CCDANCTR restricted to search terms relevant to third wave CBT was conducted in March 2013 (CCDANCTR to 01/02/13). SELECTION CRITERIA: Randomised controlled trials that compared various third wave CBT with other psychological therapies for acute depression in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently identified studies, assessed trial quality and extracted data. Study authors were contacted for additional information where required. We rated the quality of evidence using GRADE methods. MAIN RESULTS: A total of three studies involving 144 eligible participants were included in the review. Two of the studies (56 participants) compared an early version of acceptance and commitment therapy (ACT) with CBT, and one study (88 eligible participants) compared extended behavioural activation with CBT. No other studies of third wave CBT were identified. The two ACT studies were assessed as being at high risk of performance bias and researcher allegiance. Post-treatment results, which were based on dropout rates, showed no evidence of any difference between third wave CBT and other psychological therapies for the primary outcomes of efficacy (risk ratio (RR) of clinical response 1.14, 95% confidence interval (CI) 0.79 to 1.64; very low quality) and acceptability. Results at two-month follow-up showed no evidence of any difference between third wave CBT and other psychological therapies for clinical response (2 studies, 56 participants, RR 0.22, 95% CI 0.04 to 1.15). Moderate statistical heterogeneity was indicated in the acceptability analyses (I(2) = 41%). AUTHORS' CONCLUSIONS: Very low quality evidence suggests that third wave CBT and CBT approaches are equally effective and acceptable in the treatment of acute depression. Evidence is limited in quantity, quality and breadth of available studies, precluding us from drawing any conclusions as to their short- or longer-term equivalence. The increasing popularity of third wave CBT approaches in clinical practice underscores the importance of completing further studies to compare various third wave CBT approaches with other psychological therapy approaches to inform clinicians and policymakers on the most effective forms of psychological therapy in treating depression.

Research priority setting in plastic and reconstructive surgery: A systematic review.

BACKGROUND: The health research agenda has historically been led by researchers; however, their priorities may not necessarily align with those of patients, caregivers and clinicians. Research priority setting initiatives identify and prioritise topics which lack evidence. This is particularly important in plastic surgery, a speciality lacking high-quality evidence to definitively answer many common clinical questions. Research priorities direct research activity and funding, so their selection process must be representative and transparent. This review appraised all priority setting initiatives in plastic surgery using the reporting guideline for priority setting of health research (REPRISE). METHODS: OVID Medline, EMBASE, CINAHL and the James Lind Alliance (JLA) repository were searched (inception - 11/06/21) using search terms for 'research priority setting' and 'plastic and reconstructive surgery'. Dual-author screening and data extraction were conducted, according to PRISMA. RESULTS: Of 3899 de-duplicated citations, 17 were included. Most studies were conducted in national (14/17), high-income (16/17) settings. More priority setting initiatives focussed on burns (6/17) and hand surgery (4/17) than other subspecialties. The JLA (5/17) and qualitative (5/17) approaches were most used for prioritisation, followed by Delphi techniques (3/17), other surveys (3/17) and mixed methods (1/17). A minority included patient (8/17) or multi-disciplinary (8/17) stakeholders. Few reported strategies for implementing research priorities (6/17) or measuring their impact (2/17). CONCLUSIONS: Stakeholders from lower-income countries are underrepresented in priority setting initiatives for plastic surgery, despite the global burden of disease. Future studies should recruit more patient and multidisciplinary stakeholders, to achieve meaningful consensus. Clear implementation strategies are needed to maximise impact.

Exploring what is important during burn recovery: a qualitative study investigating priorities of patients and healthcare professionals over time.

OBJECTIVES: This qualitative study aimed to investigate: (1) priorities of patients and healthcare professionals during recovery from a burn injury, (2) how priorities change over time and (3) how priorities map to outcomes currently reported in burns research. DESIGN: Semi-structured interviews were conducted. Interviews were audio recorded, transcribed and analysed thematically. SETTING, PARTICIPANTS: A total of 53 patients and healthcare professionals were recruited from four National Health Service (NHS) burn services across England and Wales across England and Wales. Patient participants (n=32) included adults, adolescents and parents of paediatric patients, with a variety of burn injuries in terms of severity and cause of burn injury. Healthcare professionals (n=21) were NHS staff members involved in burn care and included professionals with a range of clinical experience and roles (eg, nurses, surgeons, occupational therapists, physiotherapist, administration). RESULTS: Ten themes relating to priorities (outcomes) during recovery from a burn injury were identified for patients and professionals. Of those, six were identified for patients and professionals ('pain and discomfort', 'psychological well-being', 'healing', 'scarring', 'function', 'infection'), three were unique to professionals ('patient knowledge, understanding and support', 'sense of control', 'survival') and one was unique to patients ('uncertainty'). Results highlighted that importance of these priorities changes over time (eg, 'survival' was only a concern in the short term). Likewise, priorities differed between patients and professionals (eg, 'pain' was important to patients throughout their recovery, but not for professionals). Seven out of 10 themes overlapped with outcomes commonly assessed in burn research. CONCLUSION: Professionals' and patients' priorities (important outcomes) change over time after burn injury and differ between those groups. Burn care research should consider measuring outcomes at different time points during the recovery from a burn injury to accurately reflect complexity of burn recovery.

Pre-diagnostic blood biomarkers for adult glioma.

Glioma is one of the most common malignant primary brain tumours in adults, of which, glioblastoma is the most prevalent and malignant entity. Glioma is often diagnosed at a later stage of disease progression, which means it is associated with significant mortality and morbidity. Therefore, there is a need for earlier diagnosis of these tumours, which would require sensitive and specific biomarkers. These biomarkers could better predict glioma onset to improve diagnosis and therapeutic options for patients. While liquid biopsies could provide a cheap and non-invasive test to improve the earlier detection of glioma, there is little known on pre-diagnostic biomarkers which predate disease detection. In this review, we examine the evidence in the literature for pre-diagnostic biomarkers in glioma, including metabolomics and proteomics. We also consider the limitations of these approaches and future research directions of pre-diagnostic biomarkers for glioma.

Genomic landscape and actionable mutations of brain metastases derived from non-small cell lung cancer: A systematic review.

Background: Brain metastases derived from non-small cell lung cancer (NSCLC) represent a significant clinical problem. We aim to characterize the genomic landscape of brain metastases derived from NSCLC and assess clinical actionability. Methods: We searched Embase, MEDLINE, Web of Science, and BIOSIS from inception to 18/19 May 2022. We extracted information on patient demographics, smoking status, genomic data, matched primary NSCLC, and programmed cell death ligand 1 expression. Results: We found 72 included papers and data on 2346 patients. The most frequently mutated genes from our data were EGFR (n = 559), TP53 (n = 331), KRAS (n = 328), CDKN2A (n = 97), and STK11 (n = 72). Common missense mutations included EGFR L858R (n = 80) and KRAS G12C (n = 17). Brain metastases of ever versus never smokers had differing missense mutations in TP53 and EGFR, except for L858R and T790M in EGFR, which were seen in both subgroups. Of the top 10 frequently mutated genes that had primary NSCLC data, we found 37% of the specific mutations assessed to be discordant between the primary NSCLC and brain metastases. Conclusions: To our knowledge, this is the first systematic review to describe the genomic landscape of brain metastases derived from NSCLC. These results provide a comprehensive outline of frequently mutated genes and missense mutations that could be clinically actionable. These data also provide evidence of differing genomic landscapes between ever versus never smokers and primary NSCLC compared to the BM. This information could have important consequences for the selection and development of targeted drugs for these patients.