East Coast Community Healthcare CIC

Neuroendocrine tumours (NETs) are relatively rare neoplasms but represent one of the most frequent types of primary small-bowel tumours. Their incidence is rising, and this is most likely because of their more frequent early-stage detection, physician awareness, and increasing availability and use of imaging and small-bowel endoscopic techniques, such as video capsule endoscopy and device-assisted enteroscopy, which enable the detection, localisation, and histological sampling of previously inaccessible and underdiagnosed small-bowel lesions. This review summarises the role of small-bowel endoscopy in the diagnosis and management of small-bowel NETs to assist clinicians in their practice. Small-bowel endoscopy may play a complementary role in the diagnosis of these tumours alongside other diagnostic tests, such as biomarkers, conventional radiology, and functional imaging. In addition, small-bowel enteroscopy may play a role in the preoperative setting for the identification and marking of these tumours for surgical resection and the management of rare complications, such as small-bowel variceal bleeding, in cases of portal hypertension due to the encasement of mesenteric vessels in fibrotic small-bowel NETs.

Aim(s) This study reports on the implementation of a registered advanced nurse practitioner intervention. Aims include improving access, service user outcomes and integration between primary and secondary care. Design This paper reports the quantitative results of a mixed methods implementation study. Qualitative data are reported separately. The PARiHS framework informs the implementation process itself, with considerations for nurses and other healthcare professionals explored. Methods The CORE‐OM 34 item rating scale was administered both pre‐ and post‐intervention. Service user attendances in secondary care was monitored. Results Findings suggest that the intervention was associated with clinically significant improvements in global or generic distress, reported by service users, as evidenced by changes in the CORE‐OM scores. Access to care was recorded at an average of 3.6 days. Implementation science supported effective and safe implementation with clear governance structures. Conclusion Registered advanced nurse practice in mental health clinics which provide full episodes of care results in improved integration and may be associated with positive patient outcomes. Implementation science is taught on Irish nursing programmes and this is important if innovative services are to be embedded in the healthcare system. Impact The development of a model of care for mental health Registered Advanced Nurse Practitioners at the interface of primary and secondary care settings may be merited. Positive Advanced Recovery Connections may be associated with improving mental health outcomes and bolstering integration of primary and secondary care services. The utilisation of implementation science highlights the need for collaboration with all stakeholders to overcome barriers and recognise facilitators to attain the necessary model of integrated care. Patient and Public Contribution Peer recovery input was provided by members of the service Recovery College, with participation evident in all stages of the project. The psychosocial assessment template was also co‐designed.

Background: Biliary tract cancers (BTCs) are aggressive in nature, often presenting asymptomatically until they are diagnosed at an advanced stage. Surgical resection or liver transplantation are potential curative options. However, a large proportion of patients present with incurable locally advanced or metastatic disease and most of these patients are only eligible for palliative chemotherapy or best supportive care. More recently, targeted therapies have proven beneficial in a molecularly selected subgroup of patients with cholangiocarcinoma who have progressed on previous lines of systemic treatment. However, only a minority of patients with BTCs whose tumours harbour specific molecular alterations can access these therapies. Methods: In relation to ADCs, studies regarding use of antibody-drug conjugates in cancer, particularly in BTCs, were searched in Embase (1974 to 2024) and Ovid MEDLINE(R) (1946 to 2024) to obtain relevant articles. Examples of current clinical trials utilising ADC treatment in BTCs were extracted from the ClinicalTrials.gov trial registry. Conclusions: Overall, this review has highlighted that ADCs have shown encouraging outcomes in cancer therapy, and this should lead to further research including in BTCs, where treatment options are often limited. The promising results observed with ADCs in various cancers underscore their potential as a transformative approach in oncology, warranting continued exploration and development and the need for education on the management of their specific toxicities. By addressing current challenges and optimising ADC design and application, future studies could potentially improve treatment outcomes for patients with BTCs and beyond, potentially in both early and advanced stage settings.

Simple Summary Healthcare professionals recognise the importance of fertility preservation and their responsibility to initiate discussions. However, despite advanced training within respective fields, discrepancies in knowledge remain regarding techniques of fertility preservation, referral pathways and existing educational resources available to patients, preventing efficient implementation of services. Further education and training regarding the methods of fertility preservation and how to refer patients to specialist services are required. Many of the personal barriers faced by healthcare professionals could be overcome through regular teaching on communication skills used for breaking bad news. Abstract (1) Background: This study aims to establish the knowledge, attitudes and current behaviours towards female fertility preservation (FP) services amongst healthcare professionals (HCPs) in the UK. (2) Methods: An online survey was advertised publicly on the social media platform Instagram between 25 February 2021 and 11 March 2021. (3) Results: In total, 415 participants fulfilled the inclusion criteria and completed the survey. The majority of HCPs discussed FP techniques either never 39.5% (n = 164), once a year 20.7% (n = 86) or once a month 17.8% (n = 74). The majority rated their knowledge of each type of FP method as ‘very poor’ or ‘poor’ and strongly disagreed 14.2% (n = 59) or disagreed 42.2% (n = 175) with the statement they ‘felt confident to counsel a patient on FP’. The majority either agreed 37.8% (n = 157) or strongly agreed 22.2% (n = 92) that it was their responsibility to discuss FP and 38.1% (n = 158) agreed or strongly agreed 19.5% (n = 81) they considered the desire for future fertility when planning treatment. The majority 87.2% (n = 362) had not experienced formal training on FP. (4) Conclusions: Discrepancies in knowledge remain regarding techniques of FP, referral pathways, awareness of facilities offering services and existing educational resources. Many HCPs recognise the importance of FP and their responsibility to initiate discussions. The knowledge that FP may not delay the treatment of cancer has also improved; however, training in FP is scarce.

Current biomarkers do not adequately predict the behaviour of neuroendocrine neoplasms (NENs). This study assessed the NETest, a multianalyte blood biomarker, in patients with small intestinal NENs (Si-NENs). We studied two patient groups: Group 1: metastatic Si-NENs (n = 102) and Group 2: post-operatively disease-free according to 68Ga-DOTATATE PET (n = 16). NETest scores were ≤20% (normal), 21–40% (low), 41–79% (intermediate), or ≥80% (high). Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan–Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. In Group 1, the median NETest score was 40% (IQR: 33.3–46.7%). The NETest value (HR: 1.032, 95% CI: 1.003–1.062, p = 0.033) and high-risk NETest category (HR: 10.5, 95% CI: 1.35–81.7, p = 0.025) were independent predictors of PFS, along with presence of lung metastases, CgA levels > 10 × ULN, and tumour growth rate (TGR). Independent predictors of OS were the NETest value (HR: 1.035, 95% CI: 1.005–1.066, p = 0.024) and high-risk NETest category (HR: 15.2, 95% CI: 1.52–151, p = 0.02), along with presence of lung metastases and CgA levels > 10 × ULN. In Group 2, ROC analysis identified an AUC of 0.909 (95% CI: 0.75–0.100) for prediction of local or metastatic recurrence. Blood NETest scores were associated with PFS and OS in patients with metastatic Si-NENs, along with TGR, CgA > 10 × ULN, and presence of lung metastases.

BRCA genetic testing is available for UK Jewish individuals but the provision of information online for BRCA is unknown. We aimed to evaluate online provision of BRCA information by UK organisations (UKO), UK Jewish community organisations (JCO), and genetic testing providers (GTP). Google searches for organisations offering BRCA information were performed using relevant sets of keywords. The first 100 website links were categorised into UKOs/JCOs/GTPs; additional JCOs were supplemented through community experts. Websites were reviewed using customised questionnaires for BRCA information. Information provision was assessed for five domains: accessibility, scope, depth, accuracy, and quality. These domains were combined to provide a composite score (maximum score = 5). Results were screened (n = 6856) and 45 UKOs, 16 JCOs, and 18 GTPs provided BRCA information. Accessibility was high (84%,66/79). Scope was lacking with 35% (28/79) addressing >50% items. Most (82%, 65/79) described BRCA-associated cancers: breast and/or ovarian cancer was mentioned by 78%(62/79), but only 34% (27/79) mentioned ≥1 pancreatic, prostate, melanoma. Few websites provided carrier frequencies in the general (24%,19/79) and Jewish populations (20%,16/79). Only 15% (12/79) had quality information with some/minimal shortcomings. Overall information provision was low-to-moderate: median scores UKO = 2.1 (IQR = 1), JCO = 1.6 (IQR = 0.9), and GTP = 2.3 (IQR = 1) (maximum-score = 5). There is a scarcity of high-quality BRCA information online. These findings have implications for UK Jewish BRCA programmes and those considering BRCA testing.

Background: Long-term patient registries are important for evaluating treatment outcomes in patients with rare diseases, and can provide insights into natural disease history and progression in real-world clinical practice. Initiated in 2010, the Gaucher Outcome Survey (GOS) is an ongoing, international, multicenter, observational registry (ClinicalTrials.gov Identifier: NCT03291223) for patients with a diagnosis of Gaucher disease (GD), irrespective of treatment type or status, with a primary objective to monitor safety and long-term effectiveness of velaglucerase alfa. Methods: Here, we evaluated the GOS population 12 years after the registry initiation. Results: As of 25 February 2023, 2084 patients enrolled in the GOS and 1643 received GD-specific treatment. Patients exhibited broad heterogeneity at baseline: age of diagnosis (0 to 85.3 years), hemoglobin concentrations (<80.0 g/L to >150 g/L), platelet counts (<50 × 10⁹/L to >450 × 10⁹/L), and liver and spleen volumes. Most patients treated with enzyme replacement therapy or substrate reduction therapy reported improvements in clinical parameters within 1 year of treatment initiation, maintained over the course of treatment up to 12 years, whereas untreated patients had baseline values closer to standard reference thresholds and showed stability over time. Conclusion: The 12-year data from the GOS confirm the impact of long-term treatment with GD-specific agents and offer insights into disease progression and outcomes in a real-world setting.

The aim of the present study was to examine the association between a comprehensive physical testing battery and measures of golf performance in elite female amateur players. Nineteen category one (handicap ≤ 5) or better golfers (age: 16.26 ± 1.28 years, height: 166.26 ± 3.62 cm, mass: 64.04 ± 11.27 kg, wingspan: 146.53 ± 15.59 cm, handicap: +1.45 ± 0.7) volunteered to participate in this investigation. All golfers attended a single 90 min testing session where golf shot data (clubhead speed [CHS], ball speed, carry distance, and smash factor) were measured with a Trackman 4 launch monitor and a battery of physical assessments were carried out. These included anthropometric data and assessments for seated thoracic rotation, the isometric mid-thigh pull (IMTP), isometric bench press, countermovement jump (CMJ), and seated medicine ball throws for distance. Pearson’s r correlations showed CHS was the golf metric that most commonly demonstrated large associations with physical testing data, most notably with force at 100 ms during the isometric bench press (r = 0.70). Median split analysis was also conducted for the IMTP (force at 200 ms), isometric bench press (force at 100 ms), and CMJ (positive impulse). The results showed that players who produced more force at 200 ms during the IMTP exhibited a greater CHS (g = 1.13), ball speed (g = 0.90), and carry distance (g = 1.01). In addition, players with a greater positive impulse during the CMJ showed a greater ball speed (g = 0.93), carry distance (g = 1.29), and smash factor (g = 1.27). Collectively, these results highlight the relevance of explosive force production capabilities in both the lower and upper body for female golfers. This information can be used by practitioners to better target key physical attributes during testing and training of female players.

Background: Gaucher disease (GD) is a rare, autosomal, recessive condition characterized by hepatosplenomegaly, thrombocytopenia, anemia, and bone abnormalities, often requiring life-long treatment. Velaglucerase alfa has improved hematologic and visceral parameters in clinical trials; however, limited long-term efficacy and safety data are available. Methods: The Gaucher Outcome Survey (GOS), a structured and validated international registry for patients with confirmed GD, provides an opportunity to evaluate long-term data from patients receiving velaglucerase alfa. Results: This analysis included 376 treatment-naïve children and adults with GD enrolled in GOS, including 20 with type 3 GD, who initiated velaglucerase alfa through participation in clinical trials or as part of their clinical management and continued treatment for a mean (range) time of 6.6 (0.003–18.6) years. Initial improvements in hematologic and visceral parameters and the biomarkers glucosylsphingosine (lyso-GL1) and chitotriosidase were observed after one year of treatment and were maintained throughout the follow-up period. Of 129 (34.3%) patients who developed adverse events during the follow-up period, events were considered related to treatment in 33 (8.8%). None led to treatment discontinuation. There were 21 deaths overall, none of which were considered related to treatment. Conclusions: This analysis of data from the GOS registry supports the safety and efficacy of velaglucerase alfa in patients with GD.

Background/Objectives: Retrograde access of the peroneal artery (PA) is considered technically challenging and at risk of bleeding. The aim of this multicentre retrospective study was to assess the safety, feasibility, and technical success of this access route for infrainguinal endovascular recanalizations. Methods: We retrospectively analyzed 186 consecutive patients treated over a 7-year period (May 2014–August 2021) who underwent endovascular recanalization of infra-inguinal lesions using a PA access route. In all cases, retrograde PA access was obtained following a failed attempt to cross the occlusion via the antegrade route. Results: Among the 186 patients, 120 were males (60.5%) and the mean age was 76.8 ± 10.7 years old (44–94 years). One hundred and thirteen patients (60.7%) suffered from chronic limb threatening ischemia (CLTI). All patients presented with chronic total occlusions (CTO) and a failed conventional antegrade recanalization attempt. Retrograde access was performed under angiographic guidance in 185 cases (99.5%). It was successfully established in 171 cases (91.9%). The total rate of retrograde puncture-related complications was 2.1% (two puncture site bleedings of which one necessitated fasciotomy and two cases of arteriovenous fistulas managed conservatively). The Major Adverse Event (MAE) rate at 30 days was 1.6% (3/186). Conclusions: Retrograde recanalization of challenging infra-inguinal lesions via PA is safe and effective in experienced hands.

Introduction: The efficacy of de novo cardiac resynchronisation therapy (CRT) in patients with heart failure (HF), left ventricular systolic dysfunction (LVSD), and a broad QRS morphology is well established. However, the optimal stage for upgrading patients with existing pacemakers (PPMs) or implantable cardioverter-defibrillators (ICDs) and HF with high-burden right ventricular (RV) pacing remains uncertain. Thus, this multicentre retrospective analysis compared patients with pre-existing PPMs or ICDs who underwent CRT upgrades to investigate the appropriate stage for CRT implantation in these patients and to assess the validity of treating both PPM and ICD recipients under the same recommendation level in the current guidelines. Materials and Methods: A total of 151 participants underwent analysis in this study, comprising 93 upgrades to cardiac resynchronisation therapy with pacemaker (CRT-P) and 58 upgrades to cardiac resynchronisation therapy with defibrillator (CRT-D) across three centres in the UK. The aim of the study was to investigate the safety and efficacy of upgrading to CRT from an existing conventional pacemaker or an ICD in the context of high-burden RV pacing. The analysis was conducted separately for each group, assessing changes in echocardiographic parameters, functional New York Heart Association (NYHA) class, and procedure-related complications. Results: The PPM group had a higher percentage RVP burden compared to the ICD group. Post-upgrade, NYHA functional class and EF and LV volumes improved in both groups; however, the response to an upgrade from a pacemaker was greater compared to an upgrade from an ICD. Post-procedural complication risks were similar across the two subgroups but significantly higher compared to de novo implantation. Conclusions: Within the CRT-P subgroup, participants exhibited better responses than their CRT-D counterparts, evident both in echocardiographic improvements and clinical outcomes. Furthermore, patients with non-ischemic cardiomyopathy (NICM) were better responders than those with ischaemic cardiomyopathy. These findings suggest that international guidelines should consider approaching each subgroup separately in the future.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and foetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, which play a critical role in maintaining immune homeostasis, are crucial in pregnancy to prevent immune-mediated rejection of the foetus. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring foetal acceptance. In contrast, HDP is associated with Treg dysfunction, which is marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, in which Tregs fail to adequately modulate the maternal immune response against foetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs, the review explores the complexities of translating in vitro and animal model findings into effective clinical therapies. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.

(1) Objectives: This study aimed to assess the 5-year prevalence and clinical profile of attention deficit hyperactive disorder (ADHD) among adult patients seeking care in a tertiary care hospital in Oman. (2) Methods: The data were analysed using descriptive and inferential statistics and standardised prevalence estimates were calculated. (3) Results: Of the 39,881 hospital visits, 1.77% were made by adults with ADHD. This is equivalent to 17.8 visits per 1000 outpatients. The year 2021 saw the highest prevalence among the five years considered, while 2020 had the lowest prevalence. Although the age distribution indicated that the age group ‘under 20’ had the highest prevalence, the gender distribution showed that ADHD was more common among adult men. Among the various subtypes of ADHD, inattention was the most common. (4) Conclusions: This study specifically compared the prevalence and associated factors between an adult cohort with ADHD and those other psychiatric clinic attendees during the same period. The study offers important information on the prevalence and clinical profile of adults with ADHD in the population under consideration.

Liver transplantation (LT) is the only definitive treatment for end-stage liver disease, yet the UK has seen a 400% increase in liver disease-related deaths since 1970, constrained further by a critical shortage of donor organs. This shortfall has necessitated the use of extended criteria donor organs, including those with evidence of steatosis. The impact of hepatic steatosis (HS) on graft viability remains a concern, particularly for donor livers with moderate to severe steatosis which are highly sensitive to the process of ischaemia-reperfusion injury (IRI) and static cold storage (SCS) leading to poor post-transplantation outcomes. This review explores the pathophysiological predisposition of steatotic livers to IRI, the limitations of SCS, and alternative preservation strategies, including novel organ preservation solutions (OPS) and normothermic machine perfusion (NMP), to mitigate IRI and improve outcomes for steatotic donor livers. By addressing these challenges, the liver transplant community can enhance the utilisation of steatotic donor livers which is crucial in the context of the global obesity crisis and the growing need to expand the donor pool.

Current management of non-metastatic muscle invasive bladder cancer (MIBC) includes radical cystectomy and cisplatin-based neoadjuvant chemotherapy (NAC), offers a 5-year survival rate of approximately 50% and is associated with significant toxicities. A growing body of evidence supports the role of liquid biopsies including circulating tumour DNA (ctDNA) as a prognostic and predictive marker that could stratify patients according to individualised risk of progression/recurrence. Detectable ctDNA levels prior to radical cystectomy have been shown to be correlated with higher risk of recurrence and worse overall prognosis after cystectomy. In addition, ctDNA status after NAC/neoadjuvant immunotherapy is predictive of the pathological response to these treatments, with persistently detectable ctDNA being associated with residual bladder tumour at cystectomy. Finally, detectable ctDNA levels post-cystectomy have been associated with disease relapse and worse disease-free (DFS) and overall survival (OS) and might identify a population with survival benefit from adjuvant immunotherapy.

Background: Isocitrate Dehydrogenase 1/2 (IDH 1/2)-wildtype (WT) astrocytomas constitute a heterogeneous group of tumors and have undergone a series of diagnostic reclassifications over time. This study aimed to investigate molecular markers, clinical, imaging, and treatment factors predictive of outcomes in WHO grade 2/3 IDH-WT astrocytomas (‘early glioblastoma’). Methodology: Patients with WHO grade 2/3 IDH-WT astrocytomas were identified from the hospital archives. They were cross-referenced with the electronic medical records systems, including neuroimaging. The expert neuro-pathology team retrieved data on molecular markers—MGMT, TERT, IDH, and EGFR. Tumors with a TERT mutation and/or EGFR amplification were reclassified as glioblastoma. Results: Fifty-four patients were identified. Sixty-three percent of the patients could be conclusively reclassified as glioblastoma based on either TERT mutation, EGFR amplification, or both. On imaging, 65% showed gadolinium enhancement on MRI. Thirty-nine patients (72%) received long-course radiotherapy, of whom 64% received concurrent chemotherapy. The median follow-up of the group was 16 months (range: 2–90), and the median overall survival (OS) was 17.3 months. The 2-year OS of the whole cohort was 31%. On univariate analysis, older age, worse performance status (PS), and presence versus absence of contrast enhancement on diagnostic MRI were statistically significant for poorer OS. Conclusion: IDH-WT WHO grade 2/3 astrocytomas are a heterogeneous group of tumors with poor clinical outcomes. The majority can be reclassified as glioblastoma, based on current WHO classification criteria, but further understanding of the underlying biology of these tumors and the discovery of novel targeted agents are needed for better outcomes.

This article presents the report of the session on “Newborn Screening for Primary Immunodeficiencies—Now What?” organised during the International Primary Immunodeficiency Congress (IPIC) held in November 2023. This clinical conference was organised by the International Patient Organisation for Primary Immunodeficiencies (IPOPI), the global patient organisation advocating for primary immunodeficiencies (PIDs) in patients. The session aimed at exploring the advances in newborn screening (NBS) for severe combined immunodeficiency, starting with the common practice and inserting the discussion into the wider perspective of genomics whilst taking into consideration the ethical aspects of screening as well as incorporating families and the public into the discussions, so as to ensure that NBS for treatable rare disorders continues to be one of the major public health advances of the 20th century.

Clinical decision-making within occupational therapy is a complex and dynamic process shaped by numerous scientific, narrative, professional, ethical, legal and personal factors. By reflecting on these factors and by developing metacognition of one's own reasoning pathways, biases, and heuristics, patient-centred and balanced clinical decisions can be made. This reflective case study examines the factors underpinning an occupational therapist's clinical decision making for a man with terminal cancer. A critical reflective model is used in this article to provide structure and to ensure critical consideration of the case. Implications for practice aim to serve as inspiration for others to reflect on their own journey, and personal action points are detailed to develop the author's own clinical decision-making.

Background: People with serious mental illnesses (SMIs) such as schizophrenia and bipolar disorder die up to 30 years younger than individuals in the general population. Premature mortality among this population is often due to medical comorbidities, such as type 2 diabetes (T2D). Being a disease directly related to diet, adverse lifestyle choices, and side effects of psychotropic medication, an effective approach to T2D treatment and management could be non-pharmacological interventions. This systematic review and meta-analysis (1) summarise the current evidence base for non-pharmacological interventions (NPI) for diabetes management in people living with SMI and (2) evaluate the effect of these interventions on diverse health outcomes for people with SMI and comorbid diabetes. Methods: Six databases were searched to identify relevant studies: PubMed (MEDLINE), PsycINFO, Embase, Scopus, CINAHL, and Web of Science. Studies were included if they reported on non-pharmacological interventions targeted at the management of T2D in people living with SMI. To be eligible, studies had to further involve a control group or report multiple time points of data in the same study population. Whenever there were enough interventions reporting data on the same outcome, we also performed a meta-analysis. Results: Of 1867 records identified, 14 studies were included in the systematic review and 6 were also eligible for meta-analysis. The results showed that there was a reduction, although not significant, in glycated haemoglobin (HbA1c) in the NPI group compared with the control, with a mean difference of −0.14 (95% CI, −0.42, 0.14, p = 0.33). Furthermore, NPI did not significantly reduce fasting blood glucose in these participants, with a mean difference of −17.70 (95% CI, −53.77, 18.37, p = 0.34). However, the meta-analysis showed a significant reduction in psychiatric symptoms: BPRS score, −3.66 (95% CI, −6.8, −0.47, p = 0.02) and MADRS score, −2.63 (95% CI, −5.24, −0.02, p = 0.05). NPI also showed a significant reduction in the level of total cholesterol compared with the control, with a mean difference of −26.10 (95% CI, −46.54, −5.66, p = 0.01), and in low-density lipoprotein (LDL) cholesterol compared with control, with a standardised mean difference of −0.47 (95% CI, −0.90, −0.04, p = 0.03). NPI did not appear to have significant effect (p > 0.05) on body mass index (BMI), health-related quality of life (HRQL), triglycerides, and high-density lipoprotein cholesterol compared with control. Conclusions: This systematic review and meta-analysis demonstrated that NPI significantly (p < 0.05) reduced psychiatric symptoms, levels of total cholesterol, and LDL cholesterol in people with type 2 diabetes and SMI. While non-pharmacological interventions also reduced HbA1c, triglyceride, and BMI levels and improved quality of life in these people, the effects were not significant (p > 0.05).

Simple Summary Patients with oncogene-addicted lung cancers that have developed resistance to oral targeted therapy have limited treatment options. Several studies have shown conflicting results in this setting, but those using Bevacizumab and Paclitaxel in combination with immunotherapy (ABCP) have consistently shown activity. Spread to the brain is common, but it is not known how many patients with brain metastases are amenable to chemo-immunotherapy, and its effect in this patient group has not been reported to date. We present here our retrospective real-life experience in patients treated with ABCP. Our results in 34 patients underlined that spread to the brain occurred in 19 patients (56%), 17 of them without previous brain radiotherapy. In these 19 patients, chemo-immunotherapy triggered frequent and quick responses inside and outside the brain and showed similar outcomes to those shown in patients with smoking-related lung cancer and previously untreated brain metastases. Abstract Contrary to Pemetrexed-containing chemo-immunotherapy studies, Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel (ABCP) treatment has consistently shown clinical benefit in prospective studies in patients with lung cancer and actionable mutations, where intracranial metastases are common. Here, we aimed to describe the real-life population of patients fit to receive ABCP after targeted therapy and quantify its clinical effect in patients with brain metastases. Patients treated in Cheshire and Merseyside between 2019 and 2022 were identified. Data were collected retrospectively. A total of 34 patients with actionable EGFR or ALK alterations had treatment with a median age of 59 years (range 32–77). The disease control rate was 100% in patients with PDL1 ≥ 1% (n = 10). In total, 19 patients (56%) had brain metastases before starting ABCP, 17 (50%) had untreated CNS disease, and 4 (22%) had PDL1 ≥ 1%. The median time to symptom improvement was 12.5 days (range 4–21 days), with 74% intracranial disease control rates and 89.5% synchronous intracranial (IC) and extracranial (EC) responses. IC median Progression Free Survival (mPFS) was 6.48 months, EC mPFS was 10.75 months, and median Overall Survival 11.47 months. ABCP in real-life patients with brain metastases (treated or untreated) was feasible and showed similar efficacy to that described in patients without actionable mutations treated with upfront chemo-immunotherapy.