Physical Comorbidities Research Articles

(Cost-)effectiveness and implementation of a combined lifestyle intervention for outpatients with severe mental illness (GOAL!): a hybrid quasi-experimental study protocol.

People with severe mental illness (SMI) face not only impaired mental health, but also a greater risk of physical comorbidities and a shorter life expectancy compared to the general population. A poor lifestyle plays a substantial role in this disparity. Combined Lifestyle Interventions targeting multiple lifestyle behaviors can improve mental and physical health, and quality of life. However, there is currently no appropriate structural support for people with SMI in outpatient care in the Netherlands. The Combined Lifestyle Intervention for Outpatients with SMI (GOAL!) is developed to address this gap. This study examines the (cost-)effectiveness and implementation of GOAL!. In a type 1 hybrid quasi-experimental study with a mixed-method matched design, GOAL! participants (N = 50) are compared to people receiving care as usual (N = 50). The GOAL! program includes group and individual sessions, given by allied health professionals, over a period of two years. The first year starts with a 3-month intensive course on physical activity and nutrition, followed by 9 months of aftercare covering various lifestyle topics tailored to the group's needs. There is close collaboration with local stakeholders to facilitate transfer to the community setting. The second year focuses on maintaining established activities in one's daily living environment. Our primary outcome will be the change in physical activity, comparing GOAL! participants to those receiving care as usual. Secondary outcomes are changes in other lifestyle behaviors, physical health, mental well-being, and healthcare and societal costs. Additionally, achieving lifestyle-related goals, adverse effects, and barriers and facilitators to implementation are examined. Measurements are obtained at start (T0), and after 3 (T1), 12 (T2) and 24 months (T3). This study investigates the effects of GOAL! on lifestyle behaviors, health outcomes, implementation factors and cost-effectiveness after two years, aiming to offer valuable insights into the effectiveness and implementation outcomes of lifestyle interventions for outpatients with SMI. ClinicalTrials.gov (Identifier: NCT05600205). Prospectively registered on October 26, 2022.

The social determinants of distress in South Asian men with long-term conditions: a qualitative study.

People with long-term physical conditions are more likely to experience distress, depression or anxiety. Physical-mental comorbidity is associated with lower quality of life, poorer clinical outcomes, and increased mortality than physical conditions alone. South Asians (SAs) are the largest minority group in the UK, and more likely to have long-term conditions (LTCs) such as diabetes and heart disease. To explore how men of SA origin with LTCs understand and experience emotional distress as well as the experiences of GPs supporting them. UK qualitative study interviewing SA men with diabetes or coronary heart disease, and GPs working at practices with higher proportions of SAs. Online semi-structured interviews with SA men and GPs. Data were analysed via reflexive thematic analysis. Topic guides were modified iteratively as data collection and analysis progressed. An ethnically appropriate patient advisory group of SA men was involved in all stages of the research. Seventeen SA men with LTCs and 18 GPs were interviewed. Participants described contextualising distress including the interaction between having a LTC and distress, and the intersections of social determinants of distress including ethnicity, poverty and perceptions of prejudice. Participants understood distress as different to depression with the need to negotiate multiple identities as well as alternative paradigms of health. This study highlights the influence of social determinants of distress in SA men with LTCs. It provides an insight into how primary care has the potential to address health inequalities by considering the intersection of these factors.

Cognitive, adaptive and daily life functioning in adults with 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2DS) is associated with cognitive impairments and an increased risk of psychopathology. Most of the research has been conducted in children and adolescents, although the majority of affected individuals live well into adulthood. Hence, limited data are available on functional outcomes in adults. To provide more insight in cognitive and adaptive abilities, and daily life functioning (marital status, living situation and work situation) in adults with 22q11.2DS. This retrospective study included 250 Dutch-speaking adults (16-69 years) with 22q11.2DS from three sites in The Netherlands and Belgium. Data on full-scale IQ (FSIQ) scores (assessed with the Wechsler Adult Intelligence Scale), adaptive functioning (assessed with the Vineland Adaptive Behavior Scale II), and functional outcomes including marital status, living and work situation were systematically collected from clinical files. In addition, we examined predictors of adaptive functioning. The majority of individuals in our adult sample demonstrated a low level of adaptive functioning (65%). In contrast to previous findings in children and adolescents, the majority functioned at an intellectual disability level (56%). Male sex, lower FSIQ and autism spectrum disorder were predictors of lower adaptive functioning (P = 0.016, P < 0.001 and P = 0.16, respectively). These results suggest that low levels of cognitive and adaptive functioning are common in adults with 22q11.2DS. Future longitudinal and multicentre studies including older patients (>40 years) are needed to further investigate cognitive and adaptive trajectories and their interactions with physical and psychiatric comorbidities.

Telerehabilitation in post-tuberculosis lung disease: a protocol for a randomized controlled clinical trial

Background: Few studies have evaluated structured telerehabilitation programs for individuals with post-tuberculosis lung disease (PTLD), resulting in a lack of specific guidelines. This protocol aims to evaluate the physical capacity and quality of life (QoL) of PTLD patients undergoing telerehabilitation. Methods: This randomized, controlled clinical trial has received internal review board approval and will recruit participants between December 2024 and June 2025, from a referral center in Brazil. Individuals thought to have PTLD, with a mini-mental state examination score &gt;24 and no physical limitations or comorbidities unrelated to pulmonary tuberculosis (TB) will be screened using imaging, total blood count, and biochemical profile. Those with confirmed PTLD will undergo the assessments of: QoL, and physical capacity (spirometry, body composition, calf circumference, six-minute walk test (6MWT), five-times-sit-to-stand test (FTSST), handgrip and isokinetic dynamometry). After that, the participants will be randomly allocated to control or intervention groups. While both groups will receive general guidance on health education and TB prevention, the intervention group will also receive a physiotherapy booklet with instructions for exercises to be performed five times a week for eight weeks. Participants of both groups will be monitored by videoconference, and the same assessment tools will be used to reevaluate QoL and physical capacity outcomes. Conclusions: The results may demonstrate the benefits of a telerehabilitation program on the physical capacity and QoL of PTLD patients, and may improve accessibility, cost savings, and personalized care through home-based therapy by videoconferencing. Trial registration: CAAE: 10481219.9.0000.5257. This study was registered at ClinicalTrials.gov (NCT04844502).

System-wide health needs segmentation: innovating integrated care for complex needs households

Abstract Background Health needs segmentation is increasingly used in healthcare delivery and health policy planning to cater for diverse population groups and develop effective and equitable health policies. But existing models often lack a systemic approach, focusing instead on single conditions or settings. This leads to fragmentation, gaps and inefficiencies in service provision and inequities in health outcomes, particularly when addressing complexity, and specifically for children, as adversity clusters in families. Aims To develop a household health needs segmentation model to identify those households with children with high levels of complex cross-sectoral needs, to plan for integrated care services. Methods Data linkage of primary, secondary, mental, community and social care services, mortality records, residential information, and small-area multiple deprivation measures was used to design a rule-based model to identifying households with children with the most complex needs in the UK region of Cheshire and Merseyside (C&amp;M), with large variation in demography, (human) geography, and deprivation. Results Of 2,645,329 individuals in C&amp;M (97% of the registered population in 2021), 1,022,840 lived in 266,939 households with children aged 0-16: 21,527 households had complex needs. This 8% of families accounted for an estimated 34% of health and social care costs for families, £362 million in total, 42% of which spent on children in care of local authorities. Implications The model identified a specific group of families with complex service use patterns, high mental and physical comorbidity and socioeconomic vulnerabilities. These exhibit potential for improved outcomes through better integration of services and targeting of community building and family support resources. Conclusions Our model represents a significant innovation in health needs segmentation. By using whole system linked data, it provides a pragmatic way of profiling complexity for proactive care. Key messages • Complex health and social problems in children cluster in families with adults also having complex needs, so we need to transform fragmented services to support the whole family to improve outcomes. • Household level segmentation using cross-sectoral, whole system data is an innovation to identify households with complex needs with respect to their locality to improve integration of support.

Risk of physical health comorbidities in autistic adults: clinical nested cross-sectional study.

Physical health conditions are more common in individuals with autism. Some, like epilepsy, have considerable evidence supporting their increased prevalence, but many diseases lack literature to make strong conclusions. To investigate the prevalence of physical health comorbidities in autism. We undertook a nested cross-sectional study, using a sample from the National Centre for Mental Health database. It included participants from England and Wales who reported a clinician-made diagnosis of autism (n = 813), and a control sample without autism or mental illness (n = 2781). Participants had provided a medical history at enrolment. Analysis was carried out by binomial logistic regressions controlling for age, gender, smoking status, and antipsychotic and mood stabiliser use. A subanalysis of individuals with concurrent intellectual disability (n = 86) used binomial logistic regression with the same control variables. Many physical health conditions were significantly more common in autism. Sixteen out of 28 conditions showed increased odds, with the highest odds ratios observed for liver disease, chronic obstructive pulmonary disease, kidney disease, osteoporosis and rheumatoid arthritis. A subanalysis demonstrated a similar pattern of physical health in individuals with autism with and without concurrent intellectual disability. Some conditions, including osteoporosis, hyperthyroidism, head injury and liver disease, had larger odds ratios in individuals with concurrent intellectual disability. Physical health conditions occur more commonly in individuals with autism, and certain conditions are further increased in those with concurrent intellectual disability. Our findings contribute to prior evidence, including novel associations, and suggest that people with autism are at greater risk of physical health problems throughout adulthood.

An effective approach to tackling complex health policy challenges. Using a clinical microsystems approach and rethinking codesign.

That people with serious mental illness have poor physical health and face a significant life expectancy gap compared with the general population is well known. Despite considerable policy focus in some countries, the gap in life expectancy remains. Tackling complex and persistent health problems such as this requires a systems-based approach, recognising the complexity of interacting components and their effects on the problem and on each other and applying collaborative analysis, design and implementation by those with knowledge of and expertise in the problem and the context. This paper describes the methods used to develop the Australian Being Equally Well National Policy Roadmap for better physical health care and longer lives for people with severe mental illness. Whilst recognising that high rates of physical health comorbidities are caused by many factors including lifestyle, access to high-quality healthcare and medication side effects, the work was focused on what could be done within Australian primary care to improve the physical health of this cohort. A Clinical Microsystem Approach was applied to synthesise clinical evidence with professional and lived experience, and an innovative policy development process was established, creating trust across all system levels. Participants with different kinds of knowledge and experience worked in discrete groups according to their professional or expert role whilst also being supported to participate in an intensive cross-collaboration. The potential value of this methodology for tackling other complex problems in health policy is discussed.

From worries to resilience: a qualitative study of the psychosocial experiences of diverse adolescents and young adults with heart failure and their caregivers.

Despite advances in treatment and outcomes for paediatric heart failure, both physical and psychosocial comorbidities remain notable among this patient population. We aimed to qualitatively describe the psychosocial experiences of adolescent and young adults with heart failure and their caregivers' perceptions, with specific focus on personal challenges, worries, coping skills, and resilience. Structured, in-depth interviews were performed with 16 adolescent and young adults with heart failure and 14 of their caregivers. Interviews were recorded and transcribed. Content analysis was performed, and themes were generated. Transcripts were coded by independent reviewers. Ten (63%) adolescent and young adults with heart failure identified as male and six (37.5%) patients self-identified with a racial or ethnic minority group. Adolescent and young adults with heart failure generally perceived their overall illness experience more positively and less burdensome than their caregivers. Some adolescent and young adults noted specific worries related to surgeries, admissions, major complications, death, and prognostic/treatment uncertainty, while caregivers perceived their adolescent and young adult's greatest worries to be around major complications and death. Adolescent and young adults and their caregivers were able to define and reflect on adolescent and young adult experiences of resilience, with many adolescent and young adults expressing a sense of optimism and gratitude as it relates to their medical journey. This study is the first of its kind to qualitatively describe the psychosocial experiences of a racially and socioeconomically diverse sample of adolescent and young adults with heart failure, as well as their caregivers' perceptions of patient experiences. Findings underscore the importance of identifying distress and fostering resilient processes and outcomes in young people with advanced heart disease.

Recent Advances in Pharmacologic Treatments of Drug-Resistant Epilepsy: Breakthrough in Sight.

Epilepsy affects approximately 1% of the world population. Patients have recurrent seizures, increased physical and psychiatric comorbidities, and higher mortality rate than the general population. Over the last 40 years, research has resulted in 20 new antiseizure medications (ASMs) approved between 1990 and 2018. In spite of this, up to one-third of patients (~ 1 million patients in the USA) have drug-resistant epilepsy (DRE), with little change between 1982 and 2018, a period of intense new ASM development. A minority of patients with DRE may benefit from surgical treatment, but this specialized care remains challenging to scale. Therefore, the greatest hope for breakthroughs for patients with DRE is in pharmacologic therapies.Recently, several advances promise to change the outcomes for patients with DRE. Cenobamate, a drug with dual mechanisms of modulating sodium channel currents and GABA-A receptors, achieves 90-100% seizure reduction in 25-33% of patients with focal DRE, a response not observed with other ASMs. Fenfluramine, a serotonin-acting drug, dramatically reduces the frequency ofconvulsive seizuresin Dravet syndrome, a devastating developmental epileptic encephalopathy with severe DRE.Both drugs reduce mortality.In addition, the possibility of DRE prevention was recently raised in patients with tuberous sclerosis complex, a relatively common genetic form of epilepsy. A paradigm shift is emerging in the treatment of epilepsy. Seizure freedom has become attainable in a significant proportion of patients with focal DRE, and dramatic seizure reduction has been achieved in a developmental encephalopathy. Coupled with a rich pipeline of new compounds under clinical development, the long sought-after breakthrough in the treatment of epilepsy may finally be in sight.

Alexithymia and Bipolar Disorder: Virtual Reality Could Be a Useful Tool for the Treatment and Prevention of These Conditions in People with a Physical Comorbidity

Background: Alexithymia, a predictor in chronic illnesses, like cardiovascular and bipolar disorder (CD–BD), could be improved with a virtual reality (VR) cognitive remediation program. This secondary analysis of a previous randomized controlled trial (RCT) evaluates alexithymia improvement and its factors in an experimental group versus a control group, exploring extensions to individuals with comorbid non-psychiatric chronic conditions. Methods: A feasibility cross-over RCT (ClinicalTrials.gov NCT05070065) enrolled individuals aged 18–75 with mood disorders (BD, DSM-IV), excluding those with relapses, epilepsy, or severe eye conditions due to potential risks with VR. Alexithymia levels were measured using the Toronto Alexithymia Scale with 20 items (TAS-20). Results: The study included 39 individuals in the experimental group and 25 in the control group, with no significant age or sex differences observed. Significantly improved alexithymia scores were noted in the experimental group compared to controls (F = 111.9; p &lt; 0.0001) and in subgroups with chronic non-psychiatric comorbidities (F = 4.293, p = 0.048). Scores were particularly improved for difficulty in identifying feelings (F = 92.42; p &lt; 0.00001), communicating feelings (F = 61.34; p &lt; 0.00001), and externally oriented thinking (F = 173.12; p &lt; 0.00001). Conclusions: The findings highlight alexithymia enhancement in BD, even with comorbid non-psychiatric chronic diseases. Given its impact on BD progression and related conditions, like CD, developing and evaluating VR-based tools in this context is suggested by these findings.

Tipping Point: Pathogenic Stress and the Biopolitics of Euthanasia.

Hopelessness and demoralization following a terminal diagnosis can affect the capacity for self-governance. Such dispositions can increase the allostatic load-the cumulative burden of stress and anxiety-resulting in a neurophysiologic decline that can impair autonomy and influence the desire to end one's life deliberately. An allostatic overload is characterized by the inability to autoregulate stress and is associated with pathological changes to the hypothalamic-pituitary-adrenal axis and hippocampus. These changes raise concerns about the reliability of concepts of autonomy in extremis, potentially undermining arguments that are used to justify voluntary euthanasia and medically assisted death. Studies have associated depression and hopelessness with suicidal ideation in the general population. However, fewer studies have examined how patients without a history of depression or suicidal ideation may suddenly contemplate the act when facing a terminal prognosis. This paper will argue that an allostatic overload can help explain how the spectrum of physical and psychological comorbidities associated with the onset of a terminal illness can influence a decision to hasten death. Data show that patients with a terminal disease wishing to hasten death typically exhibit lower rates of clinical depression, higher rates of demoralization, and a greater likelihood of rational suicide. These differences indicate that suicidal ideation in the terminal disease patient population is different. Changes in autonomous decision-making secondary to pathological alterations in the brain may offer an explanation. Such changes have been shown to dysregulate executive control functions, specifically intentionality and voluntariness. Clinical evidence also indicates that spirituality and hopefulness can help manage the allostatic load during the palliative stages of a disease so that patients can better process end-of-life decisions. Based on these data, this paper will further argue that jurisdictions offering euthanasia are morally compelled to make mental and spiritual counseling available to patients seeking this course of action.

Measuring Exercise Self-Efficacy After Stroke: Validity and Reliability of Current Measures.

Many physically capable stroke survivors are insufficiently active, with low self-efficacy considered an important contributor. However, validity and reliability of self-efficacy measures in stroke survivors have not been established. This research aims to evaluate the test-retest reliability and construct validity of 3 self-efficacy measures: Self-Efficacy for Exercise Scale (SEE), Spinal Cord Injury Exercise Self-Efficacy Scale (SCI-ESES), and Participation Strategies Self-Efficacy Scale (PS-SES). A repeated measures study with community-dwelling, independently mobile adult stroke survivors (n=51, mean age 74years, 45% female, median 22months poststroke) was completed. Test-retest reliability was assessed using intraclass correlation coefficients and Bland-Altman analyses. Construct validity was assessed using 8 pre-determined hypotheses concerning physical activity level (subjective and objective), comorbidities, work and volunteering, and measures of function. Retest reliability was established for the SEE (intraclass correlation coefficient, ICC=0.77) and PS-SES (ICC=0.78) but not for the SCI-ESES (ICC=0.68). Bland-Altman analysis showed participants consistently scored higher on the second test for all measures. The SEE achieved construct validity by meeting 75% of hypotheses, whereas the PS-SES and SCI-ESES did not. Self-efficacy was positively related to steps/day, functional capacity, self-reported activity levels, and work or volunteering participation. The SEE was found to be the most appropriate tool to measure exercise self-efficacy in independently mobile chronic stroke survivors in terms of retest reliability and validity. N/A. for more insights from the authors (see the Video, Supplemental Digital Content 1 "Espernberger-JNPT-Video-Abstract," available at: http://links.lww.com/JNPT/A489).

The Neuroconnective Endophenotype, A New Approach Toward Typing Functional Neurological Disorder: A Case-Control Study.

Functional neurological disorder (FND) is a core neuropsychiatric condition that includes both physical and mental symptoms. Recently, a validated clinical phenotype termed neuroconnective endophenotype (NEP), which includes several physical and psychological characteristics together with joint hypermobility (hypermobility spectrum disorders), was found at a significantly higher frequency among patients with anxiety. The purpose of the present study was to examine the presence of the NEP among patients with FND. The authors conducted a multicenter case-control study comprising 27 FND patients and 27 healthy control participants (matched by sex and age) ages 13 to 58 years. Eight questionnaires were administered. Proportional differences were examined with Student's t tests, one-way analyses of variance, and chi-square tests. Differences between FND patients and control participants were observed. FND patients had higher sensory sensitivity, increased prevalence of hypermobility features (including relevant physical signs and symptoms), greater frequency of polarized behaviors, a greater number of both psychiatric and physical comorbidities, and an increase in the characteristics and sensations typical of anxiety. Particularly striking was the presence of the hypermobility spectrum in more than 75% of FND patients compared with 15% among control participants. FND patients presented higher scores in all five dimensions included in the NEP. Thus, this phenotype, solidifying the original association between anxiety and the hypermobility spectrum, could help to identify an FND subtype when evaluating and managing FND patients, because it provides a new global view of patients' physical and mental symptoms.

Psychological Distress Among Ethnically Diverse Participants From Eastern and Southern Africa

Psychological distress is characterized by anxiety and depressive symptoms. Although prior research has investigated the occurrence and factors associated with psychological distress in low- and middle-income countries, including those in Africa, these studies' findings are not very generalizable and have focused on different kinds of population groups. To investigate the prevalence and characteristics (sociodemographic, psychosocial, and clinical) associated with psychological distress among African participants. This case-control study analyzed data of participants in the Neuropsychiatric Genetics in African Populations-Psychosis (NeuroGAP-Psychosis) study, which recruited from general outpatient clinics in Eastern (Uganda, Kenya, and Ethiopia) and Southern (South Africa) Africa. Individuals who participated in the control group of NeuroGAP-Psychosis from 2018 to 2023 were analyzed as part of this study. Data were analyzed from May 2023 to January 2024. The prevalence of psychological distress was determined using the Kessler Psychological Distress Scale (K10), which measures distress on a scale of 10 to 50, with higher scores indicating more distress. Participants from the NeuroGAP-Psychosis study were categorized into cases as mild (score of 20-24), moderate (score of 25-29), and severe (score of 30-50), and participants with scores less than 20 were considered controls. Factors that were associated with psychological distress were examined using binomial logistic regression. From the data on 21 308 participants, the mean (SD) age was 36.5 (11.8) years, and 12 096 participants (56.8%) were male. The majority of the participants were married or cohabiting (10 279 participants [48.2%]), most had attained secondary education as their highest form of learning (9133 participants [42.9%]), and most lived with their families (17 231 participants [80.9%]). The prevalence of mild, moderate, and severe psychological distress was 4.2% (869 participants), 1.5% (308 participants), and 0.8% (170 participants), respectively. There were 19 961 participants (93.7%) who served as controls. Binomial logistic regression analyses indicated that the independent associations of psychological distress were experience of traumatic events, substance use (alcohol, tobacco, or cannabis), the physical comorbidity of arthritis, chronic neck or back pain, and frequent or severe headaches. In this case-control study among ethnically diverse African participants, psychological distress was associated with traumatic stress, substance use, and physical symptoms. These findings were observed to be consistent with previous research that emphasizes the importance of traumatic events as a factor associated with risk for psychopathology and notes the frequent co-occurrence of conditions such as physical symptoms, depression, and anxiety.

The contribution of non-communicable and infectious diseases to the effect of depression on mortality: a longitudinal causal mediation analysis

Background: The increased prevalence of physical diseases among individuals with mental illness contributes to their increased risk of mortality. However, the mediating role of specific diseases in the effect of mental illness on mortality is not well understood. Method: We conducted a longitudinal causal mediation analysis using data from beneficiaries of a South African medical insurance scheme from 2011-2020. We estimated the overall effect of major depressive disorder (MDD) on mortality and evaluated reductions in this overall effect through hypothetical interventions on the risks of mediating physical diseases using an interventional effects approach. A Monte Carlo simulation-based g-computation was used for estimation. Results: Among 981,540 individuals, 143,314 (14.6%) were diagnosed with MDD. Mortality risk after 8 years was 6.5% under MDD, and 5.3% under no MDD (risk ratio 1.23, 95% CI 1.19-1.26). Overall, 43.4% of this disparity could be attributed to higher rates of physical comorbidities due to MDD. Cardiovascular diseases accounted for 17,8%, followed by chronic respiratory diseases (8.6%), cancers (7.5%), diabetes and chronic kidney disease (5.8%), tuberculosis (4.3%), and HIV (2.7%). Conclusion: Within the privately insured population of South Africa, MDD is associated with increased mortality. We estimate that the increased risks of non-communicable diseases under MDD, rather than infectious diseases, are important mediators of the effect of MDD on mortality.

Efficacy and Tolerance of First-Line Afatinib in Elderly NSCLC Patients with EGFR Mutations in Vietnam: A Multicenter Real-World Study.

Afatinib, a second-generation epidermal growth factor receptor(EGFR) tyrosine kinase, has proven effective for non-small-cell lung cancer (NSCLC) patients with EGFR mutations through randomized controlled trials and real-world studies. Elderly patients exhibit unique characteristics in terms of physical condition and comorbidities, leading to differences in clinical practice for selecting the initial dosage and making dose adjustments compared to younger patients. This study aims to evaluate the effectiveness and adverse effects of first-line Afatinib treatment in elderly patients with NSCLC harboring EGFR mutations in Vietnam in a real-world context. We conducted a retrospective analysis of 135 patients, aged 65 years and older, across nine cancer centers in Vietnam. These patients, who harbored drug-sensitive EGFR mutations (excluding de novo T790M), received first-line Afatinib treatment between April 2018 and June 2022. The primary endpoints, time to treatment failure (TTF), and overall survival (OS) were assessed using the Kaplan-Meier method, and comparisons were conducted using the log-rank test. Secondary endpoints included the overall response rate (ORR) according to RECIST 1.1 and adverse effects as classified by CTCAE 4.0. The median age was 71.2 years (SD ± 5.3). Comorbidities included cardiovascular disease (20.7%), diabetes (5.2%), chronic obstructive pulmonary disease (2.2%), and hepatitis B (0.7%). Common mutations constituted 71.9% of cases, with uncommon mutations representing 28.1%. Brain metastases were observed in 24.4% of patients. Initial treatment doses were 40 mg for 35.6% of patients and 30 mg for 62.2%. With a median follow-up of 34.3 months, the median TTF was 16.3 months (95% CI: 15.4-19.5), and the median OS was 32.9 months (95% CI: 28.9-37.5). Factors associated with decreased OS included poor performance status, current smoking, and the presence of uncommon mutations. The ORR was 77.8%, with a complete response of 11.1% and a disease control rate of 94.1%. The most common toxicities were dermatologic and mucosal, including diarrhea (55.6%), rash (48.9%), and stomatitis (40.7%), predominantly in grades 1 and 2. Initiating treatment at doses below 40 mg significantly reduced most toxicities compared to the 40 mg dose. The presence of brain metastases did not significantly affect ORR, TTF, or OS. Starting treatment at doses below 40 mg significantly lowered the response rate but did not impact TTF or OS. First-line treatment with Afatinib in elderly patients with NSCLC and EGFR mutations demonstrates significant efficacy and manageable toxicity in a Vietnamese multicenter real-life setting. The effectiveness of Afatinib was confirmed, with known and well-controlled adverse effects, supporting its use in this patient population.

Treatment-Resistant Mood Disorders.

The objective of the study was to explore the presentation of symptoms in patients suffering from treatment-resistant mood disorder (TRMD), and associated clinical features, including age, gender, and comorbid conditions, that lead towards the development of treatment-resistant mood disorder. Furthermore, the study analyses the available psychotherapeutic treatment modalities and evidence-based non-medical treatment approaches for TRMD. The current study utilized a systematic review approach where 37 articles were studied and three articles were theoretically sampled to authenticate and signify the findings. PRISMA guidelines were followed and the review was conducted by searching social sciences databases and electronic libraries including Google Scholar, Sage Journal, and Science Direct (1990-2020). The results suggested that psychotherapeutic interventions including cognitive behavior therapy, mindful-based cognitive therapy; and interpersonal and social rhythm therapeutic interventions are efficacious modalities for treatment when in augmentation with psychopharmacological treatment. Bipolar diathesis and comorbid conditions of anxiety and personality disorders are possible causal factors in developing the condition of treatment resistance in mood disorders. The prevalence rate of TRMD is more common in females and in late adulthood. The analysis also suggests that there are numerous risk factors contributing to making a mood disorder treatment-resistant over a period of time; the most observed conditions were physical and psychological comorbidity, inaccurate diagnosis, lack of proper medical treatment, illness severity, and late age diagnosis. In evidence-based non-medical treatment approaches aerobics demonstrated promising results in improving the condition of complex mood disorders. It was concluded that psychotherapeutic interventions in augmentation with pharmacological modalities enhance the efficacy of treatment.

Average Daily Dose Trajectories for Episodes of Buprenorphine Treatment for Opioid Use Disorder.

High-dose (≥24 mg) buprenorphine daily doses (BDD) may be important in treating patients with opioid use disorder (OUD) to improve retention and prevent overdose, particularly in the context of increased illicit fentanyl use. This study sought to: (1) identify trajectories for average BDD among patients initiating buprenorphine treatment for OUD and (2) assess patient characteristics associated with these identified trajectories. Buprenorphine treatment episodes among patients in the US Veterans Healthcare Administration (VHA) from federal fiscal years 2006 to 2020 were identified. Group-based trajectory modeling (GBTM) was used to identify BDD trajectories based on weekly averages of BDD over the 180 days after buprenorphine episode initiation. A total of 79 303 buprenorphine treatment episodes among 44 583 patients were included in the analytic sample. GBTM identified 9 latent trajectories for BDD: (1) moderate dose, early discontinuation (10.1%), (2) moderate dose, delayed discontinuation (4.5%), (3) moderate dose, moderate-paced discontinuation (5.2%), (4) low-moderate dose, delayed discontinuation (7.0%), and (5) low-moderate dose, early discontinuation (21.1%), (6) low dose retention (9.6%), (7) low-moderate dose retention (16.7%), (8) moderate dose retention (18.6%), and (9) high dose retention (7.4%). Patient BDD can broadly be characterized as low [2-4 mg/day], low-moderate (6-8 mg/day), moderate (12-18 mg/day), and high dose (≥ 24 mg/day). Patients with episodes in the high BDD trajectory have the lowest social risk (eg, lowest rate of past-year history of homelessness) and the lowest diagnosed rate of physical and mental health-related comorbidities compared to those following other trajectories. BDD ranges widely and patient characteristics are significantly different between those episodes following differing BDD trajectories. Future research on the association between BDD and subsequent patient outcomes (eg, overdose) needs to carefully consider these differences in baseline characteristics.

The Cognitive Profile of Older Adults With Treatment-Resistant Depression: An Analysis of the OPTIMUM Randomized Controlled Trial

ObjectiveMajor depressive disorder in older adults (late-life depression; LLD) is frequently associated with cognitive impairment, and some deficits (e.g., executive function) have been associated with a higher level of treatment resistance. However, the cognitive profile of treatment-resistant LLD (TR-LLD) has not been characterized. We hypothesized that patients with TR-LLD would show deficits in cognitive function, especially executive function, and that executive function deficits would predict poorer response to pharmacotherapy. DesignSecondary analysis of baseline cognitive data from OPTIMUM, a multicenter RCT evaluating pharmacotherapy strategies for TR-LLD. SettingFive outpatient academic medical centers (4 US, 1 Canada). ParticipantsAbout 369 participants aged 60 and older from the OPTIMUM study. MeasurementsBaseline scores on individual tasks and composite scores from the NIH Toolbox-Cognition Battery were transformed into demographically-adjusted T-scores and compared to published norms. Impairments in the set shifting and inhibitory control tasks were investigated as predictors of depressive symptom change following treatment using ANCOVA models. ResultsParticipants had low performance on tasks evaluating inhibitory control, processing speed, verbal/nonverbal memory, and the fluid composite, but normative performance on working memory and set shifting. Participants had high estimated premorbid IQ (superior Performance on oral reading recognition). Age and physical comorbidity negatively associated with processing speed. Impairments in set shifting predicted less improvement in depressive symptoms; impairments in inhibitory control did not. ConclusionsParticipants with TR-LLD presented with broad cognitive deficits relative to healthy norms. Given poorer outcomes following standard pharmacotherapy associated with impaired set shifting, future research needs to identify alternative treatment strategies.

Prevalence of Antidepressant Prescriptions for Community-Dwelling Adults Diagnosed with Depressive Disorder in the UK: A Systematic Review.

The UK National Institute for Health and Care Excellence (NICE) guidance for the treatment of depression is widely followed and has international influence. According to these guidelines, antidepressant medications are recommended for moderate to severe depression. Nonetheless, antidepressants are increasingly prescribed, including for cases of subthreshold and mild depression. This may indicate that a proportion of depressed patients uses pharmacological interventions with unclear evidence-base, though other factors such as physical and mental health comorbidities need to be accounted for. This study aims to investigate the prevalence and trends of antidepressant prescriptions among community-dwelling adults diagnosed with depression according to NICE recommendations. We conducted a systematic review of PsycInfo, PubMed/MEDLINE, and Scopus databases. Observational studies reporting on the prevalence of antidepressant treatments in UK adults diagnosed with depression were sought. Fifteen studies were included. The prevalence of antidepressants for depression treatment ranged from 30.8 to 95% and mainly concerned selective serotonin reuptake inhibitors (SSRIs) among classes of antidepressant drugs. Little information about depression severity as well as comorbid conditions was reported. High prevalence rates of antidepressant drug use highlight the widespread adoption of pharmacological interventions, while also raising concerns about compliance with NICE guidelines. Careful assessment of depressive illness severity and comorbidities is needed to ensure the delivery of adequate care to people with depression. Systematic Review Registration Number (PROSPERO) CRD42023448152.