Family-based interventions versus standard care for people with schizophrenia.

BACKGROUND: People with schizophrenia often experience long-term psychosocial disabilities and frequent relapse. Family plays a key role in caring for ill relatives, which in turn probably contributes to high levels of distress and burdens for the family. Family-based interventions have been developed and applied to family members and their relatives with schizophrenia to improve their outcomes. This is an update of a Cochrane review that was last updated in 2011, which has been split into this review, one on group- versus individual-based family interventions and one on family-based cognitive versus behavioural management interventions. OBJECTIVES: To assess the effects of family-based interventions for people with schizophrenia or schizophrenia-like disorders and their families compared with standard care. SEARCH METHODS: We searched the following electronic databases from inception until April 2023: CENTRAL, Medline, Embase, PsycInfo, CINAHL, WHO International Clinical Trials Registry Platform (ICTRP), Clinicaltrials.gov, SinoMed, China Network Knowledge Infrastructure (CNKI), Wanfang, and Chinese Scientific Journals Database (VIP). We also searched the reference lists of included studies and accessible reviews for additional references. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared the effects of family-based interventions for people with schizophrenia or schizophrenia-like disorders and their families and reported at least one patient's and one family member's outcomes. In this update, we only investigated standard care as the comparator. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. The review authors independently screened studies, extracted data, and assessed risk of bias for each study using the Cochrane risk of bias tool for RCTs. We pooled data and estimated effects with the mean difference (MD), standardised mean difference (SMD), or risk ratio (RR) with 95% confidence interval (CI). We judged the certainty of evidence using GRADEpro GDT. We divided the outcomes into short-term (≤ 1 month postintervention), medium-term (> 1 to 6 months postintervention), and long-term follow-up (> 6 months postintervention), if available. MAIN RESULTS: We identified 26 RCTs in this review, with 1985 people with schizophrenia or schizophrenia-like disorders, and 2056 family members. Most family-based interventions were conducted on a weekly or biweekly basis, with duration ranging from five weeks to two years. We had substantial concerns regarding the methodological quality of the included studies given that we judged all studies at high risk of performance bias and several studies at high risk of detection, attrition or reporting bias. Low-certainty evidence indicated that family-based interventions may reduce patients' relapse at one month or less postintervention (RR 0.66, 95% CI 0.49 to 0.89; 4 RCTs, 229 participants). We downgraded the evidence by two levels due to imprecision (small number of participants) and high risk of performance, detection and attrition bias. Compared to standard care, family-based interventions probably reduce caregiver burden at one month or less postintervention (MD -5.84, 95% CI -6.77 to -4.92; 8 RCTs, 563 participants; moderate-certainty evidence) and may result in more family members shifting from high to low expressed emotion (RR 3.90, 95% CI 1.11 to 13.71; 2 RCTs, 72 participants; low-certainty evidence). Family interventions may result in little to no difference in patients' death (RR 0.48, 95% CI 0.18 to 1.32; 6 RCTs, 304 participants; low-certainty evidence) and hospital admission (≤ 1 month postintervention; RR 0.81, 95% CI 0.51 to 1.29; 2 RCTs, 153 participants; low-certainty evidence) in comparison with standard care. Due to the heterogeneous measures and various follow-up periods, we were unable to provide pooled effect estimates for patients' compliance with medication and quality of life. We were very uncertain whether family interventions resulted in enhanced compliance with medication and improved quality of life for patients. We downgraded the evidence to very low certainty due to high risk of bias across studies, inconsistency (different directions of effects across studies), and imprecision (small number of participants or CIs of most studies including the possibility of no effect). AUTHORS' CONCLUSIONS: This review synthesised the latest evidence on family interventions versus standard care for people with schizophrenia or schizophrenia-like disorders and their families. This review suggests that family interventions might improve patients' outcomes (e.g. relapse) and families' outcomes (e.g. caregiver burden and expressed emotion), with little to no difference in patients' hospital admission and adverse effects in terms of death. However, evidence on patients' compliance with medication and quality of life was very uncertain. Overall, the evidence was of moderate to very low certainty. Future large and well-designed RCTs are needed to provide more reliable evaluation of effects of family interventions in people with schizophrenia or schizophrenia-like disorders and their families.

Refining the standard of care in immune thrombotic thrombocytopenic purpura.

Acute immune thrombotic thrombocytopenic purpura (iTTP) is a medical emergency. In the setting of any thrombotic microangiopathy (TMA), blood should be drawn to measure ADAMTS13 activity and inhibitor levels, and an assessment should be made of TTP risk before receiving ADAMTS13 results. This can include the use of PLASMIC and French scores. Plasma exchange (PE) is then initiated. Upon confirmation of iTTP, with ADAMTS13 less than 10% in the presence of an inhibitor, interventions targeting all facets of iTTP pathophysiology should be instituted: replenishing ADAMTS13 via continued PE; suppressing anti-ADAMTS13 autoantibodies with glucocorticoids and rituximab; and inhibiting the thrombotic process-uncontrolled formation of platelet/Von Willebrand factor (VWF) microthrombi-with caplacizumab. The latter, an addition to existing standards of care, is based on International Society on Thrombosis and Haemostasis guidelines and emphasizes tracking of ADAMTS13 activity. In HERCULES, a pivotal randomized controlled trial, caplacizumab use resulted in fewer recurrent iTTP episodes, decreased PE, and shortened hospital stay. In settings of high suspicion for iTTP, clinicians should consider the administration of caplacizumab before receiving ADAMTS13 results because the greatest benefits of caplacizumab accrued starting it within 3 days of TMA recognition. In HERCULES, serious bleeding events occurred among 11% of those in the caplacizumab group vs 1% in the placebo group, but all resolved, most without intervention. iTTP survivors receiving PE and immunosuppression alone are at a heightened risk for stroke, other cardiovascular disorders, neurocognitive impairment, and kidney disease. Whether rapid prevention of VWF multimer/platelet formation with caplacizumab can suppress such long-term sequelae, and whether caplacizumab can replace PE in initial therapy, are under investigation.

A Prospective Randomized Controlled Study of Stratafix versus Standard-of-Care for Deep Tissue Closure in Orthopedic Surgery.

Background: Orthopedic deep surgical incisions require the approximation of 1 or multiple tissue layers. This prospective randomized controlled study aimed to assess the usefulness and effectiveness of a barbed suture technique (Stratafix symmetric PDS plus) versus the conventional interrupted knotted suture technique for deep tissue closure in orthopedic surgery by comparing deep fascia suture time, relative cost, and wound-related complications. Methods: A total of 254 patients with deep surgical incisions who underwent orthopedic surgery between October 1, 2020, and June 30, 2021, were recruited. Their general characteristics (age, sex, weight, height, body mass index, American Society of Anesthesiologists physical status score, total operation time, and length of deep incision) and factors related to deep incision wounds (suture type and number, wound closure time, and operation site outcomes) were collected. Results: The general characteristics did not differ between the Stratafix and conventional groups. There were no between-group differences observed in total operation time or total anesthesia time. The wound suture times differed significantly. In the conventional group, the suture time per unit length was lower in the group with the length of deep incision under 20 cm but did not differ significantly for each wound size. In the Stratafix group, the suture time per unit length was lower in the group under 15 cm, with the shortest time observed for 10-14.9 cm, followed by 5.0-9.9 cm and the group under 5 cm. The conventional group developed 4 cases of superficial wound infection or surgical wound necrosis. One case of protruded suture tap occurred in the Stratafix group. Conclusions: The average suture time per unit length increased for lengths under 5 cm as barbed sutures required more time from the start of the first suture to finish of the last suture. There was no significant benefit for very short suture length. One barbed suture material allows a suture of approximately 10-12 cm; sutures beyond that require more time because the surgeon has to start again. The Stratafix group used less suture material than the conventional group.

Pharmacogenomics-assisted treatment versus standard of care in schizophrenia: a systematic review and meta-analysis.

BACKGROUND: Pharmacogenomic (PGx) factors significantly influence how patients respond to antipsychotic medications This systematic review was performed to synthesize the clinical utility of PGx-assisted treatment versus standard of care in schizophrenia. METHODS: PubMed, Embase, and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) from inception till June 2024 that had compared the clinical utility of PGx-assisted intervention as compared to the standard of care in schizophrenia. The primary outcome was safety, and the secondary outcomes were efficacy and medication adherence. Pooled standardized mean differences (SMD) along with a 95% confidence interval (CI) were calculated (random-effects model) wherever feasible. RESULTS: A total of 18,821 studies were screened, and five were included for review. All the RCTs had a high risk of bias. Four studies included the commonly used antipsychotics. Three studies reported negative outcomes (safety, efficacy, and medication adherence) and two reported positive outcomes (safety) using different scales. In the meta-analysis, there were significant differences in the total Udvalg for Kliniske Undersogelser Side-Effect Rating scale score [SMD 0.95 (95% CI: 0.76-1.13), p < 0.001); I2 = 0%] and the total Positive and Negative Syndrome Scale score [SMD 10.65 (95% CI: 2.37-18.93), p = 0.01); I2 = 100%] between the PGx-assisted treatment and standard of care arms. However, the results were inconsistent, and the certainty of evidence (GRADE criteria) was very low. CONCLUSION: Current evidence on the clinical utility of PGx-assisted treatment in schizophrenia is limited and inconsistent and further evidence is required in this regard.

Investigating ethical tradeoffs in crisis standards of care through simulation of ventilator allocation protocols.

INTRODUCTION: Arguments over the appropriate Crisis Standards of Care (CSC) for public health emergencies often assume that there is a tradeoff between saving the most lives, saving the most life-years, and preventing racial disparities. However, these assumptions have rarely been explored empirically. To quantitatively characterize possible ethical tradeoffs, we aimed to simulate the implementation of five proposed CSC protocols for rationing ventilators in the context of the COVID-19 pandemic. METHODS: A Monte Carlo simulation was used to estimate the number of lives saved and life-years saved by implementing clinical acuity-, comorbidity- and age-based CSC protocols under different shortage conditions. This model was populated with patient data from 3707 adult admissions requiring ventilator support in a New York hospital system between April 2020 and May 2021. To estimate lives and life-years saved by each protocol, we determined survival to discharge and estimated remaining life expectancy for each admission. RESULTS: The simulation demonstrated stronger performance for age-sensitive protocols. For a capacity of 1 bed per 2 patients, ranking by age bands saves approximately 29 lives and 3400 life-years per thousand patients. Proposed protocols from New York and Maryland which allocated without considering age saved the fewest lives (~13.2 and 8.5 lives) and life-years (~416 and 420 years). Unlike other protocols, the New York and Maryland algorithms did not generate significant disparities in lives saved and life-years saved between White non-Hispanic, Black non-Hispanic, and Hispanic sub-populations. For all protocols, we observed a positive correlation between lives saved and life-years saved, but also between lives saved overall and inequality in the number of lives saved in different race and ethnicity sub-populations. CONCLUSION: While there is significant variance in the number of lives saved and life-years saved, we did not find a tradeoff between saving the most lives and saving the most life-years. Moreover, concerns about racial discrimination in triage protocols require thinking carefully about the tradeoff between enforcing equality of survival rates and maximizing the lives saved in each sub-population.

Percentage area reduction at week 4 as a prognostic indicator of complete healing in patients treated with standard of care: a post hoc analysis.

Early indicators of healing provide valuable information on the potential benefit of treatment. In patients with hard-to-heal (chronic) diabetic foot ulcers (DFUs), timely intervention is critical. Ulcers that fail to show measurable progress within four weeks of treatment are considered recalcitrant. These ulcers increase the risk of soft tissue infection, osteomyelitis and lower extremity amputation. A prognostic indicator or surrogate marker allows for rapid evaluation of treatment efficacy and safety. An inverse correlation between a percentage area reduction (PAR) of ≤50% at week 4 and complete healing by week 12 has been previously established; however, the data were derived from a standard of care (SoC) arm of clinical trials that are over a decade old. In this post hoc analysis, data from a large multicentre prospective randomised controlled trial were reviewed to assess PAR at week 4 as a prognostic indicator in patients treated with SoC. Overall, 65.4% (17/26) of patients with PAR >50% at week 4 achieved complete closure at week 12. The receiver operating characteristic (ROC) curve for area reduction by week 4 showed strong discrimination for predicting non-healing (area under the ROC curve: 0.92; p<0.001; positive predictive value: 70.6%; negative predictive value: 87.2%). These findings are consistent with previous studies and support the use of four-week PAR as a prognostic indicator.

Protocol to generate two distinct standard-of-care murine glioblastoma models for evaluating novel combination therapies.

In cancer research, murine models play a crucial role as highly valuable preclinical tools. Here, we present a protocol to generate a murine model of glioblastoma through the direct intracranial injection of tumor cells. We describe steps for cell culture, intracranial implantation, and standard-of-care treatments. We then detail procedures for monitoring tumor growth using bioluminescent imaging. For complete details on the use and execution of this protocol, please refer to Pelizzari-Raymundo et al.1.

Remifentanil Target-controlled Infusion Versus Standard of Care for Conscious Sedation During Ultrasound-guided Transbronchial Needle Aspiration and Biopsy: A Randomized, Prospective, Control Study.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure that has become an important tool in the diagnosis and staging of mediastinal lymph node lesions in lung cancer. Adequate sedation is an important part of the procedure as it provides patient comfort and potentially increases diagnostic yield. The sedation modality varies among centers and includes moderate sedation/conscious sedation, deep sedation, and general anesthesia. The object of this study will be the evaluation of patient's comfort and level of satisfaction with the involved health care providers (bronchoscopist and anesthesiologist) of remifentanil administration in target-controlled infusion (TCI) for conscious sedation in patients undergoing EBUS­TBNA, with a prospective randomized study design versus the of standard sedation protocol with midazolam and/or fentanest and/or propofol. METHODS: This study was carried out at the "Campus Biomedico di Roma" University Hospital between September 2021 and November 2021, with a total number of 30 patients enrolled who met the eligibility criteria, randomly divided into 2 groups: group 1 "REMIFENTANIL TCI" (experimental group) where the patients performed the EBUS-TBNA procedure under conscious sedation with infusion of remifentanil TCI with a target between 3 ng/mL and 6 ng/mL and group 2 "STANDARD" (control group) with patients undergoing conscious sedation with the association of midazolam and/or fentanest and/or propofol in refracted boluses based on clinical needs. Complications, safety, and level of satisfaction of the operator, the anesthesiologist, and the patient were evaluated. RESULTS: The results show that sedation with remifentanil in TCI can improve the comfort level of patients, reducing the risks associated with the procedure (lower frequency of oversedations and hypotension), allowing for greater intraprocedural safety. Furthermore, the level of satisfaction of the anesthesiologist and that of the operator appears to be significantly higher in the Remifentanil group. CONCLUSION: The execution of a mild to moderate sedation with Remifentanil in TCI in patients undergoing EBUS is safe, tolerated, and allows to obtain greater intraprocedural comfort. Further studies and larger and more representative samples are obviously needed to confirm and strengthen the validity of a remifentanil TCI-based sedation in endoscopic diagnostics.

Uptake of Cancer Genetic Services for Chatbot vs Standard-of-Care Delivery Models: The BRIDGE Randomized Clinical Trial.

Importance: Increasing numbers of unaffected individuals could benefit from genetic evaluation for inherited cancer susceptibility. Automated conversational agents (ie, chatbots) are being developed for cancer genetics contexts; however, randomized comparisons with standard of care (SOC) are needed. Objective: To examine whether chatbot and SOC approaches are equivalent in completion of pretest cancer genetic services and genetic testing. Design, Setting, and Participants: This equivalence trial (Broadening the Reach, Impact, and Delivery of Genetic Services [BRIDGE] randomized clinical trial) was conducted between August 15, 2020, and August 31, 2023, at 2 US health care systems (University of Utah Health and NYU Langone Health). Participants were aged 25 to 60 years, had had a primary care visit in the previous 3 years, were eligible for cancer genetic evaluation, were English or Spanish speaking, had no prior cancer diagnosis other than nonmelanoma skin cancer, had no prior cancer genetic counseling or testing, and had an electronic patient portal account. Intervention: Participants were randomized 1:1 at the patient level to the study groups at each site. In the chatbot intervention group, patients were invited in a patient portal outreach message to complete a pretest genetics education chat. In the enhanced SOC control group, patients were invited to complete an SOC pretest appointment with a certified genetic counselor. Main Outcomes and Measures: Primary outcomes were completion of pretest cancer genetic services (ie, pretest genetics education chat or pretest genetic counseling appointment) and completion of genetic testing. Equivalence hypothesis testing was used to compare the study groups. Results: This study included 3073 patients (1554 in the chatbot group and 1519 in the enhanced SOC control group). Their mean (SD) age at outreach was 43.8 (9.9) years, and most (2233 of 3063 [72.9%]) were women. A total of 204 patients (7.3%) were Black, 317 (11.4%) were Latinx, and 2094 (75.0%) were White. The estimated percentage point difference for completion of pretest cancer genetic services between groups was 2.0 (95% CI, -1.1 to 5.0). The estimated percentage point difference for completion of genetic testing was -1.3 (95% CI, -3.7 to 1.1). Analyses suggested equivalence in the primary outcomes. Conclusions and Relevance: The findings of the BRIDGE equivalence trial support the use of chatbot approaches to offer cancer genetic services. Chatbot tools can be a key component of sustainable and scalable population health management strategies to enhance access to cancer genetic services. Trial Registration: ClinicalTrials.gov Identifier: NCT03985852.

Health care resource utilization and direct costs incurred over 24 months after initiating galcanezumab or standard-of-care preventive migraine treatments in the United States.

BACKGROUND: Health care resource utilization (HCRU) and direct costs incurred over 12 months following initiation of galcanezumab (GMB) or standard-of-care (SOC) preventive migraine treatments have been evaluated. However, a gap in knowledge exists in understanding longer-term HCRU and direct costs. OBJECTIVE: To compare all-cause and migraine-related HCRU and direct costs in patients with migraine initiating GMB or SOC preventive migraine treatments over a 24-month follow-up. METHODS: This retrospective study used Optum deidentified Market Clarity Data. The study included adults diagnosed with migraine, with at least 1 claim for GMB or SOC preventive migraine therapy (September 2018 to March 2020), with continuous enrollment for 12 months before and 24 months after (follow-up) the index date (date of first GMB or SOC claim). Propensity score (PS) matching (1:1) was used to balance cohorts. All-cause and migraine-related HCRU and direct costs for GMB vs SOC cohorts were reported as mean (SD) per patient per year (PPPY) over a 24-month follow-up and compared using a Z-test. Costs were inflated to 2022 US$. RESULTS: After PS matching, 2,307 patient pairs (mean age: 44.4 years; female sex: 87.3%) were identified. Compared with the SOC cohort, the GMB cohort had lower mean (SD) PPPY all-cause office visits (17.9 [17.7] vs 19.1 [18.7]; P = 0.023) and migraine-related office visits (2.6 [3.3] vs 3.0 [4.7]; P = 0.002) at follow-up. No significant differences were observed between cohorts in other all-cause and migraine-related events assessed including outpatient visits, emergency department (ED) visits, inpatient stays, and other medical visits. The mean (SD) costs PPPY were lower in the GMB cohort compared with the SOC cohort for all-cause office visits ($4,321 [7,518] vs $5,033 [7,211]; P < 0.001) at follow-up. However, the GMB cohort had higher mean (SD) PPPY all-cause total costs ($24,704 [30,705] vs $21,902 [28,213]; P = 0.001) and pharmacy costs ($9,507 [12,659] vs $5,623 [12,605]; P < 0.001) compared with the SOC cohort. Mean (SD) costs PPPY were lower in the GMB cohort for migraine-related office visits ($806 [1,690] vs $1,353 [2,805]; P < 0.001) compared with the SOC cohort. However, the GMB cohort had higher mean (SD) PPPY migraine-related total costs ($8,248 [11,486] vs $5,047 [9,749]; P < 0.001) and migraine-related pharmacy costs ($5,394 [3,986] vs $1,761 [4,133]; P < 0.001) compared with the SOC cohort. There were no significant differences between cohorts in all-cause and migraine-related costs for outpatient visits, ED visits, inpatient stays, and other medical visits. CONCLUSIONS: Although total costs were greater for GMB vs SOC following initiation, changes in a few categories of all-cause and migraine-related HCRU and direct costs were lower for GMB over a 24-month follow-up. Additional analysis evaluating indirect health care costs may offer insights into further cost savings incurred with preventive migraine treatment.

Translational modeling-based evidence for enhanced efficacy of standard-of-care drugs in combination with anti-microRNA-155 in non-small-cell lung cancer.

BACKGROUND: Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. Therapeutic targeting of miR-155 through its antagonist, anti-miR-155, has proven challenging due to its dual molecular effects. METHODS: We developed a multiscale mechanistic model, calibrated with in vivo data and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs. RESULTS: Model simulations and analyses of the clinical scenario revealed that monotherapy with anti-miR-155 at a dose of 2.5 mg/kg administered once every three weeks has substantial anti-cancer activity. It led to a median progression-free survival (PFS) of 6.7 months, which compared favorably to cisplatin and immune checkpoint inhibitors. Further, we explored the combinations of anti-miR-155 with standard-of-care drugs, and found strongly synergistic two- and three-drug combinations. A three-drug combination of anti-miR-155, cisplatin, and pembrolizumab resulted in a median PFS of 13.1 months, while a two-drug combination of anti-miR-155 and cisplatin resulted in a median PFS of 11.3 months, which emerged as a more practical option due to its simple design and cost-effectiveness. Our analyses also provided valuable insights into unfavorable dose ratios for drug combinations, highlighting the need for optimizing dose regimens to prevent antagonistic effects. CONCLUSIONS: This work bridges the gap between preclinical development and clinical translation of anti-miR-155 and unravels the potential of anti-miR-155 combination therapies in NSCLC.

Quality-of-care standards in adult type 3 intestinal failure caused by benign disease: A European society of clinical nutrition and metabolism (ESPEN) position paper.

BACKGROUND: Outcomes related to chronic intestinal failure (CIF) vary significantly within and between countries. While there are extensive European Society of Clinical Nutrition and Metabolism (ESPEN) guidelines on the delivery of optimal care in CIF, there are no international consensus recommendations on the structure or resources required, nor on the process and appropriate outcome measures for delivering such quality care in CIF. AIM: The aim of this position paper is therefore to devise ESPEN-endorsed, internationally agreed quality of care standards, covering the resources, systems and standards that centres should aim for in order to deliver optimal CIF care. METHODS: Members of the Home Artificial Nutrition-CIF Special Interest Group of ESPEN proposed an initial set of quality-of-care standards which was submitted to voting amongst clinicians from international CIF centres using a modified Delphi process, with participants rating each proposed statement as 'essential', 'recommended' or 'not required'. Any statement receiving 80% of more 'not required' responses was excluded. RESULTS: All 30 proposed standards relating to the structure, 18 relating to the process and 16 to the outcome measures of CIF care were deemed to be essential or recommended in more than 80% of respondents. CONCLUSION: This is the first paper to determine and describe internationally-agreed quality of care standards in CIF, which are now aimed at forming the basis for all CIF teams to develop and monitor their service, while also informing policymakers and payers on the infrastructure required for the optimal approach to multi-disciplinary team CIF care delivery. The recording of standardised outcomes should also allow internal and external benchmarking of care delivery within and between CIF centres.