DEVELOPING THERAPIES FOR C3G: REPORT OF THE KIDNEY HEALTH INITIATIVE C3G TRIAL ENDPOINTS WORK GROUP.

Randomized clinical trials are underway to evaluate the efficacy of novel agents targeting the alternative complement pathway in patients with C3G, a rare glomerular disease. The Kidney Health Initiative (KHI) convened a panel of experts in C3G to: (1) assess the data supporting the use of the prespecified trial endpoints as measures of clinical benefit; and (2) opine on efficacy findings they would consider compelling as treatment(s) for C3G in native kidneys. Two subpanels of the C3G Trial Endpoints Work group reviewed the available evidence and uncertainties for the association between the three prespecified endpoints -- (1) proteinuria; (2) estimated glomerular filtration rate (eGFR); and (3) histopathology -- and anticipated outcomes. The full work group provided feedback on the summaries provided by the subpanels and on what potential treatment effects on the proposed endpoints they would consider compelling to support evidence of an investigational product's effectiveness for treating C3G. Members of the full work group agreed with the characterization of the data, the evidence, and uncertainties, supporting the endpoints. Given the limitations of the available data, the workgroup was unable to define a minimum threshold for change in any of the endpoints that might be considered clinically meaningful. The workgroup concluded that a favorable treatment effect on all three endpoints would provide convincing evidence of efficacy in the setting of a therapy that targeted the complement pathway. A therapy might be considered effective in the absence of complete alignment in all three endpoints if there was meaningful lowering of proteinuria and stabilization or improvement in eGFR. The panel unanimously supported efforts to foster data sharing between academic and industry partners to address the gaps in the current knowledge identified by the review of the endpoints in the aforementioned trials.

The impact of carbohydrate restriction-induced elevations in low-density lipoprotein cholesterol on progression of coronary atherosclerosis: the ketogenic diet trial study design.

BACKGROUND: Despite innovations in pharmacotherapy to lower lipoprotein cholesterol and apolipoprotein B, risk factors for atherosclerotic cardiovascular disease (ASCVD), ASCVD persists as the leading global cause of mortality. Elevations in low-density lipoprotein cholesterol (LDL-C) are a well-known risk factor and have been a main target in the treatment of ASCVD. The latest research suggests that ketogenic diets are effective at improving most non-LDL-C/apolipoprotein B cardiometabolic risk factors. However, ketogenic diets can induce large increases in LDL-C to >190 mg/dl in some individuals. Interestingly, these individuals are often otherwise lean and healthy. The influence of increased levels of LDL-C resulting from a carbohydrate-restricted ketogenic diet on the progression of atherosclerosis in otherwise metabolically healthy individuals is poorly understood. This observational study aims to assess and describe the progression of coronary atherosclerosis in this population within 12 months. METHODS: Hundred relatively lean individuals who adopted ketogenic diets and subsequently exhibited hypercholesterolemia with LDL-C to >190 mg/dl, in association with otherwise good metabolic health markers, were enrolled and observed over a period of 12 months. Participants underwent serial coronary computed tomography angiography scans to assess the progression of coronary atherosclerosis in a year. RESULTS: Data analysis shall begin following the conclusion of the trial with results to follow. CONCLUSION: Ketogenic diets have generated debate and raised concerns within the medical community, especially in the subset exhibiting immense elevations in LDL-C, who interestingly are lean and healthy. The relationship between elevated LDL-C and ASCVD progression in this population will provide better insight into the effects of diet-induced hypercholesterolemia.

Well-Being Domains in U.S. Military Veterans: Identifying Modifiable Factors to Promote Whole Health.

The U.S. Department of Veterans Affairs is actively transitioning away from a disease-centric model of healthcare to one that prioritizes disease prevention and the promotion of overall health and well-being. Described as Whole Health, this initiative aims to provide personalized, values-centered care that optimizes physical, behavioral, spiritual, and socioeconomic well-being. To inform this initiative, we analyzed cross-sectional data from a nationally representative sample of primarily older U.S. military veterans to estimate levels of well-being across these domains, and identify sociodemographic, military, and potentially modifiable health and psychosocial correlates of them. Results revealed that, overall, veterans reported high domain-specific well-being (average scores ranging from 6.7 to 8.3 out of 10), with the highest levels in the socioeconomic domain and lowest in the physical domain. Several modifiable factors, including purpose in life, resilience, and social support, were strongly associated with the examined well-being domains. Interventions targeting these constructs may help promote well-being among U.S. veterans.

Peroneal Nerve Decompression in Patients with Multiple Hereditary Exostoses: Indications, Complications, and Recurrence.

BACKGROUND: To our knowledge, there have been no studies examining peroneal nerve decompression and proximal fibular osteochondroma excision exclusively in patients with multiple hereditary exostoses (MHE). The purpose of this study was to evaluate the indications, complications, and recurrence associated with nerve decompression and proximal fibular osteochondroma excision in patients with MHE. METHODS: The records on patients with MHE undergoing peroneal nerve decompression from 2009 to 2023 were retrospectively reviewed. Indications, clinical status, surgical technique, recurrence, and complications were recorded and were analyzed using the Fisher exact test, logistic regression, and the Kaplan-Meier method. RESULTS: There were 126 limbs identified in patients with MHE who underwent peroneal nerve decompression. The most common indications were pain over the proximal fibula, tibialis anterior and/or extensor hallucis longus weakness, and dysesthesias and/or neuropathic pain. Seven cases experienced postoperative foot drop as a complication of the decompression and osteochondroma excision. Logistic regression found significant relationships between complications and excision of anterior osteochondromas (odds ratio [OR], 5.21; p = 0.0062), proximal fibular excision (OR, 14.73; p = 0.0051), and previous decompression (OR, 5.77; p = 0.0124). The recurrence rate was 13.8%, and all recurrences occurred in patients who were skeletally immature at the index procedure. The probability of skeletally immature patients not experiencing recurrence was 88% at 3 years postoperatively and 73% at 6 years postoperatively. CONCLUSIONS: Indications for peroneal nerve decompression included neurologic symptoms and pain. The odds of a complication increased with excision of anterior osteochondromas and previous decompression. Recurrence of symptoms following decompression and osteochondroma excision was found exclusively in skeletally immature patients. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Surgery for Spinal Stenosis in Achondroplasia: Causes of Reoperation and Reduction of Risks.

BACKGROUND: Individuals with achondroplasia are prone to symptomatic spinal stenosis requiring surgery. Revision rates are thought to be high; however, the precise causes and rates of reoperation are unknown. The primary aim of this study is to investigate the causes of reoperation after initial surgical intervention in individuals with achondroplasia and spinal stenosis. In addition, we report on surgical techniques aimed at reducing the risks of these reoperations. METHODS: A retrospective review was conducted over an 8-year period of all patients with achondroplasia at a single institution that serves as a large referral center for patients with skeletal dysplasias. Patients with achondroplasia who underwent spinal surgery for stenosis were identified and the need for revision surgery was studied. Data collected included demographic, surgical, and revision details. Fisher exact test was used to determine if an association existed between construct type and the need for revisions. RESULTS: Thirty-three of the 130 (22%) patients with achondroplasia required spinal stenosis surgery. Twenty-four individuals who met the criteria were selected for analysis. The initial spine surgery was at an average age of 18.7 years (SD: 10.1 y). Nine patients (38%) required revision surgeries, and 3 required multiple revisions. Five of 9 (56%) of the revisions had primary surgery at an outside institution. Revision surgeries were due to caudal pseudarthrosis (the distal instrumented segment) (8), proximal junctional kyphosis (PJK) (7), and new neurological symptoms (7). There was a significant association found between construct type and the need for revision (P=0.0111). The pairwise comparison found that short fusions were significantly associated with the need for revision compared with the interbody group (P=0.0180). PJK was associated with short fusions when compared with the long fusion group (P=0.0294) and the interbody group (P=0.0300). Caudal pseudarthrosis was associated with short fusions when compared with the interbody group (P=0.0015). Multivariate logistic regression found long fusion with an interbody was predictive of and protective against the need for revision surgery (P=0.0246). To date, none of the initial cases that had long fusions with caudal interbody required a revision for distal pseudarthrosis. CONCLUSIONS: In patients with achondroplasia, the rate of surgery for spinal stenosis is 22% and the risk of revision is 38% and is primarily due to pseudarthrosis, PJK, and recurrent neurological symptoms. Surgeons should consider discussing spinal surgery as part of the patient's life plan and should consider wide decompression of the stenotic levels and long fusion with the use of an interbody cage at the caudal level in all patients to reduce risks of revision. LEVEL OF EVIDENCE: Level IV-Retrospective case series.

The Ethics of Hope-A Moral Imperative for Oncologists.

This Viewpoint suggests that giving patients with terminal cancer unrealistic hope based only on cure is ethically inferior to redirecting patients toward noncurative goals and noncancer-related hope.

Feeling hopeful: development and validation of the trait emotion hope scale.

While prominent measures of hope are largely cognitive in nature, many scholars and laypeople view hope primarily as an emotion. Although Snyder's Elaborated Hope Theory attempts to theoretically balance these two perspectives, no measure yet exists of hope as a purely emotional process, only as a cognitive process. Overlooking the emotional features of hope limits our ability to more fully and precisely understand this construct. As such, across three studies (N = 2,900), we develop and validate the Trait Emotion Hope Scale (TEHS). In Study 1, we report on item development and piloting of the TEHS, examining internal consistency as well as convergent and discriminant validity. Study 2 includes an exploratory factor analysis (EFA) and further examines internal consistency and construct validity. Finally, in Study 3 we report a confirmatory factor analysis (CFA) to cross-validate the factor structure identified in Study 2 in a large, international sample. Importantly, we find that the TEHS accounts for significant unique variance beyond cognitive hope, indicating that the two constructs are distinct and not redundant. Taken together, these three studies demonstrate that the TEHS is psychometrically sound and provides a valid measure for those interested in examining hope as an emotion in their research.

Hope during somber times: a defining moment.

In addition to the diverse educational materials the National Cancer Institute provides to patients, caregivers, and health-care professionals, the NCI maintains an online dictionary that provides concise definitions of terms used in modern oncology. The dictionary is regarded as a valuable data reserve because it is updated frequently and employs language that facilitates comprehension among lay users and professionals alike. In this commentary, we call attention to the absence of the word hope as an entry in this important digital resource. Moreover, we propose not only including the concept of hope in this vital reference text but also basing its meaning on C. R. Snyder's model of "hope theory," which stresses the importance of 3 entities: goals, pathways thinking, and agency. Finally, we argue that hope can be taught as a skill to relevant stakeholders (eg, patients, caregivers, and health-care professionals) through brief workshops that have recently been expanded from in-person encounters to virtual platforms revolving around a user-friendly mobile app called "Hopetimize."

Increased low-density lipoprotein cholesterol on a low-carbohydrate diet in adults with normal but not high body weight: A meta-analysis.

BACKGROUND: Low-density lipoprotein (LDL) cholesterol change with consumption of a low-carbohydrate diet (LCD) is highly variable. Identifying the source of this heterogeneity could guide clinical decision-making. OBJECTIVES: To evaluate LDL cholesterol change in randomized controlled trials involving LCDs, with a focus on body mass index (BMI) in kg/m2. METHODS: Three electronic indexes (Pubmed, EBSCO, and Scielo) were searched for studies between 1 January, 2003 and 20 December, 2022. Two independent reviewers identified randomized controlled trials involving adults consuming <130 g/d carbohydrate and reporting BMI and LDL cholesterol change or equivalent data. Two investigators extracted relevant data, which were validated by other investigators. Data were analyzed using a random-effects model and contrasted with results of pooled individual participant data. RESULTS: Forty-one trials with 1379 participants and a mean intervention duration of 19.4 wk were included. In a meta-regression accounting for 51.4% of the observed variability on LCDs, mean baseline BMI had a strong inverse association with LDL cholesterol change [ß = -2.5 mg/dL/BMI unit, 95% confidence interval (CI): -3.7, -1.4], whereas saturated fat amount was not significantly associated with LDL cholesterol change. For trials with mean baseline BMI <25, LDL cholesterol increased by 41 mg/dL (95% CI: 19.6, 63.3) on the LCD. By contrast, for trials with a mean of BMI 25-<35, LDL cholesterol did not change, and for trials with a mean BMI ≥35, LDL cholesterol decreased by 7 mg/dL (95% CI: -12.1, -1.3). Using individual participant data, the relationship between BMI and LDL cholesterol change was not observed on higher-carbohydrate diets. CONCLUSIONS: A substantial increase in LDL cholesterol is likely for individuals with low but not high BMI with consumption of an LCD, findings that may help guide individualized nutritional management of cardiovascular disease risk. As carbohydrate restriction tends to improve other lipid and nonlipid risk factors, the clinical significance of isolated LDL cholesterol elevation in this context warrants investigation. This trial was registered at PROSPERO as CRD42022299278.

Multi-professional development of a competency framework for patients with a Port-a-Cath (PAC).

PURPOSE: In France, 40,000 Port-a-Cath (PAC) are inserted each year. These medical devices are prone to complications during their insertion or use. The education of patients wearing these devices could be a lever to reduce the risk of complications. The objective of this work was to develop, in a multi-professional and consensual manner, a unique and specific skills reference framework for patients with PAC and to propose it as a reference tool for health professionals. METHODS: A multidisciplinary working group was set up to draw up this reference framework of skills. The first stage of the work consisted of a reflection leading to an exhaustive list of competencies necessary for the patient. These skills were then classified according to three different fields of knowledge (theoretical, know-how and attitudes). Finally, the working group identified priority competencies and established a grid that can be used to evaluate the level of acquisition of these competencies. RESULTS: Fifteen competencies were identified: five relating to theoretical knowledge, six relating to know-how and four relating to attitudes. These competencies were broken down into sub-competences. Seven competencies or sub-competencies were selected to constitute the list of priority competencies. DISCUSSION: This competency framework provides a reference framework for the education of patients with PAC and will help to harmonise practices within the different teams that care for patients with PAC.

A Global Outlook on Child Sexual Abuse and Sexually Explicit Material Online During COVID-19: Trends and Interdisciplinary Prevention Methods.

This scoping review investigates the impact of COVID-19 on global and national trends in online child sexually explicit material (CSEM) trafficking and production in addition to online child sexual abuse (OCSA). Globally, CSEM consumption increased dramatically during the pandemic, as well as trafficking of self-generated material. The hypothesized reasons for the increase in OCSA and CSEM that guided this review included stay-at-home orders, COVID-19-related precautions, technology use increase, economic instability, and lack of available victim and legal resources. Current global and national law enforcement procedures to prevent the proliferation of online sexual abuse are reviewed with suggestions for preventing further increases in CSEM production, distribution, and consumption at the micro and macro levels.

Purpose in life protects against the development of suicidal thoughts and behaviors in U.S. veterans without a history of suicidality: A 10-year, nationally representative, longitudinal study.

OBJECTIVES: To determine the incidence of suicidal ideation and suicide attempts (STBs) in veterans without an endorsed history of STBs and identify baseline predictors of these outcomes over a 10-year period. METHODS: Population-based prospective cohort study of 2307 US military veterans using five waves of the 2011-2021 National Health and Resilience in Veterans Study. Baseline data were collected in 2011, with follow-up assessments conducted 2-(2013), 4-(2015), 7-(2018), and 10-years (2021) later. RESULTS: In total, 10.1 % (N = 203) of veterans endorsed incident suicidal ideation (SI) over the 10-year period and 3.0 % (N = 55) endorsed an incident suicide attempt (SA). Multivariable regression analyses revealed the following baseline predictors of incident SI: lower annual household income, current posttraumatic stress disorder, current alcohol use disorder (AUD), disability with activities of daily living (i.e., ADLs) or instrumental activities of daily living (i.e., IADLs), lower perceived social support, lower community integration, and lower purpose in life. Current AUD, greater cumulative trauma burden, and lower purpose in life at baseline were predictive of incident SA. Relative importance analyses revealed that lower purpose in life was the strongest predictor of both incident SI and SA. CONCLUSIONS: Psychosocial determinants of health, such as purpose in life, may be more reliable predictors of incident suicidal thoughts and behaviors than traditional risk factors (e.g., psychiatric distress; history of SA) in those without a history of STBs. Evidence-based interventions that facilitate purpose in life and feelings of connectedness and belonging should be examined as possible treatments for STBs.

The Relationships of Hope, Optimism, and Academic Motivation With GPA Among University Students in Hong Kong.

Research demonstrates the relationship between dispositional hope and GPA, but mixed results regarding the relationship between dispositional optimism and GPA. Hope and optimism also have been shown to predict academic motivation. However, no study has yet investigated all of these factors together, and most research concerns only Western samples. In a cross-sectional sample of 129 Hong Kong university students, we administered measures of internal hope (hope regarding one's own capabilities), external-family hope (hope derived from family), optimism, and intrinsic and extrinsic academic motivation. We found significant zero-order correlations between internal hope and GPA, but not between external-family hope nor optimism and GPA. Mediation analyses showed that internal hope directly related to GPA, and did not appear mediated by academic motivation. Given our findings, future studies testing hope-based interventions in similar samples may be warranted. We discuss implications for culturally adapting hope interventions.

Suicidal Thoughts and Behaviors in Older U.S. Military Veterans: Results From the National Health and Resilience in Veterans Study.

OBJECTIVE: To identify the prevalence and correlates associated with suicidal thoughts and behaviors (STBs) in a nationally representative sample of older (55+) US military veterans. METHODS: Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study (N = 3,356; mean age = 70.6). Self-report measures of past-year suicidal ideation (SI), lifetime suicide plan, lifetime suicide attempt(s), and future suicide intent were examined in relation to sociodemographic, neuropsychiatric, trauma, physical health, and protective factors. RESULTS: A total of 6.6% (95% CI = 5.7%-7.8%) of the sample endorsed past-year SI, 4.1% (CI = 3.3%-5.1%) a lifetime suicide plan, 1.8% (CI = 1.4%-2.3%) a lifetime suicide attempt, and 0.9% (CI = 0.5%-1.3%) future suicide intent. Higher levels of loneliness and lower levels of purpose in life were most strongly associated with past-year SI; lifetime history of major depressive disorder with suicide plan and suicide attempt; and frequency of past-year SI and more negative expectations regarding emotional aging with future suicide intent. CONCLUSION: These findings provide the most up-to-date nationally representative prevalence estimates of STBs among older military veterans in the United States. Several modifiable vulnerability factors were found to be associated with suicide risk in older US military veterans, suggesting that these factors may be targets for intervention in this population.

Feasibility and acceptability of an online intervention to enhance hopefulness among oncology professionals.

BACKGROUND: Patients prefer medical communication including both hopefulness and realism, though health-care professional (HCPs) struggle to balance these. Providers could thus benefit from a detailed personal understanding of hope, allowing them to model and convey it to patients. Additionally, given that hope is associated with lower levels of burnout, HCPs may benefit from tools designed to enhance their own personal hopefulness. Several investigators have proposed offering HCPs interventions to augment hope. We developed an online workshop for this purpose. METHODS: Feasibility and acceptability of the workshop were assessed in members of the SWOG Cancer Research Network. Three measures were used: the Was-It-Worth-It scale, a survey based on the Kirkpatrick Training Evaluation Model, and a single item prompting participants to rate the degree to which they believe concepts from the workshop should be integrated into SWOG studies. RESULTS: Twenty-nine individuals signed up for the intervention, which consisted of a single 2-hour session, and 23 completed measures. Results from Was-It-Worth-It items indicate that nearly all participants found the intervention relevant, engaging, and helpful. Mean ratings for Kirkpatrick Training Evaluation Model items were high, ranging from 6.91 to 7.70 on 8-point scales. Finally, participants provided a mean rating of 4.44 on a 5-point scale to the item "To what degree do you believe it may be useful to integrate concepts from this workshop into SWOG trials/studies?" CONCLUSIONS: An online workshop to enhance hopefulness is feasible and acceptable to oncology HCPs. The tool will be integrated into SWOG studies evaluating provider and patient well-being.