A survey of generative AI for de novo drug design: new frontiers in molecule and protein generation.

Artificial intelligence (AI)-driven methods can vastly improve the historically costly drug design process, with various generative models already in widespread use. Generative models for de novo drug design, in particular, focus on the creation of novel biological compounds entirely from scratch, representing a promising future direction. Rapid development in the field, combined with the inherent complexity of the drug design process, creates a difficult landscape for new researchers to enter. In this survey, we organize de novo drug design into two overarching themes: small molecule and protein generation. Within each theme, we identify a variety of subtasks and applications, highlighting important datasets, benchmarks, and model architectures and comparing the performance of top models. We take a broad approach to AI-driven drug design, allowing for both micro-level comparisons of various methods within each subtask and macro-level observations across different fields. We discuss parallel challenges and approaches between the two applications and highlight future directions for AI-driven de novo drug design as a whole. An organized repository of all covered sources is available at https://github.com/gersteinlab/GenAI4Drug.

Recurrence of Pulmonary Arteriovenous Malformation after Embolization in Patients with Pulmonary Hypertension.

PURPOSE: To evaluate the correlation between pulmonary hypertension (PH) and recurrence of pulmonary arteriovenous malformation (PAVM) after embolization. MATERIALS AND METHODS: With institutional review board (IRB) approval, the records of 377 patients with PAVMs evaluated at a single hereditary hemorrhagic telangiectasia (HHT) center of excellence between January 1, 2013, and September 10, 2023, were retrospectively reviewed. PAVMs embolized during this time period were evaluated for recurrence. Patients and PAVMs not treated during this time period were excluded. Growth of previously untreated PAVMs was not considered recurrence. Patients without chest computed tomography (CT) follow-up were excluded. General demographics, HHT status as defined by genetic testing or Curacao criteria, presence of PH, history of smoking, anemia, and hepatic arteriovenous malformations (AVMs) were documented. Odds ratio (OR) was calculated and stratified analysis was performed to assay the correlation between PAVM recurrence, PH, and possible confounders. RESULTS: A total of 151 patients with PAVMs were treated during the study period, including 438 PAVMs, for which follow-up was available. This included 106 patients with definite, 31 with doubtful, and 14 with possible HHT. The presence of PH was significantly associated with PAVM recurrence both by patient (OR, 8.13; 95% CI, 3.50-19.67) and by lesion (OR, 4.07; 95% CI, 2.14-7.91). Multivariate analysis demonstrated that this correlation was independent of several variables including HHT status, smoking history, presence of hepatic AVMs, and anemia. CONCLUSIONS: There is a high correlation between PH and PAVM recurrence, suspected to be due to high pulmonary artery pressures causing recanalization. PH may suggest the need for shorter surveillance intervals.

The Predictive Value of Qanadli and Miller Index Scores in Patients with Intermediate-High-Risk and High-Risk Pulmonary Emboli Undergoing Aspiration Thrombectomy.

PURPOSE: To evaluate the correlation between clot burden and pulmonary artery pressures in patients undergoing suction thromboembolectomy for high-risk and intermediate-high-risk pulmonary embolism with secondary outcomes of 30-day mortality and intensive care unit (ICU) length of stay. MATERIALS AND METHODS: Institutional review board (IRB) exemption was granted for this retrospective study. The charts of 120 consecutive patients who underwent mechanical thromboembolectomy using the Flowtriever system (Inari Medical, Irvine, California) between February 2020 and August 2022 were retrospectively reviewed, and the following data were collected: (a) preprocedural B-type natriuretic peptide and creatinine levels, (b) echocardiographic findings, (c) preprocedural and postprocedural pulmonary artery pressures, (d) ICU length of stay, and (e) 30-day mortality. Clot burden was scored using Qanadli and Miller indices and correlated with the clinical outcomes. RESULTS: Of the 120 patients who underwent thromboembolectomy, pulmonary artery pressures and diagnostic-quality angiograms were available in 109 patients. In the 109 patients with adequate data, Qanadli, preprocedural Miller, and postprocedural Miller scores correlated with pulmonary artery pressures. Neither was independently associated with ICU length of stay. Freedom from 30-day mortality was 91%, and embolism-specific mortality was 92%. All-risk and high-risk patients who survived demonstrated a significantly lower preprocedural and postprocedural Miller score, respectively. CONCLUSIONS: Thrombus burden as measured by the Qanadli and Miller scores appeared to be correlated with pulmonary artery pressures. Furthermore, catheter-directed thromboembolectomy led to a reduction in Miller scores, which appeared to be correlated with a reduction in pulmonary pressures. In high-risk patients, a reduced postprocedural Miller score and pulmonary pressure demonstrated improved 30-day survival. Further investigation into the association between Miller scores and patient mortality is warranted to stratify patients who would benefit from emergency intervention.

Establishing norms on the Japanese version of the Eyberg Child Behavior Inventory.

BACKGROUND: The Eyberg Child Behavior Inventory (ECBI) is one of the standardized parent rating scales used to identify disruptive behavior problems in children in Western countries. This study aimed to determine norms for the Japanese version of the ECBI, including clinical cutoff scores among the general population in Japan. METHODS: This study established norms for the Japanese version of the ECBI using a sample of 1,992 parents of children aged 2-7, living in Japan. The research evaluates the validity and the reliability of the ECBI scores for the Intensity Scale and the Problem Scale. After validation, a clinical cutoff value of the ECBI scores was calculated, setting the cutoff to above the +1 standard deviation (SD) level based on the population distribution. RESULTS: The means of the Intensity and Problem Scale scores were 100.07 and 6.57, respectively. Cronbach's α for both the Intensity and the Problem scores was 0.91. At this point, we propose cutoff scores of 125 for the Intensity Scale and 14 for the Problem Scale. CONCLUSIONS: Our results suggest that the Japanese version of the ECBI is highly reliable and may be useful as a tool for assessing behavior problems in children.

There is little association between prehospital delay, persistent symptoms, and post-discharge healthcare utilization in patients evaluated for acute coronary syndrome.

AIMS: Test for an association between prehospital delay for symptoms suggestive of acute coronary syndrome (ACS), persistent symptoms, and healthcare utilization (HCU) 30-days and 6-months post hospital discharge. BACKGROUND: Delayed treatment for ACS increases patient morbidity and mortality. Prehospital delay is the largest factor in delayed treatment for ACS. METHODS: Secondary analysis of data collected from a multi-center prospective study. Included were 722 patients presenting to the Emergency Department (ED) with symptoms that triggered a cardiac evaluation. Symptoms and HCU were measured using the 13-item ACS Symptom Checklist and the Froelicher's Health Services Utilization Questionnaire-Revised instrument. Logistic regression models were used to examine hypothesized associations. RESULTS: For patients with ACS (n = 325), longer prehospital delay was associated with fewer MD/NP visits (OR, 0.986) at 30 days. Longer prehospital delay was associated with higher odds of calling 911 for any reason (OR, 1.015), and calling 911 for chest related symptoms (OR, 1.016) 6 months following discharge. For non-ACS patients (n = 397), longer prehospital delay was associated with higher odds of experiencing chest pressure (OR, 1.009) and chest discomfort (OR, 1.008) at 30 days. At 6 months, longer prehospital delay was associated with higher odds of upper back pain (OR, 1.013), palpitations (OR 1.014), indigestion (OR, 1.010), and calls to the MD/NP for chest symptoms (OR, 1.014). CONCLUSIONS: There were few associations between prehospital delay and HCU for patients evaluated for ACS in the ED. Associations between prolonged delay and persistent symptoms may lead to increased HCU for those without ACS.

Evaluation of a sterile surgical skin marker to indicate the optimal vein for venepuncture in the blood donation setting.

BACKGROUND AND OBJECTIVES: Phlebotomy is a central task for blood donation; however, not all blood donors have veins that are easy to see or feel. This study aimed to determine whether use of a surgical skin marker to highlight the donors' vein location and direction prior to venepuncture increased blood donation success. METHODS: All blood donors who participated in this study were eligible to donate according to Australian guidelines. Ten donor centres with phlebotomy success rates <95% were selected. A randomized cluster trial design assigned five sites to test the skin marking device and five sites as controls. Single-use sterile Gentian violet skin marker pens were used to mark donors' veins. Phlebotomy site skin bacterial load after using the skin marking device was tested on a subset of 100 donors. Phlebotomy success rates and donor adverse events were recorded. RESULTS: Of the control donors, 6993 had successful phlebotomies and 225 failed. Of the skin marker donors, 6998 had successful phlebotomies and 248 failed. No statistically significant differences in phlebotomy success were found between the two groups (OR: 0·91, 96·4% CI [96·0, 96·8], P-value 0·348). CONCLUSION: The use of skin marker pens did not increase overall phlebotomy success rate. There was no increase in phlebotomy site skin bacterial load, and amendments to standard skin disinfection techniques were not required. Blood donors were not concerned about the pen mark on their arms. Generally, staff indicated that the markers may be valuable to assist with phlebotomies for donors with difficult or deep veins.

Autism Insurance Mandates in the US: Comparison of Mandated Commercial Insurance Benefits Across States.

INTRODUCTION: Autism mandates are laws that require commercial insurers to cover certain evidence-based treatments for Autism Spectrum Disorder (ASD). The purpose of this study was to review state variability in autism insurance mandates and the benefits they cover and to discuss recommendations for research and policy to improve ASD services across states. METHODS: Data were extracted from 2001 to 2020 from all 50 states plus the District of Columbia (N = 51) from policy text. News articles and websites of ASD advocacy organizations were also reviewed to ensure inclusion of the most recent policy changes. Descriptive statistics and heatmaps were used to characterize the autism mandate landscape and visualize variability in benefit parameters across states. RESULTS: Autism mandates vary greatly in benefit parameters across US states, but there is a common set of benefits that most states have adopted. These include coverage of provider-recommended ASD services except for medical equipment, coverage up to an age limit of 18 to 21, an annual dollar limit of $36,000 with no restriction on the number of hours or visits, no lifetime cap on benefits, and requirement of BCBA® certification or its equivalent for providers of ABA. DISCUSSION: There is a need for continued research evaluating the impact of autism mandates and benefit parameters on access to care, service utilization, and clinical outcomes for the ASD population. Stakeholder engagement and understanding the impact of autism mandates on clinical and patient-centered outcomes may provide direction for policy advocacy and public health initiatives.

Evaluation of a tool to score donor vein suitability for blood donation.

BACKGROUND AND OBJECTIVES: Phlebotomy is a central task for whole blood donation, yet there are no published standards regarding systematic donor vein assessment or the impact of vein quality on successful blood donation. Blood donation failures and related adverse events are highly predictive of donors not returning for future blood donation. A specific blood donation vein scoring tool was assessed to measure donor vein suitability for whole blood collection and investigate the correlation of the donor's veins with donation outcomes. MATERIALS AND METHODS: The vein assessment tool consisted of three questions using a 5-point Likert-type scale to measure responses. Two phlebotomists performed blinded assessments of each donor's veins on each arm using the tool. The individual measures were then aggregated to provide a total vein score out of 12. Inter-rater reliability of the vein score tool was assessed by calculating the intraclass correlation coefficient for absolute agreement. RESULTS: Fifty-seven phlebotomists across four fixed blood donation centres performed paired vein assessments on 553 blood donors. The intraclass correlation coefficient indicated moderate inter-rater reliability was achieved. The median scores for viable donations were 10, for non-viable donations were 6·5 and for failed phlebotomies were 4. Donation histories of donors with lower vein scores indicated lower success during blood donation. CONCLUSION: The vein score tool appears to be predictive of a successful donation outcome, however, since there was not a suitably high correlation between the scores of the two assessors, further refinement of the tool will be required prior to wider use.

Symptom Trajectories After an Emergency Department Visit for Potential Acute Coronary Syndrome.

BACKGROUND: Many patients evaluated for acute coronary syndrome (ACS) in emergency departments (EDs) continue to experience troubling symptoms after discharge-regardless of their ultimate medical diagnosis. However, comprehensive understanding of common post-ED symptom trajectories is lacking. OBJECTIVES: The aim of this study was to identify common trajectories of symptom severity in the 6 months after an ED visit for potential ACS. METHODS: This was a secondary analysis of data from a larger observational, prospective study conducted in five U.S. EDs. Patients (N = 1005) who had electrocardiogram and biomarker testing ordered, and were identified by the triage nurse as potentially having ACS, were enrolled. Symptom severity was assessed in the hospital after initial stabilization and by telephone at 30 days and 6 months using the validated 13-item ACS Symptom Checklist. Growth mixture modeling was used for the secondary analysis. The eight most commonly reported symptoms (chest discomfort, chest pain, chest pressure, light-headedness, shortness of breath, shoulder pain, unusual fatigue, and upper back pain) were modeled across the three study time points. Models with increasing numbers of classes were compared, and final model selection was based on a combination of interpretability, theoretical justification, and statistical fit indices. RESULTS: The sample was 62.6% male with a mean age of 60.2 years (SD = 14.17 years), and 57.1% ruled out for ACS. Between two and four distinct trajectory classes were identified for each symptom. The seven different types of trajectories identified across the eight symptoms were labeled "tapering off," "mild/persistent," "moderate/persistent," "moderate/worsening," "moderate/improving," "late onset, "and "severe/improving." Trajectories differed on age, gender, and diagnosis. DISCUSSION: Research on the individual nature of symptom trajectories can contribute to patient-centered, rather than disease-centered, care. Further research is needed to verify the existence of multiple symptoms trajectories in diverse populations and to assess the antecedents and consequences of individual symptom trajectories.

A patient-focused framework integrating self-management and informatics.

PURPOSE: This article introduces a framework to (a) guide chronic illness self-management interventions through the integration of self-management and nursing informatics, (b) focus self-management research, and (c) promote ethical, patient-empowering technology use by practicing nurses. METHODS: Existing theory and research focusing on chronic illness, self-management, health-enabling technology, and nursing informatics were reviewed and examined and key concepts were identified. A care paradigm focusing on concordance, rather than compliance, served as the overall guiding principle. FINDINGS: This framework identifies key relationships among self-management (patient behaviors), health force (patient characteristics), and patient-defined goals. The role of health-enabling technology supporting these relationships is explored in the context of nursing informatics. CONCLUSIONS: The Empowerment Informatics framework can guide intervention design and evaluation and support practicing nurses' ethical use of technology as part of self-management support. CLINICAL RELEVANCE: Nurses worldwide provide support to patients who are living with chronic illnesses. As pressures related to cost and access to care increase, technology-enabled self-management interventions will become increasingly common. This patient-focused framework can guide nursing practice using technology that prioritizes patient needs.

A primer for quantum computing and its applications to healthcare and biomedical research.

OBJECTIVES: To introduce quantum computing technologies as a tool for biomedical research and highlight future applications within healthcare, focusing on its capabilities, benefits, and limitations. TARGET AUDIENCE: Investigators seeking to explore quantum computing and create quantum-based applications for healthcare and biomedical research. SCOPE: Quantum computing requires specialized hardware, known as quantum processing units, that use quantum bits (qubits) instead of classical bits to perform computations. This article will cover (1) proposed applications where quantum computing offers advantages to classical computing in biomedicine; (2) an introduction to how quantum computers operate, tailored for biomedical researchers; (3) recent progress that has expanded access to quantum computing; and (4) challenges, opportunities, and proposed solutions to integrate quantum computing in biomedical applications.

Using cluster analysis to explore COVID-19 vaccine booster hesitancy by levels of medical mistrust in fully vaccinated US adults.

BACKGROUND: Underlying causes of vaccine hesitancy could significantly affect successful uptake of the SARS-CoV2 vaccine booster doses during new waves of COVID-19. Booster rates among US adults are far below what is needed for immunity, but little is known about booster hesitancy among fully vaccinated adults and whether medical mistrust exacerbates barriers to uptake. METHODS: A cross-sectional survey was completed among 119 adults in Philadelphia, PA who reported having received the primary SARS-CoV2 vaccine series but not a booster dose. Using the LaVeist Medical Mistrust (MM) Index, a k-means cluster analysis showed two clusters (Low MM, High MM) and differences in attitudes and perceptions about COVID-19 booster vaccines were assessed using F-tests. RESULTS: Respondents were 62% Black and female; mean age was 41; 46% reported earning less than $25,000 and 53% had a high school education or less. Overall intention to get boosted was low (mean 3.3 on 0-10 scale). Differences in COVID-19 booster perceptions between those with High (n = 56) vs. Low (n = 59) MM were found, independent of any demographic differences. Most statements (7/10) related to reasons to not be boosted were significant, with those with High MM indicating more concern about feeling sick from the vaccine (F=-3.91, p≤ .001), beliefs that boosters are ineffective for vaccinated people (F= -3.46, p≤ .001), and long-term side effect worries (F=-4.34, p≤ .001). Those with High MM were also more concerned about the adverse effects of the vaccine (F=-2.48, p=.02), but were more likely to trust getting information from doctors or healthcare providers (F= -2.25, p=.03). CONCLUSIONS: Results indicate that medical mistrust is an important independent construct when understanding current COVID-19 booster hesitancy. While much work has looked at demographic differences to explain vaccine hesitancy, these results suggest that further research into understanding and addressing medical mistrust could be important for implementing interventions to increase booster rates.

Patient-reported outcomes of serum eye drops manufactured from Australian blood donations and packaged using Meise vials.

Introduction: Serum eye drops (SED) are an effective treatment for dry eye syndrome. However, autologous serum collection can have challenges. Patient-tailored (allogeneic) SED (PT-SED) can be made from healthy blood donors. Australian Red Cross Lifeblood has manufactured both autologous SED (Auto-SED) and PT-SED and, in May 2021, introduced Meise vial packaging. This study aimed to explore SED patient-reported outcomes and vial packaging satisfaction. Methods: A prospective cohort study was conducted with recruitment between 1 November 2021 and 30 June 2022. Participants completed the dry eye questionnaire (DEQ5), health-related quality-of-life (SF-8™), functional assessment of chronic illness therapy-treatment satisfaction-general (FACIT-TS-G), and general wellbeing surveys. Existing patients completed these once, and new patients were surveyed at baseline, 3 months post-treatment, and 6 months post-treatment. Results: Participants who completed all study requirements were 24 existing and 40 new Auto-SED and 10 existing and 8 new PT-SED patients. Auto-SED patients were younger [56.2 (±14.7) years] than PT-SED patients [71.4 (±10.0) years]. Participants used a mean of 1.8 (±1.1) SED, 5.3 (±2.9) times per day. In new patients, DEQ5 scores improved within 6 months from 14.0 (±2.9) to 10.6 (±3.4) for Auto-SED and from 12.9 (±3.7) to 11.4 (±2.8) for PT-SED. General wellbeing measures improved in the new Auto-SED from 7.0 (±1.9) to 7.8 (±1.7) but were reduced for new PT-SED from 6.7 (±2.9) to 6.1 (±2.9). Discussion: SED improved dry eye symptoms in most patients, regardless of the serum source. Patients using PT-SED showed decreases in some quality-of-life measures; however, recruitment was reduced due to operational constraints, and concurrent comorbidities were not assessed. General feedback for SED and vial packaging was positive, with some improvements identified.

Regional delivery in graduate nursing programs for students living in rural communities.

Oregon has a lack of primary care providers in rural areas. To address this issue, employers have indicated they plan to hire greater numbers of advanced practice registered nurses (APRNs). Oregon Health & Science University (OHSU) School of Nursing (SoN) responded to this need by developing a statewide delivery model to educate APRN students in their communities. A performance improvement work group including practice faculty, statewide academic leaders, and staff created a project charter with scope of work, timelines, and outcomes with the goal of improving the systems supporting APRN education. An initial distance APRN education delivery model emerged from this effort and was refined over the following year. Strategies were implemented to address identified challenges using small cycles of change. The final model has three main principles: being learner-centered, equitable, and sustainable. The central outcome is graduating students committed to practicing in rural and urban underserved communities to meet workforce needs in Oregon.

Treatment Readiness among Primarily Latine Families Seeking Parent-Child Interaction Therapy (PCIT) in an Urban Setting.

(1) Background: Given the high prevalence of childhood mental health problems and their long-lasting negative consequences if left untreated, it is important to investigate factors that affect family engagement in psychological interventions such as Parent-Child Interaction Therapy (PCIT), including caregiver treatment readiness and readiness for change (RFC). Specifically, Latine families experience greater mental health disparities and have unique cultural factors that affect engagement. The current project examined caregiver pretreatment readiness among primarily Latine Spanish- and English-speaking families. (2) Methods: Participants were 100 caregivers (96% female) of young children ages 2 to 7 who sought PCIT services from a community mental health center in Washington, D.C. Families completed written and observational assessment measures at pretreatment and throughout PCIT, which were used for the current study. (3) Results: Caregivers reported high readiness and importance of treatment at intake, with higher RFC among Spanish-speaking caregivers. Regardless of language, caregivers who reported more frequent and problematic child misbehavior and who were from a multi-caregiver household tended to report more RFC and treatment importance at intake. Pretreatment RFC also predicted family completion of the first phase of PCIT although there was a high attrition rate for the sample as only 18% of families completed treatment. (4) Conclusions: These findings provide insight into the implementation of standard PCIT among Spanish- and English speaking families and highlight the benefits of assessing pretreatment caregiver readiness to inform clinical decision-making.

Disseminated Tele-OSCE During a Pandemic: One University's Experience.

BACKGROUND: Due to coronavirus disease 2019 (COVID-19), in-person educational activities were suspended across the globe throughout 2020. In health care education, this required a swift, creative response to maintain the flow of trained clinicians into the workforce without compromising the integrity of core learning outcomes. Early during the pandemic, remote synchronous simulation emerged as a compelling focus of the overall strategy. METHOD: At one large health sciences university in the northwestern United States, family nurse practitioner faculty worked closely with the Simulation Operations team to plan, deliver, and assess a pilot tele-OSCE (objective structured clinical examination). RESULTS: In postevent debriefs and surveys, both standardized patients and students affirmed that the activity was generally safe, accessible, and high value. CONCLUSION: With appropriate planning, consensus building, and technology readiness assessment, tele-OSCEs can play a critical role in sustaining the flow of health care students into the workforce during a pandemic. [J Nurs Educ. 2022;61(2):107-110.].

Patient Outcomes After Applied Behavior Analysis for Autism Spectrum Disorder.

OBJECTIVES: The purpose of this study was to examine patterns of service receipt and patient outcomes for children receiving applied behavior analysis (ABA) for autism spectrum disorder (ASD) in an integrated health care system in which commercially insured children were covered by a state autism mandate. METHODS: This retrospective, observational study used a random sample of children with ASD (3-17 yrs) who were members of a large integrated health care system in Southern California and referred for ABA between January 2016 and November 2018. From the 4145 children referred, a random stratified sample of 334 was selected to extract data from clinical reports over 24 months of services. The primary outcome measures were time in ABA and child adaptive behavior. RESULTS: Thirteen percent of the sample never received ABA after referral. Of those who were referred for ABA, 66% initiated ABA and remained in services for 12 months, whereas less than half (46%) remained in services for 24 months. Having a history of special education was associated with longer time spent in ABA, whereas having a single parent was associated with discontinuation of ABA. A minority of children received a full ABA dose (28%), but the lowest functioning children still experienced clinically significant adaptive behavior gains after 24 months of ABA (p = 0.02). CONCLUSION: In a health system implementation of ABA for children with ASD, there were high rates of ABA discontinuation and low ABA dosing. These challenges may diminish the potential benefits of ABA, even in a context in which there is mandated commercial insurance coverage.

Habilitative Teletherapy for Children with Autism Spectrum Disorder: A Survey of Parents.

OBJECTIVE: The purpose of this study was to investigate whether service losses during the coronavirus disease 2019 (COVID-19) pandemic were associated with worsened parent mental health or child behavioral health among families of children with autism spectrum disorder and to identify factors associated with favorable parent appraisals of habilitative teletherapy (applied behavior analysis; speech, occupational, physical therapy) for their child. METHOD: This web-based survey study was conducted from May to July 2021 with parents whose children were receiving habilitative therapy for autism from an integrated health system. A total of 322 parents responded to the survey (20% response rate). The outcome variables were pandemic-related parent mental health, pandemic-related child behavioral health, and appraisal of habilitative teletherapy. Predictors were COVID-19-related services changes in health care or child care, COVID-19 history (COVID-19 stress, testing positive for COVID-19), and child autism factors (autistic behaviors, caregiving strain). RESULTS: Loss of regular child care was associated with higher odds of worsened parent mental health (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.5-4.8); higher levels of caregiving strain were associated with worsened child behavioral health (OR = 2.3, 95% CI = 1.4-3.8). Higher levels of COVID-19 stress were associated with more favorable appraisals of telehealth (ß = 0.4, p < 0.01), whereas higher caregiving strain scores were associated with less favorable appraisals of telehealth (ß = -0.2, p < 0.01). CONCLUSION: During COVID-19, caregiving factors were associated with worsened parent mental health and worsened child behavioral health, and telehealth is not preferred by all families. Policy interventions to support caregivers, such as affordable, high-quality child care and paid family leave, are a high priority.

Differential structure-function network coupling in the inattentive and combined types of attention deficit hyperactivity disorder.

The heterogeneous presentation of inattentive and hyperactive-impulsive core symptoms in attention deficit hyperactivity disorder (ADHD) warrants further investigation into brain network connectivity as a basis for subtype divisions in this prevalent disorder. With diffusion and resting-state functional magnetic resonance imaging data from the Healthy Brain Network database, we analyzed both structural and functional network efficiency and structure-functional network (SC-FC) coupling at the default mode (DMN), executive control (ECN), and salience (SAN) intrinsic networks in 201 children diagnosed with the inattentive subtype (ADHD-I), the combined subtype (ADHD-C), and typically developing children (TDC) to characterize ADHD symptoms relative to TDC and to test differences between ADHD subtypes. Relative to TDC, children with ADHD had lower structural connectivity and network efficiency in the DMN, without significant group differences in functional networks. Children with ADHD-C had higher SC-FC coupling, a finding consistent with diminished cognitive flexibility, for all subnetworks compared to TDC. The ADHD-C group also demonstrated increased SC-FC coupling in the DMN compared to the ADHD-I group. The correlation between SC-FC coupling and hyperactivity scores was negative in the ADHD-I, but not in the ADHD-C group. The current study suggests that ADHD-C and ADHD-I may differ with respect to their underlying neuronal connectivity and that the added dimensionality of hyperactivity may not explain this distinction.

Reinfection with hepatitis C virus following sustained virological response in injection drug users.

BACKGROUND AND AIM: Despite that 60-90% of injection drug users (IDUs) are infected with hepatitis C virus (HCV) infection, IDUs are often denied therapy based on concerns of reinfection following treatment. However, there are little data in this regard. We evaluated HCV re-infection following sustained virologic response (SVR) among HCV-infected IDUs having received HCV treatment in a multidisciplinary program. METHODS: Following treatment, participants were encouraged to return at follow-up intervals of 1 year and illicit drug use histories were obtained. In those with SVR, HCV RNA testing by PCR was performed to determine if relapse or reinfection occurred. RESULTS: Among 58 receiving HCV treatment between January 2002 and December 2006, 60% (35 of 58) achieved an SVR. Patients were followed for a median of 2.0 years following SVR (range, 0.4-5.0 years), with ongoing illicit and injection drug use reported in 54% (19 of 35) and 46% (16 of 35). Of the 35 with SVR, 28 remained HCV RNA negative during follow-up (80%), with four lost to follow-up and one dying of hepatocellular carcinoma and two cases of reinfection were observed (2 of 35). The rates of reinfection were 3.2 per 100 p-y (95% CI:0.4, 11.5) overall and 5.3 per 100 p-y (95% CI:0.6, 19.0) among those reporting injecting following SVR (n = 16). One of two participants with HCV re-infection spontaneously cleared virus following reinfection. CONCLUSION: The rate of reinfection following treatment for HCV infection among current and former IDUs engaged in a multidisciplinary program is low.