Adapting methadone inductions to the fentanyl era.

Since 2013, fentanyl and fentanyl analogs, which are significantly more potent than heroin, have been increasingly prevalent in the opioid drug supply. A need exists to adapt methadone dosing from opioid treatment programs (OTPs) in this era. Current methadone protocols at many clinics in the United States are based on expert consensus documents that were created prior to the introduction of fentanyl into the drug supply and are relatively conservative.

Impact of Kidney Failure Risk Prediction Clinical Decision Support on Monitoring and Referral in Primary Care Management of CKD: A Randomized Pragmatic Clinical Trial.

Rationale & Objective: To design and implement clinical decision support incorporating a validated risk prediction estimate of kidney failure in primary care clinics and to evaluate the impact on stage-appropriate monitoring and referral.

Study Design: Block-randomized, pragmatic clinical trial.

Setting & Participants: Ten primary care clinics in the greater Boston area.

Guidelines for non-transplant chemotherapy for treatment of systemic AL amyloidosis: EHA-ISA working group.

Background: This guideline has been developed jointly by the European Society of Haematology and International Society of Amyloidosis recommending non-transplant chemotherapy treatment for patients with AL amyloidosis.

Methods: A review of literature and grading of evidence as well as expert recommendations by the ESH and ISA guideline committees.

Results And Conclusions: The recommendations of this committee suggest that treatment follows the clinical presentation which determines treatment tolerance tempered by potential side effects to select and modify use of drugs in AL amyloidosis.

Prevalence of HIV Preexposure Prophylaxis Prescribing Among Persons With Commercial Insurance and Likely Injection Drug Use.

Importance: Although HIV preexposure prophylaxis (PrEP) implementation among persons who inject drugs has been inadequate, national HIV monitoring programs do not include data on PrEP, and specific trends in PrEP use are not well understood.

Objective: To estimate HIV PrEP uptake among commercially insured persons with opioid or stimulant use disorder by injection drug use (IDU) status.

Design, Setting, And Participants: This cross-sectional study used deidentified data from the MarketScan Commercial Claims and Encounters Database to identify a sample of 547 709 commercially insured persons without HIV but with opioid and/or stimulant use disorder, including 110 592 with evidence of IDU between January 1, 2010, and December 31, 2019.

Plasma Biomarkers as Risk Factors for Incident CKD.

Introduction: Earlier identification of individuals at high risk of chronic kidney disease (CKD) may facilitate improved risk factor mitigation.

Methods: We evaluated the association of novel plasma biomarkers with incident CKD using a case-cohort design in participants without diabetes and with baseline estimated glomerular filtration rate (eGFR) ≥ 60 ml/min per 1.73 m in the Multi-Ethnic Study of Atherosclerosis (MESA) and Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohorts.

Association between cord blood metabolites in tryptophan pathway and childhood risk of autism spectrum disorder and attention-deficit hyperactivity disorder.

Alterations in tryptophan and serotonin have been implicated in various mental disorders; but studies are limited on child neurodevelopmental disabilities such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). This prospective cohort study examined the associations between levels of tryptophan and select metabolites (5-methoxytryptophol (5-MTX), 5-hydroxytryptophan (5-HTP), serotonin, N-acetyltrytophan) in cord plasma (collected at birth) and physician-diagnosed ASD, ADHD and other developmental disabilities (DD) in childhood. The study sample (n = 996) derived from the Boston Birth Cohort, which included 326 neurotypical children, 87 ASD, 269 ADHD, and 314 other DD children (mutually exclusive).

Automated detection of mild cognitive impairment and dementia from voice recordings: A natural language processing approach.

Introduction: Automated computational assessment of neuropsychological tests would enable widespread, cost-effective screening for dementia.

Methods: A novel natural language processing approach is developed and validated to identify different stages of dementia based on automated transcription of digital voice recordings of subjects' neuropsychological tests conducted by the Framingham Heart Study (n = 1084). Transcribed sentences from the test were encoded into quantitative data and several models were trained and tested using these data and the participants' demographic characteristics.

Association of mitochondrial DNA content, heteroplasmies and inter-generational transmission with autism.

Mitochondria are essential for brain development. While previous studies linked dysfunctional mitochondria with autism spectrum disorder (ASD), the role of the mitochondrial genome (mtDNA) in ASD risk is largely unexplored. This study investigates the association of mtDNA heteroplasmies (co-existence of mutated and unmutated mtDNA) and content with ASD, as well as its inter-generational transmission and sex differences among two independent samples: a family-based study (n = 1,938 families with parents, probands and sibling controls) and a prospective birth cohort (n = 997 mother-child pairs).

IMM-BCP-01, a patient-derived anti-SARS-CoV-2 antibody cocktail, is active across variants of concern including Omicron BA.1 and BA.2.

Monoclonal antibodies are an efficacious therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, rapid viral mutagenesis led to escape from most of these therapies, outlining the need for an antibody cocktail with a broad neutralizing potency. Using an unbiased interrogation of the memory B cell repertoire of patients with convalescent COVID-19, we identified human antibodies with broad antiviral activity in vitro and efficacy in vivo against all tested SARS-CoV-2 variants of concern, including Delta and Omicron BA.

Therapeutic Vulnerability to ATR Inhibition in Concurrent and -Deficient/ALT-Positive High-Grade Solid Tumors.

Subsets of Neurofibromatosis Type 1 (NF1)-associated solid tumors have been shown to display high frequencies of ATRX mutations and the presence of alternative lengthening of telomeres (ALT). We studied the phenotype of combined NF1 and ATRX deficiency in malignant solid tumors. Cell lines derived from NF1-deficient sporadic glioblastomas (U251, SF188), an NF1-associated ATRX mutant glioblastoma cell line (JHH-NF1-GBM1), an NF1-derived sarcoma cell line (JHH-CRC65), and two NF1-deficient MPNST cell lines (ST88-14, NF90.

Functional Impairment and Cognitive Symptoms Among People with HIV Infection on Chronic Opioid Therapy for Pain: The Impact of Gabapentin and Other Sedating Medications.

Gabapentin is associated with dizziness, falls, and somnolence yet commonly prescribed to people with HIV (PWH) treated with chronic opioid therapy (COT). Physical function and cognition are understudied when prescribed together. Among PWH on COT, we evaluated whether co-prescribed gabapentin is associated with (a) functional impairment; (b) trouble thinking clearly; and (c) difficulty controlling drowsiness using logistic regression models adjusted for prescribed opioid dose, other (non-gabapentin) sedating medication, substance use disorder, and mental/physical health indicators in a cross-sectional study.

Life-Years Lost After Newly Diagnosed Atrial Fibrillation in Patients with Heart Failure.

Objective: Prior work estimated excess death rates associated with atrial fibrillation (AF) in heart failure (HF) with hazard ratios (HR). The aim was to estimate the life-years lost after newly diagnosed AF in HF patients.

Methods: Among patients diagnosed with HF in 2008-2018 in the nationwide Danish Heart Failure Registry, we compared patients with incident AF to referents matched on age, sex, and time since HF.

The Impact of Care Partners on the Mobility of Older Adults Receiving Hemodialysis.

Rationale & Objective: Many older adults receiving hemodialysis have mobility limitations and rely on care partners, yet data are sparse regarding the support provided by care partners. Our aim was to examine how care partners support the mobility of an older adult receiving hemodialysis.

Study Design: Qualitative study.

Multi-system trajectories and the incidence of heart failure in the Framingham Offspring Study.

Background: Heart failure is a multi-system disease, with non-cardiac systems playing a key role in disease pathogenesis.

Objective: Investigate whether longitudinal multi-system trajectories incrementally predict heart failure risk compared to single-occasion traits.

Methods: We evaluated 3,412 participants from the Framingham Heart Study Offspring cohort, free of heart failure, who attended examination cycle 5 and at least one examination between 1995-2008 (mean age 67 years, 54% women).

Early Introduction and Rise of the Omicron Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant in Highly Vaccinated University Populations.

Background: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible in vaccinated and unvaccinated populations. The dynamics that govern its establishment and propensity toward fixation (reaching 100% frequency in the SARS-CoV-2 population) in communities remain unknown. Here, we describe the dynamics of Omicron at 3 institutions of higher education (IHEs) in the greater Boston area.

Bridge clinic implementation of "72-hour rule" methadone for opioid withdrawal management: Impact on opioid treatment program linkage and retention in care.

Background: Methadone for opioid use disorder (OUD) treatment is restricted to licensed opioid treatment programs (OTPs) with substantial barriers to entry. Underutilized regulations allow non-OTP providers to administer methadone for opioid withdrawal for up to 72 h while arranging ongoing care. Our low-barrier bridge clinic implemented a new pathway to treat opioid withdrawal and facilitate OTP linkage utilizing the "72-hour rule.

Smartphone-Guided Self-prone Positioning vs Usual Care in Nonintubated Hospital Ward Patients With COVID-19: A Pragmatic Randomized Clinical Trial.

Background: Safe, effective, and easily implementable treatments that reduce the progression of respiratory failure in COVID-19 are urgently needed. Despite the increased adoption of prone positioning during the pandemic, the effectiveness of this technique on progression of respiratory failure among nonintubated patients is unclear.

Research Question: What is the effectiveness of smartphone-guided self-prone positioning recommendations and instructions compared with usual care in reducing progression of respiratory failure among nonintubated patients with COVID-19?

Study Design And Methods: Awake Prone Position for Early Hypoxemia in COVID-19 (APPEX-19) is a multicenter randomized clinical trial that randomized nonintubated adults with COVID-19 on < 6 L/min of supplemental oxygen to receive a smartphone-guided self-prone positioning intervention or usual care.

Treatment effect modifiers for individuals with acute low back pain: secondary analysis of the TARGET trial.

Treatment effect modifiers identify patient characteristics associated with treatment responses. The purpose of this secondary analysis was to identify potential treatment effect modifiers for disability from the TARGET trial that compared usual care (control) with usual care + psychologically informed physical therapy (PIPT). The sample consisted of a STarT Back tool identified high-risk patients with acute low back pain that completed Oswestry Disability Index (ODI) data at index visit and 6 months later (n = 1250).