Impact of Hepatitis B Virus Point-of-care DNA Viral Load Testing Compared With Laboratory-based Standard-of-care Approaches on Uptake of HBV Viral Load Testing, Treatment, and Turnaround Times: A Systematic Review and Meta-analysis.

Background: Point-of-care (PoC) hepatitis B virus (HBV) DNA viral load (VL) assays represent an alternative to laboratory-based standard-of-care (SoC) VL assays to accelerate diagnosis and treatment. We evaluated the impact of using PoC versus SoC approaches on the uptake of VL testing, treatment, and turnaround times from testing to treatment across the HBV care cascade. Methods: We searched 5 databases, 6 conference websites, and contacted manufacturers for unpublished reports, for articles with or without a comparator (SoC VL testing), and had data on the uptake of VL testing, treatment, or turnaround times between hepatitis B surface antigen (HBsAg) testing, VL testing, and treatment in the cascade. We performed a random-effects meta-analysis on rates of VL testing and treatment initiation. Results: Six studies, composing 9 arms, were included. Three PoC arms reported less than 1 day between screening for HBsAg positivity and VL testing, and the other one (2 arms) reported it between 7 and 11 days. Five arms reported the time to available VL test results (<1 day). Three studies reported 1-8 days between VL testing results and treatment initiation. Two studies reported the turnaround times between a positive HBsAg screening and treatment initiation (the same day and 27 days). Overall, 84.1% of those with HBsAg positivity were tested for DNA VL and 88.3% of eligible people initiated treatment. Conclusions: HBV PoC DNA testing appears to be associated with a turnaround time of <1 day for receipt of VL results and appears associated with high rates of DNA testing and initiation of treatment among those eligible. Clinical Trials Registration: PROSPERO CRD42023398440.

Screening and Supplementation for Iron Deficiency and Iron Deficiency Anemia During Pregnancy: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: In 2015 the US Preventive Services Task Force (USPSTF) found insufficient evidence to assess the balance of benefits and harms of routine screening and supplementation for iron deficiency anemia during pregnancy. Objective: To update the 2015 review on screening for iron deficiency anemia, in addition to iron deficiency during pregnancy, to inform the USPSTF. Data Sources: Ovid MEDLINE and Cochrane databases through May 24, 2023; surveillance through May 24, 2024. Study Selection: Randomized clinical trials of iron supplementation, screening effectiveness, treatment, and harms; observational studies of screening. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, study quality, and data abstraction. Data were pooled using a random-effects model. Main Outcomes and Measures: Maternal and infant clinical outcomes, hematologic indices, and harms. Results: Seventeen trials (N = 24 023) on maternal iron supplementation were included. Iron supplementation was associated with decreased risk of maternal iron deficiency anemia at term (4 trials, n = 2230; 8.6% vs 19.8%; relative risk, 0.40 [95% CI, 0.26-0.61]; I2 = 20.5%) and maternal iron deficiency at term (6 trials, n = 2361; 46% vs 70%; relative risk, 0.47 [95% CI, 0.33-0.67]; I2 = 81.9%) compared with placebo or no iron supplement. There were no statistically significant differences in maternal quality of life, rates of gestational diabetes, maternal hemorrhage, hypertensive disorders of pregnancy, cesarean delivery, preterm birth, infant low birth weight, or infants small for gestational age for maternal iron supplementation compared with placebo or no supplementation. Harms of iron supplementation included transient gastrointestinal adverse effects. No studies evaluated the benefits or harms of screening for iron deficiency or iron deficiency anemia during pregnancy. Data on the association between iron status and health outcomes, such as hypertensive disorders of pregnancy and preterm birth, were very limited. Conclusions and Relevance: Routine prenatal iron supplementation reduces the incidence of iron deficiency and iron deficiency anemia during pregnancy, but evidence on health outcomes is limited or indicates no benefit. No studies addressed screening for iron deficiency or iron deficiency anemia during pregnancy. Research is needed to understand the association between changes in maternal iron status measures and health outcomes.

Predictive Accuracy of Infant Clinical Sign Algorithms for Mortality in Young Infants Aged 0 to 59 Days: A Systematic Review.

CONTEXT: Clinical sign algorithms are a key strategy to identify young infants at risk of mortality. OBJECTIVE: Synthesize the evidence on the accuracy of clinical sign algorithms to predict all-cause mortality in young infants 0-59 days. DATA SOURCES: MEDLINE, Embase, CINAHL, Global Index Medicus, and Cochrane CENTRAL Registry of Trials. STUDY SELECTION: Studies evaluating the accuracy of infant clinical sign algorithms to predict mortality. DATA EXTRACTION: We used Cochrane methods for study screening, data extraction, and risk of bias assessment. We determined certainty of evidence using Grading of Recommendations Assessment Development and Evaluation. RESULTS: We included 11 studies examining 26 algorithms. Three studies from non-hospital/community settings examined sign-based checklists (n = 13). Eight hospital-based studies validated regression models (n = 13), which were administered as weighted scores (n = 8), regression formulas (n = 4), and a nomogram (n = 1). One checklist from India had a sensitivity of 98% (95% CI: 88%-100%) and specificity of 94% (93%-95%) for predicting sepsis-related deaths. However, external validation in Bangladesh showed very low sensitivity of 3% (0%-10%) with specificity of 99% (99%-99%) for all-cause mortality (ages 0-9 days). For hospital-based prediction models, area under the curve (AUC) ranged from 0.76-0.93 (n = 13). The Score for Essential Neonatal Symptoms and Signs had an AUC of 0.89 (0.84-0.93) in the derivation cohort for mortality, and external validation showed an AUC of 0.83 (0.83-0.84). LIMITATIONS: Heterogeneity of algorithms and lack of external validation limited the evidence. CONCLUSIONS: Clinical sign algorithms may help identify at-risk young infants, particularly in hospital settings; however, overall certainty of evidence is low with limited external validation.

Efficacy of Antibiotic Regimens for Pneumonia in Young Infants Aged 0-59 Days: A Systematic Review.

CONTEXT: Pneumonia is a leading cause of death in young infants. OBJECTIVES: To evaluate the efficacy of different antibiotic regimens to treat young infant pneumonia on critical clinical outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, World Health Organization (WHO) Global Index Medicus, Cochrane Central Registry of Trials. STUDY SELECTION: We included randomized controlled trials of young infants aged 0 to 59 days with pneumonia (population) comparing the efficacy of antibiotic regimens (intervention) with alternate regimens or management (control) on clinical outcomes. DATA EXTRACTION: We extracted data and assessed risk of bias in duplicate. We used Grading of Recommendations, Assessment, Development, and Evaluation to assess certainty of evidence. LIMITATIONS: Trials were heterogeneous, which precluded data pooling. RESULTS: Of 2601 publications screened, 10 randomized controlled trials were included. Seven trials were hospital-based (n = 869) and 3 were nonhospital-based (n = 4329). No hospital-based trials evaluated WHO-recommended first-choice regimens. One trial found the WHO-recommended second-choice antibiotic, cefotaxime, to have similar rates of treatment success as non-WHO-recommended regimens of either amoxicillin-clavulanate (RR 0.99, 95% confidence interval 0.82-1.10) or amoxicillin-clavulanate/cefotaxime (RR 1.02, 95% confidence interval 0.86-1.12). Among 3 nonhospital-based trials comparing oral amoxicillin to alternate regimens to treat isolated tachypnea among infants aged 7-59 days, there were no differences in treatment failure between amoxicillin and alternate regimens. Certainty of evidence was low or very low for all primary outcomes. CONCLUSIONS: We found limited evidence to support the superiority of any single antibiotic regimen over alternate regimens to treat young infant pneumonia.

Efficacy of Antibiotic Regimens for Meningitis in Young Infants Aged 0-59 Days: A Systematic Review.

CONTEXT: Meningitis is associated with high mortality risk in young infants, yet the optimal treatment regimen is unclear. OBJECTIVES: To systematically evaluate the efficacy of antibiotic regimens to treat meningitis in young infants aged 0 to 59 days on critical clinical outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, WHO Global Index Medicus, and Cochrane Central Registry of Trials. STUDY SELECTION: We included randomized controlled trials (RCTs) of young infants with meningitis (population) comparing the efficacy of antibiotic regimens (interventions) with alternate regimens (control) on clinical outcomes. DATA EXTRACTION: We extracted data on study characteristics and assessed risk of bias in duplicate. Grading of Recommendations Assessment, Development, and Evaluation was used to assess certainty of evidence. RESULTS: Of 1088 studies screened, only 2 RCTs were identified. They included 168 infants from 5 countries and were conducted between 1976 and 2015. Neither study compared current World Health Organization-recommended regimens. One multisite trial from 4 countries compared intrathecal gentamicin plus systemic ampicillin/gentamicin to systemic ampicillin/gentamicin and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41-1.53; 1 trial, n = 98, very low certainty of evidence) or adverse events (no events in either trial arm). Another trial in India compared a 10-day versus 14-day course of antibiotics and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41-1.53; 1 trial, n = 98, very low certainty of evidence) or other outcomes. CONCLUSIONS: Trial data on the efficacy of antibiotic regimens in young infant meningitis are scarce. Rigorous RCTs are needed to inform recommendations for optimal antibiotic regimens for meningitis treatment in this vulnerable population, particularly within the context of changing epidemiology and increasing antimicrobial resistance.

Efficacy of Antibiotic Regimens for Sepsis or Possible Serious Bacterial Infection in Young Infants Aged 0 to 59 Days: A Systematic Review and Meta-analysis.

CONTEXT: Sepsis is a leading cause of young infant mortality. OBJECTIVE: To evaluate the efficacy of different antibiotic regimens to treat young infant sepsis or possible serious bacterial infection (PSBI) on clinical outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, World Health Organization Global Index Medicus, Cochrane Central Registry of Trials. STUDY SELECTION: We included randomized controlled trials (RCTs) of young infants 0 to 59 days with sepsis or PBSI (population) comparing the efficacy of antibiotic regimens (intervention) with alternate regimens or management (control) on clinical outcomes. DATA EXTRACTION: We extracted data and assessed risk of bias in duplicate. We performed random-effects meta-analysis, and used Grading of Recommendations, Assessment, Development, and Evaluation to assess certainty of evidence. RESULTS: Of 2390 publications, we included 41 RCTs (n = 18 054). Thirty-five trials were hospital-based and 6 were nonhospital-based. Meta-analysis of 4 trials demonstrated similar rates of treatment success with intramuscular/intravenous third generation cephalosporins versus intramuscular/intravenous penicillin or ampicillin + gentamicin (RR 1.03, 95% CI 0.93-1.13]; n = 1083; moderate certainty of evidence). Meta-analysis of 3 trials demonstrated similar rates of treatment failure with oral amoxicillin + intramuscular gentamicin versus intramuscular penicillin + gentamicin for nonhospital treatment of clinical severe illness (RR 0.86, 95% CI 0.72-1.02]; n = 5054; low certainty of evidence). Other studies were heterogeneous. LIMITATIONS: RCTs evaluated heterogeneous regimens, limiting our ability to pool data. CONCLUSIONS: We found limited evidence to support any single antibiotic regimen as superior to alternate regimens to treat young infant sepsis or PSBI.

Diagnostic Accuracy of Clinical Sign Algorithms to Identify Sepsis in Young Infants Aged 0 to 59 Days: A Systematic Review and Meta-analysis.

CONTEXT: Accurate identification of possible sepsis in young infants is needed to effectively manage and reduce sepsis-related morbidity and mortality. OBJECTIVE: Synthesize evidence on the diagnostic accuracy of clinical sign algorithms to identify young infants (aged 0-59 days) with suspected sepsis. DATA SOURCES: MEDLINE, Embase, CINAHL, Global Index Medicus, and Cochrane CENTRAL Registry of Trials. STUDY SELECTION: Studies reporting diagnostic accuracy measures of algorithms including infant clinical signs to identify young infants with suspected sepsis. DATA EXTRACTION: We used Cochrane methods for study screening, data extraction, risk of bias assessment, and determining certainty of evidence using Grading of Recommendations Assessment Development and Evaluation. RESULTS: We included 19 studies (12 Integrated Management of Childhood Illness [IMCI] and 7 non-IMCI studies). The current World Health Organization (WHO) 7-sign IMCI algorithm had a sensitivity of 79% (95% CI 77%-82%) and specificity of 77% (95% CI 76%-78%) for identifying sick infants aged 0-59 days requiring hospitalization/antibiotics (1 study, N = 8889). Any IMCI algorithm had a pooled sensitivity of 84% (95% CI 75%-90%) and specificity of 80% (95% CI 64%-90%) for identifying suspected sepsis (11 studies, N = 15523). When restricting the reference standard to laboratory-supported sepsis, any IMCI algorithm had a pooled sensitivity of 86% (95% CI 82%-90%) and lower specificity of 61% (95% CI 49%-72%) (6 studies, N = 14278). LIMITATIONS: Heterogeneity of algorithms and reference standards limited the evidence. CONCLUSIONS: IMCI algorithms had acceptable sensitivity for identifying young infants with suspected sepsis. Specificity was lower using a reference standard of laboratory-supported sepsis diagnosis.

Evidence From the USPSTF and New Approaches to Evaluate Interventions to Prevent Child Maltreatment.

Importance: The United States Preventive Services Task Force (USPSTF) has considered the topic of prevention of child maltreatment multiple times over its nearly 40-year history, each time reaching the conclusion that the evidence is insufficient to recommend for or against interventions aimed at preventing this important health problem with significant negative sequelae before it occurs. In the most recent evidence review, which was conducted from August 2021 to November 2023 and published in March 2024, the USPSTF considered contextual questions on the evidence for bias in reporting and diagnosis of maltreatment in addition to key questions regarding effectiveness of interventions to prevent child maltreatment. Observations: A comprehensive literature review found evidence of inaccuracies in risk assessment and racial and ethnic bias in the reporting of child maltreatment and in the evaluation of injuries concerning for maltreatment, such as skull fractures. When children are incorrectly identified as being maltreated, harms, such as unnecessary family separation, may occur. Conversely, when children who are being maltreated are missed, harms, such as ongoing injury to the child, continue. Interventions focusing primarily on preventing child maltreatment did not demonstrate consistent benefit or information was insufficient. Additionally, the interventions may expose children to the risk of harm as a result of these inaccuracies and biases in reporting and evaluation. These inaccuracies and biases also complicate assessment of the evidence for making clinical prevention guidelines. Conclusions and Relevance: There are several potential strategies for consideration in future efforts to evaluate interventions aimed at the prevention of child maltreatment while minimizing the risk of exposing children to known biases in reporting and diagnosis. Promising strategies to explore might include a broader array of outcome measures for addressing child well-being, using population-level metrics for child maltreatment, and assessments of policy-level interventions aimed at improving child and family well-being. These future considerations for research in addressing child maltreatment complement the USPSTF's research considerations on this topic. Both can serve as guides to researchers seeking to study the ways in which we can help all children thrive.

Development and Evaluation of a Framework for Identifying and Addressing Spin for Harms in Systematic Reviews of Interventions.

"Spin" refers to misleading reporting, interpretation, and extrapolation of findings in primary and secondary research (such as in systematic reviews). The study of spin primarily focuses on beneficial outcomes. The objectives of this research were threefold: first, to develop a framework for identifying spin associated with harms in systematic reviews of interventions; second, to apply the framework to a set of reviews, thereby pinpointing instances where spin may be present; and finally, to revise the spin examples, offering guidance on how spin can be rectified.The authors developed their framework through an iterative process that engaged an international group of researchers specializing in spin and reporting bias. The framework comprises 12 specific types of spin for harms, grouped by 7 categories across the 3 domains (reporting, interpretation, and extrapolation). The authors subsequently gathered instances of spin from a random sample of 100 systematic reviews of interventions. Of the 58 reviews that assessed harm and the 42 that did not, they found that 28 (48%) and 6 (14%), respectively, had at least 1 of the 12 types of spin for harms. Inappropriate extrapolation of the results and conclusions for harms to populations, interventions, outcomes, or settings not assessed in a review was the most common category of spin in 17 of 100 reviews.The authors revised the examples to remove spin, taking into consideration the context (for example, medical discipline, source population), findings for harms, and methodological limitations of the original reviews. They provide guidance for authors, peer reviewers, and editors in recognizing and rectifying or (preferably) avoiding spin, ultimately enhancing the clarity and accuracy of harms reporting in systematic review publications.

Long COVID Definitions and Models of Care : A Scoping Review.

BACKGROUND: Definitions of long COVID are evolving, and optimal models of care are uncertain. PURPOSE: To perform a scoping review on definitions of long COVID and provide an overview of care models, including a proposed framework to describe and distinguish models. DATA SOURCES: English-language articles from Ovid MEDLINE, PsycINFO, the Cochrane Library, SocINDEX, Scopus, Embase, and CINAHL published between January 2021 and November 2023; gray literature; and discussions with 18 key informants. STUDY SELECTION: Publications describing long COVID definitions or models of care, supplemented by models described by key informants. DATA EXTRACTION: Data were extracted by one reviewer and verified for accuracy by another reviewer. DATA SYNTHESIS: Of 1960 screened citations, 38 were included. Five clinical definitions of long COVID varied with regard to timing since symptom onset and the minimum duration required for diagnosis; 1 additional definition was symptom score-based. Forty-nine long COVID care models were informed by 5 key principles: a core "lead" team, multidisciplinary expertise, comprehensive access to diagnostic and therapeutic services, a patient-centered approach, and providing capacity to meet demand. Seven characteristics provided a framework for distinguishing models: home department or clinical setting, clinical lead, collocation of other specialties, primary care role, population managed, use of teleservices, and whether the model was practice- or systems-based. Using this framework, 10 representative practice-based and 3 systems-based models of care were identified. LIMITATIONS: Published literature often lacked key model details, data were insufficient to assess model outcomes, and there was overlap between and variability within models. CONCLUSION: Definitions of long COVID and care models are evolving. Research is needed to optimize models and evaluate outcomes of different models. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (Protocol posted at https://effectivehealthcare.ahrq.gov/products/long-covid-models-care/protocol.).

A narrative review of global and national physical activity and sedentary behaviour guidelines development processes - The GUidelines Standards (GUS) project.

BACKGROUND: Clinical and public health guidelines serve to direct clinical practice and policy, based on the best available evidence. The World Health Organization (WHO) and national health bodies of many countries have released physical activity and sedentary behaviour guidelines. Despite significant overlap in the body of evidence reviewed, the guidelines differ across jurisdictions. This study aimed to review the processes used to develop global and national physical activity and sedentary behaviour guidelines and examine the extent to which they conform with a recommended methodological standard for the development of guidelines. METHODS: We extracted data on nine sets of guidelines from seven jurisdictions (WHO, Australia, Canada, Japan, the Netherlands, United Kingdom, and United States). We rated each set of guidelines as high, medium, or low quality on criteria related to the rigour of the development process. RESULTS: We observed variation in the quality of guidelines development processes across jurisdictions and across different criteria. Guidelines received the strongest overall ratings for criteria on clearly describing the evidence selected and stating an explicit link between the recommendations and the supporting evidence. Guidelines received the weakest overall ratings for criteria related to clearly describing the methods used to formulate the recommendations and reporting external review by experts prior to publication. Evaluated against the selected criteria, the strongest processes were undertaken by the WHO and Canada. CONCLUSIONS: Reaching agreement on acceptable guideline development processes, as well as the inclusion and appraisal procedures of different types of evidence, would help to strengthen and align future guidelines.

Primary Care Interventions to Prevent Child Maltreatment: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Child maltreatment is associated with serious negative physical, psychological, and behavioral consequences. Objective: To review the evidence on primary care-feasible or referable interventions to prevent child maltreatment to inform the US Preventive Services Task Force. Data Sources: PubMed, Cochrane Library, and trial registries through February 2, 2023; references, experts, and surveillance through December 6, 2023. Study Selection: English-language, randomized clinical trials of youth through age 18 years (or their caregivers) with no known exposure or signs or symptoms of current or past maltreatment. Data Extraction and Synthesis: Two reviewers assessed titles/abstracts, full-text articles, and study quality, and extracted data; when at least 3 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures: Directly measured reports of child abuse or neglect (reports to Child Protective Services or removal of the child from the home); proxy measures of abuse or neglect (injury, visits to the emergency department, hospitalization); behavioral, developmental, emotional, mental, or physical health and well-being; mortality; harms. Results: Twenty-five trials (N = 14 355 participants) were included; 23 included home visits. Evidence from 11 studies (5311 participants) indicated no differences in likelihood of reports to Child Protective Services within 1 year of intervention completion (pooled odds ratio, 1.03 [95% CI, 0.84-1.27]). Five studies (3336 participants) found no differences in removal of the child from the home within 1 to 3 years of follow-up (pooled risk ratio, 1.06 [95% CI, 0.37-2.99]). The evidence suggested no benefit for emergency department visits in the short term (<2 years) and hospitalizations. The evidence was inconclusive for all other outcomes because of the limited number of trials on each outcome and imprecise results. Among 2 trials reporting harms, neither reported statistically significant differences. Contextual evidence indicated (1) widely varying practices when screening, identifying, and reporting child maltreatment to Child Protective Services, including variations by race or ethnicity; (2) widely varying accuracy of screening instruments; and (3) evidence that child maltreatment interventions may be associated with improvements in some social determinants of health. Conclusion and Relevance: The evidence base on interventions feasible in or referable from primary care settings to prevent child maltreatment suggested no benefit or insufficient evidence for direct or proxy measures of child maltreatment. Little information was available about possible harms. Contextual evidence pointed to the potential for bias or inaccuracy in screening, identification, and reporting of child maltreatment but also highlighted the importance of addressing social determinants when intervening to prevent child maltreatment.

Quality Indicators for Major Depressive Disorder in Adults: A Review of Performance Measures by the American College of Physicians.

Major depressive disorder (MDD) is a severe mood disorder that affects at least 8.4% of the adult population in the United States. Characteristics of MDD include persistent sadness, diminished interest in daily activities, and a state of hopelessness. The illness may progress quickly and have devastating consequences if left untreated. Eight performance measures are available to evaluate screening, diagnosis, and successful management of MDD. However, many performance measures do not meet the criteria for validity, reliability, evidence, and meaningfulness.The American College of Physicians (ACP) embraces performance measurement as a means to externally validate the quality of care of practices, medical groups, and health plans and to drive reimbursement processes. However, a plethora of performance measures that provide low or no value to patient care have inundated physicians, practices, and systems and burdened them with collecting and reporting of data. The ACP's Performance Measurement Committee (PMC) reviews performance measures using a validated process to inform regulatory and accreditation bodies in an effort to recognize high-quality performance measures, address gaps and areas for improvement in performance measures, and help reduce reporting burden. Out of 8 performance measures, the PMC found only 1 measure (suicide risk assessment) that was valid at all levels of attribution. This paper presents a review of MDD performance measures and highlights opportunities to improve performance measures addressing MDD management.

Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part III: Salvage Therapy After Radiotherapy or Focal Therapy, Pelvic Nodal Recurrence and Oligometastasis, and Future Directions.

PURPOSE: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part III of a three-part series focusing on evaluation and management of suspected non-metastatic recurrence after radiotherapy (RT) and focal therapy, evaluation and management of regional recurrence, management for molecular imaging metastatic recurrence, and future directions. Please refer to Part I for discussion of treatment decision-making and Part II for discussion of treatment delivery for non-metastatic biochemical recurrence (BCR) after radical prostatectomy (RP). MATERIALS AND METHODS: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. RESULTS: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Guideline Panel developed evidence- and consensus-based guideline statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. CONCLUSIONS: Continuous and deliberate efforts for multidisciplinary care in prostate cancer will be required to optimize and improve the oncologic and functional outcomes of patients treated with salvage therapies in the future.

Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part I: Introduction and Treatment Decision-Making at the Time of Suspected Biochemical Recurrence after Radical Prostatectomy.

PURPOSE: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part I of a three-part series focusing on treatment decision-making at the time of suspected biochemical recurrence (BCR) after radical prostatectomy (RP). Please refer to Part II for discussion of treatment delivery for non-metastatic BCR after RP and Part III for discussion of evaluation and management of recurrence after radiotherapy (RT) and focal therapy, regional recurrence, and oligometastasis. MATERIALS AND METHODS: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. RESULTS: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Panel developed evidence- and consensus-based statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. CONCLUSIONS: Advancing work in the area of diagnostic tools (particularly imaging), biomarkers, radiation delivery, and biological manipulation with the evolving armamentarium of therapeutic agents will undoubtedly present new opportunities for patients to experience long-term control of their cancer while minimizing toxicity.

Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part II: Treatment Delivery for Non-metastatic Biochemical Recurrence After Primary Radical Prostatectomy.

PURPOSE: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part II of a three-part series focusing on treatment delivery for non-metastatic biochemical recurrence (BCR) after primary radical prostatectomy (RP). Please refer to Part I for discussion of treatment decision-making and Part III for discussion of evaluation and management of recurrence after radiotherapy (RT) and focal therapy, regional recurrence, and oligometastasis. MATERIALS AND METHODS: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. RESULTS: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. CONCLUSIONS: Optimizing and personalizing the approach to salvage therapy remains an ongoing area of work in the field of genitourinary oncology and represents an area of research and clinical care that requires well-coordinated, multi-disciplinary efforts.

Screening for Speech and Language Delay and Disorders in Children 5 Years or Younger: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Children with speech and language difficulties are at risk for learning and behavioral problems. Objective: To review the evidence on screening for speech and language delay or disorders in children 5 years or younger to inform the US Preventive Services Task Force. Data Sources: PubMed/MEDLINE, Cochrane Library, PsycInfo, ERIC, Linguistic and Language Behavior Abstracts (ProQuest), and trial registries through January 17, 2023; surveillance through November 24, 2023. Study Selection: English-language studies of screening test accuracy, trials or cohort studies comparing screening vs no screening; randomized clinical trials (RCTs) of interventions. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, study quality, and data extraction; results were narratively summarized. Main Outcomes and Measures: Screening test accuracy, speech and language outcomes, school performance, function, quality of life, and harms. Results: Thirty-eight studies in 41 articles were included (N = 9006). No study evaluated the direct benefits of screening vs no screening. Twenty-one studies (n = 7489) assessed the accuracy of 23 different screening tools that varied with regard to whether they were designed to be completed by parents vs trained examiners, and to screen for global (any) language problems vs specific skills (eg, expressive language). Three studies assessing parent-reported tools for expressive language skills found consistently high sensitivity (range, 88%-93%) and specificity (range, 88%-85%). The accuracy of other screening tools varied widely. Seventeen RCTs (n = 1517) evaluated interventions for speech and language delay or disorders, although none enrolled children identified by routine screening in primary care. Two RCTs evaluating relatively intensive parental group training interventions (11 sessions) found benefit for different measures of expressive language skills, and 1 evaluating a less intensive intervention (6 sessions) found no difference between groups for any outcome. Two RCTs (n = 76) evaluating the Lidcombe Program of Early Stuttering Intervention delivered by speech-language pathologists featuring parent training found a 2.3% to 3.0% lower proportion of syllables stuttered at 9 months compared with the control group when delivered in clinic and via telehealth, respectively. Evidence on other interventions was limited. No RCTs reported on the harms of interventions. Conclusions and Relevance: No studies directly assessed the benefits and harms of screening. Some parent-reported screening tools for expressive language skills had reasonable accuracy for detecting expressive language delay. Group parent training programs for speech delay that provided at least 11 parental training sessions improved expressive language skills, and a stuttering intervention delivered by speech-language pathologists reduced stuttering frequency.

Efficacy and safety of DAA in children and adolescents with chronic HCV infection: A systematic review and meta-analysis.

BACKGROUND AND AIMS: We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct-acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)-infected adolescents (12-18 years), older children (6-11 years), and young children (3-5 years). The purpose of this systematic review and meta-analysis was to inform the World Health Organization (WHO) guidelines. METHODS: We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV-infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS-I tool. Data were pooled using random-effects models, and certainty of the evidence was assessed using the GRADE approach. RESULTS: A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96-100), 96% (90-100), and 96% (83-100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90-99), 93% (86-98), and 83% (70-93), for SOF/VEL, respectively; and 100% (97-100) and 100% (94-100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%). CONCLUSIONS: All three pan-genotypic DAA regimens were highly effective and well-tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single-arm non-randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co-infection that precluded evaluation of the impact of these factors on outcomes. PROSPERO RECORD: CRD42020146752.