Changes In Guidelines Research Articles

The efficacy of first and second immunotherapy exposure in patients with recurrent or metastatic cervical cancer.

Immunotherapy has led to changes in cervical cancer guidelines. Therefore, additional biomarkers to identify the ideal patient who would experience the most benefit may be important. We retrospectively collected 208 patients with R/M CC and recorded clinicopathologic information, peripheral blood markers and treatments to analyze the prognostic factors of clinical outcomes. Response rate comparison, univariate, and multivariate analyses were performed to assess the efficacy of different factors. A total of 43.27% patients achieved objective responses, including 18 with complete response and 72 with partial response. Patients receiving first-line immunotherapy had much higher objective response rate (ORR) than the remaining patients (53.8% vs. 34.8%, p = 0.006). CRP >3 ECOG ≥1 and recurrence in 6 months predicted shorter progression free survival (PFS). CRP >3, GLU >6.1 independently predicted unfavorable overall survival (OS). Compared with no antiangiogenic therapy, previous antiangiogenic therapy reduced the median OS by nearly 14 months. Immunotherapy rechallenge was still effective after first immunotherapy failure, and combined with dual-immunotherapy or bevacizumab combined with chemoradiotherapy resulted in a 60.00% or 62.50% ORR, respectively. Patients with squamous cell carcinoma, with stable disease or objective response in the first immunotherapy or without chemotherapy in second immunotherapy had favorable clinical outcome. The baseline CRP levels in serum was an independent factor for PFS and OS of R/M CC patients treated with immunotherapy, and previous antiangiogenic therapy was associated with poor OS. Patients still show response to immunotherapy rechallenge and combined treatment with bevacizumab or candonilimab showed higher response rate than anti-PD-1 after immunotherapy failure.

Manifestation of national identity in the socio-political values of student youth

The problem of national identity is one of the most controversial, not losing scientific and socio-political relevance for many centuries. National identity is based on a system of value guidelines that unites individuals into a single historical, cultural and social community. The formation of national self-awareness occurs in the process of internalization by an individual of the value system of his country. At the same time, the self-perception of belonging to a certain nation is not predetermined by formal citizenship and is not given once and for all; throughout the life of an individual there is the possibility of choice and change of national identity. This choice is inevitable when the country’s value guidelines change. The modern period in Russian history, and indeed the whole world, is a kind of bifurcation point; the values of the globalizing world, the so-called Western values, come into conflict with traditional Russian values. For the preservation of Russian national identity, the choice of young people is of particular importance. The future of the country depends on what value guidelines form the basis of the national self-determination of today's Russian youth. The article presents the results of a study of the relationship between socio-political values and the choice of national identity of Russian students. It is not by chance that students are identified as the object of observation. As the avant-garde, the most educated part of young people with high ambitions and a desire for social independence, students are the most receptive to change. For the analysis, empirical data from a study by the Center for Political Science of the Institute of Socio-Political Research of FCTAS RAS “Students of Russia: civic culture and life strategies” were used. Using the method of factor analysis, based on the results of an empirical study, three basic types of identity were identified: “Russian, person of his city”, “person of the world, the Internet”, “Asian”. It has been proven that the prevailing type of student identity is closely related to his socio-political attitudes and guidelines. The types that differ most in their views are “Russian, person of the city” and “person of the world, the Internet.” The first type is characterized by pronounced positive assessments of Russia's situation on the world stage, optimistic forecasts for the development of both the economy and the development of the country as a whole in 10-15 years. Representatives of this type see the main national idea in the unity of the peoples of Russia in order to revive the country as a great power. Representatives of the “person of the world, Internet” type are characterized by less positive assessments of the present and future of Russia. The main national idea for them is to create a legal and modern democratic state, the path of development is a free market economy. Among the values, such concepts as human rights, freedom and democracy are more significantly represented. But the most important difference between the second type is the pronounced migration sentiment.

Assigning credit where it is due: an information content score to capture the clinical value of multiplexed assays of variant effect

BackgroundA variant can be pathogenic or benign with relation to a human disease. Current classification categories from benign to pathogenic reflect a probabilistic summary of the current understanding. A primary metric of clinical utility for multiplexed assays of variant effect (MAVE) is the number of variants that can be reclassified from uncertain significance (VUS). However, a gap in this measure of utility is that it underrepresents the information gained from MAVEs. The aim of this study was to develop an improved quantification metric for MAVE utility. We propose adopting an information content approach that includes data that does not reclassify variants will better reflect true information gain. We adopted an information content approach to evaluate the information gain, in bits, for MAVEs of BRCA1, PTEN, and TP53. Here, one bit represents the amount of information required to completely classify a single variant starting from no information.ResultsBRCA1 MAVEs produced a total of 831.2 bits of information, 6.58% of the total missense information in BRCA1 and a 22-fold increase over the information that only contributed to VUS reclassification. PTEN MAVEs produced 2059.6 bits of information which represents 32.8% of the total missense information in PTEN and an 85-fold increase over the information that contributed to VUS reclassification. TP53 MAVEs produced 277.8 bits of information which represents 6.22% of the total missense information in TP53 and a 3.5-fold increase over the information that contributed to VUS reclassification.ConclusionsAn information content approach will more accurately portray information gained through MAVE mapping efforts than by counting the number of variants reclassified. This information content approach may also help define the impact of guideline changes that modify the information definitions used to classify groups of variants.

Respiratory rates among rural Gambian children: a community-based cohort study

Normal respiratory rates (RR) for children under five in the tropics are well-documented, but data for older children are limited. This study tracked RR changes with age and examined associations with nutritional status and environmental factors. We monitored rural Gambian children aged 6 months to 14 years, recording RR during home visits twice weekly over two rainy seasons. Using a generalized additive model, we constructed RR reference curves, and a linear mixed-effect model identified factors influencing RR. A total of 830 children provided 67,512 RR measurements. Their median age was 6.07 years (interquartile range 4.21–8.55) and 400 (48.2%) were female. Age, stunting, ambient temperature, and time of RR measurement were independent predictors of respiratory rate. Strikingly, children showing signs of illness had greater variability in repeat RR measurements. We constructed a RR reference chart for children aged one to 13 years and proposed a cutoff of > 26 breaths/min for raised RR among children aged > 5 years bridging an important gap in this age group. Although the time of data collection, nutritional status, and ambient temperature were predictors of RR, their effect size is not clinically significant enough to warrant a change in the current WHO guidelines owing to the prevailing uncertainty in the measurement of RR. The finding that RRs between repeat measurements were more variable among children with signs of illness suggests that a single RR measurement may be inadequate to reliably assess the status of sick children—a population in which accurate diagnosis is essential to enable targeted interventions with lifesaving treatment.

Definition Change and Update of Clinical Guidelines for Interstitial Cystitis and Bladder Pain Syndrome.

The clinical guidelines for interstitial cystitis (IC) and bladder pain syndrome (BPS) have been revised by updating our previous guidelines. The symptoms of IC and BPS, collectively called as hypersensitive bladder (HSB) symptoms, are virtually indistinguishable between IC and BPS; however, IC and BPS should be considered as a separate entity of disorders. We define IC as a bladder disease with Hunner lesions, usually associated with HSB symptoms and bladder inflammation, and BPS as a condition with HSB symptoms in the absence of Hunner lesions and any confusable diseases. Pathophysiology totally differs between IC and BPS. IC involves immunological inflammation probably resulting from autoimmunity, while BPS is associated with the interaction of multiple factors such as neurogenic inflammation, exogenous substances, urothelial defects, psychological stress, and neural hyperactivity. Histopathology also differs between IC and BPS. IC is associated with severe inflammation of the whole bladder accompanied by plasma cell infiltration and urothelial denudation, while BPS shows little pathological changes. Management should begin with a differential diagnosis of IC or BPS, which would require cystoscopy to determine the presence or absence of Hunner lesions. The patients should be treated differently based on the diagnosis following the algorithm, although pain management would be common to IC and BPS. Clinical studies are also to be designed and analyzed separately for IC and BPS.

Health Policy Reforms and Their Effect on Healthcare Delivery: Utilizing Natural Language Processing (NLP) to Analyze Public Sentiment and Policy Feedback

For health policy reforms, they've a profound impact on the healthcare transport structures, shaping how services are given and obtained. For lawmakers to make knowledgeable decisions that cope with the concerns and wishes of the society, they need to be able to apprehend what the public senses and says about the ones changes. The effectiveness and acceptability of health policy reforms can be better understood by the use of Natural Language Processing (NLP), which has advanced strategies for analyzing huge quantities of public discourse. Decoding diverse and unstructured records resources along with open forums, social media posts as well as news tales is one out of several troubles this assignment tackles. Natural Language Processing-Based Integrated Sentiment Analysis (NLP-ISA) is a new approach to evaluating how healthcare delivery has been converted by using changes in health policy. To process big data sets consisting of public speeches, NLP-ISA combines sentiment evaluation with present day herbal language processing algorithms. This technique analyzes public temper to show worries approximately the change in guidelines, gratification, and potential challenges that want interest when it comes to it. This paper helps policymakers to improve carrier conveyance by demonstrating real-time outcomes that their regulations create. It could screen public response in the direction of new hints while ascertaining trends in opinion among contributors of the public. The efficiency will confirm if NLP-ISA is effective or now not through simulation analysis.This process includes comparing previous polls on health care deliveries with the results from previous polls concerning past improvements made on health policies. By simulating the effect of public opinion on policy outcomes, this simulation will show how well NLP-ISA can formulate evidence-based suggestions for policy changes.

Overtreatment and Undertreatment of Early-Stage Breast Cancer in Older Women: Evaluating the POWER Trial

IntroductionRadiation therapy (RT) omission is acceptable in older women with early-stage estrogen receptor + breast cancer treated with breast-conserving surgery (BCS) and adjuvant endocrine therapy (AET). However, RT rates in this population remain high, causing concern for overtreatment. Conversely, patients who omit RT and do not complete a course of AET are at risk of undertreatment. In the Pre-Operative Window of Endocrine Therapy to Inform Radiation Therapy Decisions (POWER) trial, participants receive 90 days of preoperative endocrine therapy to assess tolerance before deciding about RT. This study aimed to determine the rates of undertreatment and overtreatment institutionally and among POWER trial participants. MethodsData were retrospectively collected from medical records of women aged ≥ 65 years diagnosed with invasive, estrogen receptor +/human epidermal growth factor receptor 2- breast cancer, ≤ 3 cm, who had BCS between 2012 and 2022. Patients were categorized as undertreated (BCS alone), overtreated (BCS + RT + AET), or appropriately treated (BCS + RT or BCS + AET). ResultsThe cohort included 478 patients, of whom 62 (12.97%) were undertreated, 202 (42.26%) were overtreated, and 214 (44.77%) were appropriately treated. Appropriately treated patients were more likely to be aged 70-79 years (P < 0.0001) and have high health literacy (P = 0.0003). Of the 37 patients (7.71%) in the POWER trial, more were appropriately treated than patients not in the POWER trial (81.1% versus 44.8%) (P < 0.0001). ConclusionsDespite long-standing guideline changes, RT utilization remains high. This study highlights how a novel patient-centered approach to guide adjuvant therapy decisions may increase the number of appropriately treated patients.

Increasing Fluroquinolone Susceptibility and Genetic Diversity of ESBL-Producing E. coli from the Lower Respiratory Tract during the COVID-19 Pandemic.

Lower respiratory tract infections (LRTIs) are the fourth leading cause of death worldwide, among which Escherichia coli (E. coli) pneumonia is considered a rare phenomenon. Treatment options for LRTIs have become limited, especially for extended-spectrum β-lactamase-producing E. coli (ESBL-EC), which are usually resistant to other groups of antimicrobials as well. The aim of our study was to compare the phenotypic resistance profiles and genotypes of ESBL-EC isolates associated with LRTIs before (pre-COVID-19) and during (COVID-19) the COVID-19 pandemic. All isolates were screened for antimicrobial resistance genes (ARGs) and virulence-associated genes (VAGs) and assigned to phylogenetic groups, sequence types and clonal groups by PCR. During the pandemic, a significantly lower proportion of ciprofloxacin-, levofloxacin- and trimethoprim-sulfamethoxazole-resistant ESBL-EC isolates was retrieved from lower respiratory tract (LRT) samples. PCR-based genotypization revealed greater clonal diversity and a significantly lower proportion of isolates with blaTEM, aac(6')-Ib-cr and qacEΔ1 genes. In addition, a higher proportion of isolates with the integrase gene int1 and virulence genes sat and tsh was confirmed. The lower prevalence of fluoroquinolone resistance and greater genetic diversity of ESBL-EC isolated during the COVID-19 period may have been due to the introduction of new bacterial strains into the hospital environment, along with changes in clinical establishment guidelines and practices.

Prescribing Trends for Oral Vancomycin and Fidaxomicin after Guideline and Formulary Changes in Ontario, Canada: An Interrupted Time-Series Analysis.

Clostridioides difficile is a pathogen causing diarrheal illness, which can be treated with vancomycin or fidaxomicin. To evaluate changes in monthly prescription volumes for oral vancomycin and fidaxomicin in Ontario community pharmacies following implementation of the 2017 and 2021 updates to guidelines from the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) and after a 2019 provincial formulary change for vancomycin. An interrupted time-series analysis was conducted from November 2015 to October 2021 using monthly projected prescription volumes obtained from IQVIA's Compuscript database. Level and slope (trend) changes in prescribing were assessed using segmented linear regression. The volume of vancomycin prescriptions increased by 74 prescriptions per month (95% confidence interval [CI] 16 to 132) following implementation of the 2017 guideline update and by 73 prescriptions per month (95% CI 13 to 133) after the 2019 formulary change; however, no statistically significant changes were observed after implementation of the 2021 guideline update. No significant trend changes were observed for fidaxomicin. Guidelines and formulary changes were correlated with increased volume of vancomycin prescriptions.

Comparative effectiveness of vancomycin and metronidazole on event-free survival after initial infection in patients with Clostridioides difficile—a German multicentre cohort study

ObjectivesThe objective of this study is to examine the comparative effectiveness of vancomycin and metronidazole in a confirmatory analysis of event-free survival (EFS) after initial infection in patients with Clostridioides difficile from a German multicentre cohort study. MethodsThe IBIS multicentre cohort enrolled patients with an index episode of C. difficile infection between August 2017 and September 2020. The primary endpoint was EFS, defined as response to treatment with metronidazole or vancomycin within 10 days of initiation, absence of recurrence and death from any cause up to 90 days post-treatment. A Cox proportional hazards model with inverse probability of treatment weighting was used to investigate the comparative effectiveness of this outcome. Additionally, subgroup analyses were performed based on severe and non-severe infections. ResultsOf the 489 patients included, 118 (24%) received initial treatment with metronidazole and 371 (76%) with vancomycin. Of these, 78/118 (66.1%) and 247/371 (66.6%), respectively, responded to treatment within 10 days, neither developed a recurrence nor died within 90 days and thus achieved the outcome of EFS. In the subgroup of non-severe infections, 74/293 patients (25.3%) received metronidazole, and 219/293 (74.7%) received vancomycin. Of these, 33/74 (44.6%) metronidazole patients and 150/219 (68.5%) vancomycin patients survived event free. The Cox proportional hazards model revealed differences in EFS for the overall population and both subgroups (reference metronidazole: all severity levels: hazard ratio [HR] 0.46, [95% CI, 0.33–0.65]; non-severe: HR 0.39; [95% CI, 0.24–0.60]; severe: HR 0.52; [95% CI, 0.28–0.95]). DiscussionOur analysis confirms current changes in guidelines, as it supports the superiority of vancomycin compared with metronidazole across all severity levels.

Breaking down barriers to COPD management in primary care: applying the updated 2023 Canadian Thoracic Society guideline for pharmacotherapy.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent yet under-recognized and sub-optimally managed disease that is associated with substantial morbidity and mortality. Primary care providers (PCPs) are at the frontlines of COPD management, and they play a critical role across the full spectrum of the COPD patient journey from initial recognition and diagnosis to treatment optimization and referral to specialty care. The Canadian Thoracic Society (CTS) recently updated their guideline on pharmacotherapy in patients with stable COPD, and there are several key changes that have a direct impact on COPD management in the primary care setting. Notably, it is the first guideline to formally make recommendations on mortality reduction in COPD, which elevates this disease to the same league as other chronic diseases that are commonly managed in primary care and where optimized pharmacotherapy can reduce all-cause mortality. It also recommends earlier and more aggressive initial maintenance inhaler therapy across all severities of COPD, and preferentially favors the use of single inhaler therapies over multiple inhaler regimens. This review summarizes some of the key guideline changes and offers practical tips on how to implement the new recommendations in primary care. It also addresses other barriers to optimal COPD management in the primary care setting that are not addressed by the guideline update and suggests strategies on how they could be overcome.

More than a new name: Updates in the management of Clostridioides difficile infection.

Infections from Clostridioides difficile (often called C. diff) have long presented challenges for both patients and clinicians. Traditionally, C. diff has been considered a nosocomial infection, but in recent years, a noticeable spike in community-acquired cases has occurred. C. diff infection (CDI) testing is often complicated, as various testing options with differing sensitivity and specificity for active infection are available. Also, recent guideline changes have altered the recommended treatment of infection. This article discusses recent changes to both the diagnosis and management of CDI and how they can be applied to everyday NP practice.

Survival and patient-reported outcomes of real-world high-risk stage II and stage III colon cancer patients after reduction of adjuvant CAPOX duration from 6 to 3 months

AimAdjuvant chemotherapy has been advised for high-risk stage II and III colon cancer since 2004. After the IDEA study showed no clinically relevant difference in outcome, reduction of adjuvant CAPOX duration from 6 to 3 months was rapidly adopted in the Dutch treatment guideline in 2017. This study investigates the real-world impact of the guideline change on overall survival (OS) and patient-reported outcomes (PROs). MethodsPatients with high-risk stage II (pT4 +) and III (pN+) colon cancer were selected from the Netherlands Cancer Registry, based on surgical resection and adjuvant CAPOX before (2015–2016) versus after (2018–2019) the guideline change. Both groups were compared on OS, using multivariable Cox regression, and on PROs. ResultsPatients treated before (n = 2330) and after (n = 2108) the guideline change showed similar OS (HR 1.02; 95 %CI [0.89–1.16]), also in high-risk stage III (pT4/N2, HR 1.06 [0.89–1.26]). After the guideline change, 90 % of patients were treated for 3 months with no inferior OS to those still receiving 6 months (HR 0.89 [0.66–1.20]). PROs 2 years after CAPOX completion, available for a subset of patients, suggest a lower neuropathy (n = 366; 26.2 [21.3–31.1] to 16.5 [14.4–18.6]) and better quality of life (n = 396; 80.9 [78.6–83.2] to 83.9 [82.8–84.9]), but no significant difference in workability (n = 120; 31.5 [27.9–35.1]) to 35.3 [33.8–36.7]), with reduction from 6 to 3 months of CAPOX. ConclusionThis real-world study confirmed that shorter adjuvant CAPOX did not compromise OS and may improve PROs, complementing the IDEA study and supporting 3 months of adjuvant CAPOX in daily clinical practice.

Intermediate-sized follicular thyroid cancer surgical trends before and after the 2015 American thyroid association guideline changes

In 2015, the ATA updated the guidelines to advocate for a lobectomy for tumors <1.0 ​cm and total thyroidectomy for tumors >4.0 ​cm. Treatment for tumors of intermediate size 1.0–4.0 ​cm is dependent on high-risk characteristics. There is limited research comparing the impact of the updated ATA guidelines on clinical practice on intermediate-sized tumors. In this study, the impact of the 2015 ATA guidelines on the surgical treatment of intermediated-sized FTC will be evaluated using the Surveillance, Epidemiology, and End Results (SEER) database. A total of 9983 patients were included; 7769 patients (74.1 ​%) were diagnosed pre-ATA guidelines and 2709 patients (25.9 ​%) post-ATA guidelines. The mean rate of lobectomy for intermediate-sized tumors was 22.1 ​% which increased to 33.4 ​% post-ATA updates. The results of the logistic regression showed the rate of lobectomy increased significantly in the post-ATA changes period (p ​< ​0.001). Future research could benefit from evaluating how these trends impact patient outcome measures.

Changing colon cancer screening guidelines to age 45: Has it made a difference?

BackgroundA concerning increase in early-onset colorectal cancer led to guideline changes in 2018 by the American Cancer Society to lower the age for initial colorectal cancer screening from 50 to 45 years of age. Although this would be expected to result in increased screening rates and subsequent earlier detection of colorectal cancer, the effect of this guideline change at a national level is not yet fully understood. MethodsUsing the National Cancer Database, we identified patients newly targeted for screening (age 45–49 years) diagnosed with colon cancer in either 2017 (early cohort) or 2019 (late cohort). The relationship between time period and stage of disease at presentation was examined by univariate analysis and in a multivariable logistic regression model. ResultsIn total, 5,479 patients met inclusion criteria. The median age at diagnosis did not differ between patients in the late and early cohorts (47 years for both cohorts, P = .41). Patients in the late and early cohorts had equal odds of having stage III-IV disease (odds ratio for late cohort to early cohort, 1.05, 95% confidence interval, 0.94–1.17), and patients in the late cohort showed slightly increased odds of having higher T-stage (pT3 or pT4) disease (odds ratio, 1.20, 95% confidence interval, 1.05–1.35). ConclusionDespite recommendations of earlier initial colorectal cancer screening, a clinically meaningful earlier shift in colon cancer stage was not observed in patients newly targeted for screening. Further studies will be needed to assess uptake of these recommendations by providers and patients and identify areas of improvement.

Efficacy and Safety of Lerodalcibep in Patients With or at High Risk of Cardiovascular Disease

Recent changes in national and international lipid guidelines for reducing cardiovascular events recommend additional drugs, greater reductions, and lower targets for low-density lipoprotein cholesterol (LDL-C) if not attained with statins. The achievement of these targets with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has not yet been evaluated in a randomized clinical trial. To evaluate the 52-week safety and efficacy of lerodalcibep, a small anti-PCSK9-binding protein, in patients with cardiovascular disease (CVD) or who are at very high or high risk of CVD and requiring addition LDL-C-lowering treatment. This was a randomized, double-blind, placebo-controlled phase 3 trial. The trial was conducted at 66 clinics in 11 countries between April 23, 2021, and November 15, 2023. Individuals 18 years and older taking maximally tolerated statin therapy with LDL-C of 70 mg/dL or greater with CVD or 100 mg/dL or greater if at high risk of CVD were included. Patients were randomized 2:1 to monthly 1.2-mL subcutaneous lerodalcibep, 300 mg, or placebo for 52 weeks. The safety analysis included all randomized patients. The co-primary efficacy end points were percent change from baseline in LDL-C at week 52 and the mean of weeks 50 and 52. Secondary efficacy outcomes included additional lipid apolipoprotein measures and achievement of guideline-recommended LDL-C targets. Of 922 randomized participants (mean [range] age, 64.5 [27-87] years; 414 [44.9%] female; mean [SD] baseline LDL-C, 116.2 [43.5] mg/dL), 811 (88%) completed the trial. The mean (SE) placebo-adjusted reduction in LDL-C with lerodalcibep by modified intention-to-treat (mITT) analysis was 56.2% (2.2%) at week 52 and 62.7% (1.9%) for the mean of weeks 50 and 52; 49.7% (2.4%) and 55.3% (2.2%) by ITT with imputation using a washout model, and 60.3% (2.3%) and 65.9% (1.9%) by per-protocol analysis at week 52 and the mean of weeks 50 and 52, respectively (P < .001 for all). With lerodalcibep, 555 of 615 participants (90%) achieved both a reduction in LDL-C of 50% or greater and recommended LDL-C targets during the study. Treatment-emergent adverse events were similar between lerodalcibep and placebo, except for injection site reactions. These occurred in 42 of 613 participants receiving lerodalcibep (6.9%) compared to 1 of 307 receiving placebo (0.3%), were graded mild or moderate, and did not result in higher discontinuation of treatment, at 26 of 613 (4.2%) and 14 of 307 (4.6%), respectively. Sporadic in vitro antidrug antibodies were detected, which had no impact on free PCSK9 or LDL-C-lowering efficacy. In this trial, lerodalcibep, a novel anti-PCSK9 small binding protein, dosed monthly and stable at ambient temperatures significantly reduced LDL-C in patients with CVD or at high risk of atherosclerotic cardiovascular disease with a safety profile similar to placebo. These results support long-term use of lerodalcibep in patients with CVD or at high risk of CVD who are unable to achieve adequate LDL-C reduction while receiving maximal tolerated statins alone. ClinicalTrials.gov Identifier: NCT04806893.

Betamethasone treatment-to-delivery interval, retreatment, and severe intraventricular hemorrhage in infants

Antenatal corticosteroids decrease the incidence of severe intraventricular hemorrhages (grades 3,4) in preterm infants. It is unclear whether their beneficial effects on intraventricular hemorrhage wane with time (as occurs in neonatal respiratory distress) and if repeat courses can restore this effect. Prior randomized controlled trials of betamethasone retreatment found no benefit on severe intraventricular hemorrhage rates. However, the trials may have included an insufficient number of infants at risk for intraventricular hemorrhage to be able to adequately address this question. Severe intraventricular hemorrhages occur almost exclusively in infants born <28 weeks, whereas only 7% (0%-16%) of the retreatment trials' populations were <28 weeks. To determine if the risk of severe intraventricular hemorrhage in infants delivered <28 weeks increases when the betamethasone treatment-to-delivery interval increases beyond 9 days and to determine if betamethasone retreatment prior to delivery decreases the rate of hemorrhage. Observational study examining the incidence of intraventricular hemorrhage before (epoch 1) and after (epoch 2) a practice change that encouraged obstetricians to retreat pregnant women still at high risk of delivery before 28 weeks' gestation when >9 days elapsed from the first dose of betamethasone. Multivariable analyses with logistic regression using generalized estimating equations techniques were conducted to examine the rates of intraventricular hemorrhage among 410 infants <28 weeks' gestation who either delivered between 1-9 days (n=290) after the first 2-dose betamethasone course or delivered ≥10 days (and eligible for retreatment) (n=120). After adjusting for potential confounding variables, infants who delivered ≥10 days after a single betamethasone course had an increased risk of either severe intraventricular hemorrhage alone or the combined outcome severe intraventricular hemorrhage or death before 4 days (OR (95%CI): 2.8 (1.2, 6.6)) compared with infants who delivered between 1-9 days after betamethasone. Among the 120 infants who delivered ≥10 days after the first dose of betamethasone, 64 (53%) received a second/retreatment course of antenatal betamethasone. The severe intraventricular hemorrhage rate in infants whose mothers received a second/retreatment course of betamethasone was similar to the rate in infants who delivered within 1-9 days and significantly lower than in those who delivered ≥10 days without retreatment (OR (95%CI): 0.10 (0.02, 0.65). Following the change in guidelines, the rate of retreatment in infants who delivered ≥10 days after the first betamethasone course (and before 28 weeks) increased from epoch 1 to epoch 2 (25% to 87%, p<0.001) and the rate of severe intraventricular hemorrhage decreased from 22% to 0% (p<0.001). In contrast, the rate of severe intraventricular hemorrhage in infants who delivered 1-9 days after the initial betamethasone dose (who were not eligible for retreatment) did not change between epochs 1 and 2 (12% and 11%, respectively). Although betamethasone's benefits on severe intraventricular hemorrhage appear to wane after the first dose, retreatment with a second course appears to restore its beneficial effects. Encouraging earlier retreatment of women at high risk of delivery before 28 weeks was associated with a lower rate of severe intraventricular hemorrhages among infants delivering <28 weeks.

Evaluating Danish Breast Cancer Group locoregional radiotherapy guideline adherence in clinical treatment data 2008–2016: The DBCG RT Nation study

Background and purposeGuideline adherence in radiotherapy is crucial for maintaining treatment quality and consistency, particularly in non-trial patient settings where most treatments occur. The study aimed to assess the impact of guideline changes on treatment planning practices and compare manual registry data accuracy with treatment planning data. Materials and methodsThis study utilised the DBCG RT Nation cohort, a collection of breast cancer radiotherapy data in Denmark, to evaluate adherence to guidelines from 2008 to 2016. The cohort included 7448 high-risk breast cancer patients. National guideline changes included, fractionation, introduction of respiratory gating, irradiation of the internal mammary lymph nodes, use of the simultaneous integrated boost technique and inclusion of the Left Anterior Descending coronary artery in delineation practice. Methods for structure name mapping, laterality detection, detection of temporal changes in population mean lung volume, and dose evaluation were presented and applied. Manually registered treatment characteristic data was obtained from the Danish Breast Cancer Database for comparison. ResultsThe study found immediate and consistent adherence to guideline changes across Danish radiotherapy centres. Treatment practices before guideline implementation were documented and showed a variation among centres. Discrepancies between manual registry data and actual treatment planning data were as high as 10% for some measures. ConclusionNational guideline changes could be detected in the routine treatment data, with a high degree of compliance and short implementation time. Data extracted from treatment planning data files provides a more accurate and detailed characterisation of treatments and guideline adherence than medical register data.

Parents' Perceptions of Schools' COVID-19 Mitigation Strategies: A Phenomenological Study.

At the onset of the COVID-19 pandemic, schools closed across the United States. Given the impact of virtual learning and lost access to school resources, schools eventually reopened with COVID-19 mitigation protocols in place. This qualitative study sought to understand parental perceptions of school-based COVID-19 mitigation strategies. Using a phenomenology approach, nine focus groups were completed with 40 parents of children in grades K-8 representing eight Maryland counties. Based on acceptance of masking policies (as indicated on a survey), parents were sorted into 2 groups-lower and higher masking acceptance. A thematic analysis was conducted for each group and themes were compared between the 2 groups. The main themes were related to parents' general sentiments regarding COVID-19, compliance, pandemic-related changes over time, changes in personal opinions, and in-person learning. Both groups described challenges related to inconsistent COVID-19 mitigation policies and practices, the challenges of rapid and frequent changes in guidelines during the pandemic, and the benefits of in-person learning. Parents of elementary and middle school children, regardless of general acceptance of masking policies, shared concerns about implementation and guidance regarding school-based mitigation strategies.

New tatt? We're ok with that! Relaxing the tattoo deferral for plasmapheresis donors maintains safety and increases donations.

Tattooing is one of the leading donor deferral reasons in Australia. Until September 2020, donors were deferred from all donation types for 4 months after a tattoo. At this time, our guideline changed such that donations of plasma for further manufacture were accepted immediately, provided the tattoo was administered in a licensed or regulated Australian establishment. We examined the effects of this change. Donors with a tattoo deferral in the 2 years before or after the guideline change were identified and followed up until 3 November 2022. Between the two periods, we compared blood-borne virus (BBV) incidence, donor return, and the number of donors and donations regained after deferral. The incidence of BBV infection in donors after a tattoo deferral was zero in both periods. To exceed a residual risk of 1 in 1 million for hepatitis C virus, 190 donors would need to be infected yearly from a tattoo. Donors returned to donate significantly faster after the change (median return 85 days compared with 278 days). An extra 187 donations per 10,000 person-years of observation were gained, yielding a total of 44,674 additional plasma donations nationally 0-4 months after getting a tattoo. Allowing plasma donations immediately post-tattoo resulted in a substantial donation gain with no adverse safety effect. Lifeblood subsequently reduced the deferral for transfusible component donations to 7 days for tattoos in Australian licensed/regulated establishments.