Enrollment Period Research Articles

Improving morbidity and mortality in patients with pulmonary hypertension: insights from a nation-wide registry

Abstract Background and aims In this retrospective analysis of a nation-wide registry on pulmonary arterial hypertension (PAH), group IV and V, we evaluated management strategies, morbidity and mortality across three consecutive time periods. Methods This study included 903 patients enrolled from 24 cardiology centers participating in the RegiStry on clInical outcoMe and sUrvival in pulmonaRy hypertension Groups (SIMURG II). Patients were divided into three enrollment periods: before 2016, the era of monotherapy or sequential combination therapies; between 2016 and 2019, post-approval and re-imbursement of macitentan in our country, marking a shift towards more proactive sequential combinations; and after 2019, signifying the initiation of earlier sequential combinations with selexipag in PAH. ESC/ERS 2022, COMPERA 2.0 and REVEAL lite 2 models were used for risk predictions. Composite endpoint (CEP) definitions were adopted from the SERAPHIN and GRIPHON trials. Results Age (mean +SD) was 51.27 + 21.37 years, and 72 % were female. Incident cases were noted in 65.9 % of patients. Idiopathic PAH (IPAH), PAH-associated with congenital heart diseases (CHD-PAH), PAH-associated with connective tissue diseases (CTD-PAH), porto-PAH, Group IV and V pulmonary hypertension (PH) were documented in 33 %, 33.5 %, 12 %, 1.6 %, 20 % and 1.7 % of patients, respectively. Background mono and dual targeted combinations, and sequential triple combinations were noted in 17 %, 57 % and 26 % of patients, respectively. Baseline low-, intermediate-, and high-risk were noted in 1.2 %, 14.1 %, and 84.7 %, respectively. Median follow-up time (day) was 867 (412-1667). Overall rates of mortality and CEP were 26 % and 39%, respectively. There were increases in the % of PAH and group IV PH, and decreases in the % of CHD-PAH across the three periods. Prevalent versus incident cases were associated signifinatly lower mortality and CEP ( p=0.028 and p=0.024, respectively). Outcomes for mortality and CEP were predicted by three risk models (p<0.0001 for all). Mortality and CEP rates were 31 % and 44 % in IPAH, 20 % and 39 % in CHD-PAH, 31 % and 43 % in CTD-PAH, and 25 % and 30 % in group IV patients, respectively. In overall PH population, rates of mortality and CEP documented at 1st, 2nd and 3rd periods were 64 % and 67 %, 29 % and 31 %, and 3.5 % and 5.1 %, respectively (p< 0.001, for all). Mortality rates for 1st, 2nd and 3rd periods were 49 %, 39 % and 11 % in IPAH, 62 %, 33 % and 5.3 % in CHD-PAH, 47 %, 45 % and 7.7 in CTD-PAH, and 37 %, 52 % and 11 % in group IV, respectively (p< 0.001, for all). However, mortality curves showed sudden increases in 2020 that might be attributed to COVID-19. Conclusions Our nation-wide data revealed improving survival in the overall PH population, PAH and Group IV PH that might be associated with risk-based earlier targeted combination strategies. However, this trend seems to be counterbalanced with COVID-19 pandemic.

Impact of observability period on the classification of COPD diagnosis timing among Medicare beneficiaries with lung cancer.

Investigators often use claims data to estimate the diagnosis timing of chronic conditions. However, misclassification of chronic conditions is common due to variability in healthcare utilization and in claims history across patients. We aimed to quantify the effect of various Medicare fee-for-service continuous enrollment period and lookback period (LBP) on misclassification of COPD and sample size. A stepwise tutorial to classify COPD, based on its diagnosis timing relative to lung cancer diagnosis using the Surveillance Epidemiology and End Results cancer registry linked to Medicare insurance claims. We used 3 approaches varying the LBP and required continuous enrollment (i.e., observability) period between 1 to 5 years. Patients with lung cancer were classified based on their COPD related healthcare utilization into 3 groups: pre-existing COPD (diagnosis at least 3 months before lung cancer diagnosis), concurrent COPD (diagnosis during the -/+ 3months of lung cancer diagnosis), and non-COPD. Among those with 5 years of continuous enrollment, we estimated the sensitivity of the LBP to ascertain COPD diagnosis as the number of patients with pre-existing COPD using a shorter LBP divided by the number of patients with pre-existing COPD using a longer LBP. Extending the LBP from 1 to 5 years increased prevalence of pre-existing COPD from ~ 36% to 51%, decreased both concurrent COPD from ~ 34% to 23% and non-COPD from ~ 29% to 25%. There was minimal effect of extending the required continuous enrollment period beyond one year across various LBPs. In those with 5 years of continuous enrollment, sensitivity of COPD classification (95% CI) increased with longer LBP from 70.1% (69.7% to 70.4%) for one-year LBP to 100% for 5-years LBP. The length of optimum LBP and continuous enrollment period depends on the context of the research question and the data generating mechanisms. Among Medicare beneficiaries, the best approach to identify diagnosis timing of COPD relative to lung cancer diagnosis is to use all available LBP with at least one year of required continuous enrollment.

The basic income for care leavers in Wales pilot evaluation: Protocol of a quasi-experimental evaluation.

This study will evaluate the Basic Income for Care Leavers in Wales pilot (BIP), which is the most generous basic income scheme in the world. A cohort of care-experienced young people who become aged 18 during a 12-month enrolment period (July 2022-June 2023) are receiving £1,600 (before tax) per month for two years, and the Welsh Government intends this to have a range of benefits. This evaluation will examine the impact of BIP, the implementation of the pilot and how it is experienced, and its value for money. The study is a theory-based quasi-experimental evaluation, and the design and methods are informed by ongoing co-production with care-experienced young people. We will estimate the impact of BIP on participants using self-reported survey data and routinely collected administrative data. This will include outcomes across a range of domains, including psychological wellbeing, physical and mental health, financial impact, education, training and volunteering. Comparisons between temporal (Welsh) and geographical (English, using administrative data) controls will be done using coarsened exact matching and difference in differences analysis. The process evaluation will examine how BIP is implemented and experienced, primarily through monitoring data (quantitative) and interview, observational, and focus group data (qualitative). The economic evaluation will take a public sector and a societal perspective to identify, measure and value the costs and outcomes of BIP, and to synthesise the evidence to inform a social cost-benefit analysis at 24 months post-intervention. BIP is unusual in that it targets a wide range of outcomes and is available to an entire national cohort of participants. The evaluation also has several practical constraints. Therefore, the study will use a range of methods and triangulate between different analyses to assess how successful it is. Findings will inform policy in relation to care leavers, social security and basic income studies worldwide.

Efficacy of a portable non-mydriatic fundus camera for "rule-out papilledema" consultations: A prospective study.

Ophthalmology is frequently consulted to "rule-out papilledema." We assessed the efficacy of a portable, non-mydriatic fundus camera in detecting optic disc edema in the inpatient and emergency room settings during "rule-out papilledema" consultations, comparing to the gold standard dilated fundus examination (DFE). This prospective, blinded, cohort study included 124 non-mydriatic fundus photographs (62 patients) that were obtained over the 11-month enrollment period. The images, along with a brief clinical history, were evaluated independently by an attending neuro-ophthalmologist (NO), general ophthalmologist (GO), emergency room (ER) physician, and ophthalmology resident (OR), for the presence of disc edema and indication for consultation. Results were compared to DFE. Sensitivity, specificity, and area under receiver operating characteristic (ROC) curves were determined to evaluate the efficacy of the camera. On DFE, disc edema was present in 51 eyes (41.1%). Compared to DFE, NO assessment had the greatest combined sensitivity (84.3%) and specificity (97.3%) for the detection of disc edema, followed by that of GO (sensitivity 77.4%, specificity 100%), OR (sensitivity 96.1%, specificity 80.8%), and ER clinician (sensitivity 68.6%, specificity 89.0%). Areas under ROC curves for NO, GO, OR, and ER physician were all statistically significant for the detection of disc edema (0.908, P < 0.001; 0.892, P < 0.001; 0.885, P < 0.001; 0.788, P < 0.001, respectively). Clinicians were able to correctly identify optic disc edema using non-mydriatic fundus photography. Non-mydriatic fundus photography may be an effective inpatient or telemedicine tool to assess for optic disc edema.

Can salivary cortisol be used in diagnosing adrenal insufficiency during the acute and subacute phases of traumatic brain injury?

The diagnosis of adrenal insufficiency (AI) related to traumatic brain injury (TBI) remains a challenge. We investigated the basal and low-dose adrenocorticotropic hormone (ACTH)-stimulated serum cortisol and salivary cortisol (SaC) levels and the diagnostic utility of SaC levels during 28 days following TBI. Blood samples were collected for basal levels [sequentially from day 1 (D1) to D7 and on D28)] and for peak serum cortisol and SaC responses to the low-dose ACTH stimulation test (on D1, D7, and D28). After the patient enrollment period was completed, patients were retrospectively categorized as AI or AS (adrenal sufficiency) for each day separately, based on a basal serum cortisol cut-off level of 11 µg/dL, and data analysis was performed between the groups. Thirty-seven patients and 40 healthy controls were included. Median basal serum cortisol levels were higher in patients on D1 but were similar on other days. Median basal SaC levels were higher in patients on D1 and D2 but were similar on other days. Median peak serum cortisol and SaC levels were similar on D1 but were lower in patients on D7 and D28. Median basal SaC levels were higher in the AS group than in the AI group on all days. When evaluating AI during the course of TBI, the cut-off for basal SaC levels is 0.5-0.6 µg/dL throughout the first week, except for 1.38 µg/dL on D2. SaC levels may serve as a surrogate marker for accurately reflecting circulating glucocorticoid activity.

Descemet Endothelial Thickness Comparison Trial II (DETECT II): multicentre, outcome assessor-masked, placebo-controlled trial comparing Descemet membrane endothelial keratoplasty (DMEK) to Descemet stripping only (DSO) with adjunctive ripasudil for Fuchs dystrophy

IntroductionIt remains uncertain whether Descemet membrane endothelial keratoplasty (DMEK) or Descemet stripping only (DSO) yields better outcomes in patients with symptomatic Fuchs endothelial corneal dystrophy (FECD). This paper presents the...

Adverse selection and consumer inertia: empirical evidence from the Dutch health insurance market

AbstractThis paper examines to what extent consumer inertia can reduce adverse selection in health insurance markets. To this end, we investigate consumer choice of deductible in the Dutch health insurance market over the period 2013–2018, using panel data based on a large random sample (266 k) of all insured individuals in the Netherlands. The Dutch health insurance market offers a unique setting for studying adverse selection, because during annual open enrollment periods all adults are free to choose an extra deductible up to 500 euro per year. By focusing on deductible choices of those who do not switch health plans, we are able to examine the ‘pure’ adverse selection effect (i.e., not distorted by other health plan attributes). We estimate a dynamic logit model to examine individuals’ deductible choice. We find evidence of adverse selection, as people with higher previous health care cost are substantially less likely to take up or keep a 500-euro deductible. We also find that adverse selection is counteracted by a high level of consumer inertia, as the average partial effect on deductible choice of the previous selected deductible level is much larger than the average partial effect of a change in health care costs.

Feasibility of automated measurement of fetal right ventricular modified myocardial performance index with development of reference values and clinical application.

To establish normal reference ranges for fetal right ventricular modified myocardial performance index (RV Mod-MPI) using automatic synchronization of the RV inflow and outflow images (MPI+TM). Additionally, we aimed to clinically apply RV Mod-MPI to investigate its changes in fetal right congenital diaphragmatic hernia (CDH) compared to normal fetuses. This prospective study included uncomplicated singleton pregnancies between 16 and 38 weeks of gestational age. Cases with any maternal or fetal complications that developed during the enrollment period were excluded. Two experienced operators measured the RV Mod-MPI using the automated and manual methods. The intraclass correlation coefficients (ICC) were calculated for intra- and inter-operator reproducibility. The mean differences between the manual and automated measurements were also compared. The RV Mod-MPI was then compared between the right CDH fetuses and normal fetuses. Seventy normal fetuses were analyzed for the feasibility of an automated system, and 364 examinations from 272 fetuses were analyzed for developing the normal references. The automated system showed significantly higher intra- and inter-operator reproducibility of Mod-MPI than those of manual measurements (ICC = 0.962 vs. 0.913 and 0.961 vs. 0.889, respectively). The mean difference in Mod-MPI between the manual and automated method was 0.0002 ± 0.0586 with a 95% confidence interval of -0.0095-0.0099. The Mod-MPI and isovolumetric relaxation time increased throughout the gestational weeks. The isovolumetric contraction time increased until 24 weeks of gestation and then slightly decreased afterwards, and the ejection time also increased until 31 weeks of gestation and then decreased. There was no significant difference in the Mod-MPI between right CDH and normal fetuses. The automated system showed high inter- and intra-operator reproducibility. Furthermore, the normal reference values of Mod-MPI for each gestational age were established. Our results suggest that the automated system might be clinically feasible for evaluating fetal cardiac function.

Temporal trends in the treatment and outcome of nonagenarians with acute coronary syndrome.

Nonagenarians are a fast-growing age group among acute coronary syndrome (ACS) patients. While new therapeutic options have improved outcomes of ACS patients, data regarding very elderly ACS patients are limited. We aimed to evaluate temporal trends in the treatment and outcomes of nonagenarian ACS patients. Included were ACS patients aged below 90 years enrolled in ACS Israeli Survey. Patients were divided into two groups according to enrolment period: early (2000-2010) and recent (2012-2021). The primary endpoints were 30-day major adverse cardiovascular events and all-cause mortality. Secondary outcomes included in-hospital and 1-year all-cause mortality. Included were 316 elderly ACS patients. Of them, 184 were enrolled in the early and 132 in recent surveys. Patients enrolled in the recent period were more commonly referred for an invasive strategy and more commonly received guideline-based medical therapy. All-cause mortality at 30 days was significantly lower in the recent group compared with the early group (12.5 and 26.1%, respectively, P = 0.005). Rates of 30-day major adverse cardiovascular events were also significantly lower in the recent group (21.9 and 35.9%, respectively, P = 0.012). Patients in the recent group received more aggressive medical therapy in discharge but at 30-day follow-up, no difference in medical treatment was observed in the two groups. There were no significant differences in 1-year mortality rates. Treatment of nonagenarians with ACS has improved over the past decade. Treatment improvement was associated with a significant improvement in 30-day outcomes without any effect in 1 year. Nevertheless, even with contemporary treatment, nonagenarians with ACS remain a high-risk group with high mortality rates.

Early intravenous high-dose vitamin C in postcardiac arrest shock (VICEPAC): study protocol for a randomised, single-blind, open-label, multicentre, controlled trial

IntroductionThe high incidence of morbidity and mortality associated with the post-cardiac arrest (CA) period highlights the need for novel therapeutic interventions to improve the outcome of out-of-hospital cardiac arrest (OHCA)...

Use of EMPAgliflozin in the prevention of CARDiotoxicity: the EMPACARD – PILOT trial

BackgroundAnthracycline-based chemotherapy represents a cornerstone treatment for a number of common cancers, including breast cancer, lymphoma, and sarcoma. However, anthracycline-induced cardiotoxicity remains a significant concern, often presenting as a decline in cardiac function which can ultimately lead to heart failure (HF) or asymptomatic left ventricular dysfunction, in up to 10–15% of patients.Sodium-glucose transport protein 2 inhibitor (SGLT2i) therapies have been demonstrated to reduce the incidence of HF in high-risk non-cancer patients. Preliminary retrospective data suggest their role in mitigating the incidence of HF during or after anthracycline treatmentMethodsThe EMPACARD-PILOT trial was a prospective case‒control study involving breast cancer patients scheduled to undergo anthracycline-based chemotherapy in a 4-cycle protocol of 60 mg/m2 doxorubicin. We used the HFA/ICOS risk score to identify patients at high or very high risk of cardiotoxicity. Patients with diabetes mellitus or stable heart failure with preserved ejection fraction (HFpEF) were prescribed empagliflozin (10 mg per day), starting seven days before the administration of anthracyclines and continuing for a period of six months. Those not meeting these criteria served as controls. The primary endpoint was cancer therapy-related cardiac dysfunction (CTRCD) incidence. CTRCD was defined as either a decrease in left ventricular ejection fraction (LVEF) of at least 10% to a final value below 50% or a reduction in global longitudinal strain (GLS) of at least 15% from baseline at any point during the study. The secondary endpoints included mortality and hospitalization due to cardiovascular causes or clinical heart failure. Exploratory endpoints included increases in serum troponin and NT-proBNP levels and a decrease in the glomerular filtration rate (GFR). The safety endpoints tracked includedketoacidosis, hypoglycemia, sepsis, neutropenic fever, and urinary tract infections.ResultsDuring the enrollment period, 785 breast cancer patients were analysed. Of these, 107 met the inclusion criteria, and 76 subsequently provided informed consent. The study was conducted with comparable adherence rates of 81.5% in both the empagliflozin group (n = 38) and the control group (n = 38). The follow-up data from 62 patients revealed a significant reduction in the primary outcome within 6 months for the empagliflozin group compared with the control group (6.5% vs. 35.5%, p = 0.005), with a relative risk of 0.18 (95% CI: 0.04–0.75). Compared with the control treatment, treatment with empagliflozin also significantly preserved the ejection fraction at 6 months follow-up (56.8% ± 5.8% vs. 53.7% ± 6.7, p = 0.029). However, there were no significant differences between the groups in terms of NT-proBNP, cTnI, clinical heart failure, GFR, or mortality/hospitalization due to heart failure.ConclusionEmpagliflozin is associated with reduced incidence of CTRCD in high-risk patients treated with anthracyclines. These data should serve as the foundation for a clinical trial to test whether SGLT2 inhibitors can reduce the incidence of heart failure in this patient group.

The impact of anti-thrombotic therapy on bleeding outcomes and thrombosis following laparoscopic cholecystectomy: a meta-analysis.

Acute cholecyctitis is a common condition which requires immediate or elective surgical interventions and this condition is one among the common causes for emergency hospitalization among the elderly population. However, controversies have been observed with the use of anti-thrombotic agents in patients undergoing laparoscopic cholecyctectomy. Few studies have reported increased risk of bleeding in patients with anticoagulants whereas other studies have reported no significant bleeding outcomes. Nevertheless, the lack of evidence-based guidelines further complicates decision-making. In this analysis we aimed to systematically assess the impact of anti-thrombotic therapy on bleeding outcomes and thrombosis following laparoscopic cholecystectomy. MEDLINE, EMBASE, Cochrane database, Google scholar, Web of Science and http://www.ClinicalTrials.gov were searched for relevant publications based on anti-thrombotic therapy among patients who underwent laparoscopic cholecystectomy. The endpoints in this analysis included: intra-operative bleeding, post-operative bleeding, blood loss, patients requiring blood transfusion and thrombotic complications. The Revman 5.4 software was used to analyze data in this analysis. Risk ratio (RR) with 95% confidence intervals (CIs) were used to represent the data following analysis. A total number of 4008 participants (enrollment period 2002-2019) were included in this analysis whereby 756 participants were assigned to an anti-thrombotic therapy and 3592 participants were in the control group. Our results showed that antithrombotic therapy was associated with significantly higher risk of intra-operative bleeding (RR: 2.23, 95% CI: 1.77-2.79; P = 0.00001), post-operative bleeding (RR: 4.77, 95% CI: 1.13-20.10; P = 0.03), and blood loss (RR: 3.01, 95% CI: 1.13-8.06; P = 0.03). Patients requiring blood transfusion (RR: 4.80, 95% CI: 1.90-12.13; P = 0.0009) were also significantly higher in the anti-thrombotic group. However, thrombotic complications (RR: 2.17, 95% CI: 0.50-9.42; P = 0.30) were not significantly higher. Through this analysis, we concluded that anti-thrombotic therapy was associated with significantly increased risks of intra-operative and post-operative bleeding events following laparoscopic cholecystectomy. Patients requiring blood transfusion were also significantly higher. Therefore, stopping anti-thrombotic agents prior to laparoscopic cholecystectomy could significantly minimize bleeding risks.

Email Nudges Increased Eligibility Verification And Subsidy Receipt In California's ACA Marketplace.

In the Affordable Care Act (ACA) Marketplaces, enrollees must periodically demonstrate their eligibility to receive income-linked health insurance premium subsidies. Marketplaces can verify eligibility using existing records, but only with consumers' consent, which must be renewed at specified times. In a randomized experiment in September2020, we tested the effect of email nudges reminding consumers to provide consent for verification of their continued eligibility for premium subsidies in California's ACA Marketplace. More than 20,000 households that had applied for subsidies but whose consent for eligibility verification would soon expire were sent one, two, or three emails reminding them to renew consent. Sending three emails increased consent updates by 1.9percentage points (3.2percent) and increased receipt of subsidies by 2.0percentage points (4.0percent). However, nearly 40percent of households receiving three emails did not update their consent by the end of the open enrollment period, thus preventing their continued receipt of subsidies. To improve the affordability of Marketplace coverage, new policies and structural changes may be needed to reduce administrative barriers that can inhibit access to subsidies.

Effectiveness of Machine Learning in Predicting Orthodontic Tooth Extractions: A Multi-Institutional Study.

The study aimed to evaluate the effectiveness of machine learning in predicting whether orthodontic patients would require extraction or non-extraction treatment using data from two university datasets. A total of 1135 patients, with 297 from University 1 and 838 from University 2, were included during consecutive enrollment periods. The study identified 20 inputs including 9 clinical features and 11 cephalometric measurements based on previous research. Random forest (RF) models were used to make predictions for both institutions. The performance of each model was assessed using sensitivity (SEN), specificity (SPE), accuracy (ACC), and feature ranking. The model trained on the combined data from two universities demonstrated the highest performance, achieving 50% sensitivity, 97% specificity, and 85% accuracy. When cross-predicting, where the University 1 (U1) model was applied to the University 2 (U2) data and vice versa, there was a slight decrease in performance metrics (ranging from 0% to 20%). Maxillary and mandibular crowding were identified as the most significant features influencing extraction decisions in both institutions. This study is among the first to utilize datasets from two United States institutions, marking progress toward developing an artificial intelligence model to support orthodontists in clinical practice.

A multicenter epidemiological survey of iNO use in preterm infants in China.

To investigate the use of inhaled nitric oxide (iNO) in hospitalized preterm infants in China over 10 years and its clinical outcomes. A total of 616 premature infants who were administered iNO in the Neonatology Departments of 5 Class A tertiary hospitals in China for ten years from January 2013 to December 2022 were included retrospectively. Based on their enrollment periods, the patients were divided into two groups: Group 1 from January 2013 to December 2017 and Group 2 from January 2018 to December 2022, respectively. The perinatal characteristics, short-term clinical outcomes, and mortality rates were compared between these two groups. The utilization of iNO in preterm infants grew annually over the past10 years; the utilization of iNO in Group 2 infants increased approximately one-fold when compared with Group 1 (1.52% vs. 0.80%, p < .001), and the increase was greater in gestational age (GA) < 34 weeks compared with 34-36 weeks preterm infants. Moreover, the iNO usage in Group 1 infants with GA < 34 weeks increased from 1.14% to 2.46% and 0.60% to 0.99% in 34-36 weeks preterm infants (p < .001) in Group 2, respectively. Apart from a smaller GA (32.9 w vs. 33.5 w, p < .001) and birth weight (BW, 1900 g vs. 2141 g, p < .001), the initial [14 parts per million (ppm) versus 10 ppm, p < .001] and maximum (15 ppm vs. 10 ppm, p < .001) doses of Group 2 were larger; however, their recent clinical outcomes did not improve with increasing iNO utilization (p > .05)as compared to Group 1, respectively. Although the overall iNO preterm mortality rates over the past 10 years were 25.8%, the mortality rates for preterm infants at 34-36 weeks were significantly lower than for preterm infants at GA < 34 weeks (15.4% vs. 33.8%, p < .001). Nonetheless, no improvement in mortality was observed in Group 2 preterm infants with GA < 34 weeks for the past 5 years when compared with Group 1 (32.9% vs. 35.8%, p > .05) infants, and significantly lower mortality rates were noticed in preterm infants with 34-36 weeks (11.2% vs. 22.7%, p < .001). Patients with hypoxic respiratory failure (HRF) or persistent pulmonary hypertension of the newborn (PPHN) iNO preterm infants did not show lower mortality rates with the increase of iNO use rate (p > .05). The overall mortality rates of preterm PPHN infants with iNO were lower than that of HRF (20.2% vs. 36.5%, p < .001), while the mortality rates of Group 2 preterm PPHN infants with iNO significantly lower than that of HRF (17.7% vs 36.0%, p < .001). The iNO has been extensively used in Chinese preterm infants over the past 10 years, this increase was more significant in preterm infants with GA < 34 weeks. Moreover, preterm infants using iNO have lower GA and BW, larger initial and maximum doses, and more aggressive strategies in the last past 5 years. Although iNO use in preterm infants with GA of 34-36 weeks has significantly reduced mortality, mortality rates and short-term clinical outcomes of iNO in preterm infants <34 weeks of GA has no obvious improvement. Further studies are required to investigate the efficacy and safety of iNO in preterm infants <34 weeks of GA.

Locoregional recurrence in studies of primary systemic therapy in early invasive breast cancer

IntroductionThe use of primary systemic therapy (PST) in early invasive breast cancer is routine but there are concerns about risk of locoregional recurrence. MethodsWe conducted a systematic literature review to identify studies of locoregional treatment and recurrence in patients with early invasive breast cancer who received non-endocrine PST. ResultsWe identified 112 studies (18 prospective trials and 94 non-interventional studies). The use of surgery and radiotherapy after PST was recorded in 65 (58 %) and 50 (45 %) of studies respectively. 66 (59 %) studies reported locoregional recurrence. Cumulative 5-year locoregional recurrence risks varied from 1 % to 23 %. Locoregional recurrence was higher in patients under the age of 40, those who did not achieve a pathological complete remission after PST, had ER-negative or HER2 negative tumours, were recorded to have inoperable disease before PST, and did not have radiotherapy. LRR rates in these studies have not fallen over the overall calendar period of patient enrollment (1999–2016). ConclusionThe recording of locoregional treatments and outcomes is suboptimal in studies of PST and efforts to improve this are required. In the absence of randomised evidence, our findings may help to inform care and guideline development. We were unable to exclude concern that the use of PST is associated with a higher than desired risk of locoregional recurrence.

Advancing high quality longitudinal data collection: Implications for the HEALthy Brain and Child Development (HBCD) Study design and recruitment

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The HBCD Study aims to reflect the sociodemographic diversity of pregnant individuals in the U.S. The study will also oversample individuals who use substances during pregnancy and enroll similar individuals who do not use to allow for generalizable inferences of the impact of prenatal substance use on trajectories of child development. Without probability sampling or a randomization-based design, the study requires innovation during enrollment, close monitoring of group differences, and rigorous evaluation of external and internal validity across the enrollment period. In this article, we discuss the HBCD Study recruitment and enrollment data collection processes and potential analytic strategies to account for sources of heterogeneity and potential bias. First, we introduce the adaptive design and enrollment monitoring indices to assess and enhance external and internal validity. Second, we describe the visit schedule for in-person and remote data collection where dyads are randomly assigned to visit windows based on a jittered design to optimize longitudinal trajectory estimation. Lastly, we provide an overview of analytic procedures planned for estimating trajectories.

Application study on the prevention and treatment of spleen aminopeptide oral solution on seasonal allergic rhinitis

Methods: A total of 392 patients with seasonal allergic rhinitis were selected from the population of the epidemiological investigation project of allergic diseases in Hohhot, Inner Mongolia. The project was led by Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, and assisted by Hohhot First Hospital from April to May 2023. The patients were randomly divided into a spleen aminopeptide group (296 cases) and control group (96 cases) at a ratio of 3∶1, and the enrollment period was from June 1 to 14, 2023. The treatment group was treated with spleen aminopeptide oral solution for 12 weeks starting from 4-6 weeks (±7 days) before the pollen dispersal period, while the control group was treated with a simulated agent of spleen aminopeptide oral solution. Both the treatment group and the control group were treated with oral antihistamines and/or nasal glucocorticoids as needed during the pollen dispersal period. Evaluate the therapeutic effect by comparing the symptom scores, drug scores and quality of life scores of the two groups, and detect the expression levels of cytokines in serum. Symptom scores, quality of life scores, drug scores and laboratory results were compared by independent sample t test/Kruskal-Wallis test and χ2 test/Fisher's exact test. Results: Compared with the control group, spleen aminopeptide treatment for 12 weeks significantly improved symptoms of nasal congestion [M(Q1,Q3):2(1, 2) vs. 2(1, 3), H=6.308, P<0.05], nasal itching [M(Q1,Q3):2(1, 2) vs. 2(1, 3), H=4.966, P<0.05], sneezing [M(Q1,Q3):2(1, 2) vs. 2(1, 3), H=5.245, P<0.05], runny nose [M(Q1,Q3):2(1, 2) vs. 2(1, 3), H=5.41, P<0.05] and tearing [M(Q1,Q3):1(0, 2) vs. 1(0, 3), H=4.664, P<0.05]. At 12 weeks of treatment, the scores of nasal symptoms and ocular symptoms in control group and experimental group were significantly increased compared with baseline (P<0.05). In experimental group, nasal congestion [M(Q1,Q3):1(0, 1) vs. 1(0, 2), H=4.042, P<0.05], eye itching/foreign body sensation/redness symptom scores [M(Q1,Q3):1(0, 2) vs. 1(0, 2), H=5.302, P<0.05] and total scores [M(Q1,Q3):4(-1, 9) vs. 5(0, 12.5), H=3.958, P<0.05] were significantly increased. The antihistamine drug score of the splenic peptide treatment group at 6 weeks were lower than that of the control group (H=4.232, P<0.05). After 12 weeks of treatment, the antihistamine drug score [M(Q1,Q3):10(0, 24) vs. 19(2, 36.5), H=6.67, P<0.05] and the total drug score [M(Q1,Q3):28.5(5, 77.5) vs. 46(6, 155.5), H=3.995, P<0.05] were significantly lower than those of the control group. The serum IL-17A levels of the treatment group were significantly lower than those of the control group after 6 weeks (0.7±1.77 vs. 0.85±1.67,H=10.08, P<0.05) and 12 weeks (0.81±1.63 vs. 0.94±1.73,H=5.196, P<0.05) of splenic aminopeptide treatment. Conclusions: Early treatment with spleen aminopeptide oral solution can significantly improve nasal and ocular symptoms of patients with seasonal allergic rhinitis, reduce the use of drugs during the onset period, and improve the quality of life. It may exert an immunomodulatory effect by reducing the expression level of IL-17A in the serum of patients. Objects: To conduct a study on the prevention and treatment of seasonal allergic rhinitis in Hohhot, Inner Mongolia, evaluate the preventive and therapeutic effects of spleen aminopeptide oral solution on seasonal allergic rhinitis, and explore its related mechanisms.

Running the enrollment numbers on ophthalmic clinical trials in the United States.

This is one of the first reports to summarize the enrollment metrics for ophthalmology trials completed in the United States (US). This study aimed to describe US ophthalmology clinical trial enrollment metrics to facilitate planning and budgeting of US Food and Drug Administration-regulated ophthalmological drugs trials. A GlobalData PLC search was conducted on or before February 27, 2024, to evaluate the clinical trial landscape for completed ophthalmology clinical trials conducted in the US. The primary search contained only the term "ophthalmology," which was restricted to trials that were completed and were conducted within the US. Trials were classified as multicenter when trials included three sites or more, and when the enrollment search resulted in ≥30 multicenter trials for an individual indication, enrollment data were further broken down by Food and Drug Administration trial phase. The search yielded 2229 trials, which analyzed 980 different drugs produced by 854 different sponsors. The most common indications evaluated in US trials were macular degeneration, glaucoma, macular edema, allergies, and keratoconjunctivitis. Multicenter trials by indication had an overall median enrollment period range of 4.8 to 35.1 months; number of subjects enrollment, range of 36 to 518 subjects; number of sites utilized, range of 4 to 74 sites; and enrollment rate, range of 0.11 to 4.04 subjects/sites per month. There were 17 indications with ≥30 multicenter trials, which allowed for enrollment metric calculation by trial phase. This study provides sponsors with an understanding of the number of subjects and sites needed to complete a trial while also setting realistic enrollment timelines. Although this work represents the US market, more work is needed to better understand other countries given that country-specific guidelines and subject beliefs may impact enrollment metrics.

Prior traumatic brain injury is a risk factor for in-hospital mortality in moderate to severe traumatic brain injury: a TRACK-TBI cohort study

ObjectivesAn estimated 14–23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is...