Two-phase Cohort Study Research Articles

The Nurse-Implemented Chronotherapeutic Bundle in Critically Ill Children, RESTORE Resilience (R2): Pilot Testing in a Two-Phase Cohort Study, 2017-2021.

Pilot test the nurse-led chronotherapeutic bundle in critically ill children, RESTORE Resilience (R2). A two-phase cohort study was carried out from 2017 to 2021. Two similarly sized and organized PICUs in the United States. Children 6 months to 17 years old who were mechanically ventilated for acute respiratory failure. R2 seven-item chronotherapeutic bundle, including: 1) replication of child's pre-hospital daily routine (i.e., sleep/wake, feeding, activity patterns); 2) cycled day-night light/sound modulation; 3) minimal effective sedation; 4) night fasting with bolus enteral daytime feedings; 5) early progressive mobility; 6) nursing care continuity; and 7) parent diaries. Children underwent environmental (light, sound) and patient (actigraphy, activity log, salivary melatonin, electroencephalogram) monitoring. Parents completed the Child's Daily Routine and Sleep Survey (CDRSS) and Family-Centered Care Scale. The primary outcome was post-extubation daytime activity consolidation (Daytime Activity Ratio Estimate [DARE]). Twenty baseline-phase (2017-2019) and 36 intervention-phase (2019-2021) participants were enrolled. During the intervention phase, nurses used the CDRSS to construct children's PICU schedules. Overall compliance with nurse-implemented R2 elements 1-5 increased from 18% (interquartile range, 13-30%) at baseline to 63% (53-68%) during the intervention phase (p < 0.001). Intervention participants were exposed to their pre-hospitalization daily routine (p = 0.002), cycled day-night light/sound modulation (p < 0.001), and early progressive mobility on more PICU days (p = 0.02). Sedation target identification, enteral feeding schedules, and nursing care continuity did not differ between phases. Parent diaries were seldom used. DARE improved during the intervention phase and was higher pre-extubation (median 62% vs. 53%; p = 0.04) but not post-extubation (62% vs. 57%; p = 0.56). In the PICU, implementation of an individualized nurse-implemented chronotherapeutic bundle is feasible. Children who received the R2 bundle had increased pre-extubation daytime activity consolidation compared to children receiving usual care. Given variation in protocol adherence, further R2 testing should include interprofessional collaboration, pragmatic trial design, and implementation science strategies.

Improved efficiency in the management of newborns with infectious risk factors by the sepsis risk calculator and clinical observation

ObjectiveTo evaluate the efficiency of the sepsis risk calculator and the serial clinical observation in the management of late preterm and term newborns with infectious risk factors. MethodSingle-center, observational, two-phase cohort study comparing the rates of neonates born ≥35 weeks' gestation, ≥2000 g birthweight, and without major congenital anomalies, who were screened and/or received antibiotics for early-onset neonatal sepsis risk at our center during two periods, before (January/2018–June/2019) and after (July/2019–December/2020) the implementation of the sepsis risk calculator. ResultsA total of 1796 (Period 1) and 1867 (Period 2) patients with infectious risk factors were included. During the second period, tests to rule out sepsis were reduced by 34.0 % (RR, 95 %CI): 0.66 (0.61, 0.71), blood cultures by 13.1 %: 0.87 (0.77, 0.98), hospital admissions by 13.5 %: 0.86 (0.76, 0.98) and antibiotic administration by 45.9 %: 0.54 (0.47, 0.63). Three cases of early-onset neonatal sepsis occurred in the first period and two in the second. Clinical serial evaluation would have detected all true cases. ConclusionsThe implementation of a sepsis risk calculator in the management of newborns ≥35 weeks GA, ≥2000 g birthweight, without major congenital anomalies, with infectious risk factors is safe and adequate to reduce laboratory tests, blood cultures, hospital admissions, and antibiotics administration. Serial clinical observation, in addition, could be instrumental to achieve or even improve this goal.

Concussion in Non-athletes: Assessment of Cognition and Symptomatology (CONTACTS) study protocol – an exploratory cohort study investigating the utility of sports concussion assessment tools and salivary microRNAs to diagnose concussion in NHS patients

IntroductionConcussion is a complex pathophysiological process with a wide range of non-specific signs and symptoms. There are currently no objective diagnostic tests to identify concussion, and diagnosis relies solely on...

Transition through smoking stages in adolescents: an innovative perspective using growth mixture models

Little has been studied about the transition from initial smoking experimentation to future regular smoking in adolescents. We therefore aimed to describe the stages of the transition to smoking process in adolescents using growth mixture models (GMMs). In this two-phase cohort study, a representative sample of 4903 10th-grade students was assessed using multistage sampling in Tabriz, Iran. The main outcomes comprising smoking status, intention to start smoking, and smoking during the past week/month, were collected in addition to the predictors, using valid and reliable instruments. The optimal number of classes was determined, and GMMs were conducted with covariates. Decisively, GMMs emerged as a three-class optimal model comprising “Smokers and intending smokers” (5.5%), “Occasional smokers” (17.7%), and “Non-smokers” (76.8%). GMMs lead in significant intercepts (range over 1.3 to 37.8) and significant and positive slopes (range over 0.32 to 1.44) for the change in outcomes (all p < 0.05). Higher age, being male, higher socio-economic status, having a smoker friend, having a smoker in the family, substance abuse, and self-injury, higher attitude toward smoking, and general risk-taking behavior were directly related to a positive change in outcomes (all p < 0.05). The GMMs, highlighted two substantial initiations and transitions through smoking stages in adolescents with effective and directed programs, and second, the importance of implementing educational campaigns, public-awareness initiatives, and targeted interventions in the future.

Dealing With Sparse Data Bias in Medical Sciences: Comprehensive Review of Methods and Applications

This study aims to illustrate the problem of (Quasi) Complete Separation in the sparse data pattern occurring medical data. We presented the failure of traditional methods and then provided an overview of popular remedial approaches to reduce bias through vivid examples. Penalized maximum likelihood estimation and Bayesian methods are some remedial tools introduced to reduce bias. Data from the Tehran Thyroid and Pregnancy Study, a two-phase cohort study conducted from September 2013 through February 2016, was applied for illustration. The bias reduction of the estimate showed how sufficient these methods are compared to the traditional method. Extremely large measures of association such as the Risk ratios along with an extraordinarily wide range of confidence interval proved the traditional estimation methods futile in case of sparse data while it is still widely applying and reporting. In this review paper, we introduce some advanced methods such as data augmentation to provide unbiased estimations.

Evaluating Discrimination of a Lung Cancer Risk Prediction Model Using Partial Risk-Score in a Two-Phase Study.

Independent validation of risk prediction models in prospective cohorts is required for risk-stratified cancer prevention. Such studies often have a two-phase design, where information on expensive biomarkers are ascertained in a nested substudy of the original cohort. We propose a simple approach for evaluating model discrimination that accounts for incomplete follow-up and gains efficiency by using data from all individuals in the cohort irrespective of whether they were sampled in the substudy. For evaluating the AUC, we estimated probabilities of risk-scores for cases being larger than those in controls conditional on partial risk-scores, computed using partial covariate information. The proposed method was compared with an inverse probability weighted (IPW) approach that used information only from the subjects in the substudy. We evaluated age-stratified AUC of a model including questionnaire-based risk factors and inflammation biomarkers to predict 10-year risk of lung cancer using data from the Prostate, Lung, Colorectal, and Ovarian Cancer (1993-2009) trial (30,297 ever-smokers, 1,253 patients with lung cancer). For estimating age-stratified AUC of the combined lung cancer risk model, the proposed method was 3.8 to 5.3 times more efficient compared with the IPW approach across the different age groups. Extensive simulation studies also demonstrated substantial efficiency gain compared with the IPW approach. Incorporating information from all individuals in a two-phase cohort study can substantially improve precision of discrimination measures of lung cancer risk models. Novel, simple, and practically useful methods are proposed for evaluating risk models, a critical step toward risk-stratified cancer prevention.

Early pregnancy metabolic factors associated with gestational diabetes mellitus in normal-weight women with polycystic ovary syndrome: a two-phase cohort study

BackgroundPolycystic ovary syndrome (PCOS) has been consistently associated with subsequent gestational diabetes mellitus (GDM). Women with PCOS showed a high prevalence of obesity, which raises the question regarding the role of obesity or PCOS pe ser in development of GDM. In this study we conducted a 2-phase study to compare the risk of GDM and its associated early pregnancy metabolic factors in women with and without PCOS, stratified by pre-pregnancy body mass index (BMI).MethodsA 2-phase design was used in this study. The initial phase of the study included 566 age- and pre-pregnancy BMI-matched singleton pregnant women (242 with and 324 without PCOS). Risk of GDM and associated early-pregnancy risk factors were explored between women with and without PCOS, after stratification by pre-pregnancy BMI. Stratified analysis was conducted in normal weight (pre-pregnancy BMI < 25 kg/m2) and overweight/obese (pre-pregnancy BMI ≥ 25 kg/m2) groups. Subsequently, the findings was confirmed in a separate cohort study with 18,106 participants (877 with and 17,229 without PCOS).ResultsOverall, prevalence of GDM is higher in women with PCOS. Results from the initial study showed that in normal-weight subjects, there is a significant increase in GDM prevalence in PCOS women than non-PCOS women (26.5% vs. 16.2%, p = 0.02). Additionally, normal-weight PCOS women showed higher triglycerides levels (1.51 ± 0.84 mmol/L vs. 1.30 ± 0.75 mmol/L, p = 0.02), lower SHBG levels (277.8 ± 110.2 nmol/L vs. 330.5 ± 180.4 nmol/L, p = 0.001) and a possible trend towards higher insulin resistance (LogHoMA-IR 0.70 ± 0.55 vs. 0.57 ± 0.57, p = 0.05) during early pregnancy. However, in overweight/obese group, no difference in risk of GDM was observed between PCOS and non-PCOS subjects (p = 0.7). Results from the independent cohort confirmed the risk for GDM associated with PCOS in normal weight women (p < 0.0001).ConclusionConsistent findings from the 2-phase study showed an increased risk of GDM in normal-weight, but not overweight/obese PCOS women. Analysis of early-pregnancy risk factors of GDM suggested that the pathogenesis of GDM in normal weight and overweight/obese women with PCOS may be different.

Feasibility of Informed Consent for Computed Tomography in Acute Trauma Patients.

Computed tomography (CT) is common for trauma victims, but is usually done without informing patients of potential risks or obtaining informed consent. The objective of this study was to determine the feasibility of two elements (time and normal level of alertness) necessary for informed consent for CT in adult trauma patients. We conducted this prospective observational, two-phase cohort study at two urban, Level I trauma centers. In the first phase, we determined the median time needed to obtain informed consent for CT by performing sham consent on 11 injured patients at each site. In the second phase, we observed all adult trauma activation cases that presented during specified time blocks and recorded Glasgow Coma Scale (GCS) scores and the time available for consent (TAC) for CT-defined as the time between the end of the secondary trauma survey and when the patient left the resuscitation room to go to CT. We defined, a priori, feasible consent cases as those in which the patient had a GCS of 15 and a TAC greater than the median sham consent time at that site. The median times for sham CT consent at the two sites were 3:36 and 2:09 minutes:seconds (range = 1:12-4:54). Of the 729 trauma patients enrolled during phase II, 646 (89%) had a CT scan, and of these 646 patients, 461 (71.4% [95% confidence interval = 67.8%- 74.7%]) met feasible consent criteria. Of the 185 patients who failed to meet feasible consent criteria, 171 (92.4%) had a GCS < 15, one (0.5%) had a TAC less than the sham consent time, and 13 (7.0%) had both. We found that informed consent for CT was likely feasible in over two-thirds of acute, adult trauma patients.

Visual Fixation in the ICU: A Strong Predictor of Long-Term Recovery After Moderate-to-Severe Traumatic Brain Injury.

Posttraumatic amnesia is superior to the initial Glasgow Coma Scale score for predicting traumatic brain injury recovery, but it takes days/weeks to assess. Here, we examined whether return of visual fixation-a potential marker of higher cognitive function-within 24 hours of ICU admission could be used as an early predictor of traumatic brain injury recovery. Two-phase cohort study. Level-I trauma ICU. Moderate-to-severe traumatic brain injury discharged alive between 2010 and 2013. None. Return of visual fixation was assessed through standard behavioral assessments in 181 traumatic brain injury patients who had lost the ability to fixate at ICU admission (phase 1) and compared with posttraumatic amnesia duration and the initial Glasgow Coma Scale score to predict performance on the Glasgow Outcome Scale-Extended 10-40 months after injury (n = 144; phase 2a). A subgroup also completed a visual attention task (n = 35; phase 2b) and a brain MRI after traumatic brain injury (n = 23; phase 2c). With an area under the curve equal to 0.85, presence/absence of visual fixation at 24 hours of ICU admission was found as performant as posttraumatic amnesia (area under the curve, 0.81; difference between area under the curve, 0.04; p = 0.28) for predicting patients' Glasgow Outcome Scale-Extended score. Conversely, the initial Glasgow Coma Scale score was not (area under the curve, 0.63). Even when controlling for age/medication/CT scan findings, fixation remained a significant predictor of Glasgow Outcome Scale-Extended scores (β, -0.29; p < 0.05). Poorer attention performances and greater regional brain volume deficits were also observed in patients who could not fixate at 24 hours of ICU admission versus those who could. Visual fixation within 24 hours of ICU admission could be as performant as posttraumatic amnesia for predicting traumatic brain injury recovery, introducing a new variable of interest in traumatic brain injury outcome research.

Pharmacokinetics of Repeated Melatonin Drug Administrations Prior to and After Surgery.

Recent clinical studies have documented the analgesic, anti-inflammatory, antioxidative and anxiolytic effects of exogenous melatonin. The pharmacokinetic properties of melatonin have primarily been investigated in experimental studies. The aim of this study was to estimate the pharmacokinetics of melatonin in patients undergoing surgery and general anesthesia. The study was designed as a prospective, two-phase cohort study. Patients were candidates for subpectoral breast augmentation surgery, and surgical procedures were performed by a single surgeon. The perioperative treatment protocol was standardized between patients. During the study, each patient received two separate oral administrations of melatonin 10mg. Melatonin was administered 60min before surgery, and at 9:00 p.m. the evening after surgery. The pharmacokinetic variables absorption half-life (t ½ absorption), time to maximal plasma concentration (T max), maximal plasma concentration (C max), elimination half-life (t ½ elimination), and area under the melatonin plasma concentration-time curve from time zero to infinity (AUC ∞) were estimated for both study phases. Median (interquartile range) values of t ½ absorption and T max were significantly increased during the postoperative phase [10.8 (6.9-15.1)min; 90.0 (48.8-120.0)min] compared with perioperatively [9.5 (6.3-16.5)min; 30.0 (15.0-30.0)min] (p=0.034; p=0.002), respectively. C max values were significantly higher during surgery [5497.5 (2077.1-13,233.8) pg/ml] compared with postoperative values [2340.5 (1672.4-8871.4) pg/ml] (p=0.005). Correspondingly, t ½ elimination was significantly extended during the postoperative phase [103.5 (57.8-237.8)min] compared with the perioperative phase [60.5 (47.8-83.6)min] (p=0.015). AUC ∞ did not differ between the study phases (p>0.05). These preliminary results indicate that postoperative melatonin dose should be augmented compared with preoperative administration if corresponding melatonin plasma levels are intended. Furthermore, postoperative administration times should be advanced compared with preoperative administration.

Irritable bowel syndrome in the UK military after deployment to Iraq: what are the risk factors?

Diarrhoea and vomiting (D & V) was common in military personnel during deployment to the initial phases of the Iraq war. D & V is an established risk factor for irritable bowel syndrome (IBS). This study examined the prevalence of IBS in a military sample with a history of deployment to Iraq and the association between D & V and common mental disorder (CMD) with IBS. The study used data from a two-phase cohort study of military/personnel. The sample was restricted to individuals who had been deployed to Iraq before phase 1 of the study and who had completed the self-report D & V question. A measure of probable IBS was derived at both phases of the study based on self-reported symptoms in the previous month. CMD was assessed by the General Health Questionnaire (GHQ-12). Fifty-nine percent of the sample reported a D & V event and 6.6 % met the criteria for probable IBS at phase 1. Reporting D & V, thinking one might be killed on deployment, poor physical health and CMD were associated with probable IBS at phase 1. CMD at phase 1 was strongly associated with chronic symptoms of IBS. There was a high prevalence of D & V during deployment to the early stages of the Iraq war, yet the prevalence of probable IBS on return from deployment was relatively low. D & V was strongly associated with IBS after deployment, and CMD was a risk factor for chronic symptoms of IBS.

Alcohol misuse in the UK armed forces

ObjectivesThere are concerns that alcohol misuse among military personnel could have serious consequences for both individual and organisational functioning. Research has found alcohol misuse to be particularly high in the...

Psychological and Physical Workload and the Development of Musculoskeletal Symptoms Among Female Elderly-Care Workers

The aim of the present study was to investigate the relations between psychological and physical workload and musculoskeletal neck, shoulder and upper back symptoms. In this longitudinal two-phase cohort study a survey was con- ducted among non-managerial female elderly-care workers (n = 553). The analyses were based on respondents who were considered free from the respective symptoms at initial ratings, resulting in study samples of n = 230 for neck symptoms, n = 211 for shoulder symptoms, n = 400 for upper back symptoms, and n = 204 for low back symptoms. The results indi- cate that psychological workload is related to the development of musculoskeletal (neck and upper back) symptoms measured at an 18-month follow-up, both in itself and in combination with physical workload. The most important finding was that psychological workload shows significant temporal relations to neck and upper back symptoms.

Chronic fatigue syndrome and related disorders in UK veterans of the Gulf War 1990–1991: results from a two-phase cohort study

The aim was to determine the prevalence of chronic fatigue syndrome (CFS), chronic fatigue and fibromyalgia in UK military personnel after the Gulf War 1990-1991. A two-phase cohort study was used. Three randomly selected subsamples identified from a population-based cross-sectional postal survey of over 10,000 current and ex-service UK military personnel (Gulf veterans were those deployed to the Gulf War 1990-1991; non-Gulf veterans were Bosnia peacekeepers 1992-1997 and those on active duty during the Gulf War 1990-1991 but not deployed) were recruited. Their disability status was assessed using the Short Form 36 physical functioning scale; Gulf veterans who reported physical disability (n=111) were compared with non-Gulf (n=133) veterans who reported similar levels of physical disability. Screening for known medical and psychiatric conditions was conducted to exclude medical explanations for disability and symptomatic distress. Standardised criteria for CFS, chronic fatigue and fibromyalgia were used. Disabled Gulf veterans were more likely to be overweight, have elevated gamma-glutamyl transferase levels and screen positive for hypertension. There were no other clinically significant differences in clinical markers for medically explainable conditions. Disabled Gulf veterans were more likely than similarly disabled Bosnia and Era veterans (adjusted odds ratio 7.8, 95% confidence interval 2.5-24.5) to meet the criteria for CFS. Rates for other medically unexplained conditions were not significantly increased. Symptoms in keeping with CFS account for a significant part of the symptomatic distress in Gulf veterans.