Observational Studies Of Screening Research Articles

Can we screen for heart disease in children at public health centres? A multicentre observational study of screening for heart disease with a risk of sudden death in children

Sudden cardiac death in children is a rare event, but of great social significance. Generally, it is related to heart disease with a risk of sudden cardiac death (SCD), which may occur with cardiovascular symptoms and/or electrocardiographic markers; thus, a primary care paediatrician (PCP) could detect them. Therefore, we proposed a study that assesses how to put into practice and conduct a cardiovascular assessment within the routine healthy-child check-ups at six and twelve years of age; that reflects cardiovascular signs and symptoms, as well as the electrocardiographic alterations that children with a risk of SCD in the selected population present; and that assesses the PCP’s skill at electrocardiogram (ECG) interpretation. In collaboration with PCPs, primary care nurses, and paediatric cardiologists, an observational, descriptive, multicentre, cross-sectional study was carried out in the Balearic Islands (Spain), from April 2021 to January 2022, inclusive. The PCPs gathered patient data through forms (medical record, electrocardiogram, and physical examination) and sent them to the investigator, together with the informed consent document and electrocardiogram. The investigator passed the electrocardiogram on to the paediatric cardiologists for reading, in an identical form to those the paediatricians had filled in. The variables were collected, and a descriptive analysis performed. Three paediatric cardiologists, twelve PCPs, and nine nurses from seven public health centres took part. They collected the data from 641 patients, but 233 patients did not participate (in 81.11% due to the PCP’s workload). Therefore, the study coverage was around 64%, representing the quotient of the total number of patients who participated, divided by the total number of patients who were eligible for the study. We detected 30 patients with electrocardiographic alterations compatible with SCD risk. Nine of these had been examined by a paediatric cardiologist at some time (functional murmur in 8/9), five had reported shortness of breath with exercise, and four had reported a family history of sudden death. The physical examination of all the patients whose ECG was compatible with a risk of SCD was normal. Upon analysing to what extent the ECG results of the PCP and the paediatric cardiologist agreed, the percentage of agreement in the final interpretation (normal/altered) was 91.9%, while Cohen’s kappa coefficient was 31.2% (CI 95%: 13.8–48.6%). The sensitivity of the ECG interpretation by the PCP to detect an ECG compatible with a risk of SCD was 29% and the positive predictive value 45%. Conclusions: This study lays the foundations for future SCD risk screening in children, performed by PCPs. However, previously, it would be important to optimise their training in reading and interpreting paediatric ECGs.What is Known:• In Spain at present, there is a programme in place to detect heart disease with a risk of sudden death [1], but it targets only children who are starting on or are doing a physical activity as a federated sport. Implementing such screening programmes has proven effective in several countries [2]. However, several studies showed that the incidence of sudden cardiac death is no higher in children competing in sport activities than in those who do not do any sport [3]. This poses an ethical conflict, because at present, children who do not do any federated sport are excluded from screening. According to the revised literature, so far, only in two studies did they screen the child population at schools, and in both, they successfully detected patients with heart disease associated to the risk of sudden death [4, 5]. We have found no studies where the screening of these features was included within the routine healthy-child check-ups by primary care paediatricians.What is New:• We did not know whether—in our setting, at present—the primary care paediatrician could perform a screening method within the routine healthy-child check-ups, in order to detect presumably healthy children at risk of sudden cardiac death, as they present one of the SCD risks. In this regard, we proposed our project: to assess how to put into practice and conduct a cardiovascular assessment via SCD risk screening in the healthy child population by primary care paediatricians and appraise primary care paediatricians’ skills in identifying the electrocardiographic alterations associated with SCD risk. The ultimate intention of this pilot study was to make it possible, in the future, to design and justify a study aimed at universalising cardiovascular screening and achieving a long-term decrease in sudden cardiac death events in children.

Depression, anxiety and stress levels of operating room workers during the COVID-19 pandemic period

Purpose: The objective of this study was to determine the depression, anxiety, and stress levels of operating room workers during the COVID-19 pandemic.
 Materials and Methods: The data were collected using the “Personal Information Form” and "Depression Anxiety Stress-21 (DASS-21)" scale. The personal information form consisted of eight questions including age, gender, profession, professional seniority, status of being diagnosed with COVID-19, being afraid of developing COVID-19, presence of chronic diseases and change in weight during the pandemic period. DASS-21 scale is a 4-point Likert type (never=0; always=3) scale and consists of seven questions with each predicting "depression, stress and anxiety dimensions".
 Results: A total of 253 volunteers with 161 (63.6%) being female and 92 (36.4%) male were included in this observational screening study. Anxiety score of female participants (5.65±4.44) was found to be statistically significantly higher compared to the male participants (3.94±4.68). Depression (5.97±4.41), anxiety (5.48±4.53) and stress (6.94±4.59) scores were significantly higher in the participants who were afraid of developing COVID-19. Depression, anxiety and stress scores were significantly higher in the participants with chronic diseases than in those without chronic diseases. 
 Conclusion: The findings of our study indicate that the mean depression, anxiety and stress scores of the operating room personnel were mild.

A Propensity Score-Adjusted Comparison of Lenalidomide + R-CHOP Versus R-CHOP for MYC-Rearranged DLBCL Patients

Introduction Patients with MYC rearranged (MYC-R) diffuse large B-cell lymphoma (DLBCL) generally have a poor prognosis following standard treatment with R-CHOP. Previously, we demonstrated in a single-arm phase II trial (HOVON-130) that addition of lenalidomide to R-CHOP (R2CHOP) is well-tolerated and yields similar complete metabolic remission (CMR) rates and survival as more intensive chemotherapy regimens such as DA-EPOCH-R [Chamuleau, Haematologica 2020]. In parallel with this single-arm interventional trial, a prospective observational screening cohort (HOVON-900) was open in which we identified all newly diagnosed DLBCL patients treated with R-CHOP in the Netherlands, including MYC-R patients who were not included in the interventional trial due to logistic reasons. These two cohorts enable to evaluate the added value of lenalidomide to R-CHOP in first-line treatment of newly diagnosed MYC-R DLBCL patients. Methods In the single-arm, phase-II HOVON-130 trial, MYC-R DLBCL patients ≥ 18 years were treated with R-CHOP21 plus lenalidomide 15 mg day 1-15 for 6 cycles [Chamuleau, Haematologica 2020]. Additional inclusion criteria were Ann-Arbor stage II-IV, WHO performance status 0-3, ≥ one lesion of ≥ 1.5 cm on contrast-enhanced CT scan and ≥ one FDG-positive lesion on PET-CT scan. In the observational screening study HOVON-900, MYC, BCL2 and BCL6 fluorescent in situ hybridization (FISH) diagnostics were advocated as part of routine procedures and reviewed by the HOVON Pathology Facility. As a control group, we selected MYC-R patients from this observational cohort who met the inclusion criteria for the interventional trial but were not included, and who were treated with standard R-CHOP. Clinical information at presentation and treatment and outcome data were retrieved from the Netherlands Cancer Registry. We explored three statistical methods that account for baseline imbalances. First, we used multivariable regression, with baseline variables as covariates in the model. Second, we performed one-to-one matching on the IPI risk (low, intermediate, or high). Third, we performed inverse probability of treatment weighting (IPTW) using a propensity score. We calculated a propensity score for being included in the HOVON-130 trial based on the separate components of the IPI score (i.e., age, Ann Arbor stage, WHO performance score, extra-nodal localizations, serum LDH level), sex and rearrangement status. To allow for some degree of misspecification of the model for the propensity score, we used a doubly-robust estimator. Subgroup analyses were performed in single hit (SH: only MYC rearrangement), versus double hit and triple hit (DH/TH: MYC rearrangement with BCL2 and/or BCL6 rearrangement). Results Patients from the interventional trial treated with R2CHOP (n=77) were younger than patients in the control cohort (n=56) treated with R-CHOP (median age 63 versus 70 years, p=0.018) and they were more likely to have a lower WHO performance score (p=0.013). Ann Arbor stage, LDH level, number of extranodal localizations and median days before treatment (15 and 19 in the R-CHOP and R2CHOP group, respectively) did not significantly differ between the groups. Complete remission rates were 69.8% and 80.5% in the R-CHOP and R2CHOP group, respectively (p=0.209). Multivariable analysis, 1:1 matching and weighting using the propensity score consistently showed improved outcome after R2CHOP with HRs of 0.53, 0.53, and 0.59 (Figure 1A), respectively, for OS, and 0.59, 0.53, and 0.60 for PFS (Figure 1B). In the subgroups determined by rearrangement status, we performed unadjusted OS and PFS analysis only, because we were not able to adjust for baseline imbalances because of the low number of events within the subgroups. Both SH patients and DH/TH patients tended to have a longer OS when treated with R2CHOP with HRs of 0.34 and 0.57, respectively. Similarly, for PFS the HRs were 0.66 in the SH subgroup and 0.48 in the DH/TH subgroup. Conclusion In conclusion, this propensity score-adjusted comparison study supports the addition of lenalidomide to R-CHOP as a valuable treatment option for MYC-R DLBCL patients. R2CHOP can be administered on a full outpatient basis, with minimal hospitalization visits. Future studies will explore whether adding next-generation cereblon targeting antigens to R-CHOP can improve the observed effects. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A validated Screening instrument for Child Abuse and Neglect (SCAN) at the emergency department

The objective of this study is to develop and validate a screening instrument for the recognition of child maltreatment in the emergency department (ED). Existing data on screening questions and outcomes (diagnosis of child maltreatment) from three large observational screening studies at eight different EDs in the Netherlands were harmonized. A multivariate logistic regression was performed to develop the Screening instrument for Child Abuse and Neglect (SCAN). The SCAN was validated by performing a cross-validation and calculating the discriminative ability. A total of 24,963 patients were included. Out of the potential screening questions the following questions were included in the final instrument: is the injury compatible with the history, and does it correspond to the child’s developmental level? (aOR 10.40, 95% CI 5.69–19.02), was there an unnecessary delay in seeking medical help? (aOR 3.45, 95% CI 1.73–6.88) and is the behaviour/interaction of the child and parents (carers) appropriate? (aOR 14.67, 95% CI 7.93–27.13). The SCAN had a pooled AUC of 0.75 (95% CI 0.63–0.87) in the cross-validation. The question “Are there other signals that make you doubt the safety of the child and/or family?” (available in only one of the original datasets, OR 182.9; 95% CI 102.3–327.4) was by consensus added to the final SCAN.Conclusion: This validated and brief Screening instrument for Child Abuse and Neglect (SCAN) is designed to improve early recognition of child maltreatment in the ED. A positive screening result of the SCAN warrants a thorough work-up for child maltreatment, including a top-toe examination, if necessary additional diagnostics and adequate safety measures.What is Known:• Screening instruments increase the detection of possible cases of child maltreatment in the emergency department and support health care professionals to identify these cases.• The application of different screening instruments led to the need for one brief validated instrument.What is New:• This study presents a validated and brief Screening instrument for Child Abuse and Neglect (SCAN), consisting of four questions.• The SCAN supports professionals in detecting signals of child maltreatment, and a positive screening result should lead to a thorough work-up, including a top-toe examination, complete history, additional diagnostic tests and consultation of a child abuse expert.

Measures implemented in the school setting to contain the COVID-19 pandemic

Measures implemented in the school setting to contain the COVID-19 pandemic

Vitamin K Effects on Gas6 and Soluble Axl Receptors in Intensive Care Patients: An Observational Screening Study.

Growth arrest-specific gene 6 protein (Gas6) is avitamin K-dependent tissue bound protein. Gas6 has been shown to promote growth and therapy resistance among different types of cancer as well as thromboembolism. The aim of this prospective screening study: ClinicalTrials.gov; Identifier: NTC3782025, was to evaluate the effects of intravenously administered vitamin K1 on Gas6 and its soluble (s)Axl receptor plasma levels in intensive care patients. Vitamin K1 was intravenously injected in non-warfarin treated patients with prolonged Owren prothrombin time international normalized ratio (PT-INR) > 1.2 and blood samples were retrieved before and 20–28 h after injection. Citrate plasma samples from 52 intensive care patients were analysed for different vitamin K dependent proteins. There was a significant, but small increase in median Gas6. Only one patient had a large increase in sAxl, but overall, no significant changes in sAxl Gas6 did not correlate to PT-INR, thrombin generation assay, coagulation factors II, VII, IX and X, but to protein S and decarboxylated matrix Gla protein (dp-ucMGP). In conclusion, there was a small increase in Gas6 over 20–28 h. The pathophysiology and clinical importance of this remains to be investigated. To verify a true vitamin K effect, improvement of Gas6 carboxylation defects needs to be studied.

КЛИНИКО-ДИАГНОСТИЧЕСКИЕ ПРИЗНАКИ НЕДИФФЕРЕНЦИРОВАННОЙ ДИСПЛАЗИИ СОЕДИНИТЕЛЬНОЙ ТКАНИ У ДЕТЕЙ С ДИСПЛАЗИЕЙ ТАЗОБЕДРЕННЫХ СУСТАВОВ

Developmental dysplasia of the hip (DDH) is characterized by varying degrees of underdevelopment of the hip joint (HJ) and para-articular tissues with numerous variants of clinical and anatomical criteria. It is now considered one of the manifestations of undifferentiated connective tissue dysplasia (UCTD), which is confirmed by genetic testing. Undoubtedly, children with DDH also have other manifestations of UCTD, the clinical combination of which must be taken into account for the overall prognosis of the patient's quality of life, as well as the determination of control points in the treatment and prevention of the disease. Materials and methods of research: a singlestage observational screening study was carried out involving 785 children (578 girls and 207 boys) from 2 to 14 years old (7,5±1,5 years) with a radiographically confirmed diagnosis of DDH of various variants (torsion-valgus deformity, subluxation , dislocation in the vehicle). The control group consisted of 259 children (140 girls and 119 boys) without HJ pathology, who were examined at the Research Institute of Traumatology, Orthopedics and Neurosurgery for preparation for a kindergarten/school/sports section, comparable in age (6,5±1,3 years). The criteria for selecting UCTD was the Bayesian classifier modified by T.I. Kadurina and V.N. Gorbunova, including the 50 most common clinical markers. For analysis the clinical anamnestic method, instrumental data of somatic symptom disorder test was used. Results: after summing up the scores in children with DDH, grade I UCTD was diagnosed in 40,0% (314), grade II – in 36,1% (283) and grade III – in 23,9% (188). In most cases, symptoms of UCTD with an Ehlers-Danlos-like syndrome were noted, which are characterized by changes in the musculoskeletal system, skin, connective tissue elements of internal organs (hypermobility of the joints, stretchable skin, anatomical disorders of the heart valves, bile ducts, etc.) or signs of UCTD with an unclassifiable phenotype when there is a variety of stigmas. All children in this group have joint hypermobility, myotonic syndrome, and various types of posture disorders. In the control group with DDH, 27,4% (71) noted the burdened heredity in the pathology of the musculoskeletal system on the mother's or father's side. In the control group the signs of UCTD stigma were also diagnosed, however, the degree of their severity and occurrence were significantly lower (p<0,05). In these children, the most significant were changes in the organ of vision, nervous system, maxillofacial region, digestive tract and a decrease in immune function. Conclusion: manifestations of UCTD are significantly more common in children with DDH compared with healthy children; pathology of the musculoskeletal and cardiovascular systems prevails in the structure of UCTD stigmas. In the pathogenesis of DDH, a genetic predisposition is realized (45,5%, 357 children), hypermobility of joints, myatonic syndrome were observed in all children in the study group. Manifestations of UCTD were also found in the control group, however, the stigmas were of a visceral nature of lesions and impairments from the sense organs, which is not the subject of a pediatric orthopedist's study. Thus, the features of UCTD in children with DDH are considered as a predictor of the pathology severity.

Clinical validation of p16/Ki-67 dual-stained cytology triage of HPV-positive women: Results from the IMPACT trial.

Triage strategies are needed for primary human papillomavirus (HPV)‐based cervical cancer screening to identify women requiring colposcopy/biopsy. We assessed the performance of p16/Ki‐67 dual‐stained (DS) immunocytochemistry to triage HPV‐positive women and compared it to cytology, with or without HPV16/18 genotyping. A prospective observational screening study enrolled 35 263 women aged 25 to 65 years at 32 U.S. sites. Cervical samples had HPV and cytology testing, with colposcopy/biopsy for women with positive tests. Women without cervical intraepithelial neoplasia Grade 2 or worse (≥CIN2) at baseline (n = 3876) were retested after 1 year. In all, 4927 HPV‐positive women with valid DS results were included in this analysis. DS sensitivity for ≥CIN2 and ≥CIN3 at baseline was 91.2% (95% confidence interval [CI]: 86.8%‐94.2%) and 91.9% (95% CI: 86.1%‐95.4%), respectively, in HPV16/18‐positive women and 83.0% (95% CI: 78.4%‐86.8%) and 86.0% (95% CI: 77.5%‐91.6%) in women with 12 “other” genotypes. Using DS alone to triage HPV‐positive women showed significantly higher sensitivity and specificity than HPV16/18 genotyping with cytology triage of 12 “other” genotypes, and substantially higher sensitivity but lower specificity than using cytology alone. The risk of ≥CIN2 was significantly lower in HPV‐positive, DS‐negative women (3.6%; 95% CI: 2.9%‐4.4%), compared to triage‐negative women using HPV16/18 genotyping with cytology for 12 “other” genotypes (7.4%; 95% CI: 6.4%‐8.5%; P < .0001) or cytology alone (7.5%; 95% CI: 6.7%‐8.4%; P < .0001). DS showed better risk stratification than cytology‐based strategies and provided high reassurance against pre‐cancers both at baseline and at 1‐year follow‐up, irrespective of the HPV genotype. DS allows for the safe triage of primary screening HPV‐positive women.

Travel-related control measures to contain the COVID-19 pandemic: a rapid review.

Background In late 2019, first cases of coronavirus disease 2019, or COVID‐19, caused by the novel coronavirus SARS‐CoV‐2, were reported in Wuhan, China. Subsequently COVID‐19 spread rapidly around the world. To contain the ensuing pandemic, numerous countries have implemented control measures related to international travel, including border closures, partial travel restrictions, entry or exit screening, and quarantine of travellers. Objectives To assess the effectiveness of travel‐related control measures during the COVID‐19 pandemic on infectious disease and screening‐related outcomes. Search methods We searched MEDLINE, Embase and COVID‐19‐specific databases, including the WHO Global Database on COVID‐19 Research, the Cochrane COVID‐19 Study Register, and the CDC COVID‐19 Research Database on 26 June 2020. We also conducted backward‐citation searches with existing reviews. Selection criteria We considered experimental, quasi‐experimental, observational and modelling studies assessing the effects of travel‐related control measures affecting human travel across national borders during the COVID‐19 pandemic. We also included studies concerned with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) as indirect evidence. Primary outcomes were cases avoided, cases detected and a shift in epidemic development due to the measures. Secondary outcomes were other infectious disease transmission outcomes, healthcare utilisation, resource requirements and adverse effects if identified in studies assessing at least one primary outcome. Data collection and analysis One review author screened titles and abstracts; all excluded abstracts were screened in duplicate. Two review authors independently screened full texts. One review author extracted data, assessed risk of bias and appraised study quality. At least one additional review author checked for correctness of all data reported in the 'Risk of bias' assessment, quality appraisal and data synthesis. For assessing the risk of bias and quality of included studies, we used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool for observational studies concerned with screening, ROBINS‐I for observational ecological studies and a bespoke tool for modelling studies. We synthesised findings narratively. One review author assessed certainty of evidence with GRADE, and the review author team discussed ratings. Main results We included 40 records reporting on 36 unique studies. We found 17 modelling studies, 7 observational screening studies and one observational ecological study on COVID‐19, four modelling and six observational studies on SARS, and one modelling study on SARS and MERS, covering a variety of settings and epidemic stages. Most studies compared travel‐related control measures against a counterfactual scenario in which the intervention measure was not implemented. However, some modelling studies described additional comparator scenarios, such as different levels of travel restrictions, or a combination of measures. There were concerns with the quality of many modelling studies and the risk of bias of observational studies. Many modelling studies used potentially inappropriate assumptions about the structure and input parameters of models, and failed to adequately assess uncertainty. Concerns with observational screening studies commonly related to the reference test and the flow of the screening process.

Dentification and correction of the lead-time bias and length bias in cancer screening studies

Lead-time bias and length bias were common systematic errors in observational screening studies, which might be a common cause of overstating or distorting the true screening effects. One of key concerns in observational screening studies was how to estimate the screening effects based on the consideration of these two biases. This paper illustrated how to identify and correct the lead-time bias using the tumor volume doubling time and the non-homogeneous Poisson process, and how to correct the length bias using a weighted method. The application conditions of each method were also discussed to present several useful toolboxes to correct the lead-time bias and length bias appropriately and evaluate the effectiveness of the cancer screening program accurately.

An observational study of screening, diagnosis, and management of operable cases of cervical cancer in a tertiary institute

An observational study of screening, diagnosis, and management of operable cases of cervical cancer in a tertiary institute

Pulse Oximetry and Auscultation for Congenital Heart Disease Detection.

Pulse oximetry (POX) has been confirmed as a specific screening modality for critical congenital heart disease (CCHD), with moderate sensitivity. However, POX is not able to detect most serious and critical cardiac lesions (major congenital heart disease [CHD]) without hypoxemia. In this study, we investigated the accuracy and feasibility of the addition of cardiac auscultation to POX as a screening method for asymptomatic major CHD. A multicenter prospective observational screening study was conducted at 15 hospitals in Shanghai between July 1, 2012, and December 31, 2014. Newborns with either an abnormal POX or cardiac auscultation were defined as screen positive. All screen-positive newborns underwent further echocardiography. False-negative results were identified by clinical follow-up, parents' feedback, and telephone review. We assessed the accuracy of POX plus cardiac auscultation for the detection of major CHD. CHD screening was completed in all 15 hospitals, with a screening rate of 94.0% to 99.8%. In total, 167 190 consecutive asymptomatic newborn infants were screened, of which 203 had major CHD (44 critical and 159 serious). The sensitivity of POX plus cardiac auscultation was 95.5% (95% confidence interval 84.9%-98.7%) for CCHD and 92.1% (95% confidence interval 87.7%-95.1%) for major CHD. The false-positive rate was 1.2% for detecting CCHD and 1.1% for detecting major CHD. In our current study, we show that using POX plus cardiac auscultation significantly improved the detection rate of major CHD in the early neonatal stage, with high sensitivity and a reasonable false-positive rate. It provides strong evidence and a reliable method for neonatal CHD screening.

Screening for Adult Attention-Deficit/Hyperactivity Disorder in a Psychiatric Outpatient Population with Specific Focus on Sex Differences.

Attention-deficit/hyperactivity disorder (ADHD) is often overlooked in adults; moreover, the problem seems to be even more critical in women. In the present, observational screening study, a clinical, particularly adult outpatient population was examined regarding frequency and severity of a likely ADHD, whereby sex differences were of particular interest. 224 participants, 146 men and 78 women, were included. Based on data recorded with the self-rating WHO screening instrument Adult ADHD Self-Report Scale (ASRS-v1.1), it was examined how many participants were conspicuous for adult ADHD by exceeding a predefined cutoff value (COV) (COV ≥ 4 for ASRS-6, and ≥12 for ASRS-18). To examine frequency distributions, χ2 tests were conducted. For the inferential statistical comparison of means, t-tests for independent samples or Mann-Whitney U tests were calculated. 34.4% of the sample was screened positive in the ASRS-v1.1 screener short version, ASRS-6, while 17.4% were conspicuous in the symptom checklist, ASRS-18. There were indeed more men screened positive, but the difference in the frequency between the sexes was not statistically significant, indicating a balanced sex ratio. Further, severity of ADHD core symptoms inattention and hyperactivity/impulsivity was examined by comparing ASRS-18 symptom subscale scores. In concordance with the hypothesis, men and women did not differ in severity of symptoms. Results indicate that women might be affected by ADHD in a comparable manner as men; this emphasizes the importance for the awareness of ADHD in both sexes in clinical practice.

Screening for hereditary angioedema (HAE) at 13 emergency centers in Osaka, Japan: A prospective observational study.

Hereditary angioedema (HAE) with deficiency of C1 inhibitor (C1-INH) is an autosomal-dominant disease characterized by recurrent episodes of potentially life-threatening angioedema. The objective is to study the incidence of HAE among patients who visit the emergency department.This was a 3-year prospective observational screening study involving 13 urban tertiary emergency centers in Osaka prefecture, Japan. Patients were included if they met the following criteria: unexplained edema of the body, upper airway obstruction accompanied by edema, anaphylaxis, acute abdomen with intestinal edema (including ileus and acute pancreatitis), or asthma attack. C1-INH activity and C4 level were measured at the time of emergency department admission during the period between July 2011 and June 2014.This study comprised 66 patients with a median age of 54.0 (IQR: 37.5-68.3) years. Three patients were newly diagnosed as having HAE, and 1 patient had already been diagnosed as having HAE. C1-INH activity levels of the patients with HAE were below the detection limit (<25%), whereas those of non-HAE patients (n = 62) were 106% (IQR: 85.5%-127.0%) (normal range, 70%-130%). The median level of C4 was significantly lower in the patients with HAE compared with those without HAE (1.2 [IQR: 1-3] mg/dL vs 22 [IQR: 16.5-29.5] mg/dL, P < 0.01) (normal range, 17-45 mg/dL).Three patients with undiagnosed HAE were diagnosed as having HAE in the emergency department during the 3-year period. If patients have signs and symptoms suspicious of HAE, the levels of C1-INH activity and C4 should be measured.

Effectiveness of Breast Cancer Screening: Systematic Review and Meta-analysis to Update the 2009 U.S. Preventive Services Task Force Recommendation.

In 2009, the U.S. Preventive Services Task Force recommended biennial mammography screening for women aged 50 to 74 years and selective screening for those aged 40 to 49 years. To review studies of the effectiveness of breast cancer screening in average-risk women. MEDLINE and Cochrane databases to 4 June 2015. English-language randomized, controlled trials and observational studies of screening with mammography, magnetic resonance imaging, and ultrasonography that reported breast cancer mortality, all-cause mortality, or advanced breast cancer outcomes. Investigators extracted and confirmed data and dual rated study quality; discrepancies were resolved through consensus. Fair-quality evidence from a meta-analysis of mammography trials indicated relative risks (RRs) for breast cancer mortality of 0.92 for women aged 39 to 49 years (95% CI, 0.75 to 1.02) (9 trials; 3 deaths prevented per 10,000 women over 10 years); 0.86 for those aged 50 to 59 years (CI, 0.68 to 0.97) (7 trials; 8 deaths prevented per 10,000 women over 10 years); 0.67 for those aged 60 to 69 years (CI, 0.54 to 0.83) (5 trials; 21 deaths prevented per 10,000 women over 10 years); and 0.80 for those aged 70 to 74 years (CI, 0.51 to 1.28) (3 trials; 13 deaths prevented per 10,000 women over 10 years). Risk reduction was 25% to 31% for women aged 50 to 69 years in observational studies of mammography screening. All-cause mortality was not reduced with screening. Advanced breast cancer was reduced for women aged 50 years or older (RR, 0.62 [CI, 0.46 to 0.83]) (3 trials) but not those aged 39 to 49 years (RR, 0.98 [CI, 0.74 to 1.37]) (4 trials); less evidence supported this outcome. Most trials used imaging technologies and treatments that are now outdated, and definitions of advanced breast cancer were heterogeneous. Studies of effectiveness based on risk factors, intervals, or other modalities were unavailable or methodologically limited. Breast cancer mortality is generally reduced with mammography screening, although estimates are not statistically significant at all ages and the magnitudes of effect are small. Advanced cancer is reduced with screening for women aged 50 years or older. Agency for Healthcare Research and Quality.

Screening and treatment of thyroid dysfunction: an evidence review for the U.S. Preventive Services Task Force.

In 2004, the U.S. Preventive Services Task Force found insufficient evidence to recommend thyroid screening. To update the 2004 U.S. Preventive Services Task Force review on the benefits and harms of screening and treatment of subclinical and undiagnosed overt hypothyroidism and hyperthyroidism in adults without goiter or thyroid nodules. MEDLINE and Cochrane databases through July 2014. Randomized, controlled trials and observational studies of screening and treatment. One investigator abstracted data, and a second investigator confirmed; 2 investigators independently assessed study quality. No study directly assessed benefits and harms of screening versus no screening. For subclinical hypothyroidism (based on thyroid-stimulating hormone levels of 4.1 to 11.0 mIU/L), 1 fair-quality cohort study found that treatment of subclinical hypothyroidism was associated with decreased risk for coronary heart disease events versus no treatment. No study found that treatment was associated with improved quality of life, cognitive function, blood pressure, or body mass index versus no treatment. Effects of treatment versus no treatment showed potential beneficial effects on lipid levels, but effects were inconsistent, not statistically significant in most studies, and of uncertain clinical significance (difference, -0.7 to 0 mmol/L [-28 to 0 mg/dL] for total cholesterol levels and -0.6 to 0.1 mmol/L [-22 to 2 mg/dL] for low-density lipoprotein cholesterol levels). Treatment harms were poorly studied and sparsely reported. Two poor-quality studies evaluated treatment of subclinical hyperthyroidism but examined intermediate outcomes. No study evaluated treatment versus no treatment of screen-detected, undiagnosed overt thyroid dysfunction. English-language articles only, no treatment study performed in the United States, and small trials with short duration that used different dosage protocols. More research is needed to determine the clinical benefits associated with thyroid screening. Agency for Healthcare Research and Quality.

Comparison of uptake of colorectal cancer screening based on fecal immunochemical testing (FIT) in males and females: a systematic review and meta-analysis.

Colorectal cancer is the third most common cancer in males and the second in females worldwide. Incidence and mortality are higher in men than women. Colorectal cancer screening is effective in reducing mortality. Internationally, fecal immunochemical testing (FIT) is increasingly being recommended as the primary screening test. This systematic review and meta-analysis aimed to determine whether uptake of FIT screening differs between men than women. We searched PubMed and Embase for peer-reviewed articles published in English during 2000-2013 for randomized controlled trials (RCT) or observational studies of screening using FIT that quantified numbers invited and participating by gender. Meta-analysis was performed using a random effects model. Six hundred and eighty-five citations were identified, 19 meeting the inclusion criteria. Random effects meta-analysis found male uptake was significantly lower than female uptake [odds ratio (OR), 0.84; 95% confidence interval (CI), 0.75-0.95; P < 0.01]. This generally persisted throughout subgroup analysis of study design (RCTs vs. observational studies and study quality), screening organization (methods of invitation, number of samples, age range of screening, recommendations, and reminders), and setting. Meta analysis of FIT screening studies indicates significantly lower uptake among men. Further investigation is required into factors influencing acceptability and participation of FIT screening in both sexes.

Screening for hepatitis B virus infection in adolescents and adults: a systematic review to update the U.S. Preventive Services Task Force recommendation.

In 2004, the U.S. Preventive Services Task Force (USPSTF) recommended against screening for hepatitis B virus (HBV) infection. To update the 2004 USPSTF review on screening for HBV infection in adolescents and adults. MEDLINE (through January 2014), the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and PsycINFO. Randomized trials of screening and treatment and observational studies of screening or the association between intermediate and clinical outcomes after antiviral therapy. One investigator abstracted data, and a second investigator checked them; 2 investigators independently assessed study quality. No study directly evaluated the effects of screening for HBV infection versus no screening on clinical outcomes. Vaccination against HBV infection was associated with decreased risk in high-risk populations. On the basis of 11 primarily fair-quality trials, antiviral therapy may be more effective than placebo for reducing the risk for clinical outcomes associated with HBV infection. However, differences were not statistically significant. On the basis of 22 primarily fair-quality trials, antiviral therapy was more effective than placebo for various intermediate outcomes, with limited evidence that first-line antiviral agents are superior to lamivudine. Antiviral therapy was associated with a higher risk for withdrawal due to adverse events than placebo, but risk for serious adverse events did not differ. Only English-language articles were included, clinical outcome data for antiviral therapies were limited, and several studies were done in countries where the prevalence and natural history of HBV infection differ from those of the United States. Antiviral treatment for chronic HBV infection is associated with improved intermediate outcomes, but more research is needed to understand the effects of screening and subsequent interventions on clinical outcomes and to identify optimal screening strategies. Agency for Healthcare Research and Quality.

Queensland Lung Cancer Screening Study: rationale, design and methods

Lung cancer is the leading cause of cancer-related mortality in Australia. Screening using low-dose computed tomography (LDCT) can reduce lung cancer mortality. The feasibility of screening in Australia is unknown. This paper describes the rationale, design and methods of the Queensland Lung Cancer Screening Study. The aim of the study is to describe the methodology for a feasibility study of lung cancer screening by LDCT in Australia. The Queensland Lung Cancer Screening Study is an ongoing, prospective observational study of screening by LDCT at a single tertiary institution. Healthy volunteers at high risk of lung cancer (age 60-74 years; smoking history ≥30 pack years, current or quit within 15 years; forced expiratory volume in 1s ≥50% predicted) are recruited from the general public through newspaper advertisement and press release. Participants receive a LDCT scan of the chest at baseline, year 1 and year 2 using a multidetector helical computed tomography scanner and are followed up for a total of 5 years. Feasibility of screening will be assessed by cancer detection rates, lung nodule prevalence, optimal management strategies for lung nodules, economic costs, healthcare utilisation and participant quality of life. Studying LDCT screening in the Australian setting will help us understand how differences in populations, background diseases and healthcare structures modulate screening effectiveness. This information, together with results from overseas randomised studies, will inform and facilitate local policymaking.

Abstract 17252: Texas Adolescent Athlete Heart Screening Registry (TAAHSR): a Statewide Screening Study

Background: Sudden cardiac death (SCD) in athletes, though a rare event, continues to claim lives every year. Optimal athlete screening strategies have proved to be elusive. Hypothesis: Statewide screening of high school student athletes (SA) for hypertrophic cardiomyopathy (HCM) and other conditions associated with SCD is feasible and establishing a registry may lead to reduction in SCD and improved quality of life. Objective: Identify high school SA at risk for SCD due to presence of HCM and/or other conditions associated with SCD through screening events in the state of Texas, and establish a statewide data bank (registry). Methods: The target population in this observational screening study included high school age SA who voluntarily presented at screening venues in Texas from March 2010-April 2011. Demographic and cardiac history data, 12-lead ECG and limited two-dimensional echocardiogram (L-ECHO) were obtained on all SA. Studies were read either on site or remotely subsequent to data acquisition. Athletes with positive screenings (SCD-related or other abnormal findings) were referred for complete cardiology evaluation. Follow up data were compared to screening results. Results: Of 1002 SA screened, 840 agreed to participate in TAAHSR (71% male). Most SA were in grades 9 and 10 (63%), mostly White (55%) or Hispanic (34%). Fifty one percent reported positive at least once in the history. A total of 94 SA (11.2%) had positive screening on ECG (9.6%) and/or L-ECHO (2.1%) and referral was made. Of the 94 SA referred, follow up data were obtained in 91 (98%): Data were still pending at the time in 44 (48%) and complete in 47 (52%). Of the 94, 22 were referred for SCD-related findings: 19 ECG (15 HCM, 3 WPW and 1 Brugada) and 3 L-ECHO (1 HCM, 2 aortic root dilation). Of the 47 SA, screening findings were confirmed in 12 (25%), 3 with WPW (2 underwent ablation) and 1 with LVH considered ‘benign’ but not HCM. Conclusion: Establishing a registry with statewide screenings in SA for SCD-related conditions is feasible and longitudinal data to assess effectiveness is highly needed at the present time. To date, 3 SA (0.36%) were identified with SCD-related condition (WPW). Future work on cost-effectiveness analysis is imperative to determine value of widespread SA screening for SCD.