COVID-19 impacts on drinking and mental health in emerging adults: Longitudinal changes and moderation by economic disruption and sex.

BACKGROUND: There are significant concerns that the COVID-19 pandemic may have negative effects on substance use and mental health, but most studies to date are cross-sectional. In a sample of emerging adults, over a two-week period during the pandemic, the current study examined: (1) changes in drinking-related outcomes, depression, anxiety, and posttraumatic stress disorder and (2) differences in changes by sex and income loss. The intra-pandemic measures were compared to pre-pandemic measures. METHODS: Participants were 473 emerging adults (Mage  = 23.84; 41.7% male) in an existing longitudinal study on alcohol misuse who were assessed from June 17 to July 1, 2020, during acute public health restrictions in Ontario, Canada. These intra-pandemic data were matched to participant pre-pandemic reports, collected an average of 5 months earlier. Assessments included validated measures of drinking, alcohol-related consequences, and mental health indicators. RESULTS: Longitudinal analyses revealed significant decreases in heavy drinking and adverse alcohol consequences, with no moderation by sex or income loss, but with substantial heterogeneity in changes. Significant increases in continuous measures of depression and anxiety were present, both of which were moderated by sex. Females reported significantly larger increases in depression and anxiety. Income loss >50% was significantly associated with increases in depression. CONCLUSIONS: During the initial phase of the pandemic, reductions in heavy drinking and alcohol consequences were present in this sample of emerging adults, perhaps due to restrictions on socializing. In contrast, there was an increase in internalizing symptoms , especially in females, highlighting disparities in the mental health impacts of the pandemic.

Hot-Water Bathing Improves Symptoms in Patients with Cyclic Vomiting Syndrome and Is Modulated by Chronic Cannabis Use.

BACKGROUND: Cyclic vomiting syndrome (CVS) is a chronic functional GI disorder; a characteristic compulsive "hot-water bathing" pattern is reported to alleviate symptoms during an acute episode. There is limited data on this bathing pattern: proposed mechanisms include core temperature increase via effects on cannabinoid type 1 receptors in the brain, skin transient receptor potential vanilloid 1 receptor stimulation, and blood flow shift from viscera to skin. AIMS: We thus sought to characterize the hot-water bathing pattern in patients with CVS and identify differences between heavy cannabis users in comparison to occasional and non-users. METHODS: We conducted a cross-sectional study of 111 patients with CVS at a single tertiary referral center. Questionnaires regarding clinical characteristics, hot-water bathing, and cannabis use were administered. Patients were classified based on cannabis usage into regular cannabis users (≥ 4 times/week), and occasional + non-users (< 4 times/week and no current use). RESULTS: A total of 81 (73%) respondents reported the hot-water bathing behavior during an episode. The majority (> 80%) noted a marked improvement in nausea, vomiting, abdominal pain and symptoms associated with panic. Regular cannabis users were more likely to use "very-hot" water (50% vs. 16%, p = 0.01) and time to relief of symptoms was longer (> 10 min) in this group, compared to the rest of the cohort. CONCLUSIONS: Hot-water bathing relieves both GI and symptoms related to panic in most patients which appear to be modulated by chronic cannabis use. These findings can help inform future physiologic studies in CVS pathogenesis.

CYP2C9, VKORC1, and CYP4F2 polymorphisms and pediatric warfarin maintenance dose: a systematic review and meta-analysis.

Studies on the effect of cytochrome P450 2C9 (CYP2C9), vitamin K epoxide reductase complex subunit 1 (VKORC1), and cytochrome P450 4F2 (CYP4F2) polymorphisms on warfarin maintenance dose in children are conflicting. We conducted a systematic review and meta-analysis to evaluate the effect of these polymorphisms on warfarin maintenance dose in children. We searched relevant literature using the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial libraries without any language restrictions from their inception to 23 July 2017. Dose differences are expressed as standardized mean difference (SMD) or mean difference (MD) with 95% confidence intervals (CI). This review was registered in the PROSPERO prospective register of systematic reviews (CRD42015016172). We included a total of nine studies (745 participants) in the meta-analysis. Patients with CYP2C9 *1/*2, *1/*3, *2/*2, *2/*3, or *3/*3 required a lower warfarin maintenance dose compared with patients with CYP2C9 *1/*1 (SMD = -0.610, 95% CI: -0.802 to -0.419, I2 = 0%). Patients with VKORC1-1639GA or AA required a lower warfarin maintenance dose compared with patients with VKORC1-1639GG (SMD = -0.666, 95% CI: -0.887 to -0.445, I2 = 33%). However, no associations were observed between CYP4F2 polymorphisms and warfarin maintenance dose (MD = 0.005 mg/kg/day, 95% CI: -0.006 to 0.015, I2 = 0%). These results were not affected by a sensitivity analysis. Our meta-analysis provides evidence that CYP2C9 and VKORC1 variant statuses affect warfarin maintenance dose in children, but not CYP4F2.

The World Federation of Hemophilia Annual Global Survey 1999-2018.

INTRODUCTION: The World Federation of Hemophilia (WFH) strives to achieve care for all patients with inherited bleeding disorders through research, advocacy, capacity building and education. The WFH developed and implemented the Annual Global Survey (AGS), through which comprehensive demographic and treatment data on bleeding disorders are collected each year from its constituent non-governmental national organizations. AIM: To describe the development, methodology and achievements of the WFH AGS over the past 20 years. METHODS: The AGS is a yearly cross-sectional survey. Data are collected using a standardized form (available online and on paper), quality checked and reviewed, and published in English, French and Spanish. Over time, the AGS has been modified in response to changes in treatment landscape or emerging new issues. RESULTS: Over the past 20 years, the AGS has reported an increase in the number of countries participating in the survey, a tripling in the number of people identified with rare bleeding disorders and an increase in the amount of factor used to treat people with haemophilia. Yet, a large treatment inequity gap still exists across the globe. In response to this gap, the WFH has analysed the AGS reports which has stimulated further development in quality of care indicators, estimates of the global prevalence of haemophilia, patient-level data collection efforts like the World Bleeding Disorders Registry and the Gene Therapy Registry. CONCLUSION: The AGS has provided evidence to support research, programme planning and development activities of the WFH.

Protocol for the PRIMARY clinical trial, a prospective, multicentre, cross-sectional study of the additive diagnostic value of gallium-68 prostate-specific membrane antigen positron-emission tomography/computed tomography to multiparametric magnetic resonance imaging in the diagnostic setting for men being investigated for prostate cancer.

OBJECTIVES: Primary objectives: To determine the additive value of gallium-68 prostate-specific membrane antigen (PSMA) positron emission topography (PET)/computed tomography (CT) when combined with multiparametric magnetic resonance imaging (mpMRI) detecting clinically significant prostate cancer (csPCa) in men undergoing initial biopsy for suspicion of PCa, and to determine the proportion of men who could have avoided prostate biopsy with positive mpMRI (PI-RADS ≥3) but negative PSMA-PET/CT. Secondary objectives: To determine the proportion of men who had csPCa detected only by PSMA-PET/CT or only by systematic prostate biopsy; to compare index lesions by template biopsies vs targeted lesions identified on mpMRI or PSMA-PET/CT; to assess whether there may be health economic benefit or harm if PSMA-PET/CT is incorporated into the diagnostic algorithm; and to develop a nomogram which combines clinical, imaging and biomarker data to predict the likelihood of csPCa. PATIENTS AND METHODS: The PRIMARY trial is a multicentre, prospective, cross-sectional study that meets the criteria for level 1 evidence in diagnostic test evaluation. PRIMARY will investigate if a limited (pelvic-only) PSMA-PET/CT in combination with routine mpMRI can reliably discriminate men with csPCa from those without csPCa. We conducted a power calculation based on pilot data and will recruit up to 600 men who will undergo PSMA-PET/CT (the index test), mpMRI (standard test) and transperineal template + targeted (PSMA-PET/CT and/or mpMRI) biopsies (reference test). The conduct and reporting of the mpMRI and PSMA-PET/CT will be blinded to each other. RESULTS: The PRIMARY trial will measure and compare sensitivity, specificity, positive predictive value and negative predictive value of both mpMRI and PSMA-PET/CT vs targeted prostrate biopsy. The results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of csPCa. Furthermore, we will assess whether there is a health economic benefit in incorporating PSMA-PET/CT into the diagnostic algorithm. CONCLUSIONS: This trial will provide robust prospective data to determine the diagnostic ability of PSMA-PET/CT used in addition to mpMRI. It will establish if certain patients can avoid biopsy in the investigation of PCa.

Utility of ultra-sensitive qPCR to detect Plasmodium falciparum and Plasmodium vivax infections under different transmission intensities.

BACKGROUND: The use of molecular diagnostics has revealed an unexpectedly large number of asymptomatic low-density malaria infections in many malaria endemic areas. This study compared the gains in parasite prevalence obtained by the use of ultra-sensitive (us)-qPCR as compared to standard qPCR in cross-sectional surveys conducted in Thailand, Brazil and Papua New Guinea (PNG). The compared assays differed in the copy number of qPCR targets in the parasite genome. METHODS: Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) parasites were quantified by qPCR amplifying the low-copy Pf_ and Pv_18S rRNA genes or the multi-copy targets Pf_varATS and Pv_mtCOX1. Cross-sectional surveys at the three study sites included 2252 participants of all ages and represented different transmission intensities. RESULTS: In the two low-transmission areas, P. falciparum positivity was 1.3% (10/773) (Thailand) and 0.8% (5/651) (Brazil) using standard Pf_18S rRNA qPCR. In these two countries, P. falciparum positivity by Pf_varATS us-qPCR increased to 1.9% (15/773) and 1.7% (11/651). In PNG, an area with moderate transmission intensity, P. falciparum positivity significantly increased from 8.6% (71/828) by standard qPCR to 12.2% (101/828) by us-qPCR. The proportions of P. falciparum infections not detected by standard qPCR were 33%, 55% and 30% in Thailand, Brazil and PNG. Plasmodium vivax was the predominating species in Thailand and Brazil, with 3.9% (30/773) and 4.9% (32/651) positivity by Pv_18S rRNA qPCR. In PNG, P. vivax positivity was similar to P. falciparum, at 8.0% (66/828). Use of Pv_mtCOX1 us-qPCR led to a significant increase in positivity to 5.1% (39/773), 6.4% (42/651) and 11.5% (95/828) in Thailand, Brazil, and PNG. The proportions of P. vivax infections missed by standard qPCR were similar at all three sites, with 23%, 24% and 31% in Thailand, Brazil and PNG. CONCLUSION: The proportional gains in the detection of P. falciparum and P. vivax infections by ultra-sensitive diagnostic assays were substantial at all three study sites. Thus, us-qPCR yields more precise prevalence estimates for both P. falciparum and P. vivax at all studied levels of endemicity and represents a significant diagnostic improvement. Improving sensitivity in P. vivax surveillance by us-qPCR is of particular benefit, because the additionally detected P. vivax infections signal the potential presence of hypnozoites and subsequent risk of relapse and further transmission.

Composite neonatal morbidity indicators using hospital discharge data: A systematic review.

BACKGROUND: Neonatal morbidity is associated with lifelong impairments, but the absence of a consensual definition and the need for large data sets limit research. OBJECTIVES: To inform initiatives to define standard outcomes for research, we reviewed composite neonatal morbidity indicators derived from routine hospital discharge data. DATA SOURCES: PubMed (updated on October 12, 2018). The search algorithm was based on three components: "morbidity," "neonatal," and "hospital discharge data." STUDY SELECTION AND DATA EXTRACTION: Studies investigating neonatal morbidity using a composite indicator based on hospital discharge data were included. Indicators defined for specific conditions (eg congenital anomalies, maternal addictions) were excluded. The target population, objectives, component morbidities, diagnosis and procedure codes, validation methods, and prevalence of morbidity were extracted. SYNTHESIS: For each study, we assessed construct validity by describing the methods used to select the indicator components and evaluated whether the authors assessed internal and external validity. We also calculated confidence intervals for the prevalence of the morbidity composite. RESULTS: Seventeen studies fulfilled inclusion criteria. Indicators targeted all (n = 4), low-/moderate-risk (n = 9), and very preterm (VPT, n = 4) infants. Components were similar for VPT infants, but domains and diagnosis codes within domains varied widely for all and low-/moderate-risk infants. Component selection was described for 8/17 indicators and some form of validation reported for 12/17. Neonatal morbidity prevalence ranged from 4.6% to 9.0% of all infants, 0.4% to 8.0% of low-/moderate-risk infants, and 17.8% to 61.0% of VPT infants. CONCLUSIONS: Multiple neonatal morbidity indicators based on hospital discharge data have been used for research, but their heterogeneity limits comparisons between studies. Standard neonatal outcome measures are needed for benchmarking and synthesis of research results.

The effect of bed rest on balance control in healthy adults: A systematic scoping review.

The objective of this study was to determine the effect of bed rest on balance control and the mechanisms responsible for these changes. Searches were conducted in six databases. Studies had to be conducted on healthy adults who were subjected to bed rest (≥5 days), with balance control measures obtained before and after bed rest in order to be included. Risk of bias was assessed using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. After screening 9,785 articles, 18 were included for qualitative synthesis. Fifteen studies found decrements in at least one balance control measure following bed rest, either compared to baseline or controls, with eight studies observing impairments in >50% of their balance control measures. Of the 14 studies that included an intervention, four (mechanical stimuli, lower-body negative pressure, and training targeting strength, balance and/or aerobic capacity) successfully offset the majority of balance control deficits and targeted the musculoskeletal and cardiovascular systems. The findings of this review support bed rest negatively affecting balance control in healthy individuals. In clinical populations, these deficits may be further accentuated due to various comorbidities that impact balance control systems. PROSPERO Registration: CRD42018098887.

Implementation and data-related challenges in the Deepening our Understanding of Quality in Australia (DUQuA) study: implications for large-scale cross-sectional research.

Healthcare organisations vary in the degree to which they implement quality and safety systems and strategies. Large-scale cross-sectional studies have been implemented to explore whether this variation is associated with outcomes relevant at the patient level. The Deepening our Understanding of Quality in Australia (DUQuA) study draws from earlier research of this type, to examine these issues in 32 Australian hospitals. This paper outlines the key implementation and analysis challenges faced by DUQuA. Many of the logistical difficulties of implementing DUQuA derived from compliance with the administratively complex and time-consuming Australian ethics and governance system designed principally to protect patients involved in clinical trials, rather than for low-risk health services research. The complexity of these processes is compounded by a lack of organizational capacity for multi-site health services research; research is expected to be undertaken in addition to usual work, not as part of it. These issues likely contributed to a relatively low recruitment rate for hospitals (41% of eligible hospitals). Both sets of issues need to be addressed by health services researchers, policymakers and healthcare administrators, if health services research is to flourish. Large-scale research also inevitably involves multiple measurements. The timing for applying these measures needs to be coherent, to maximise the likelihood of finding real relationships between quality and safety systems and strategies, and patient outcomes; this timing was less than ideal in DUQuA, in part due to administrative delays. Other issues that affected our study include low response rates for measures requiring recruitment of clinicians and patients, missing data and a design that necessarily included multiple statistical comparisons. We discuss how these were addressed. Successful completion of these projects relies on mutual and ongoing commitment, and two-way communication between the research team and hospital staff at all levels. This will help to ensure that enthusiasm and engagement are established and maintained.

Trauma nation: Exposure to traumatic events among South African university students.

The current study investigated exposure to past trauma among South African students at a historically disadvantaged institution (HDI). The student population at HDI's are typically from low-income communities that were marginalized by apartheid-era policies and few studies have focused on trauma exposure among this population group. Respondents (N=914) completed the Life Events Checklist and a demographic questionnaire. Logistic regression analysis was conducted to identify gender differences in exposure. 97.6% of the sample reported trauma exposure. The most frequently experienced traumatic events were physical assault (69.3%) and transportation accidents (64.7%). While men were almost twice as likely to report exposure to physical assault (77.2% vs. 67%; ß=.53; odds ratio [OR]=1.70; p<.01) and assault with a weapon (59.7% vs. 44.3%; ß=.62; OR=1.86; p<.01), women were twice as likely to report unwanted or uncomfortable sexual experiences (32.3% vs. 19.4%; ß=-.69; OR=0.50; p<.01) and sexual assault (19.3% vs. 13.1%; ß=-.69; OR=0.50; p<.01). It is recommended that psycho-education on trauma be included in orientation programmes and mental health screening and early referrals for psychological services be implemented.

Screening for Developmental Dysplasia of the Hip in Infants in Tibet Identifies Increased Prevalence Associated with Altitude.

BACKGROUND Developmental dysplasia of the hip (DDH), also known as congenital hip dislocation or congenital hip dysplasia is usually diagnosed at birth. Studies on DDH at high-altitude are rare. Tibetans live mainly at altitudes above 3,500 m, and the prevalence of DDH in this population is not currently known. This cross-sectional epidemiological study aimed to identify the prevalence and associated risk factors for DDH in Tibet. MATERIAL AND METHODS Between 1st June 2015 and 30 June 2016, infants in Tibet aged between 0-6 months and from ten districts at different altitudes in Shigatse, Tibet were referred to our hospital for the assessment of DDH. All the infants underwent clinical evaluation for DDH and ultrasound testing using the Graf method. RESULTS There were 606 infants who met the study inclusion criteria, including 253 female infants and 353 male infants, of which 106 infants had DDH. The prevalence of DDH in Shigatse, Tibet was approximately 174.9/1000 infants (106/606). Altitude was strongly associated with increased risk of DDH in Tibet (r=0.82, P=0.004). CONCLUSIONS This is the first epidemiological study of DDH in the Tibetan population. The results showed that DDH is prevalent among native Tibetan people in Shigatse, and there was a significant correlation between altitude and the prevalence of DDH. Further studies are needed to investigate the mechanism of the association between altitude and the increased incidence of DDH in infants.

An Online Survey for Pharmacoepidemiological Investigation (Survey of Non-Medical Use of Prescription Drugs Program): Validation Study.

BACKGROUND: In rapidly changing fields such as the study of drug use, the need for accurate and timely data is paramount to properly inform policy and intervention decisions. Trends in drug use can change rapidly by month, and using study designs with flexible modules could present advantages. Timely data from online panels can inform proactive interventions against emerging trends, leading to a faster public response. However, threats to validity from using online panels must be addressed to create accurate estimates. OBJECTIVE: The objective of this study was to demonstrate a comprehensive methodological approach that optimizes a nonprobability, online opt-in sample to provide timely, accurate national estimates on prevalence of drug use. METHODS: The Survey of Non-Medical Use of Prescription Drugs Program from the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS) System is an online, cross-sectional survey on drug use in the United States, and several best practices were implemented. To optimize final estimates, two best practices were investigated in detail: exclusion of respondents showing careless or improbable responding patterns and calibration of weights. The approach in this work was to cumulatively implement each method, which improved key estimates during the third quarter 2018 survey launch. Cutoffs for five exclusion criteria were tested. Using a series of benchmarks, average relative bias and changes in bias were calculated for 33 different weighting variable combinations. RESULTS: There were 148,274 invitations sent to panelists, with 40,021 who initiated the survey (26.99%). After eligibility assessment, 20.23% (29,998/148,274) of the completed questionnaires were available for analysis. A total of 0.52% (157/29,998) of respondents were excluded based on careless or improbable responses; however, these exclusions had larger impacts on lower volume drugs. Number of exclusions applied were negatively correlated to total dispensing volume by drug (Spearman ρ=-.88, P<.001). A weighting scheme including three demographic and two health characteristics reduced average relative bias by 31.2%. After weighting, estimates of drug use decreased, reflecting a weighted sample that had healthier benchmarks than the unweighted sample. CONCLUSIONS: Our study illustrates a new approach to using nonprobability online panels to achieve national prevalence estimates for drug abuse. We were able to overcome challenges with using nonprobability internet samples, including misclassification due to improbable responses. Final drug use and health estimates demonstrated concurrent validity to national probability-based drug use and health surveys. Inclusion of multiple best practices cumulatively improved the estimates generated. This method can bridge the information gap when there is a need for prompt, accurate national data.

Selecting Shrinkage Parameters for Effect Estimation: The Multi-Ethnic Study of Atherosclerosis.

We present a method for improving estimation in linear regression models in samples of moderate size, using shrinkage techniques. Our work connects the theory of causal inference, which describes how variable adjustment should be performed with large samples, with shrinkage estimators such as ridge regression and the least absolute shrinkage and selection operator (LASSO), which can perform better in sample sizes seen in epidemiologic practice. Shrinkage methods reduce mean squared error by trading off some amount of bias for a reduction in variance. However, when inference is the goal, there are no standard methods for choosing the penalty "tuning" parameters that govern these tradeoffs. We propose selecting the penalty parameters for these shrinkage estimators by minimizing bias and variance in future similar data sets drawn from the posterior predictive distribution. Our method provides both the point estimate of interest and corresponding standard error estimates. Through simulations, we demonstrate that it can achieve better mean squared error than using cross-validation for penalty parameter selection. We apply our method to a cross-sectional analysis of the association between smoking and carotid intima-media thickness in the Multi-Ethnic Study of Atherosclerosis (multiple US locations, 2000-2002) and compare it with similar analyses of these data.

Intensity of Daily Drinking and Its Relation to Alcohol Use Disorders.

BACKGROUND: Daily drinking is an important public health concern and informative for evaluating diagnostic classification. In particular, daily binge drinkers might be considered as the prototype of some forms of alcoholism, as this drinking pattern may drive many alcohol use disorder (AUD) symptoms. However, daily drinking potentially captures a wide range of drinkers, including light-moderate daily drinkers who exhibit presumed control over their drinking behavior and might benefit from salutary effects on health. This study examined the heterogeneity of daily drinkers in detail. METHODS: Data from the 2 waves of the National Epidemiologic Survey on Alcohol and Related Conditions were used. Participants who reported drinking "every day" during the last 12 months were classified as daily drinkers. A series of regression and logistic regression analyses were conducted to investigate the association between daily drinking and various outcomes. RESULTS: Daily drinkers were found to vary considerably from each other with respect to diagnostic status, level of consumption, demographic composition, and a range of drinking and health correlates. Further, a substantial number of daily binge drinkers were not diagnosed with AUD under the DSM-IV or DSM-5, although in most groups, the DSM-5 criteria diagnosed a larger percentage of participants. CONCLUSIONS: Daily drinkers represent a highly heterogeneous group, and the correlates of daily drinking depend on the usual quantity of daily drinks and the frequency of alcohol-related problems in a given sample. Moreover, AUD, defined both according to DSM-IV and DSM-5, did not capture more than 68% of daily binge drinkers. Given that daily binge drinking is an extremely high threshold for use, this finding may present a challenge for our current classification system.

Challenges of DHS and MIS to capture the entire pattern of malaria parasite risk and intervention effects in countries with different ecological zones: the case of Cameroon.

BACKGROUND: In 2011, the demographic and health survey (DHS) in Cameroon was combined with the multiple indicator cluster survey. Malaria parasitological data were collected, but the survey period did not overlap with the high malaria transmission season. A malaria indicator survey (MIS) was also conducted during the same year, within the malaria peak transmission season. This study compares estimates of the geographical distribution of malaria parasite risk and of the effects of interventions obtained from the DHS and MIS survey data. METHODS: Bayesian geostatistical models were applied on DHS and MIS data to obtain georeferenced estimates of the malaria parasite prevalence and to assess the effects of interventions. Climatic predictors were retrieved from satellite sources. Geostatistical variable selection was used to identify the most important climatic predictors and indicators of malaria interventions. RESULTS: The overall observed malaria parasite risk among children was 33 and 30% in the DHS and MIS data, respectively. Both datasets identified the Normalized Difference Vegetation Index and the altitude as important predictors of the geographical distribution of the disease. However, MIS selected additional climatic factors as important disease predictors. The magnitude of the estimated malaria parasite risk at national level was similar in both surveys. Nevertheless, DHS estimates lower risk in the North and Coastal areas. MIS did not find any important intervention effects, although DHS revealed that the proportion of population with an insecticide-treated nets access in their household was statistically important. An important negative relationship between malaria parasitaemia and socioeconomic factors, such as the level of mother's education, place of residence and the household welfare were captured by both surveys. CONCLUSION: Timing of the malaria survey influences estimates of the geographical distribution of disease risk, especially in settings with seasonal transmission. In countries with different ecological zones and thus different seasonal patterns, a single survey may not be able to identify all high risk areas. A continuous MIS or a combination of MIS, health information system data and data from sentinel sites may be able to capture the disease risk distribution in space across different seasons.

Cross-sectional studies - what are they good for?

Cross-sectional studies serve many purposes, and the cross-sectional design is the most relevant design when assessing the prevalence of disease, attitudes and knowledge among patients and health personnel, in validation studies comparing, for example, different measurement instruments, and in reliability studies. This paper describes the use of cross-sectional studies and provides examples within obstetrics and gynecology. Caveats are also described; for example, when cross-sectional data is used for analytical purposes of associations between an exposure and an outcome, authors and readers should be careful not to make causal inferences, unless the exposure may safely be assumed to be stable over time and not influenced by experiencing the outcome. In such cases, analyses are also subject to selection and information bias as well as confounding.

Prevalence and Spectrum of BRCA1/2 Germline Mutations in Women with Breast Cancer in China Based on Next-Generation Sequencing.

BACKGROUND BRCA1 and BRCA2 (BRCA1/2) play important roles in the development of breast cancer, but information regarding BRCA1/2 mutations in Chinese females remains limited. The aim of this study was to investigate the prevalence and spectrum of BRCA1/2 mutations in China. MATERIAL AND METHODS In total, 595 breast cancer patients in China were screened with an amplicon-based panel for the detection of BRCA1/2 mutations in coding regions using next-generation sequencing (NGS) with a Personal Genome Machine. Every pathogenic mutation detected was confirmed by Sanger sequencing. The disease-causing potential of variants of uncertain significance (VUS) was predicted using PolyPhen-2, SIFT, PhyloP, and Grantham. RESULTS The prevalence of BRCA1/2 mutations was 8.07% in the Chinese population. Forty-two pathogenic mutations were identified in 48 cases (17 BRCA1 cases and 31 BRCA2 cases), including 19 novel mutations. Nine VUS were predicted to be deleterious by PolyPhen-2 and SIFT and subsequently predicted by PhyloP and Grantham for the evolutionary conservation. CONCLUSIONS These results suggest that NGS is useful as a rapid, high-throughput, and cost-effective screening tool for the analysis of BRCA1/2 mutations. Based on this panel, we found that BRCA1/2 germline mutations in China exhibit distinct characteristics compared to those in Western populations.

Alergológica 2015: A National Survey on Allergic Diseases in the Adult Spanish Population.

BACKGROUND AND OBJETIVE: The frequency of allergic diseases is increasing worldwide, particularly in industrialized countries. From a clinical, management, and public heath perspective, it is important to determine the reasons for consulting an allergist, the distribution by frequency of allergic diseases, and how health care is provided. Objective: Alergológica 2015 was carried out to obtain information on clinical practice in allergy departments in Spain, and compare it with the previous study editions. METHODS: The data cover the year 2014 and the first quarter of 2015. The target sample was 6000 patients seen at public and private centers throughout Spain. A total of 500 allergists were invited to participate. Data were collected on an electronic case report form. Data were compared with the Alergológica surveys for 1992 and 2005 to identify differences. RESULTS: The final study population comprised 2914 patients (mean age 33.6 [18.9] years, 58% women, 17% children), of whom 6.1% were foreign-born. The frequency distribution was as follows: rhinitis, 62%; asthma, 23.4%; drug allergy, 17.7%; urticaria/angioedema, 11.5%; food allergy, 10.4%; contact dermatitis, 4%; atopic dermatitis, 3%; insect venom allergy, 2%. A statistically significant increase was observed between data from 2005 and from 2015 with respect to the prevalence for allergic rhinitis, food allergy and drug hypersensitivity. An increase in the prevalence of a personal history of asthma, rhinitis, conjunctivitis, and eczema/atopic dermatitis were also observed. Besides, the number of relevant allergens in the same patient also increased. Most patients were referred from primary care, although a considerable percentage were referred by ENT specialists and dermatologists. CONCLUSIONS: Increasing trends were observed for allergic rhinitis, drug allergy, and food allergy, and a decreasing trend was observed for asthma. Findings for other diseases remained practically unchanged. Allergic patients are increasingly complex and present with a myriad of atopic manifestations.

Undifferentiated headache: broadening the approach to headache in children and adolescents, with supporting evidence from a nationwide school-based cross-sectional survey in Turkey.

BACKGROUND: Headache is a leading disabler in adults worldwide. In children and adolescents, the same may be true but the evidence is much poorer. It is notable that published epidemiological studies of these age groups have largely ignored headaches not fulfilling any specific set of ICHD criteria, although such headaches appear to be common. A new approach to these is needed: here we introduce, and investigate, a diagnostic category termed "undifferentiated headache" (UdH), defined in young people as recurrent mild-intensity headache of < 1 h's duration. METHODS: We conducted a nationwide cross-sectional survey in 31 schools in six regions of Turkey selected by mixed convenience-based and purposive modified cluster-sampling. A validated, standardised self-completed structured questionnaire was administered by a physician-investigator to entire classes of pupils aged 6-17 years. RESULTS: Of the identified sample of 7889 pupils, 7088 (89.8%) participated. The 1-year prevalence of UdH was 29.2%, of migraine (definite and probable) 26.7%, and of tension-type headache (TTH) (definite and probable) 12.9%. UdH differed with respect to almost all headache features and associated symptoms from both migraine and TTH. Burden of headache and use of acute medication were lower in UdH than in migraine and TTH. Headache yesterday was less common in UdH than migraine (OR 0.32; 95% CI 0.28-0.37) and TTH (OR 0.64; 95% CI 0.56-0.77). Quality of life (QoL) was better in UdH (33.6 ± 5.2) than in migraine (30.3 ± 5.6; p < 0.001) and TTH (32.4 ± 5.3; p < 0.001), but worse than in pupils without headache (35.7 ± 4.7; p < 0.001). CONCLUSIONS: This large nationwide study in Turkey of pupils aged 6-17 years has shown that many children and adolescents have a headache type that does not conform to existing accepted diagnostic criteria. This new diagnostic category of presumably still-evolving headache (undifferentiated headache) is common. UdH differs in almost all measurable respects from both migraine and TTH. Although characterised by mild headaches lasting < 1 h, UdH is associated with significant adverse impact on QoL. Longitudinal cohort studies are needed to evaluate the prognosis of UdH but, meanwhile, recognition of UdH and its distinction from migraine and TTH has implications for epidemiological studies, public-health policy and routine clinical practice.

Respondent-driven sampling for identification of HIV- and HCV-infected people who inject drugs and men who have sex with men in India: A cross-sectional, community-based analysis.

BACKGROUND: A major barrier to achieving ambitious targets for global control of HIV and hepatitis C virus (HCV) is low levels of awareness of infection among key populations such as men who have sex with men (MSM) and people who inject drugs (PWID). We explored the potential of a strategy routinely used for surveillance in these groups, respondent-driven sampling (RDS), to be used as an intervention to identify HIV- and HCV-infected PWID and MSM who are unaware of their status and those who are viremic across 26 Indian cities at various epidemic stages. METHODS AND FINDINGS: Data were collected as part of the baseline assessment of an ongoing cluster-randomized trial. RDS was used to accrue participants at 27 sites (15 PWID sites and 12 MSM sites) selected to reflect varying stages of the HIV epidemic among MSM and PWID in India. A total of 56 seeds recruited a sample of 26,447 persons (approximately 1,000 participants per site) between October 1, 2012, and December 19, 2013. Across MSM sites (n = 11,997), the median age was 25 years and the median number of lifetime male partners was 8. Across PWID sites (n = 14,450), 92.4% were male, the median age was 30 years, and 87.5% reported injection in the prior 6 months. RDS identified 4,051 HIV-infected persons, of whom 2,325 (57.4%) were unaware of their HIV infection and 2,816 (69.5%) were HIV viremic. It also identified 5,777 HCV-infected persons, of whom 5,337 (92.4%) were unaware that they were infected with HCV and 4,728 (81.8%) were viremic. In the overall sample (both MSM and PWID), the prevalence of HIV-infected persons who were unaware of their status increased with sampling depth, from 7.9% in participants recruited in waves 1 through 5 to 12.8% among those recruited in waves 26 and above (p-value for trend < 0.001). The overall detection rate of people unaware of their HIV infection was 0.5 persons per day, and the detection rate of HIV-infected persons with viremia (regardless of their awareness status) was 0.7 per day. The detection rate of HIV viremic individuals was positively associated with underlying HIV prevalence and the prevalence of HIV viremia (linear regression coefficient per 1-percentage-point increase in prevalence: 0.05 and 0.07, respectively). The median detection rate of PWID who were unaware of their HCV infection was 2.5 per day. The cost of identifying 1 unaware HIV-infected individual ranged from US$51 to US$2,072 across PWID sites and from US$189 to US$5,367 across MSM sites. The mean additional cost of identifying 1 unaware HCV-infected PWID was US$13 (site range: US$7-US$140). Limitations of the study include the exclusivity of study sites to India, lack of prior HIV/HCV diagnosis confirmation with clinic records, and lack of cost data from other case-finding approaches commonly used in India. CONCLUSIONS: In this study, RDS was able to rapidly identify at nominal cost a substantial number of unaware and viremic HIV-infected and HCV-infected individuals who were currently not being reached by existing programs and who were at high risk for transmission. Combining RDS (or other network-driven recruitment approaches) with strategies focused on linkage to care, particularly in high-burden settings, may be a viable option for achieving the 90-90-90 targets in key populations in resource-limited settings.