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This volume is a review of up-to-date methods used in human growth research.

Hypertension is common in China and its prevalence is rising, yet it remains inadequately controlled. Few studies have the capacity to characterise the epidemiology and management of hypertension across many heterogeneous subgroups. We did a study of the prevalence, awareness, treatment, and control of hypertension in China and assessed their variations across many subpopulations. We made use of data generated in the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project from Sept 15, 2014, to June 20, 2017, a population-based screening project that enrolled around 1·7 million community-dwelling adults aged 35–75 years from all 31 provinces in mainland China. In this population, we defined hypertension as systolic blood pressure of at least 140 mm Hg, or diastolic blood pressure of at least 90 mm Hg, or self-reported antihypertensive medication use in the previous 2 weeks. Hypertension awareness, treatment, and control were defined, respectively, among hypertensive adults as a self-reported diagnosis of hypertension, current use of antihypertensive medication, and blood pressure of less than 140/90 mm Hg. We assessed awareness, treatment, and control in 264 475 population subgroups—defined a priori by all possible combinations of 11 demographic and clinical factors (age [35–44, 45–54, 55–64, and 65–75 years], sex [men and women], geographical region [western, central, and eastern China], urbanity [urban vs rural], ethnic origin [Han and non-Han], occupation [farmer and non-farmer], annual household income [< ¥10 000, ¥10 000–50 000, and ≥¥50 000], education [primary school and below, middle school, high school, and college and above], previous cardiovascular events [yes or no], current smoker [yes or no], and diabetes [yes or no]), and their associations with individual and primary health-care site characteristics, using mixed models. The sample contained 1 738 886 participants with a mean age of 55·6 years (SD 9·7), 59·5% of whom were women. 44·7% (95% CI 44·6–44·8) of the sample had hypertension, of whom 44·7% (44·6–44·8) were aware of their diagnosis, 30·1% (30·0–30·2) were taking prescribed antihypertensive medications, and 7·2% (7·1–7·2) had achieved control. The age-standardised and sex-standardised rates of hypertension prevalence, awareness, treatment, and control were 37·2% (37·1–37·3), 36·0% (35·8–36·2), 22·9% (22·7–23·0), and 5·7% (5·6–5·7), respectively. The most commonly used medication class was calcium-channel blockers (55·2%, 55·0–55·4). Among individuals whose hypertension was treated but not controlled, 81·5% (81·3–81·6) were using only one medication. The proportion of participants who were aware of their hypertension and were receiving treatment varied significantly across subpopulations; lower likelihoods of awareness and treatment were associated with male sex, younger age, lower income, and an absence of previous cardiovascular events, diabetes, obesity, or alcohol use (all p<0·01). By contrast, control rate was universally low across all subgroups (<30·0%). Among Chinese adults aged 35–75 years, nearly half have hypertension, fewer than a third are being treated, and fewer than one in twelve are in control of their blood pressure. The low number of people in control is ubiquitous in all subgroups of the Chinese population and warrants broad-based, global strategy, such as greater efforts in prevention, as well as better screening and more effective and affordable treatment. Ministry of Finance and National Health and Family Planning Commission, China.

Background In southern Europe, the risk of cancer in patients with end-stage kidney disease receiving dialysis has not been well quantified. The aim of this study was to assess the overall pattern of risk for de novo malignancies (DNMs) among dialysis patients in the Friuli Venezia Giulia region, north-eastern Italy. Methods A population-based cohort study among 3407 dialysis patients was conducted through a record linkage between local healthcare databases and the cancer registry (1998–2013). Person-years (PYs) were calculated from 30 days after the date of first dialysis to the date of DNM diagnosis, kidney transplant, death, last follow-up or December 31, 2013, whichever came first. The risk of DNM, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Results During 10,798 PYs, 357 DNMs were diagnosed in 330 dialysis patients. A higher than expected risk of 1.3-fold was found for all DNMs combined (95% CI: 1.15–1.43). The risk was particularly high in younger dialysis patients (SIR = 1.88, 95% CI: 1.42–2.45 for age 40–59 years), and it decreased with age. Moreover, significantly increased DNM risks emerged during the first 3 years since dialysis initiation, especially within the first year (SIR = 8.52, 95% CI: 6.89–10.41). Elevated excess risks were observed for kidney (SIR = 3.18; 95% CI: 2.06–4.69), skin non-melanoma (SIR = 1.81, 95% CI: 1.46–2.22), oral cavity (SIR = 2.42, 95% CI: 1.36–4.00), and Kaposi’s sarcoma (SIR = 10.29, 95% CI: 1.25–37.16). Conclusions The elevated risk for DNM herein documented suggest the need to implement a targeted approach to cancer prevention and control in dialysis patients.

We evaluated the incidence, outcomes, and causative agents of bloodstream infections (BSI) in Finland during 2004–2018 by using data from the national registries. We identified a total of 173,715 BSIs; annual incidence increased from 150 to 309 cases/100,000 population. BSI incidence rose most sharply among persons >80 years of age. The 1-month case-fatality rate decreased from 13.0% to 12.6%, but the 1-month all-cause mortality rate rose from 20 to 39 deaths/100,000 population. BSIs caused by Escherichia coli increased from 26% to 30% of all BSIs. BSIs caused by multidrug-resistant microbes rose from 0.4% to 2.8%, mostly caused by extended-spectrum β-lactamase-producing E. coli. We observed an increase in community-acquired BSIs, from 67% to 78%. The proportion of patients with severe underlying conditions rose from 14% to 23%. Additional public health and healthcare prevention efforts are needed to curb the increasing trend in community-acquired BSIs and antimicrobial drug–resistant E. coli.

BackgroundAccurate knowledge of the relationship between craniofacial anomalies (CFA), intellectual disability (ID) and autism spectrum disorder (ASD) is essential to improve services and outcomes. The aim is to describe the association between CFA, ID and ASD using linked population data.MethodsAll births (1983–2005; n = 566,225) including CFA births (comprising orofacial clefts, craniosynostosis, craniofacial microsomia and mandibulofacial dysostosis) surviving to 5 years were identified from the birth, death, birth defects and midwives population data sets. Linked data from these data sets were followed for a minimum of 5 years from birth until 2010 in the intellectual disability database to identify ID and ASD. These associations were examined using a modified Poisson regression.ResultsPrevalence of ID and ASD was higher among CFA (especially with additional anomalies) than those without [prevalence ratio 5.27, 95% CI 4.44, 6.25]. It was higher among CFA than those with other gastrointestinal and urogenital anomalies but lower than nervous system and chromosomal anomalies. Children with CFA and severe ID had a higher proportion of nervous system anomalies.ConclusionsFindings indicate increased ID and ASD among CFA but lower than nervous system and chromosomal anomalies. This population evidence can improve early identification of ID/ASD among CFA and support service planning.ImpactOur study found about one in ten children born with craniofacial anomalies (CFA) are later identified with intellectual disability (ID).Prevalence of ID among CFA was higher than those with other gastrointestinal, urogenital, and musculoskeletal birth defects but lower than those with the nervous system and chromosomal abnormalities.Most children with craniofacial anomalies have a mild-to-moderate intellectual disability with an unknown aetiology.On average, intellectual disability is identified 2 years later for children born with non-syndromic craniofacial anomalies than those with syndromic conditions.Our findings can improve the early identification of ID/ASD among CFA and support service planning.

Background The current study evaluated the hypothesis that the COVID-19 pandemic is associated with higher stillbirth but lower neonatal mortality rates. Methods We compared three epochs: baseline (2016–2019, January–December, weeks 1–52, and 2020, January–February, weeks 1–8), initial pandemic (2020, March–December, weeks 9–52, and 2021, January–June, weeks 1–26), and delta pandemic (2021, July–September, weeks 27–39) periods, using Alabama Department of Public Health database including deliveries with stillbirths ≥20 weeks or live births ≥22 weeks gestation. The primary outcomes were stillbirth and neonatal mortality rates. Results A total of 325,036 deliveries were included (236,481 from baseline, 74,076 from initial pandemic, and 14,479 from delta pandemic period). The neonatal mortality rate was lower in the pandemic periods (4.4 to 3.5 and 3.6/1000 live births, in the baseline, initial, and delta pandemic periods, respectively, p  < 0.01), but the stillbirth rate did not differ (9 to 8.5 and 8.6/1000 births, p  = 0.41). On interrupted time-series analyses, there were no significant changes in either stillbirth ( p  = 0.11 for baseline vs. initial pandemic period, and p  = 0.67 for baseline vs. delta pandemic period) or neonatal mortality rates ( p  = 0.28 and 0.89, respectively). Conclusions The COVID-19 pandemic periods were not associated with a significant change in stillbirth and neonatal mortality rates compared to the baseline period. Impact The COVID-19 pandemic could have resulted in changes in fetal and neonatal outcomes. However, only a few population-based studies have compared the risk of fetal and neonatal mortality in the pandemic period to the baseline period. This population-based study identifies the changes in fetal and neonatal outcomes during the initial and delta COVID-19 pandemic period as compared to the baseline period. The current study shows that stillbirth and neonatal mortality rates were not significantly different in the initial and delta COVID-19 pandemic periods as compared to the baseline period.

ObjectiveTo determine whether adverse childhood experiences were associated with weight gain and obesity risk in adolescence.MethodsWe analyzed data from 6942 adolescents followed between 9 and 13 years of age in the Growing Up in Ireland cohort study. The main exposures were 14 adverse childhood experiences, 4 of which were included in the Adverse Childhood Experience (ACE) study. The primary outcome was incident overweight and obesity at 13 years. Secondary outcomes included prevalent overweight/obesity and weight gain.ResultsMore than 75% of the youth experienced an adverse experience and 17% experienced an ACE-specific experience before 9 years. At 13 years, 48% were female and 31.4% were overweight or obese. After adjusting for confounding, exposure to any adverse experience was associated with prevalent overweight/obesity (aOR: 1.56; 1.19–2.05) and incident overweight/obesity (adjusted IRR: 2.15; 95% CI: 1.37–3.39), while exposure to an ACE-specific exposure was associated weight gain (BMI Z score change = 0.202; 95% CI: 0.100–0.303). A significant interaction between income and adverse childhood experiences was observed for both incident overweight/obesity and weight gain (BMI Z change: −0.046; 95% CI: −0.092 to 0.000).ConclusionsAdverse childhood experiences and low income interact and independently predict obesity risk in early adolescence.

Background There are no early, accurate, scalable methods for identifying infants at high risk of poor cognitive outcomes in childhood. We aim to develop an explainable predictive model, using machine learning and population-based cohort data, for this purpose. Methods Data were from 8858 participants in the Growing Up in Ireland cohort, a nationally representative study of infants and their primary caregivers (PCGs). Maternal, infant, and socioeconomic characteristics were collected at 9-months and cognitive ability measured at age 5 years. Data preprocessing, synthetic minority oversampling, and feature selection were performed prior to training a variety of machine learning models using ten-fold cross validated grid search to tune hyperparameters. Final models were tested on an unseen test set. Results A random forest (RF) model containing 15 participant-reported features in the first year of infant life, achieved an area under the receiver operating characteristic curve (AUROC) of 0.77 for predicting low cognitive ability at age 5. This model could detect 72% of infants with low cognitive ability, with a specificity of 66%. Conclusions Model performance would need to be improved before consideration as a population-level screening tool. However, this is a first step towards early, individual, risk stratification to allow targeted childhood screening. Impact This study is among the first to investigate whether machine learning methods can be used at a population-level to predict which infants are at high risk of low cognitive ability in childhood. A random forest model using 15 features which could be easily collected in the perinatal period achieved an AUROC of 0.77 for predicting low cognitive ability. Improved predictive performance would be required to implement this model at a population level but this may be a first step towards early, individual, risk stratification.

Background Adequate cytology is limited by insufficient cytologists in a large‐scale cervical cancer screening. We aimed to develop an artificial intelligence (AI)‐assisted cytology system in cervical cancer screening program. Methods We conducted a perspective cohort study within a population‐based cervical cancer screening program for 0.7 million women, using a validated AI‐assisted cytology system. For comparison, cytologists examined all slides classified by AI as abnormal and a randomly selected 10% of normal slides. Each woman with slides classified as abnormal by either AI‐assisted or manual reading was diagnosed by colposcopy and biopsy. The outcomes were histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Results Finally, we recruited 703 103 women, of whom 98 549 were independently screened by AI and manual reading. The overall agreement rate between AI and manual reading was 94.7% (95% confidential interval [CI], 94.5%‐94.8%), and kappa was 0.92 (0.91‐0.92). The detection rates of CIN2+ increased with the severity of cytology abnormality performed by both AI and manual reading (Ptrend < 0.001). General estimated equations showed that detection of CIN2+ among women with ASC‐H or HSIL by AI were significantly higher than corresponding groups classified by cytologists (for ASC‐H: odds ratio [OR] = 1.22, 95%CI 1.11‐1.34, P < .001; for HSIL: OR = 1.41, 1.28‐1.55, P < .001). AI‐assisted cytology was 5.8% (3.0%‐8.6%) more sensitive for detection of CIN2+ than manual reading with a slight reduction in specificity. Conclusions AI‐assisted cytology system could exclude most of normal cytology, and improve sensitivity with clinically equivalent specificity for detection of CIN2+ compared with manual cytology reading. Overall, the results support AI‐based cytology system for the primary cervical cancer screening in large‐scale population. This study aims to assess the role of Artificial Intelligence (AI) in the detection of early cervical cancer in a low resource setting. Our results showed that AI‐assisted cytology could identify most of negative cytology, and showed higher positive predictive value for CIN2 or worse when compared with cytologists. This study indicates that AI‐assisted cytology could be very useful tool as a primary screening method in a large‐scale cervical cancer screening program to improve its effectiveness.

Although experience suggests a shift in the epidemiology of spinal cord injury (SCI) toward an older demographic, population studies are lacking. We aimed to evaluate (1) how the epidemiology and age profile of SCI have changed over time, and (2) how increased age impacts health outcomes up to 15 years post-injury. A population-based cohort study was performed in Ontario including adults diagnosed with traumatic SCI between 2002 and 2017. Older and younger SCI cohorts were created based on an age cutoff of 65 years. An older cohort of uninjured persons was matched to the older SCI cohort based on age, gender, and comorbidity status. Changes in crude incidence were reported as average annual percentage change (AAPC). Survival, readmissions, and costs were compared between the older and younger SCI cohorts as well as the between the older SCI and older matched uninjured cohorts. The incidence of SCI increased among females (AAPC 2.2; 95% confidence interval [CI] 0.1, 4.3), driven by a marked rise (4%/year) among elderly females (AAPC 4.3; 95% CI 0.1, 4.3). Although no change in incidence was detected for males, there was a trend toward increased incidence among older males (AAPC 1.2; 95% CI −1.3, 3.8). There were a higher proportion of cervical, incomplete, and fall-related injuries in the older than in younger SCI cohorts. Being over 65 years of age was associated with a sixfold increased risk of death (hazard ratio [HR] 5.75; 95% CI 4.72, 7.00). In comparison with the older uninjured cohort, the older SCI cohort had double the risk of death (HR 2.23; 95% CI 2.00, 2.50). Older persons with SCI had higher odds of readmission and higher costs. The incidence of SCI among the elderly is increasing, particularly among women. Prevention through fall reduction and education to improve outcomes are needed.