External validation of a minimal-resource model to predict reduced estimated glomerular filtration rate in people with type 2 diabetes without diagnosis of chronic kidney disease in Mexico: a comparison between country-level and regional performance.

Background: Patients with type 2 diabetes are at an increased risk of chronic kidney disease (CKD) hence it is recommended that they receive annual CKD screening. The huge burden of diabetes in Mexico and limited screening resource mean that CKD screening is underperformed. Consequently, patients often have a late diagnosis of CKD. A regional minimal-resource model to support risk-tailored CKD screening in patients with type 2 diabetes has been developed and globally validated. However, population heath and care services between countries within a region are expected to differ. The aim of this study was to evaluate the performance of the model within Mexico and compare this with the performance demonstrated within the Americas in the global validation. Methods: We performed a retrospective observational study with data from primary care (Clinic Specialized in Diabetes Management in Mexico City), tertiary care (Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán) and the Mexican national survey of health and nutrition (ENSANUT-MC 2016). We applied the minimal-resource model across the datasets and evaluated model performance metrics, with the primary interest in the sensitivity and increase in the positive predictive value (PPV) compared to a screen-everyone approach. Results: The model was evaluated on 2510 patients from Mexico (primary care: 1358, tertiary care: 735, ENSANUT-MC: 417). Across the Mexico data, the sensitivity was 0.730 (95% CI: 0.689 - 0.779) and the relative increase in PPV was 61.0% (95% CI: 52.1% - 70.8%). These were not statistically different to the regional performance metrics for the Americas (sensitivity: p=0.964; relative improvement: p=0.132), however considerable variability was observed across the data sources. Conclusion: The minimal-resource model performs consistently in a representative Mexican population sample compared with the Americas regional performance. In primary care settings where screening is underperformed and access to laboratory testing is limited, the model can act as a risk-tailored CKD screening solution, directing screening resources to patients who are at highest risk.

Diagnosis codes underestimate chronic kidney disease incidence compared with eGFR-based evidence: a retrospective observational study of patients with type 2 diabetes in UK primary care.

BACKGROUND: Type two diabetes (T2D) is a leading cause of both chronic kidney disease (CKD) and onward progression to end-stage renal disease. Timely diagnosis coding of CKD in patients with T2D could lead to improvements in quality of care and patient outcomes. AIM: To assess the consistency between estimated glomerular filtration rate (eGFR)-based evidence of CKD and CKD diagnosis coding in UK primary care. DESIGN & SETTING: A retrospective analysis of electronic health record data in a cohort of people with T2D from 60 primary care centres within England between 2012 and 2022. METHOD: We estimated the incidence rate of CKD per 100 person-years using eGFR-based CKD and diagnosis codes. Logistic regression was applied to establish which attributes were associated with diagnosis coding. Time from eGFR-based CKD to entry of a diagnosis code was summarised using the median and interquartile range. RESULTS: The overall incidence of CKD was 2.32 (95% confidence interval [CI] = 2.24 to 2.41) and significantly higher for eGFR-based criteria than diagnosis codes: 1.98 (95% CI = 1.90 to 2.05) versus 1.06 (95% CI = 1.00 to 1.11), respectively; P<0.001. Only 45.4% of CKD incidences identified using eGFR-based criteria had a corresponding diagnosis code. Patients who were younger, had a higher CKD stage (G4), had an observed urine albumin-to-creatinine ratio (A1), or no observed HbA1c in the past year were more likely to have a diagnosis code. CONCLUSION: Diagnosis coding of patients with eGFR-based evidence of CKD in UK primary care is poor within patients with T2D, despite CKD being a well-known complication of diabetes.

Imputation and missing indicators for handling missing data in the development and deployment of clinical prediction models: A simulation study.

Background: In clinical prediction modelling, missing data can occur at any stage of the model pipeline; development, validation or deployment. Multiple imputation is often recommended yet challenging to apply at deployment; for example, the outcome cannot be in the imputation model, as recommended under multiple imputation. Regression imputation uses a fitted model to impute the predicted value of missing predictors from observed data, and could offer a pragmatic alternative at deployment. Moreover, the use of missing indicators has been proposed to handle informative missingness, but it is currently unknown how well this method performs in the context of clinical prediction models. Methods: We simulated data under various missing data mechanisms to compare the predictive performance of clinical prediction models developed using both imputation methods. We consider deployment scenarios where missing data is permitted or prohibited, imputation models that use or omit the outcome, and clinical prediction models that include or omit missing indicators. We assume that the missingness mechanism remains constant across the model pipeline. We also apply the proposed strategies to critical care data. Results: With complete data available at deployment, our findings were in line with existing recommendations; that the outcome should be used to impute development data when using multiple imputation and omitted under regression imputation. When missingness is allowed at deployment, omitting the outcome from the imputation model at the development was preferred. Missing indicators improved model performance in many cases but can be harmful under outcome-dependent missingness. Conclusion: We provide evidence that commonly taught principles of handling missing data via multiple imputation may not apply to clinical prediction models, particularly when data can be missing at deployment. We observed comparable predictive performance under multiple imputation and regression imputation. The performance of the missing data handling method must be evaluated on a study-by-study basis, and the most appropriate strategy for handling missing data at development should consider whether missing data are allowed at deployment. Some guidance is provided.

Development of minimal resource pre-screening tools for chronic kidney disease in people with type 2 diabetes.

Regular chronic kidney disease (CKD) screening can facilitate earlier diagnosis of CKD and preventative action to reduce the risk of CKD progression. People with type 2 diabetes are at a higher risk of developing CKD; hence, it is recommended that they undergo annual screening. However, resources may be limited, particularly in lower-to-middle income countries, and those at the highest risk of having an abnormal CKD screening result should be prioritised for screening. We have developed models to determine which patients are at a high risk of renal impairment. We have shown that, for people with type 2 diabetes and no previous diagnosis of CKD stage 3-5, it is possible to use age, gender, body mass index, duration of type 2 diabetes and blood pressure information to detect those at a higher risk of a reduced glomerular filtration rate. When blood measurements are available, triglyceride and cholesterol measurements can be used to improve the estimate of the risk. Even though risk factors were associated with an increased urine albumin:creatinine ratio, we found no clinical benefit of using the model over a screen-all approach.

Informative presence and observation in routine health data: A review of methodology for clinical risk prediction.

OBJECTIVE: Informative presence (IP) is the phenomenon whereby the presence or absence of patient data is potentially informative with respect to their health condition, with informative observation (IO) being the longitudinal equivalent. These phenomena predominantly exist within routinely collected healthcare data, in which data collection is driven by the clinical requirements of patients and clinicians. The extent to which IP and IO are considered when using such data to develop clinical prediction models (CPMs) is unknown, as is the existing methodology aiming at handling these issues. This review aims to synthesize such existing methodology, thereby helping identify an agenda for future methodological work. MATERIALS AND METHODS: A systematic literature search was conducted by 2 independent reviewers using prespecified keywords. RESULTS: Thirty-six articles were included. We categorized the methods presented within as derived predictors (including some representation of the measurement process as a predictor in the model), modeling under IP, and latent structures. Including missing indicators or summary measures as predictors is the most commonly presented approach amongst the included studies (24 of 36 articles). DISCUSSION: This is the first review to collate the literature in this area under a prediction framework. A considerable body relevant of literature exists, and we present ways in which the described methods could be developed further. Guidance is required for specifying the conditions under which each method should be used to enable applied prediction modelers to use these methods. CONCLUSIONS: A growing recognition of IP and IO exists within the literature, and methodology is increasingly becoming available to leverage these phenomena for prediction purposes. IP and IO should be approached differently in a prediction context than when the primary goal is explanation. The work included in this review has demonstrated theoretical and empirical benefits of incorporating IP and IO, and therefore we recommend that applied health researchers consider incorporating these methods in their work.

Toward a framework for the design, implementation, and reporting of methodology scoping reviews.

BACKGROUND AND OBJECTIVE: In view of the growth of published articles, there is an increasing need for studies that summarize scientific research. An increasingly common review is a "methodology scoping review," which provides a summary of existing analytical methods, techniques and software that have been proposed or applied in research articles to address an analytical problem or further an analytical approach. However, guidelines for their design, implementation, and reporting are limited. METHODS: Drawing on the experiences of the authors, which were consolidated through a series of face-to-face workshops, we summarize the challenges inherent in conducting a methodology scoping review and offer suggestions of best practice to promote future guideline development. RESULTS: We identified three challenges of conducting a methodology scoping review. First, identification of search terms; one cannot usually define the search terms a priori, and the language used for a particular method can vary across the literature. Second, the scope of the review requires careful consideration because new methodology is often not described (in full) within abstracts. Third, many new methods are motivated by a specific clinical question, where the methodology may only be documented in supplementary materials. We formulated several recommendations that build upon existing review guidelines. These recommendations ranged from an iterative approach to defining search terms through to screening and data extraction processes. CONCLUSION: Although methodology scoping reviews are an important aspect of research, there is currently a lack of guidelines to standardize their design, implementation, and reporting. We recommend a wider discussion on this topic.

Missing data should be handled differently for prediction than for description or causal explanation.

Missing data are much studied in epidemiology and statistics. Theoretical development and application of methods for handling missing data have mostly been conducted in the context of prospective research data and with a goal of description or causal explanation. However, it is now common to build predictive models using routinely collected data, where missing patterns may convey important information, and one might take a pragmatic approach to optimizing prediction. Therefore, different methods to handle missing data may be preferred. Furthermore, an underappreciated issue in prediction modeling is that the missing data method used in model development may not match the method used when a model is deployed. This may lead to overoptimistic assessments of model performance. For prediction, particularly with routinely collected data, methods for handling missing data that incorporate information within the missingness pattern should be explored and further developed. Where missing data methods differ between model development and model deployment, the implications of this must be explicitly evaluated. The trade-off between building a prediction model that is causally principled, and building a prediction model that maximizes the use of all available information, should be carefully considered and will depend on the intended use of the model.

Effect of Low-Sodium versus Conventional Sodium Dialysate on Left Ventricular Mass in Home and Self-Care Satellite Facility Hemodialysis Patients: A Randomized Clinical Trial.

BACKGROUND: Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality. There is a global trend to lower dialysate sodium with the goal of reducing fluid overload. METHODS: To investigate whether lower dialysate sodium during hemodialysis reduces left ventricular mass, we conducted a randomized trial in which patients received either low-sodium dialysate (135 mM) or conventional dialysate (140 mM) for 12 months. We included participants who were aged >18 years old, had a predialysis serum sodium ≥135 mM, and were receiving hemodialysis at home or a self-care satellite facility. Exclusion criteria included hemodialysis frequency >3.5 times per week and use of sodium profiling or hemodiafiltration. The main outcome was left ventricular mass index by cardiac magnetic resonance imaging. RESULTS: The 99 participants had a median age of 51 years old; 67 were men, 31 had diabetes mellitus, and 59 had left ventricular hypertrophy. Over 12 months of follow-up, relative to control, a dialysate sodium concentration of 135 mmol/L did not change the left ventricular mass index, despite significant reductions at 6 and 12 months in interdialytic weight gain, in extracellular fluid volume, and in plasma B-type natriuretic peptide concentration (ratio of intervention to control). The intervention increased intradialytic hypotension (odds ratio [OR], 7.5; 95% confidence interval [95% CI], 1.1 to 49.8 at 6 months and OR, 3.6; 95% CI, 0.5 to 28.8 at 12 months). Five participants in the intervention arm could not complete the trial because of hypotension. We found no effect on health-related quality of life measures, perceived thirst or xerostomia, or dietary sodium intake. CONCLUSIONS: Dialysate sodium of 135 mmol/L did not reduce left ventricular mass relative to control, despite improving fluid status. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: The Australian New Zealand Clinical Trials Registry, ACTRN12611000975998.

The Association Between Hearing Impairment and Problem Behaviors in 11-Year-Old Pacific Children Living in New Zealand.

OBJECTIVES: Hearing impairment in childhood is a serious disability that can impose a heavy social and economic burden on individuals and families. It was hypothesized that hearing loss or middle ear disease in 11-year-old Pacific children living in New Zealand would be associated with higher levels of engagement in (1) delinquent behaviors, and (2) clinical level internalizing and externalizing problem behaviors than Pacific children with no hearing loss or middle ear disease. Based on earlier findings, peer pressure, self-perception, physical punishment (slapping), sex, and ethnicity were controlled for in the association between hearing difficulties and behavioral outcomes. DESIGN: In the school setting, pure-tone audiometry and immittance audiometry assessments were used to establish the hearing level in 11-year-old Pacific children (n = 920). These children also completed multidisciplinary questionnaires, which included questions about involvement in delinquent behaviors, peer pressure, and self-perception. In the home setting, maternal reports were gathered on internalizing and externalizing problem behaviors in their offspring, their parenting style, and sociodemographic details. RESULTS: A significant effect of hearing level was detected for the odds of reporting mild delinquency versus no delinquency (odds ratio: 1.02, 95% CI: 1.00 to 1.05), and odds of moderate delinquency versus no delinquency (odds ratio: 0.97, 95% CI: 0.94 to 1.00). No significant effect was detected for hearing level and severe delinquency or internalizing or externalizing behavioral problems in the clinical range. Middle ear disease (abnormal tympanogram in the worse ear) was not significantly associated with delinquency at any level or with internalizing behaviors in the clinical range. However, children with middle ear disease were significantly less likely than all other participants to exhibit disruptive externalizing behavior in the clinical range. CONCLUSIONS: Relatively young children with hearing loss reported engagement in moderate levels of delinquency that represent serious antisocial and potentially violent acts. This finding provides evidence of the significant effect that hearing loss has on child behavior. This association between hearing loss and moderate delinquency requires ethnic-specific interventions that are targeted for maximum benefit at appropriate times in childhood to mitigate potentially long-term health, educational, and behavioral risks.

Integrating health, education and culture in predicting Pacific children's English receptive vocabulary at 6 years: A classification tree approach.

AIM: Pacific children fare poorly on health and educational outcomes, including literacy. Early interventions are considered critical in reducing educational disparities. A prediction model was constructed to analyse the factors associated with Pacific children's English receptive vocabulary, an important component of English language development. METHODS: A birth cohort study of Pacific children was used to construct a classification tree model and predict the proportions of Pacific children who performed strongly in a standardised test of English receptive vocabulary at 6 years of age (n = 1019). Classification trees were constructed using 10-fold cross-validation (CV) and pruned using the one-standard-error rule. Prediction errors were directly estimated using leave-one-out CV. RESULTS: Analyses of misclassification errors from the pruned model gave false negative and positive rates of 19 and 19% from re-substitution and 54 and 21% from leave-one-out CV estimation, respectively. Of the predictors, maternal acculturation, small birthweight and performance in early developmental screening test at 4 years of age were found to have the highest goodness of split. CONCLUSIONS: The cultural environment to which Pacific children were exposed in early childhood, indicated by the maternal acculturation, was more crucial in distinguishing children with strong English-receptive vocabulary skills than socio-economic or prenatal conditions. This highlights the importance of integrating the cultural environment into designing measures for facilitating Pacific children's language development.

Vitamin D3 supplementation in adults with bronchiectasis: A pilot study.

Vitamin D supplementation prevents acute respiratory infections and, through modulating innate and adaptive immunity, could have a potential role in bronchiectasis management. The primary aims of this pilot study were to assess serum 25-hydroxyvitamin D (25(OH)D) levels in New Zealand adults with bronchiectasis, and their 25(OH)D levels after vitamin D3 supplementation. Adults with bronchiectasis received an initial 2.5 mg vitamin D3 oral loading dose and 0.625 mg vitamin D3 weekly for 24 weeks. The primary outcome was serum 25(OH)D levels before and after vitamin D3 supplementation. Secondary outcomes (time to first infective exacerbation, exacerbation frequency, spirometry, health-related quality of life measures, sputum bacteriology and cell counts and chronic rhinosinusitis) were also assessed. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12612001222831). The initial, average 25(OH)D level was 71 nmol/L (95% confidence interval (CI): [58, 84]), rising to 218 nmol/L (95% CI: [199, 237]) at 12 weeks and 205 nmol/L (95% CI: [186, 224]) at 24 weeks. The initial serum cathelicidin level was 25 nmol/L (95% CI: [17, 33]), rising to 102 nmol/L (95% CI: [48, 156]) at 12 weeks and 151 nmol/L (95% CI: [97, 205]) at 24 weeks. Over the 24-week study period, we observed statistically significant changes of 1.11 (95% CI: [0.08, 2.14]) in the Leicester Cough Questionnaire and -1.97 (95% CI: [-3.71, -0.23]) in the Dartmouth COOP charts score. No significant adverse effects were recorded. Many New Zealand adults with bronchiectasis have adequate 25(OH)D levels. Weekly vitamin D3 supplementation significantly improved 25(OH)D levels.

Efficacy of a Web-Based Safety Decision Aid for Women Experiencing Intimate Partner Violence: Randomized Controlled Trial.

BACKGROUND: Intimate partner violence (IPV) is a human rights violation and leading health burden for women. Safety planning is a hallmark of specialist family violence intervention, yet only a small proportion of women access formal services. A Web-based safety decision aid may reach a wide audience of women experiencing IPV and offer the opportunity to prioritize and plan for safety for themselves and their families. OBJECTIVE: The aim of this study was to test the efficacy of a Web-based safety decision aid (isafe) for women experiencing IPV. METHODS: We conducted a fully automated Web-based two-arm parallel randomized controlled trial (RCT) in a general population of New Zealand women who had experienced IPV in the past 6 months. Computer-generated randomization was based on a minimization scheme with stratification by severity of violence and children. Women were randomly assigned to the password-protected intervention website (safety priority setting, danger assessment, and tailored action plan components) or control website (standard, nonindividualized information). Primary endpoints were self-reported mental health (Center for Epidemiologic Studies Depression Scale-Revised, CESD-R) and IPV exposure (Severity of Violence Against Women Scale, SVAWS) at 12-month follow-up. Analyses were by intention to treat. RESULTS: Women were recruited from September 2012 to September 2014. Participants were aged between 16 and 60 years, 27% (111/412) self-identified as Maori (indigenous New Zealand), and 51% (210/412) reported at baseline that they were unsure of their future plans for their partner relationship. Among the 412 women recruited, retention at 12 months was 87%. The adjusted estimated intervention effect for SVAWS was -12.44 (95% CI -23.35 to -1.54) for Maori and 0.76 (95% CI -5.57 to 7.09) for non-Maori. The adjusted intervention effect for CESD-R was -7.75 (95% CI -15.57 to 0.07) for Maori and 1.36 (-3.16 to 5.88) for non-Maori. No study-related adverse events were reported. CONCLUSIONS: The interactive, individualized Web-based isafe decision aid was effective in reducing IPV exposure limited to indigenous Maori women. Discovery of a treatment effect in a population group that experiences significant health disparities is a welcome, important finding. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12612000708853; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000708853 (Archived by Webcite at http://www.webcitation/61MGuVXdK).

Distinguishing transient versus stable aspects of depression in New Zealand Pacific Island children using Generalizability Theory.

BACKGROUND: The distinction between temporary versus enduring or state/trait aspects of depression is important. More precise distinction would improve understanding of the aetiology of depression and those aspects most amenable to intervention thus identifying more homogeneous, dynamic targets for clinical trials. Generalizability Theory has been proposed as useful for disentangling state and trait components of psychopathology. METHODS: We applied Generalizability Theory to determine the relative contributions of temporary and enduring aspects of depression in a widely used screening measure of depression the - 10-item Children's Depression Inventory (CDI-10; Kovacs, 1985). Participants were children of Pacific Island descent living in New Zealand (n = 668). Data were collected at ages - 9, 11, and 14 years. RESULTS: The CDI-10 demonstrated acceptable generalizability across occasions (G = 0.79) with about one third of variance in total scores attributed to temporary and two thirds to more enduring aspects of depression. There were no other significant sources of error variance. Two items were identified as more sensitive than the remaining eight to more dynamic symptoms. LIMITATIONS: Studies with briefer test-retest intervals are warranted. Use of this Pacific Island cohort limits generalizability of findings to other cultures and ethnicities. No data were collected on whether participants had received intervention for depression. CONCLUSIONS: While the CDI-10 reliably measures both stable and transient aspects of depression in children, the scale does not permit clear distinction between them. We advocate application of Generalizability Theory for developing state/trait depression measures and determining which existing measures are most suitable for capturing modifiable features of depression.

Participant Recruitment and Engagement in Automated eHealth Trial Registration: Challenges and Opportunities for Recruiting Women Who Experience Violence.

BACKGROUND: Automated eHealth Web-based research trials offer people an accessible, confidential opportunity to engage in research that matters to them. eHealth trials may be particularly useful for sensitive issues when seeking health care may be accompanied by shame and mistrust. Yet little is known about people's early engagement with eHealth trials, from recruitment to preintervention autoregistration processes. A recent randomized controlled trial that tested the effectiveness of an eHealth safety decision aid for New Zealand women in the general population who experienced intimate partner violence (isafe) provided the opportunity to examine recruitment and preintervention participant engagement with a fully automated Web-based registration process. The trial aimed to recruit 340 women within 24 months. OBJECTIVE: The objective of our study was to examine participant preintervention engagement and recruitment efficiency for the isafe trial, and to analyze dropout through the registration pathway, from recruitment to eligibility screening and consent, to completion of baseline measures. METHODS: In this case study, data collection sources included the trial recruitment log, Google Analytics reports, registration and program metadata, and costs. Analysis included a qualitative narrative of the recruitment experience and descriptive statistics of preintervention participant engagement and dropout rates. A Koyck model investigated the relationship between Web-based online marketing website advertisements (ads) and participant accrual. RESULTS: The isafe trial was launched on September 17, 2012. Placement of ads in an online classified advertising platform increased the average number of recruited participants per month from 2 to 25. Over the 23-month recruitment period, the registration website recorded 4176 unique visitors. Among 1003 women meeting eligibility criteria, 51.55% (517) consented to participate; among the 501 women who enrolled (consented, validated, and randomized), 412 (82.2%) were accrued (completed baseline assessments). The majority (n=52, 58%) of the 89 women who dropped out between enrollment and accrual never logged in to the allocated isafe website. Of every 4 accrued women, 3 (314/412, 76.2%) identified the classified ad as their referral source, followed by friends and family (52/412, 12.6%). Women recruited through a friend or relative were more likely to self-identify as indigenous Maori and live in the highest-deprivation areas. Ads increased the accrual rate by a factor of 74 (95% CI 49-112). CONCLUSIONS: Print advertisements, website links, and networking were costly and inefficient methods for recruiting participants to a Web-based eHealth trial. Researchers are advised to limit their recruitment efforts to Web-based online marketplace and classified advertising platforms, as in the isafe case, or to social media. Online classified advertising in "Jobs-Other-volunteers" successfully recruited a diverse sample of women experiencing intimate partner violence. Preintervention recruitment data provide critical information to inform future research and critical analysis of Web-based eHealth trials. CLINICALTRIAL: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12612000708853; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000708853 (Archived by WebCite at http://www.webcitation/6lMGuVXdK).