Critical appraisal of the CLSI guideline EP09c "measurement procedure comparison and bias estimation using patient samples".

BACKGROUND: In laboratory setting evaluating the agreement between two measurement methods is a very frequent practice. Unfortunately, the guidelines to refer to are not free from criticisms from a statistical methodological point of view. We reviewed the Clinical and Laboratory Standards Institute guideline EP09c, 3rd ed. pointing out some drawbacks and some aspects that have not been well defined, leaving situations of uncertainty and/or of excessive subjectivity in the judgement. CONTENT: We have stressed the need of having replicates to estimate the systematic and the proportional biases of the measurement methods to be compared. Indeed, unequal variance of the two measurement methods gives a slope and intercept of the regression between the difference and the mean of the two values of the measurement methods to be compared that can be absolutely calculated from their means, their variances and their correlation coefficient. So, it is not possible to disentangle true from spurious biases. For laboratory professionals we have developed a worked exemplification of an agreement assessment. SUMMARY: We have stressed the need of other approaches than the classic Bland and Altman method to calculate the systematic and proportional biases of two measurement methods compared for their agreement in a study with replicates.

The progression trajectory of Bipolar Disorder: results from the application of a staging model over a ten-year observation.

BACKGROUND: Trying to better define Bipolar Disorder (BD) progression, different staging models have been conceptualized, each one emphasizing different aspects of illness. In a previous article we retrospectively applied the main staging models to a sample of 100 bipolar patients at four time points over a ten-year observation. In the present study, focusing on Kupka & Hillegers's model, we aimed to assess the transition of the same sample through the different stages of illness and to explore the potential role of clinical variables on the risk of progression. METHODS: Multistate Model using the mstate package in R and Markov model with stratified hazards were used for statistical analysis. RESULTS: A high hazard of transition from stage 2 to 3 emerged, with a probability of staying in stage 2 decreasing to 14 % after 3 years. BD II was significantly associated with transition from stage 1 to 2, whereas the number of lifetime episodes >3 and the elevated predominant polarity with transition from stage 3 to 4. CONCLUSION: Our results corroborated the evidence on BD progression and contributed to outline its trajectory over time. Further effort may help to define a standardized staging approach towards ever increasing tailored interventions.

Predictors of Nursing Home Placement in a Cohort of European People with Alzheimer's Disease and Other Dementia Cases Enrolled in SCU-B or Non SCU-B Centers: The RECage Study.

Background: Nursing home placement (NHP) can be the final step of patients with Alzheimer's disease. Objective: We aimed to identify NHP predictors among 508 people with dementia with a 3-year follow-up. Methods: We analyzed data from the international observational RECage study, involving 508 people with especially Alzheimer's disease and comparing a cohort enrolled by five centers with a Special Care Unit for BPSD (behavioral and psychological symptoms of dementia) and another one enrolled by six centers lacking this facility. The tertiary objective of the study was to assess the possible role of the SCU-B in delaying NHP. We assessed the relationship of the baseline characteristics with NHP by means of univariate analysis followed by Cox's multivariate model. Results: Patients' mean age was 78.1 years, 54.9% were women. Diagnosis mean age was 75.4 (±8.32) years; the main diagnosis was Alzheimer's disease (296; 58.4%). During follow-up, 96 (18.9%) patients died and 153 (30.1%) were institutionalized without a statistically significant difference between the two cohorts (p = 0.9626). The mean NHP time was 902 (95% CI: 870-934). The multivariable analysis without death as a competing risk retained four independent predictors of NHP: age increase (hazard ratio (HR) = 1.023, 95% CI: 1.000-1.046), patient education level increase (HR = 1.062, 95% CI: 1.024-1.101), Neuropsychiatric Inventory total increase (HR = 1.018; 95% CI: 1.011-1.026), and total Mini-Mental State Examination as a favorable factor (HR = 0.948, 95% CI: 0.925-0.971). Gender (females versus males: HR = 1.265, 95% CI: 0.899-1.781) was included in the final Cox's model for adjusting the estimates for. Conclusions: Our data partially agree with the predictors of NHP in literature including the effect of high education level. No caregivers' factors were statistically significant. Clinical trial registration: NCT03507504.

Utility, acceptability and applicability of a nucleic acid amplification test in comparison with a syndromic approach in the management of sexually transmitted diseases at Mulago National Referral Hospital in Uganda (ASTRHA): protocol for an open-label, randomised controlled trial.

INTRODUCTION: Sexually transmitted diseases (STDs) are a major cause of long-term disability. Urethral discharge syndrome (UDS), abnormal vaginal discharge (AVD) and genital ulcer disease (GUD) are very common in low-income and middle-income countries (LMICs), where, due to lack of resources, these infections are managed according to a syndromic approach. Although microbiological diagnosis using nuclear acid amplification tests (NAAT) is already a standard to prescribe targeted treatments in industrialised countries, no randomised clinical trials have been conducted to evaluate clinical usefulness and acceptability of NAAT in comparison with syndromic approach in LMICs. The results of this study could inform diagnostic guidelines since they may suggest an update of the current recommendation if microbiological diagnosis using NAAT in the management of STD is demonstrated to be both useful and acceptable in an LMIC context. METHODS AND ANALYSIS: The primary objective of this randomised, open-label trial is to evaluate the clinical usefulness of a NAAT and its acceptability in comparison with a clinical syndromic approach and to explore whether this test could replace the syndromic approach in the management of STDs at a national referral hospital in Uganda. 220 patients presenting to the STD clinic at Mulago Hospital in Kampala, Uganda with AVD, UDS or GUD will be randomised to either standard of care (syndromic management) or NAAT-based treatment with a 1:1 ratio. All the patients will be asked to return after 2 or 3 weeks for a control visit. Primary outcome will be therapeutic appropriateness. ETHICS AND DISSEMINATION: This trial was approved by the Mulago Hospital Research and Ethical Committee (MHREC2023-97) and the Uganda National Council for Science and Technology (HS31000ES). Patients will give informed consent to participate before taking part in the study. Results will be published in peer-reviewed journals in open-access formats and data made available in anonymised form. TRIAL REGISTRATION NUMBER: NCT05994495.