In South Africa, stigma, discrimination, social visibility and fear of loss of confidentiality impede health facility-based HIV testing. With 50% of adults having ever tested for HIV in their ...lifetime, private, alternative testing options are urgently needed. Non-invasive, oral self-tests offer a potential for a confidential, unsupervised HIV self-testing option, but global data are limited.
A pilot cross-sectional study was conducted from January to June 2012 in health care workers based at the University of Cape Town, South Africa. An innovative, unsupervised, self-testing strategy was evaluated for feasibility; defined as completion of self-testing process (i.e., self test conduct, interpretation and linkage). An oral point-of-care HIV test, an Internet and paper-based self-test HIV applications, and mobile phones were synergized to create an unsupervised strategy. Self-tests were additionally confirmed with rapid tests on site and laboratory tests. Of 270 health care workers (18 years and above, of unknown HIV status approached), 251 consented for participation.
Overall, about 91% participants rated a positive experience with the strategy. Of 251 participants, 126 evaluated the Internet and 125 the paper-based application successfully; completion rate of 99.2%. All sero-positives were linked to treatment (completion rate:100% (95% CI, 66.0-100). About half of sero-negatives were offered counselling on mobile phones; completion rate: 44.6% (95% CI, 38.0-51.0). A majority of participants (78.1%) were females, aged 18-24 years (61.4%). Nine participants were found sero-positive after confirmatory tests (prevalence 3.6% 95% CI, 1.8-6.9). Six of nine positive self-tests were accurately interpreted; sensitivity: 66.7% (95% CI, 30.9-91.0); specificity:100% (95% CI, 98.1-100).
Our unsupervised self-testing strategy was feasible to operationalize in health care workers in South Africa. Linkages were successfully operationalized with mobile phones in all sero-positives and about half of the sero-negatives sought post-test counselling. Controlled trials and implementation research studies are needed before a scale-up is considered.
Aim
To assess the stability of the Gross Motor Functional Classification System (GMFCS) in children with cerebral palsy (CP) from time of preliminary diagnosis (~2 years of age) to time of diagnosis ...(~5 years of age), and to examine factors associated with reclassification.
Method
We conducted a longitudinal study using a sample from the Canadian CP Registry. Stability was analysed by using the percentage of agreement between timepoints and a weighted prevalence and bias adjusted kappa statistic. Univariate and multivariate logistic regressions were performed to identify variables associated with reclassification.
Results
The study included 1670 children (857 males, 713 females) with a mean age of 11 years 4 months (SD 4 years, range 3 years 5 months–20 years 1 month) at time of data extraction (3rd September 2019), of which 1435 (85.9%) maintained a stable GMFCS, with a weighted kappa of 0.91 (95% confidence interval 0.89–0.92). Univariate logistic regression showed that initial GMFCS level, CP subtype, and the presence of cognitive impairment were associated with the likelihood of change in the GMFCS level (p < 0.1). In the multivariate analysis, however, the likelihood was associated with initial GMFCS level only (odds ratio 7.10–8.88, p < 0.00).
Interpretation
The GMFCS has good stability in early childhood. For the majority of children, it is predictive of their long‐term motor function.
What this paper adds
The Gross Motor Function Classification System (GMFCS) rating in early childhood is stable over time.
There is no directionality in the reclassification of the GMFCS.
The initial GMFCS level was related to the likelihood of change in follow‐up GMFCS level.
What this paper adds
The Gross Motor Function Classification System (GMFCS) rating in early childhood is stable over time.
There is no directionality in the reclassification of the GMFCS.
The initial GMFCS level was related to the likelihood of change in follow‐up GMFCS level.
This original article is commented on by Arnaud on pages 1435–1436 of this issue.
5q Spinal Muscular Atrophy (SMA) is a prototypical lower motor neuron disorder. However, the characteristic early motor impairment raises the question on the scope of brain involvement with ...implications for further investigations on the brain as a potential therapeutic target.
To review changes across the SMA clinical spectrum reported on brain magnetic resonance imaging (MRI).
We conducted a scoping review of existing literature on PubMed and EMBASE. Two reviewers searched and retrieved relevant articles on magnetic resonance brain imaging in individuals with SMA censoring to April 2022. Full-text articles published in peer-reviewed journals or abstracts accepted to conferences in English and French were included.
Twelve articles were identified describing a total of 39 patients age range: 11 days to 41 years old, type 0 (n = 5), type 1 (n = 4), type 2 (n = 2), type 3 (n = 22), type 4 (n = 6). All reported structural changes and did not explore other MRI modalities. In individuals with infantile onset SMA, cortical and subcortical brain abnormalities in white matter, basal ganglia, thalamus, hippocampus, and high intensity areas around lateral ventricles and thalami were reported over time. In individuals with later-onset SMA, reduced cerebellar and lobular volume were observed as well as increased grey matter density in motor areas.
Limited data on brain imaging in SMA highlights both cortical and subcortical involvement in SMA, supporting the hypothesis that changes are not restricted to lower motor neuron pathways. Further studies are needed to determine the extent and prevalence of structural and functional brain changes across SMA types.
Background
Parental nativity, as well as duration of residence of foreign‐born parents in the host country, has been shown to be associated with size at birth. However, most studies have focused on ...maternal nativity status only and have not accounted for important characteristics of both parents.
Objective
To explore whether maternal and paternal nativity and length of residence (LOR) are independently associated with birthweight for gestational age in a representative sample of infants in Canada.
Methods
We compared mean differences in sex‐ and gestational age‐standardised birthweight z‐score by nativity status of both parents in a nationally representative sample of 130,532 singleton infants born between May 2004 and May 2006 to mothers residing in Canada. We categorised parental nativity status into four groups (both parents Canada‐born, mother only foreign‐born, father only foreign‐born and both parents foreign‐born) and parents’ LOR into three (both ≤10 years, only one parent ≤10 years and both >10 years). We estimated mean differences in birthweight z‐score and their 95% confidence intervals in linear regression models adjusted for parity, parents’ ages, education, ethnicity and marital status of the mother.
Results
Compared with babies of Canada‐born couples, those of two foreign‐born parents had on average smaller birthweight z‐score, −0.23 (95% CI −0.28, −0.25). However, after adjustment, the mean difference in z‐score was −0.02 (95% CI −0.05, 0.00). Infants born to parents who had both resided in Canada for ≤10 years had a unadjusted mean difference in z‐score of −0.27 (95% CI −0.29, −0.26), compared infants whose parents were both Canada‐born, but the difference became negligible (−0.02, 95% CI −0.04, 0.01) after adjustment.
Conclusion
The birthweight differences by parental nativity or length of residence observed in our study population could be attributed to differences in the distribution of other parental characteristics that affect birthweight.
We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic ...(P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes.
BACKGROUNDImplementation of human immunodeficiency virus rapid and point-of-care tests (RDT/POCT) is understood to be impeded by many different factors that operate at 4 main levels—test devices, ...patients, providers, and health systems—yet a knowledge gap exists of how they act and interact to impede implementation. To fill this gap, and with a view to improving the quality of implementation, we conducted a systematic review.
METHODSFive databases were searched, 16,672 citations were retrieved, and data were abstracted on 132 studies by 2 reviewers.
FINDINGSAcross 3 levels (ie, patients, providers, and health systems), a majority (59%, 112/190) of the 190 barriers were related to the integration of RDT/POCT, followed by test-device–related concern (ie, accuracy) at 41% (78/190). At the patient level, a lack of awareness about tests (15/54, 28%) and time taken to test (12/54, 22%) dominated. At the provider and health system levels, integration of RDT/POCT in clinical workflows (7/24, 29%) and within hospitals (21/34, 62%) prevailed. Accuracy (57/78, 73%) was dominant only at the device level.
INTERPRETATIONIntegration barriers dominated the findings followed by test accuracy. Although accuracy has improved during the years, an ideal implementation could be achieved by improving the integration of RDT/POCT within clinics, hospitals, and health systems, with clear protocols, training on quality assurance and control, clear communication, and linkage plans to improve health outcomes of patients. This finding is pertinent for a future envisioned implementation and global scale-up of RDT/POCT-based initiatives.
BACKGROUND: Birth weight of a baby is a strong predictor of infant and neonatal survival. Several studies in various countries have compared perinatal outcomes by parental nativity. However, most are ...focused on maternal nativity, neglecting the father's. OBJECTIVE: Primary objective is to determine whether infant birth weight differs by maternal and paternal nativity status. Secondary objective is to examine whether there is any relation between the duration of residency in Canada of each parent and the birth weight of the offspring. METHODS: This is an observational study using 130,532 singleton, live births between May 2004 and May 2006 to mothers residing in Canada based on the 2006 Census-Birth cohort. The outcome was sex- and gestational age-standardized birth weight z-score. Parental nativity status was classified into four groups: i) both parents Canada-born, ii) mother Canada-born and father foreign-born, iii) mother foreign-born and father Canada-born, and iv) both parents foreign-born. Parents' length of residence (LOR) was classified into three groups: i) both ≤5 years, ii) either parent ≤5 years, and iii) both >5 years. We used linear regression to estimate the mean differences in birth weight z-scores and the 95% confidence interval (CI) by parental nativity status/LOR and the differences after adjusting for parity, marital status of the mother, and both parents' age, education and ethnicity. RESULTS: Crude results for parental nativity status showed that, compared with babies of two Canada-born parents, those with two foreign-born parents had a smaller adjusted birth weight for gestational age z-score -0.266 (95% CI: -0.280, -0.251) standard deviations (SD) points. For infants with one parent was foreign-born, the difference was -0.071 (95% CI: -0.097, -0.044) SD points for those with a foreign-born mother and -0.058 (95% CI: -0.084, -0.033) SD points for the father. When adjusted for parity, marital status of the mother, maternal and paternal age, ethnicity and education, the mean z-score difference between babies of two Canada-born parents and those with two foreign-born parents became negligible -0.024 (95% CI: -0.049, 0.001) SD points. When only one parent was foreign-born, the difference was -0.025 (95% CI: -0.055, 0.004) SD points for the mother and 0.003 (95% CI: - 0.025, 0.032) SD points for the father. Crude results for parents' LOR showed that, compared with babies born to Canada-born couples, those of both parents with LOR ≤5 years had on average 0.273 (95% CI: -0.296, -0.250) SD points smaller z-score. The corresponding figures were 0.130 (95% CI:-0.146, -0.113) and -0.247 (95% CI;-0.268, -0.225) for those of both parents with LOR >5 years and for those with either one parent with LOR of ≤5 years, respectively. Consistent with the primary results by parental nativity, adjustment for all covariates reduced the mean z-score differences by parents' LOR. Compared with babies of Canada-born couples, those of both parents with LOR ≤5 years had a z-score difference of -0.031 (95% CI:-0.061, -0.002) and -0.019 (95% CI:-0.040, 0.002) if parents' LOR was >5 years. If either parent's LOR was ≤5 years, the adjusted difference was -0.006 (95% CI: -0.032, 0.020) SD points. CONCLUSIONS: Our study did not find any association between parental nativity status and birth weight for gestational age and sex after adjusting for other covariates, parental ethnicity in particular. On the other hand, when adjusted for all covariates, we did observe that parents' LOR was positively associated with birth weight of the baby. Both parent's with LOR in Canada for ≤5 years, on average, had smaller babies compared with those of Canada-born parents, but no difference was found with babies born to either or both parents with LOR >5 years.
Objectives Multiplexed point-of-care (POC) devices can rapidly screen for HIV-related co-infections (eg, hepatitis C (HCV), hepatitis B (HBV), syphilis) in one patient visit, but global evidence for ...this approach remains limited. This study aimed to evaluate a multiplex POC testing strategy to expedite screening for HIV-related co-infections in at-risk populations. Methods A multiplex strategy was developed with two subsequent versions of an investigational device Miriad. It was evaluated in two non-comparable settings and populations in two countries for feasibility of conduct, detection of new infections, preference and accuracy. Version 1 was evaluated in 375 sexually transmitted disease clinic attendees in Mumbai, India; version 2 was evaluated in 119 injection drug users in Montreal, Canada. Results Feasibility (completion rate) of the multiplex strategy was high (86.1% Mumbai; 92.4% Montreal). A total of 170 new infections were detected in Mumbai (56 HIV, 75 HBV, 37 syphilis, 2 HCV) versus 2 in Montreal. Preference was 60% in Mumbai and 97% in Montreal. Miriad version 1 specificities were high: HIV 99.7% (98.3% to 100%), HBV 99.3% (97.6% to 99.9%), HCV 99.7% (98.5% to 99.9%), syphilis 85.2% (80.9% to 88.8%); sensitivities were as follows: HIV 100% (94.8% to 100%), HBV 13.3% (6.6% to 23.2%), HCV 50% (1.3% to 98.7%), syphilis 86.1% (70.5% to 95.3%). With version 2, specificities improved: HIV 100% (97.2% to 100%), HBV 100% (97.3% to 100%), HCV 85.3% (73.8% to 93.0%), syphilis 98.1% (93.3% to 99.8%); sensitivities were: HIV 100% (47.3% to 100%), HCV 80.4% (66.1% to 90.6%), syphilis 100% (22.4% to 100%). Conclusions A quad multiplex POC strategy for HIV and co-infections was feasible to operationalise and preferred by patients in both settings. Many new infections were identified in Mumbai and accuracy improved with version 2 of the assay. Such a strategy will help expedite screening for co-infections, particularly where baseline screening is low. These findings are valuable to practitioners, researchers, policymakers and funders involved in initiatives for all four diseases with implications for scale-up.