Retrospective Longitudinal Study Research Articles

HIV-1 low-level viraemia predicts virological failure in first-line and second-line ART-experienced individuals in India: A retrospective longitudinal study.

To study the prevalence of low-level viraemia (LLV) and its association with virological failure (VF). We conducted a retrospective analysis of 3498 participants at YRG CARE, Chennai, India (2013-2018) on antiretroviral therapy (ART) for ≥6 months with two or more plasma viral load (pVL) measurements. Results were stratified for those with pVL <1000 copies/mL: fully suppressed (FS) (pVL <40), low-LLV (pVL 40-199), mid-LLV (pVL 200-399), and high-LLV (pVL 400-999). The study assessed the association with VF (pVL >1000 copies/mL) using Cox proportional hazard model. Among 3498 participants, 2965 (84.8%) were FS and 533 (15.2%) were LLV. During the follow-up, 348 (10%) experienced VF, with 222 (6.3%) experienced after LLV (42% of LLV) and 126 (3.6%) experienced after FS (4.3% of FS). When compared with FS, those with LLV had a greater risk of VF [adjusted hazard ratio (aHR) = 12.7; 95% confidence interval (CI): 10.2-15.9]. First-line participants had a higher VF incidence (aHR = 15.8, 95% CI: 11.4-21.9) than second-line participants (aHR = 5.6, 95% CI: 4.1-7.7). Those with high-LLV had the highest VF risk (aHR = 22.856, 95% CI: 15.204-34.359 vs. aHR = 8.186, 95% CI: 5.564-12.043, for first-line vs. second-line participants, respectively), followed by those with mid-LLV (aHR = 13.375, 95% CI: 8.327-21.483 vs. aHR = 6.261, 95% CI: 4.044-9.695) and low-LLV (aHR = 12.976, 95% CI: 7.974-21.118 vs. aHR = 4.158, 95% CI: 2.826-6.119). The prevalence of LLV was intermediate in our study population. There was a higher risk of VF among individuals with LLV, and this risk increased with the increasing levels of LLV. Close monitoring of individuals experiencing LLV could help in the early identification of VF.

The relationship between participation in leisure activities and incidence of falls in residential aged care.

Active engagement in leisure activities has positive effects on individuals' health outcomes and social functioning; however, there is limited understanding of the link between participation in leisure activities, particularly non-exercise activities, and falls in older adults. This study aimed to determine the relationship between participation in leisure activities and the incidence of falls, and the variation of this relationship by dementia status in residential aged care facilities (RACFs). A retrospective longitudinal cohort study utilising routinely collected data (January 2021-August 2022) from 25 RACFs in Sydney, Australia, was conducted. The cohort included 3,024 older permanent residents (1,493 with dementia and 1,531 without) aged ≥65 and with a stay of ≥1 week. The level of participation in leisure activities was measured using the number of leisure activities per 1,000 resident days and divided into quartiles. Outcome measures were the incidence rate of all falls and injurious falls (i.e., number of falls per 1,000 resident days). We used multilevel negative binary regression to examine the relationship between leisure participation and fall incidence. For the whole sample, leisure participation was significantly inversely associated with the incidence rate of all falls and injurious falls. For example, residents in the high leisure participation group were 26% less likely to experience a fall compared to those in the low leisure participation group after controlling for confounders (incidence rate ratio = 0.74, 95% confidence interval = 0.60, 0.91). Such inverse relationship was observed in both exercise and non-exercise activities and was stronger among residents without dementia. Leisure participation is associated with a lower rate of falls, a key quality indicator by which RACFs are benchmarked and funded in Australia and many other countries. More recognition and attention are needed for the currently underfunded leisure activities in RACFs in future funding arrangement.

Predicting clinical outcomes of SARS-CoV-2 infection during the Omicron wave using machine learning.

The Omicron SARS-CoV-2 variant continues to strain healthcare systems. Developing tools that facilitate the identification of patients at highest risk of adverse outcomes is a priority. The study objectives are to develop population-scale predictive models that: 1) identify predictors of adverse outcomes with Omicron surge SARS-CoV-2 infections, and 2) predict the impact of prioritized vaccination of high-risk groups for said outcome. We prepared a retrospective longitudinal observational study of a national cohort of 172,814 patients in the U.S. Veteran Health Administration who tested positive for SARS-CoV-2 from January 15 to August 15, 2022. We utilized sociodemographic characteristics, comorbidities, and vaccination status, at time of testing positive for SARS-CoV-2 to predict hospitalization, escalation of care (high-flow oxygen, mechanical ventilation, vasopressor use, dialysis, or extracorporeal membrane oxygenation), and death within 30 days. Machine learning models demonstrated that advanced age, high comorbidity burden, lower body mass index, unvaccinated status, and oral anticoagulant use were the important predictors of hospitalization and escalation of care. Similar factors predicted death. However, anticoagulant use did not predict mortality risk. The all-cause death model showed the highest discrimination (Area Under the Curve (AUC) = 0.903, 95% Confidence Interval (CI): 0.895, 0.911) followed by hospitalization (AUC = 0.822, CI: 0.818, 0.826), then escalation of care (AUC = 0.793, CI: 0.784, 0.805). Assuming a vaccine efficacy range of 70.8 to 78.7%, our simulations projected that targeted prevention in the highest risk group may have reduced 30-day hospitalization and death in more than 2 of 5 unvaccinated patients.

A Longitudinal Multiinstitutional Study of Vulvar Lichen Sclerosus: From Childhood to Perimenopause.

The main outcome of this study was the evaluation of clinical characteristics, comorbidities, and therapeutic approaches in patients with vulvar lichen sclerosus (VLS) aged from childhood to perimenopause. Secondly, it was intended to compare these characteristics according to the menarchal status. Patients less than 45 years of age with a diagnosis of VLS from January 2002 to June 2022 in 10 referral centers were included in this retrospective longitudinal study. The univariate analysis compared the dependent variables according to menarchal status. One hundred eighty-six patients met the inclusion criteria. At diagnosis, between 25% and 40% of premenarchal patients reported signs related to subepithelial hemorrhage. A significantly greater presence of bleeding (p < .005), easy bruising (p = .028), fissures (p = .008), petechiae/splinter hemorrhages (p < .001), and bleeding/blistering or open sores (p = .011) was observed in premenarchal patients with respect to the postmenarchal group. The perineum (p = .013) and the perianal region (p < .001) were significantly more involved in the premenarchal group. Topical calcineurin inhibitors were more used in the premenarchal population (p = .004), whereas vitamin E oil and moisturizers were more used in the postmenarchal population (p = .047). Vulvar lichen sclerosus is a chronic condition that can cause vulvar changes that result in severe morbidity and affects sexual function and quality of life, even before menopause. Vulvar lichen sclerosus continues to be misdiagnosed in this population. This may lead to an average delay from symptom onset to diagnosis. Evaluating clinical manifestations of VLS in premenarchal and postmenarchal age allowed us to find different clinical characteristics between the 2 periods suggestive of the diagnosis.

Donor Lymphocyte Infusion (DLI) post allogeneic stem cell transplant (allo-SCT) in Acute Myeloid Leukemia (AML) and High-Grade Myelodysplastic Syndrome (MDS). A longitudinal retrospective study using peripheral blood (PB) CD34+ and CD3+ donor chimerism (DC) monitoring

IntroductionThis longitudinal study was based on the outcomes of Donor Lymphocyte Infusion (DLI) for falling peripheral blood (PB) CD34+ and CD3+ donor chimerism (DC). MethodsFrom 2012 to 2018, data was collected from the BMT database and electronic medical records (EMR). The primary objective was to compare the indication for DLI based on falling PB CD34+ or CD3+ DC in patients post allo-SCT for AML and MDS and their overall survival (OS). Results18/70 patients met the inclusion criteria. Indications for DLI were i) falling PB CD34+ DC ≤ 80 % with morphological relapse, ii) falling PB CD34+ DC ≤ 80 % without morphological relapse and iii) falling PB CD3+ DC ≤ 80 % without falling PB CD34+ DC. Log rank analysis showed falling PB CD34+ DC and morphological relapse had significantly lower OS. Linear regression demonstrated better OS post DLI if there was PB CD34+ and CD3+ chimerism response at 30 days (p = 0.029), GVHD (p = 0.032) and tapering immunosuppression at the time of falling DC (p = 0.042). ConclusionDLI for PB CD34+ DC values ≤ 80 % and morphological relapse had the lowest OS. In this study, full DC was achieved after DLI even with a PB CD3+DC value as low as 13 %, provided the PB CD34+ DC remained > 80 %. Further research is vital in CD34+ DC as a biomarker for disease relapse and loss of engraftment.

LRRK2 G2019S impact on Parkinson disease; clinical phenotype and treatment in Tunisian patients.

LRRK2-G2019S is the most frequent mutation in North African Parkinson's disease (PD) patients.Data on its impact on disease progression and treatment response remains elusive.Therefore, we aimed to explore the clinical features,treatments,and complications through the disease course of PD Tunisian patients according to their LRRK2-G2019S profile. Longitudinal retrospective study conducted in the department of Neurology,Razi University Hospital.We included clinically diagnosed PD patients according to the MDS criteria and reviewed their medical records for clinical,treatment, and neuropsychological assessments.LRRK2-G2019S mutation was screened among all cases using Sanger sequencing.The correlation of LRRK2-G2019S and the clinical PD features was then evaluated. We included 393 PD patients with 41.5% of cases were mutated for LRRK2-G2019S. Those with mutation exhibited an earlier age of onset(p=0.017),and female-PD cases had a higher mutation frequency (p=0.008).Mutation carriers displayed distinct clinical features,with a higher frequency of postural instability gait difficulty (PIGD)forms(adjusted-p<0.001).Throughout the disease progression,carriers showed a faster annual progression in UPDRS-III scores (adjusted-p=0.009) and a significantly higher Levodopa Equivalent Dosevalues in later stages(1060.81 vs. 877.83 for 6-8 years).Motor complications such as dyskinesia (adjusted-p<0.001) and motor fluctuations(31.9% vs. 25.7%,adjusted-p<0.001) were more prevalent in carriers,particularly in later stages.LRRK2-G2019S carriers also exhibited a lower prevalence of non-motor symptoms including cognitive disordersfor episodic memory(adjusted-p<0.001),attention(adjusted-p<0.001),and dysexecutive disorders (adjusted-p=0.039),as well asneuropsychiatric symptoms and dysautonomic signs. This study demonstrated the variability of clinical profile among Tunisian PD cases explained by the incomplete penetrance of LRRK2-G2019S that increases with age.Further studies with biomarker and disease progression data are necessary to improve PD management.

Trabecular bone score (TBS) in Cushing's disease: TBS gain after hypercortisolism normalization

ContextHypercortisolism frequently induces trabecular bone loss, more pronounced at the lumbar spine, resulting in osteoporosis, and thus an increase in fracture risk. Several studies have shown bone mass recovery in patients with Cushing's disease (CD) after treatment. ObjectiveTo examine treatment effects on TBS (trabecular bone score) in addition to aBMD (areal bone mineral density) in a cohort of patients with CD. Design and settingSingle-center retrospective longitudinal study in patients diagnosed with CD and successfully treated following surgery and/or medical treatment. PatientsWe included 31 patients with median age and BMI (body mass index) of 37.7 [28.4;43.3] years old and 27.7 [25.8;30.4] kg/m2, respectively. Median 24 h urinary cortisol before treatment was 213.4 [168.5;478.5] μg/24 h. All subjects were completely biochemically controlled or cured after treatment. Main outcome measuresaBMD and TBS were evaluated at AP Spine (L1-L4) with DXA prodigy (GE-Lunar), QDR 4500 (Hologic), and TBS iNsight® (Med-Imaps) before and after treatment. ResultsAbsolute TBS and aBMD gains following cure of CD were significant (p < 0.0001, and p < 0.001, respectively). aBMD and TBS increased by +3.9 and 8.2 % respectively after cure of CD. aBMD and TBS were not correlated before (p = 0.43) and after treatment (p = 0.53). Linear regression analyses showed that TBS gain was independent of baseline BMI and that low TBS at baseline was predictive of TBS gain after treatment. ConclusionThe more significant improvement of microarchitecture assessed by TBS than aBMD and the absence of correlation between TBS and aBMD suggest that TBS may be an adequate marker of bone restoration after cure of CD. To support this conclusion, future studies with larger sample sizes and longer follow-up periods should be carried out.

Impact of Early Access Reform on Oncology Innovation in France: Approvals, Patients, and Costs.

An ambitious reform of the early access (EA) process was set up in July 2021 in France, aiming to simplify procedures and accelerate access to innovative drugs. This study analyzes the characteristics of oncology drug approvals through the EA process and its impact on real-life data for oncology patients. The number and characteristics of EA demands concerning oncology drugs submitted to the National Health Authority (HAS, Haute Autorité de Santé) were reviewed until 31 December 2022. A longitudinal retrospective study on patients treated with an EA oncology drug between 1 January 2019 and 31 December 2022 was also performed using the French nationwide claims database (Systeme National des Données de Santé [SNDS]) to assess the impact of the reform on the number of indications and patients, and the costs. Among 110 published decisions, the HAS granted 88 (80%) EA indications within 70 days of assessment on average, including 46 (52%) in oncology (67% in solid tumors and 33% in hematological malignancies). Approved indications were mostly supported by randomized phase III trials (67%), whereas refused EA relied more on non-randomized (57%) trials. Overall survival was the primary endpoint of 28% of EA approvals versus none of denied EAs. In the SNDS data, the annual number of patients with cancer treated with an EA drug increased from 3137 patients in 2019 to 18,341 in 2022 (+ 484%), whereas the number of indications rose from 12 to 62, mainly in oncohematology (n=17), lung (n=12), digestive (n=9) and breast cancer (n=9). Reimbursement costs for EA treatments surged from €42 to €526 million (+ 1159%). The French EA reform contributed to enabling rapid access to innovations in a wide range of indications for oncology patients. However, the findings highlight ongoing challenges in financial sustainability, warranting continued evaluation and adjustments.

Evaluation of dynamic corneal response parameters and the biomechanical E-staging after Intacs® SK implantation in keratoconus.

This retrospective longitudinal study evaluated the biomechanical E-staging in KC corneas before and after intracorneal ring segment (ICRS) implantation (Intacs® SK, Addition Technology, Illinois, United States). Biomechanical E-staging for ectatic corneal diseases was applied retrospectively on 49 KC corneas of 41 patients who underwent ICRS implantation. The main outcome parameters included the Corvis Biomechanical Factor (CBiF, the linearized Corvis Biomechanical Index and the biomechanical parameters included), the resulting biomechanical E-staging, the stress-strain index, thinnest corneal thickness (TCT), maximal anterior keratometry (Kmax), and the anterior radius of curvature (ARC). They were evaluated at 1.9 ± 1.1 months preoperatively and postoperatively after 2.8 ± 0.7, 5.8 ± 1.0, and 10.6 ± 2.3 months. The CBiF decreased (4.9 ± 0.5 | 4.7 ± 0.5, P = 0.0013), and the E-staging increased significantly (2.8 ± 0.8 | 3.1 ± 0.9, P = 0.0012, paired t-test) from preoperatively to the first postoperative follow-up. The difference remained significant after 6 months; however, there was no more difference after 11 months. TCT was stable, whereas Kmax and ARC significantly decreased after ICRS implantation (TCT: 464 ± 49, 470 ± 51, 467 ± 38, 461 ± 48; Kmax: 56.3 ± 4.5, 54.7 ± 4.5, 54.2 ± 4.8, 54.1 ± 4.3; ARC: 51.5 ± 3.4, 48.3 ± 3.8, 48.6 ± 3.0, 48.6 ± 3.2 preoperatively and 3, 6, and 11 months postoperatively, respectively). Besides Kmax and ARC, Ambrósio's relational thickness to the horizontal profile (ARTh) was the only parameter that was significantly lower than preoperatively at any follow-up (P ≤ 0.0024, Wilcoxon matched-pairs test). Intacs® SK implantation results in an increasing biomechanical E-staging in the first postoperative months with stabilization near preoperative values after 1 year. Significantly lower ARTh values at any follow-up document the ICRS effect and contribute to a slightly higher postoperative biomechanical E-staging value.

Patterns of use of a myoelectric prosthesis in a cohort of children with transverse defects below the level of the elbow.

Myoelectric prostheses have become the accepted standard of care for pediatric upper-limb amputees. To describe the clinical characteristics and patterns of prosthesis use and to analyze the changes that occur during the growth process of these patients. This is a longitudinal retrospective study comparing the results of surveys carried out in 2015 and 2022. The variables measured included clinical and demographic characteristics, patterns of use, and satisfaction with the prosthesis. Twenty-one patients with transverse defects were fitted with myoelectric prostheses. With increasing age, there was a statistically nonsignificant decrease in the duration of use and a decrease in the number of patients using the prosthesis for activities of daily living from 13 to 10 (p = 0.045), with a 28% dropout rate, higher in patients with more distal defects. Since 2015, we have observed a decrease in the number of hours of prosthesis use, while maintaining a high percentage of patients using the prosthesis.

Changes in ocular blood flow in patients with neovascular age-related macular degeneration after intravitreal injection of ranibizumab biosimilar and brolucizumab.

To assess ocular blood flow (OBF) changes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal injections of ranibizumab biosimilar (IVRbs) or brolucizumab (IVBr). This retrospective longitudinal study included 43 eyes of 43 patients (74.5 ± 9.8 years old, male to female ratio 31:12) with nAMD treated with IVBr (29 eyes) or IVRbs (14 eyes). OBF in the optic nerve head (ONH) and choroid (Ch) was measured with laser speckle flowgraphy (Softcare Co., Ltd., Fukutsu, Japan) before and one month after treatment. Changes in mean blur rate (MBR) before and after each treatment were tested using Wilcoxon's signed-rank tests and mixed-effect models for repeated measures. In the IVBr group, MBR was significantly reduced in both the ONH and Ch (p < 0.01). In contrast, the IVRbs group showed no significant change in MBR in either the ONH or Ch (p = 0.56, p = 1). The linear mixed effect model showed a significant interaction between time and anti-VEGF drugs for MBR in both the ONH and Ch (ONH: p = 0.04; Ch: p = 0.002). A post hoc pairwise comparison of estimated marginal means showed that MBR decreased significantly only after IVBr (p < 0.001). Our findings suggest that the short-term impact on OBF varies depending on the drug used for nAMD.

[Diffuse interstitial lung disease of possible occupational origin treated at the Navarra Health Service. Navarra, Spain, 2017-2022].

Diffuse interstitial lung disease (ILD) describes a broad group of pulmonary inflammatory and fibrosis disorders. Asbestosis and silicosis are the main causes linked to occupational exposure. The aim of this study was to estimate the proportion of cases with possible occupational origin and describe their exposure, clinical, and occupational status. We conducted a retrospective longitudinal study of ILD cases between 2017 - 2022 at the University Hospital of Navarra was conducted. Information was supplemented with interviews of cases with possible occupational origin. The occupational proportion was calculated, labor and clinical characteristics analyzed, by statistical comparison of percentages and means. Out of 1067 ILD cases, 56 had a possible occupational origin 5,2% (95% CI 3,9-6,6%). 36 (64,3%) corresponded to asbestosis, 15 (26,8%) to silicosis, and 5 (8,9%) to unspecified pneumoconiosis. The most frequent activities in silicosis were "stone cutting-carving" and in asbestosis "manufacture of iron products". The average age of asbestosis cases was higher than that of silicosis cases (78,2 vs. 67,3 years), as well as their clinical manifestation. Five cases (8,9%) had been recognized as occupational diseases. The implementation of a computer tool in medical records has made it possible to estimate the magnitude and assess the evolution of occupational ILD treated in the Public Health Service. Economic activities reflect the economic risk structure of the region. However, there is a lack of recognition of these diseases as occupational illnesses and they represent a preventable burden of respiratory disease.

Depression, Anxiety, and Risk of Metabolic Syndrome in Women With Polycystic Ovary Syndrome: A Longitudinal Study.

Patients with PCOS are at high risk of depression, anxiety, and metabolic syndrome (MetSyn), a key predictor of cardiovascular disease. The impact of depression and/or anxiety on MetSyn is unknown in this population. To compare the risk of developing MetSyn in patients with PCOS with and without a history of depression and/or anxiety. Retrospective longitudinal cohort study (2008-2022) with median follow-up of 7 years. Tertiary care ambulatory practice. Patients with hyperandrogenic PCOS and at least 2 evaluations for MetSyn ≥3 years apart (n=321). N/A. The primary outcome was risk of developing MetSyn. We hypothesized that this risk would be higher with a history of depression and/or anxiety. At the first visit, 33.0% had a history of depression and/or anxiety, with a third prescribed antidepressants or anxiolytics. Depression and/or anxiety increased risk of developing MetSyn during the study period (adjusted hazard ratio [aHR] 1.45, 95% CI 1.02-2.06, p=0.04) with an incidence of MetSyn of 75.3 compared to 47.6 cases per 100 person-years among those without (p=0.002). This was primarily driven by depression (aHR 1.56, 95% CI 1.10-2.20, p=0.01). Patients with PCOS and depression and/or anxiety have a high risk of developing MetSyn, with a stronger association between depression and MetSyn. Our findings highlight the urgent need for guideline-directed screening for depression and anxiety at time of diagnosis of PCOS as well as screening at subsequent visits to facilitate risk stratification for metabolic monitoring and early intervention in this high-risk group.

Longitudinal Natural History Study of Visual Function in Bietti Crystalline Dystrophy: Implications for Early Intervention.

To delineate the natural history of visual function parameters over time in individuals with Bietti crystalline dystrophy. This was a single-center retrospective longitudinal cohort study. Participants (n = 29) with a clinical diagnosis of Bietti crystalline dystrophy who harbored two alleles of disease-causing variants of the cytochrome P450 family 4 subfamily V member 2 gene (CYP4V2) were enrolled. Best-corrected visual acuity (BCVA), visual field (VF), and full-field ERG (ffERG) at baseline and their changes during the follow-up period were evaluated. Annual progression rates were calculated using three methods. The mean age at the initial visit was 34.2 ± 7.5 years, with 5.9 ± 3.1 years follow-up. The annual progression rate from the longitudinal analysis using averaged individual progression rates was 0.079 logMAR units for BCVA, 1.14dB for mean defect (MD) value of VF, and -18.06µV and -5.45µV for the b-wave amplitudes of scotopic 3.0 ERG and photopic 3.0 ERG, respectively. Mixed-model linear regression revealed annual progression rates of 0.068 logMAR units, 0.86dB, -13.29µV, and -3.75µV, respectively. Cross-sectional progression rates from visual function versus age at baseline were 0.011 logMAR units, 0.47dB, -1.85 µV, and -1.07 µV, respectively, which were significantly slower than those from the longitudinal data. Interocular symmetries for the MD values of VF and ffERG were good. Annual BCVA, VF, and ffERG progression rates were rapid, emphasizing the need for regular follow-up and early intervention. The progression rate cannot be inferred accurately from cross-sectional data from patients of different ages.

Trajectory patterns and cumulative burden of CEA during follow-up with non-small cell lung cancer outcomes: A retrospective longitudinal cohort study.

Previous studies of non-small cell lung cancer (NSCLC) focused on CEA measured at a single time point, ignoring serial CEA measurements. This retrospective cohort included 2959 patients underwent surgery for stage I-III NSCLC. CEA trajectory patterns and long-term cumulative CEA burden were evaluated using the latent class growth mixture model. Four CEA trajectory groups were identified, named as low-stable, decreasing, early-rising and later-rising. Compared with the low-stable group, the adjusted hazard ratios associated with death were 1.27, 4.50, and 3.68 for the other groups. Cumulative CEA burden were positively associated with the risk of death in patients not belonging to the low-stable group. The 5-year overall survival (OS) rates decreased from 62.3% to 33.0% for the first and fourth quantile groups of cumulative CEA burden. Jointly, patients with decreasing CEA trajectory could be further divided into the decreasing & low and decreasing & high group, with 5-year OS rates to be 77.9% and 47.1%. Patients with rising CEA trajectory and high cumulative CEA were found to be more likely to develop bone metastasis. Longitudinal trajectory patterns and long-term cumulative burden of CEA were independent prognostic factors of NSCLC. We recommend CEA in postoperative surveillance of NSCLC.

Nusinersen in adults with type 3 spinal muscular atrophy: long-term outcomes on motor and respiratory function.

Nusinersen was approved for 5q spinal muscular atrophy (SMA), irrespective of age, SMA type or functional status. Nonetheless, long-term data on adults with milder phenotypes are scarce. We aimed to characterize evolution on motor and respiratory function in our cohort of adults with type 3 SMA. We conducted a longitudinal retrospective single-center study, including adults (≥18years) with type 3 SMA under nusinersen for > 22months. We reported on motor scores and spirometry parameters. Ten patients were included, with a median follow-up of 34months (range = 22-46). Four patients (40%) were walkers. None used non-invasive ventilation. In Revised Upper Limb Module (RULM) and Expanded Hammersmith Functional Motor Scale (HFMSE), difference of medians increased at 6, 22 and 46months comparing to baseline (-0.5 vs. + 1.5 vs. + 2.5 in RULM; + 4.0 vs. + 7.5 vs. + 6.0 in HFMSE). Two (50%) walkers presented a clinically meaningful improvement in 6-min walk distance. We did not report any clinically meaningful decrement in motor scores. Spirometry parameters showed an increasing difference of medians in maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) (-3 vs. + 13.4 vs. + 28.7 percentage points of predicted value for MIP; + 11.8 vs. + 13.1 vs. 13.3 percentage points of predicted value for MEP). Our cohort supports a sustained benefit of nusinersen in adults with type 3 SMA, in motor and respiratory function. Multicentric studies are still warranted.

Progression to corticobasal syndrome: a longitudinal study of patients with nonfluent primary progressive aphasia and primary progressive apraxia of speech.

Nonfluent variant primary progressive aphasia (nfvPPA) and primary progressive apraxia of speech (PPAOS) can be precursors to corticobasal syndrome (CBS). Details on their progression remain unclear. We aimed to examine the clinical and neuroimaging evolution of nfvPPA and PPAOS into CBS. We conducted a retrospective longitudinal study in 140 nfvPPA or PPAOS patients and applied the consensus criteria for possible and probable CBS for every visit, evaluating limb rigidity, akinesia, limb dystonia, myoclonus, ideomotor apraxia, alien limb phenomenon, and nonverbal oral apraxia (NVOA). Given the association of NVOA with AOS, we also modified the CBS criteria by excluding NVOA and assigned every patient to either a progressors or non-progressors group. We evaluated the frequency of every CBS feature by year from disease onset, and assessed gray and white matter volume loss using SPM12. Asymmetric akinesia, NVOA, and limb apraxia were the most common CBS features that developed; while limb dystonia, myoclonus, and alien limb were rare. Eighty-two patients progressed to possible CBS; only four to probable CBS. nfvPPA and PPAOS had a similar proportion of progressors, although nfvPPA progressed to CBS earlier (p-value = 0.046), driven by an early appearance of limb apraxia (p-value = 0.0041). The non-progressors and progressors both showed premotor/motor cortex involvement at baseline, with spread into prefrontal cortex over time. An important proportion of patients with nfvPPA and PPAOS progress to possible CBS, while they rarely develop features of probable CBS even after long follow-up.

Neurobehavioral Progress and Signs of Transition in Children With Prolonged Disorders of Consciousness: A Retrospective Longitudinal Study With the Coma Recovery Scale-Revised

BackgroundResearch on disorders of consciousness in children is scarce and includes disparate and barely comparable participants and assessment instruments and therefore provides inconclusive information on the clinical progress and recovery in this population. This study retrospectively investigated the neurobehavioral progress and the signs of transition between states of consciousness in a group of children admitted to a rehabilitation program either with an unresponsive wakefulness syndrome (UWS) or in a minimally conscious state (MCS). MethodsSystematic weekly assessments were conducted with the Coma Recovery Scale-Revised (CRS-R) until emergence from MCS, discharge, or death. ResultsTwenty-one children, nine admitted with a UWS and 12 admitted in an MCS, were included in the study. Four children with a UWS transitioned to an MCS with a CRS-R of 10 (9.2 to 12.2) by showing visual pursuit, visual fixation, or localization to noxious stimulation. Twelve children emerged from the MCS with a CRS-R of 20.5 (19 to 21.7). Children who emerged from the MCS had had a shorter time postinjury and higher CRS-R at admission, compared with those who did not emerge. ConclusionsAlmost half of the children who were admitted with a UWS transitioned to an MCS, and almost all who were admitted in an MCS emerged from this state. Children who emerged had shorter times since injury and higher scores on the CRS-R at admission, compared with those who did not emerge.

Short-Term Changes in Weight, Body Composition, and Metabolic Biomarkers After Laparoscopic Sleeve Gastrectomy in Patients with Obesity: A Comparative Prospective Study.

To investigate the changes in weight, body composition, and metabolic biomarkers in patients with obesity after laparoscopic sleeve gastrectomy (LSG) and compare those changes between patients with and without metabolic syndrome (MS). This retrospective longitudinal study included 76 patients who underwent LSG, among whom 32 had complete 1-year postoperative body composition and metabolic biomarkers. Body composition was measured by quantitative CT. Weight changes were compared between the MS and non-MS groups at 1-, 3-, 6-, and 12-month post-LSG in all patients; changes in body compositions and metabolic biomarkers from one day pre-LSG to 12-month post-LSG were also compared in those 32 patients. MS occurred in 46% (35/76) of all patients and 44% (14/32) of patients with complete follow-up data. Excess weight loss was lower in the MS group than that in the non-MS group at 1-, 3-, 6-, and 12-month post-LSG; the 12-month difference was significant (MS vs. non-MS: 0.91 ± 0.22 vs. 1.07 ± 0.42, P = 0.04). The greatest rate of visceral fat area (VFA) change occurred 12-month post-LSG in both the non-MS [0.62(0.55,0.7)] and MS [0.6(0.51,0.63)] groups. The most significant reduction in ectopic fat occurred in liver fat (LF) [non-MS, 0.45(0.22,0.58); MS, 0.39(0.23,0.58)]. LGS significantly improves weight, body composition, and metabolic biomarkers in populations with obesity, regardless of whether they have MS. Among the body composition, VFA and LF were the most significantly improved body composition measurements.

Trends in Utilization of Emergency Contraceptives in Tanzania: A Retrospective Longitudinal Study From 2018 to 2023.

Introduction Emergency contraceptives (ECs) are a critical method for preventing unwanted pregnancies following unprotected sexual intercourse. However, Tanzania is experiencing an alarming surge in the misuse ofECs among reproductive-aged females, particularly younger girls and women. Reports of their use as regular contraceptives are a rising concern. Deviations from their intended use in emergencies may not only increase the risk of contraceptive failure but also increase the risk of adverse health events. This study aims to delineate and evaluate the utilization patterns of ECs over six consecutive years using importation data obtained from the Tanzania Medicines and Medical Devices Authority (TMDA). Materials and methods We analyzed the ECdata collected by TMDA over six consecutive years using a retrospective longitudinal design. Microsoft Power BI (Microsoft® Corp., Redmond, WA) was used to clean, organize, and aggregate the data. IBMSPSSStatistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York, United States)was used to analyze annual trend utilization using linear regression. Results We analyzed 114 importation consignments for ECs, identifying 95.6% (109 records) as oral ECs and 4.4% (five records)as intrauterine devices (IUDs) between 2018 and 2023. This data revealed a significant increase in the volume of EC imports, with its contribution increasing from 1.9% in 2018 to 60.1% in 2023. This highlights the marked increase in EC consumption in Tanzania. In 2023, the defined daily dose per 1000 inhabitants per year (DID) peaked at 3.917826, indicating an unprecedented increase of 4,983.06% compared to the lowest DID observed in 2019 at 0.0873552. The year 2023 alone accounted for 41.63% of the total DID (9.43) over the entire study period. In 2019 and 2020, there was a decrease in EC consumption, followed by a rapid increase from 2021 to 2023. The reduction in EC consumption from 2019 to 2020 was 36.9% compared to that between 2021 and 2022. Conclusions The significant rise in EC importation and utilization in Tanzania between 2018 and 2023, marked by fluctuating consumption trends and a notable surge, highlights the urgent need for targeted educational and policy intervention. This will guide the rational and informed use of ECs, ensuring access aligns with best practices for reproductive health.