Longitudinal Case-control Study Research Articles

Longitudinal FDG-PET Metabolic Change Along the Lewy Body Continuum

Although 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established cross-sectional biomarker of brain metabolism in dementia with Lewy bodies (DLB), the longitudinal change in FDG-PET has not been characterized. To investigate longitudinal FDG-PET in prodromal DLB and DLB, including a subsample with autopsy data, and report estimated sample sizes for a hypothetical clinical trial in DLB. Longitudinal case-control study with mean (SD) follow-up of 3.8 (2.3) years. Cases were recruited consecutively between 2007 and 2022 at a referral center and among the population. Patients with probable DLB or mild cognitive impairment with Lewy bodies (MCI-LB) were included. Individuals without cognitive impairment were included from a population-based cohort balanced on age and sex for comparison. All participants completed at least 1 follow-up assessment by design. Patients with MCI-LB and DLB. Rate of change in FDG-PET was assessed as standardized uptake value ratios (SUVr). Clinical progression was assessed with the Clinical Dementia Rating Sum of Boxes (CDR-SB) score. Thirty-five patients with probable DLB, 37 patients with MCI-LB, and 100 individuals without cognitive impairment were included. The mean (SD) age of the DLB and MCI-LB groups combined (n = 72) was 69.6 (8.2) years; 66 patients (92%) were men and 6 (8%) were women. At follow-up, 18 participants (49%) with MCI-LB had progressed to probable DLB. Patients with MCI-LB had a faster decline in FDG-SUVr, compared with that of participants without cognitive impairment, in the posterior cingulate, occipital, parietal, temporal, and lateral frontal cortices. The same regions showed greater metabolic decline in patients with DLB than in participants without cognitive impairment, with the addition of anterior-middle cingulate, insula, and medial frontal orbital cortices. Rates of change in FDG-PET in these brain regions were combined into a region of interest (ROI) labeled longitudinal FDG-PET LB meta-ROI. The rate of change in FDG-SUVr in the meta-ROI correlated with the rate of change in CDR-SB, and sample size estimates were reported for potential clinical trials in DLB. Findings were confirmed in the subsample with neuropathologic confirmation (n = 20). This study found that brain hypometabolism begins to evolve during the prodromal stages of DLB with changes paralleling symptomatic progression. These data may inform clinical practice and trials planning to use FDG-PET for biologic staging, monitoring disease progression, and potentially assessing treatment response.

Automatic measurement of choroidal thickness with swept-source optical coherence tomography in chronic Vogt-Koyanagi-Harada disease: 3 years’ follow-up

PurposeThe course of Vogt-Koyanagi-Harada (VKH) disease is typically assessed qualitatively using indocyanine green angiography (ICGA) and enhanced-depth imaging optical coherence tomography (EDI-OCT). However, a quantitative approach could improve accuracy and objectivity. The aim of this study was to assess the clinical value of the automated measurement capabilities of swept-source optical coherence tomography (SS-OCT) to measure choroidal thickness (quantitative approach) in chronic VKH.MethodsProspective, longitudinal case–control study at a tertiary university hospital involving 23 chronic VKH patients (9 convalescent and 14 quiescent) and 17 age-matched controls. Choroidal thickness was automatically measured with SS-OCT.ResultsChoroidal thinning and improved vision were associated with treatment while increasing thickness and worsening vision were associated with posterior relapse. Overall, 41.6% of asymptomatic (no change in visual acuity) recurrences in the convalescent group and 25% of recurrences in the quiescent group were detected by SS-OCT. All recurrences diagnosed by SS-OCT showed signs of inflammation on ICGA.ConclusionsAutomatic measurement of choroidal thickness with SS-OCT is a rapid, non-invasive method of detecting posterior segment recurrences and treatment response in VKH patients, and could reduce the need for angiography to monitor this disease.

Microcirculatory parameters as risk factors for predicting progression of posterior staphyloma in highly myopic eyes: a case–control study

BackgroundTo assess the rate of macular blood flow decreasing in adults with and without posterior staphyloma (PS) using optical coherence tomography angiography (OCTA) and to identify risk factors associated with PS progression.MethodsThis longitudinal case-control study enrolled 122 eyes of 122 patients—64 patients with PS (PS group) and 58 patients without PS (NPS group). Participants underwent OCTA and clinical examinations at least twice, and those followed for at least one year were included in the analysis. Logistic regression analysis and machine learning were applied to explore the risk factors for PS and its progression.ResultsPatients in the PS group exhibited faster growth rates of spherical equivalent refraction (SER), axial length (AL), curvature index (CI), and posterior scleral height (PSH) as well as higher loss rates of choriocapillaris perfusion area (CCPA), choroid perfusion area (CPA) and choroidal vascularity index (CVI) compared to the NPS group (all P < 0.05). The baseline SER (B = − 1.291, OR = 0.275, P = 0.008), baseline subfoveal scleral thickness (B = − 1.621, OR = 0.198, P = 0.046), baseline PSH (B = 2.959, OR = 19.282, P = 0.001) and foveal CVI changes per year (B = − 2.776, OR = 0.062, P < 0.001) were the risk factors for PS. Baseline AL (B = 0.561, OR = 1.752, P = 0.033), parafoveal choroidal thickness changes per year (B = − 0.094, OR = 0.910, P = 0.032), foveal retinal vascular density changes per year (B = 0.104, OR = 1.110, P = 0.013) and foveal CCPA changes per year (B = − 0.214, OR = 0.807, P = 0.038) were the risk factors for the PS progression.ConclusionsDuring the progression of myopia in adults, changes in the morphology of the eye's posterior pole are not limited to axial lengthening alone; there also will be a phase of compensatory lateral expansion. Baseline AL and changes in the microcirculation can be utilized to predict the progression of PS.

Cycling sensitivity across migraine phases: A longitudinal case-control study.

Functional neuroimaging studies indicate that central transmission of trigeminal pain may commence up to 48 h prior to the onset of headache. Whether these cyclic changes are associated with somatosensory alteration remains incompletely understood. The present study aimed to investigate the temporal progression of somatosensory alterations preceding the onset of a migraine attack. Patients with menstrually related migraine (n = 10) and matched healthy controls (n = 13) underwent consecutive daily quantitative sensory tests, commencing 6 days prior to the expected onset of the migraine attack and menstruation. Each subject was investigated for 7-11 consecutive days, resulting in 85 and 91 days of experimentation for the respective cohorts. Electrical/heat/cold pain thresholds showed a phase-dependent decline towards the spontaneous migraine attack, which had commenced 48 h prior to the onset of the headache. The pain thresholds further declined towards the ictal phase, with only the electrical pain threshold reaching statistical significance (ictal vs. preictal). In healthy controls, the pain thresholds remained stable and unaltered during the consecutive daily measurements. In an exploratory analysis, the pain thresholds at baseline (interictal phase) were comparable between both cohorts. The data suggest the existence of a trigeminal somatosensory alteration in the preictal phase of migraine, occurring up to 48 h prior to the onset of the headache. This change occurred in a chronologically synchronous manner with the brain activation in the preictal phase in functional neuroimaging studies. It will be important to combine pain threshold measurement and functional neuroimaging in future studies. Our data suggest the existence of a somatosensory behavioural correlate of the functional neuroimaging changes starting 48 h before the onset of headache. Despite the concurrence of the behavioural and functional neuroimaging changes in a chronological sequence, the next step in elucidating the cause of migraine is to combine the behavioural and functional neuroimaging changes in a temporal sequence, i.e. to identify the generator behind the cyclic sensory fluctuation.

Associations of Clinical Characteristics With Sudden Cardiac Arrest in People With Type 2 Diabetes With and Without Cardiovascular Disease: A Longitudinal Case-Control Study Using Routine Primary Care Data.

To assess longitudinal associations with sudden cardiac arrest (SCA) of clinical characteristics recorded in primary care in people with type 2 diabetes (T2D), both with and without cardiovascular disease (CVD). We performed a case-control study, with SCA case subjects with T2D from the Amsterdam Resuscitation Studies (ARREST) registry of out-of-hospital resuscitation attempts in the Dutch Noord-Holland region (2010-2020) and up to five matched (age, sex, T2D, general practitioner [GP] practice) non-SCA control subjects. We collected relevant clinical measurements, medication use, and medical history from GPs' electronic health care records. We analyzed the associations of clinical characteristics and medication use with SCA in the total sample and in subgroups with or without CVD using multivariable time-dependent Cox regression (hazard ratios, 95% confidence intervals). We included 689 SCA case subjects and 3,230 non-SCA control subjects. In multivariable models, low fasting glucose (<4.5 mmol/mol: 1.91 [1.00-3.64]), antihypertensive (1.80 [1.39-2.33]), glucose lowering (oral only: 1.32 [1.06-1.63]; insulin only: 2.31 [1.71-3.12]; oral and insulin: 1.64 [1.21-2.22]), heart failure (1.91 [1.55-2.35]), and QTc-prolonging prokinetic (1.78 [1.27-2.50]), antibiotic (1.35 [1.05-1.73]), and antipsychotic (2.10 [1.42-3.09]) medication were associated with SCA in the total sample. In subgroup effect modification analyses, QTc-prolonging antibiotic (1.82 [1.26-2.63]) and antipsychotic (3.10 [2.09-4.59]) medication use were associated with SCA only in those without CVD. In people with T2D, low fasting glucose and QTc-prolonging prokinetic, antibiotic, or antipsychotic medication use and a history of heart failure are associated with SCA risk. Subgroup analyses indicate antibiotic and antipsychotic medication use increases SCA risk specifically in those without CVD.

Eye diseases in chronic kidney disease: A nationwide longitudinal case–control study in Sweden

AbstractBackgroundChronic kidney disease (CKD) is a growing health issue that is becoming more prevalent globally, increasing financial cost on healthcare systems. The purpose of this study is to investigate the incidence of eye diseases in patients diagnosed with CKD in Sweden and to evaluate which eye diseases are most likely to develop.MethodsA longitudinal population‐based retrospective case–control study was conducted including all individuals diagnosed with chronic kidney disease during the time period 2001–2019. A total of 19 455 cases and 38 890 controls were included. For each case, two controls were matched with the same sex, age, and county of residence.ResultsCKD patients had a significantly higher risk of contracting any eye disease compared to individuals without kidney disease HR 1.73 (CI 1.67–1.79), with an elevated risk for all blocks of diagnoses except for glaucoma HR 0.95 (CI 0.85–1.06). However, this condition developed earlier in cases than in controls. Subanalyses showed an increased risk for chronic eye disease patients to develop cataract HR 1.70 (CI 1.63–1.78), other retinal disorders HR 1.86 (CI 1.72–2.02), and retinal vascular occlusions HR 2.08 (CI 1.73–2.51). In general, diagnosis of an eye disease occurred earlier in cases than controls.ConclusionsThe results from this study suggest that CKD patients have an increased risk to develop eye disease. Ocular disease seems to develop considerably earlier in CKD, even without staging the severity of the disease, with particularly high risk of developing retinal diseases and cataracts. Screening for eye disease in CKD should be considered.

COVID-19 pandemic and the neurodevelopment of Brazilian infants: Analysis of predictors according to the Nurturing Care Framework

IntroductionConcerns have been raised about the potential negative impacts of the COVID-19 pandemic on child development; this issue can be analyzed using the Nurturing Care Framework (NCF). ObjectiveTo analyze the predictors of neurodevelopment at 12 months in infants born during the pandemic in Brazil, according to the NCF. MethodsIt is a longitudinal case-control study involving 284 infants born between April and August 2021. Mothers were interviewed at birth and at six months postpartum. At 12 months, the infants' neurodevelopment was assessed using the Bayley III Scale. The explanatory variables were grouped according to NCF components, and their association with Bayley III results was examined using hierarchical logistic regression, adjusting for socioeconomic status and gestational exposure to SARS-CoV-2. ResultsTwenty percent of the sample exhibited delays in at least one Bayley III domain (3% cognitive, 16 % language, and 7 % motor). We found an increased risk of cognitive (OR = 5.78; 95 % CI 1.07–31.09) and motor delays (OR = 6.97; 95 % CI 2.17–22.38) for children who had not undergone regular well-child care in their first six months. The likelihood of a child showing some delay at 12 months was 2.23 times higher when the mother reported concerns about the child's development at six months (95 % CI 1.11–4.50). ConclusionWell-child care emerged as a protective factor against cognitive and motor delays, while the mother's concerns were predictive of future developmental issues.

Metabolomic fingerprinting of milk fever cows: Pre- and postpartum metabolite alterations.

Milk fever (MF), a metabolic disorder in dairy cows characterized by low blood calcium concentrations postpartum, is well-recognized clinically. However, comprehensive data on the alteration of metabolites associated with this condition remains sparse. Delineate serum metabolite profiles and metabolic pathways preceding, coinciding with, and after the onset of MF. Twenty-six cows, including 20 healthy cows and 6 cows initially affected by MF. Because of culling, the number of MF-affected cows decreased to 4 at MF week, +4 weeks, and +8 weeks postpartum. A nested case-control longitudinal study was conducted, with blood samples collected at -8 and -4 weeks prepartum, MF week, and +4 and +8 weeks postpartum. Serum analysis utilized direct injection/liquid chromatography/tandem mass spectrometry (DI/LC/MS/MS) techniques. Key findings included the identification of diverse metabolites such as hexose, amino acids, phosphatidylcholines, lysophosphatidylcholines, and sphingomyelin, which varied between studied groups (P < .05). The most marked metabolic alterations were observed 4 weeks prepartum. In total, 42, 56, 38, 29, and 24 metabolites distinguished the MF group at the respective time points (P < .05). Additionally, 33 metabolic pathways, including amino acid, antioxidant metabolism, fatty acid degradation, and carbohydrate processing, were impacted (P < .05). Metabolic disruptions in dairy cows begin several weeks before the clinical manifestation of MF and persist up to 8 weeks postpartum. These findings emphasize the complexity of MF, extending beyond only hypocalcemia and indicate the necessity for preemptive monitoring in dairy herd management.

Ex-vivo evaluation of Plasmodium falciparum-induced cytokine expression in chronic hepatitis B virus-infected and uninfected individuals

Background Chronic Hepatitis B virus (CHB) infection remains a significant public health problem. Exhaustion of T cells usually contribute to the progression of HBV infection to the chronic state, which can impact the induction of immune responses to other pathogens like Plasmodium falciparum. This, in turn, may affect the effectiveness of malaria vaccines when deployed. This case-control longitudinal study sought to determine how early this T cell exhaustion state establishes, since most of the available data relates to CHB cases that have persisted for much longer times. Methods This longitudinal case-control study compared the expression of 13 cytokines between cases and controls at four time points over one year. These cytokines were induced using whole blood ex-vivo stimulation with three Plasmodium falciparum (3D7 strain) antigens. Results Hepatitis B virus-negative and CHB individuals had comparable levels of TNF-α, IL-1β, IL-6 and IL-10. Interleukin 6 which is important for the elimination of HBV was produced in very high amounts by the two groups. There was no significant difference between the groups in their ability to produce pro-inflammatory cytokines in response to malaria antigens. Conclusion Cytokine responses to the vaccine candidates from both groups were similar, indicating no impairment to the effective immune responses to malaria vaccines and probably parasites in this category of early CHB infected individuals.

COVID-19 related cognitive, structural and functional brain changes among Italian adolescents and young adults: a multimodal longitudinal case-control study

Coronavirus disease 2019 (COVID-19) has been associated with brain functional, structural, and cognitive changes that persist months after infection. Most studies of the neurologic outcomes related to COVID-19 focus on severe infection and aging populations. Here, we investigated the neural activities underlying COVID-19 related outcomes in a case-control study of mildly infected youth enrolled in a longitudinal study in Lombardy, Italy, a global hotspot of COVID-19. All participants (13 cases, 27 controls, mean age 24 years) completed resting-state functional (fMRI), structural MRI, cognitive assessments (CANTAB spatial working memory) at baseline (pre-COVID) and follow-up (post-COVID). Using graph theory eigenvector centrality (EC) and data-driven statistical methods, we examined differences in ECdelta (i.e., the difference in EC values pre- and post-COVID-19) and Volumetricdelta (i.e., the difference in cortical volume of cortical and subcortical areas pre- and post-COVID) between COVID-19 cases and controls. We found that ECdelta significantly between COVID-19 and healthy participants in five brain regions; right intracalcarine cortex, right lingual gyrus, left hippocampus, left amygdala, left frontal orbital cortex. The left hippocampus showed a significant decrease in Volumetricdelta between groups (p = 0.041). The reduced ECdelta in the left amygdala associated with COVID-19 status mediated the association between COVID-19 and disrupted spatial working memory. Our results show persistent structural, functional and cognitive brain changes in key brain areas associated with olfaction and cognition. These results may guide treatment efforts to assess the longevity, reversibility and impact of the observed brain and cognitive changes following COVID-19.

Relation between Irritable Bowel Syndrome and Acute Infectious Gastroenteritis in Children

Abstract Background Post-infectious irritable bowel syndrome (PI-IBS) has been defined as a new onset of IBS following an episode of acute infectious diarrhea. Objective To determine the frequency of postinfectious irritable bowel syndrome (PI-IBS) among children who have an episode of acute infectious diarrhea. Subjects and Methods A case control longitudinal study was conducted on 93 children who fulfilled the criteria for diagnosis of acute infectious gastroenteritis. Patients were recruited from the Outpatient Clinic, Children’s Hospital, Ain Shams University, during a period of 6 months and were followed up for 3 months for the development of symptoms of IBS according to Rome IV criteria for diagnosis of IBS. They were compared to 100 age- and sex-matched controls who do not have history of acute infectious gastroenteritis during the last 3 months before enrollment. Result The age of studied cases ranged between (4-15) years old with a mean ±SD=9.26 ± 3.20 years. Females represented 61.3% of cases. PI-IBS occurred in 14%of cases with age ranged between (4-14) years old and females represented 61.5% of PI-IBS cases. Meanwhile, the incidence of IBS 3.2% of uninfected controls (relative risk, RR = 4.33). Most cases of PI-IBS were diarrhea prominent. There was no significant association with the causative organism identified among cases. Rota virus represented the most common organism among our patients with incidence of (32.3%) followed by campylobacter, salmonella, adeno virus, and giardia with incidence of (9.7%), (8.6%), (5.4%), (6.5%), respectively, while (37.6%) of patients have negative stool cultures for the mentioned organisms. Conclusion The frequency of PI-IBS is common among pediatrics but does not seem to be associated with the causative organism of the preceding episode of infectious diarrhea. Raising the awareness about this entity is of outmost importance as this will allow targeted treatment.

Rates of Visual Field Progression Before and After the Onset of Atrial Fibrillation.

This case-control study investigated the effect of atrial fibrillation (AF) on the progression of glaucoma. The presence of AF and related microvascular damage was associated with a slightly faster visual field loss in glaucoma patients. To investigate the effect of atrial fibrillation (AF) on glaucoma progression. In this longitudinal case-control study, a total of 144 eyes from 105 patients with primary open angle glaucoma were included. Forty-eight eyes of case developed AF during the follow-up followed for 15.6 years. Ninety-six eyes of control that did not have AF at baseline or during follow-up matched for age, baseline glaucoma severity, and follow-up period were followed for an average of 14.7 years. Mixed-effects linear models were used to calculate the difference in the VF MD slopes before and after the AF. CHADS 2 and CHA 2 DS 2 -VASc scores were used to evaluate the risk of thrombosis event, and related microvascular damage was assessed based on these scores. The rate of VF MD change was -0.20 (-0.42 to 0.02) dB/y before AF and -0.28 (-0.47 to -0.09) dB/y after AF for the patients with AF, and -0.21 (-0.25 to -0.17) dB/y for the control. In the multivariable models, the VF slope difference before and after the onset of AF [-0.10 (-0.14 to -0.05) dB/y, P <0.001], higher CHADS 2 score [-0.07 (-0.13 to 0.00) dB/y per 1 unit, P =0.040], and higher CHA 2 DS 2 -VASc score [-0.05 (-0.10 to 0.00) dB/y per 1 unit, P =0.039] were associated with faster VF MD loss. The presence of atrial fibrillation and related microvascular damage might accelerate visual field loss. This underscores the need for a comprehensive medical history and management of cardiovascular risk factors to mitigate increased VF loss in glaucoma.

Hispanic Cancer Survivors Exposed to Multiple Natural Disasters: Pre-Post-Disaster Changes in Anxiety, Depression, PTSD, Perceived Stress, and Physical Symptom Burden.

Studies evaluating the effects of natural disasters on cancer outcomes are scarce, especially among USA ethnic minority groups, and none have focused on the effects of concurrent natural disasters and the COVID-19 pandemic. The goal of this secondary data analysis is to explore the impact of concurrent exposure to COVID-19 and earthquakes on psychological distress and symptom burden among Puerto Rican cancer survivors. This secondary data analysis (n = 101) was part of a longitudinal case-control cohort study (n = 402) aimed at describing unmet psychological needs among Puerto Rican cancer patients and non-cancer subjects previously exposed to Hurricane María in 2017. The research team pooled data from participants (cancer survivors and non-cancer group) from their baseline assessments and from follow-up assessments conducted during January-July 2020 (earthquake and the lockdown period). A descriptive, paired t-test, non-parametric mean rank test, and two-sided Pearson correlation analyses were performed. Psychological distress and cancer symptom burden diminished over time. Resilience was significantly correlated with all the psychological and symptom burden variables during both pre- and post-earthquake and COVID-19 assessment periods. The results support the role of resilience, social support, and post-traumatic growth as potential protective factors preventing psychological distress and diminishing cancer symptom burden among cancer survivors exposed to natural disasters and the COVID-19 pandemic.

Neonatal Markers of Prematurity as Predictors of Permanent Childhood Hearing Loss and Neurodevelopmental Impairment in Children Admitted to the Neonatal Intensive Care Unit.

Need for admission to the neonatal intensive care unit (NICU) confers an increased risk of hearing loss in the newborn and of later neurodevelopmental impairment. In this retrospective longitudinal case-controlled study, we assess how the degree of prematurity, measured via gestational age, birth weight, and z-scores, in 138 infants admitted to the NICU are associated with permanent childhood hearing loss (PCHI) and 2-year developmental outcomes. Logistic regression analyses, Kruskal-Wallis analysis of variance, and Chi-squared tests were used. Independent of prematurity, PCHI and NICU admission were predictive of poor developmental outcomes. Twenty-one (47%) children with PCHI had a moderate-to-severe developmental delay, compared to three (7%) matched controls. Days in the NICU but not z-scores predicted PCHI. Z-score was not prognostic of moderate or severe developmental impairment in children with PCHI. The odds ratio of moderate-to-severe neurodevelopmental impairment with PCHI was high, at 12.48 [95% CI = 3.37-46.40]. Children with PCHI were significantly more likely to have cerebral palsy than their matched counterparts (30% vs. 2%). These findings challenge the conventional focus on gestational age and birth weight on neurodevelopmental outcomes for children with PCHI and NICU admission. A more nuanced approach to monitoring and intervention is needed.

Cognitive and functional brain changes among Italian adolescents and young adults with COVID-19 infection: a longitudinal case control study

Cognitive and functional brain changes among Italian adolescents and young adults with COVID-19 infection: a longitudinal case control study

Increase in Testosterone Levels and Improvement of Clinical Symptoms in Eugonadic men With a Prolactin-secreting Adenoma.

Testosterone concentrations, albeit rarely, may be in the normal range (>3.0 ng/mL) in men with a prolactin-secreting pituitary adenoma (PSPA-nt). The evolution of total, bioavailable testosterone, gonadotropin levels, and that of graded symptoms of testosterone deficiency (TD) are uncertain in these patients. Retrospective case-control longitudinal study at a tertiary referral center. From 287 men, we selected 25 PSPA-nt men undergoing prolactin normalization (<20.0 ng/mL) during the follow-up. Graded symptoms of TD were investigated by structured interviews. Biochemical changes and TD symptoms were compared to those of a matched cohort of 61 men with pituitary neoplasms and normal testosterone levels (PA-nt). Baseline testosterone levels were similar between PSPA-nt and PA-nt subjects. The prevalence of specific and suggestive symptoms of TD was higher in PSPA-nt (20% and 68%) than in PAnt (3.3 and 29.5%; P = .02 and P = .0015, respectively). At the follow-up, total and bioavailable testosterone levels increased in PSPA-nt but not in PA-nt patients (Δ change: 1.28 ± 2.1 vs0.03 ± 1.5 ng/mL, + 0.33 ± 0.55 vs-0.26 ± 0.60 ng/mL; P = .0028 and P = .0088, respectively). LH and FSH levels also increased in PSPA-nt men (P < .05). Specific and suggestive, but not nonspecific symptoms of TD, improved only in PSPA-nt men (P < .05 for both). Baseline testosterone and LH were the strongest predictors of testosterone improvement in PSPA-nt patients. Despite having normal testosterone levels at baseline, patients with PSPA-nt experience a relief of TD symptoms and an improvement of their pituitary-gonadal axis function following prolactin normalization, especially when baseline TT and LH levels are in the low-normal range.

Cognitive performance in young adult women with a history of premature adrenarche.

Girls with premature adrenarche (PA) mature earlier than peers and have been found to have greater symptom accounts reflecting anxiety compared to peers. It is not known, however, whether PA effects cognitive development. This longitudinal case-control cohort study aimed: (1) To investigate whether a history of PA leads to measurable changes in adulthood cognitive performance, and (2) to assess whether findings characteristic of PA girls predict adulthood cognitive performance. Twenty-seven girls with PA and 27 age-matched control girls were examined and followed from mid-childhood (mean age 7.2 years) until early adult age (18.5 years). Wechsler Adult Intelligence Scale, Fourth Edition scores were used as main outcome measure. Allostatic load (AL) scores, which compile multisystem variables to reflect the overall wear and tear of the body from increased and prolonged stress, were higher in the PA group in both prepuberty and adulthood, but there were no differences in WAIS-IV results between the groups (full-scale IQ 92.7 vs. 97.5, p 0.376; no differences in separate indexes). Childhood androgen levels, glucose metabolism biomarkers, and AL scores failed to predict adulthood cognitive performance outcomes. The study suggests that PA does not predispose to adverse adulthood outcomes of cognitive development. The study suggests that a history of premature adrenarche (PA) does not affect cognitive performance in adult age. Childhood androgen levels and biomarkers of glucose metabolism failed to predict adulthood cognitive outcomes in this study. Allostatic load scores were elevated in the PA group both in childhood and adulthood but did not predict adulthood cognitive outcomes.

Results of neck-specific exercise for altered postural sway in individuals with chronic whiplash-associated disorders: a longitudinal case–control study

Postural sway has not been investigated before or after a neck exercise intervention in individuals with chronic whiplash-associated disorders (WAD). The aim of the study was to investigate postural sway in individuals with chronic WAD grades 2 and 3: (a) compared with healthy matched controls at baseline; (b) after three months of neck-specific exercise and (c) to investigate the correlation between postural sway with self-reported dizziness during motion and balance problems/unsteadiness. This is a longitudinal prospective experimental case–control intervention study. Individuals with WAD (n = 30) and age- and gender-matched healthy volunteers (n = 30) participated. Postural sway was assessed using an iPhone application. Measurements were carried out at baseline, and for those with WAD a second measurement was performed at the three-month follow-up when neck-specific exercise intervention ended. The WAD group performed significantly worse than the healthy group in both pathway and ellipse area double stance eyes closed at baseline (main outcome), but not at the three-month follow-up. The WAD group significantly improved after rehabilitation in both pathway double stance eyes closed and pathway single stance eyes open. The correlation between postural sway and self-rated dizziness during motion and balance problems was low to moderate. One may conclude that postural sway was improved after a neck-specific exercise programme. The study results strengthen earlier findings that individuals with WAD have worse balance outcome when they have to rely on neck proprioception (eyes closed). The study results may be important for the development of improved rehabilitation methods for WAD.

Relationship between social cognition and emotional markers and acoustic-verbal hallucination in youth with post-traumatic stress disorder: Protocol for a prospective, 2-year, longitudinal case-control study.

Auditory-verbal hallucinatory experiences (AVH) have a 12% prevalence in the general pediatric population. Literature reports a higher risk of developing AVH in post-traumatic stress disorder (PTSD). The persistence of AVHs during adolescence represents a risk of evolution into psychotic disorders. Social cognition and emotional markers could be considered prodromes markers of this evolution. The objectives of this prospective observational study are to observe social cognition and emotional markers correlation with the presence and persistence of AVH over two years and with the evolution of PTSD and psychotic diagnosis. This prospective case-control study, longitudinal over two years (with an interim reassessment at six months and one year), will include 40 participants aged 8 to 16 years old with a diagnosis of PTSD and without a diagnosis of psychosis according to the criteria of DSM-5 (K-SADS-PL). Subjects included are divided into two groups with AVH and without AVH matched by gender, age and diagnosis. The primary outcome measure will be the correlation between social cognition and emotional makers and the presence of AVH in the PTSD pediatric population without psychotic disorders. The social cognition marker is assessed with the NEPSY II test. The emotional marker is assessed with the Differential Emotion Scale IV and the Revised Beliefs About Voices Questionnaire. The secondary outcome measures are the correlation of these markers with the persistence of AVH and the evolution of the patient's initial diagnosis two years later. The originality of our protocol is to explore the potential progression to psychosis from PTSD by cognitive biases. This study supports the hypothesis of connections between PTSD and AVH through sensory, emotional and cognitive biases. It proposes a continuum model from PTSD to psychotic disorder due to impaired perception like AVH. Clinical trial registration: ClinicalTrials.gov Identifier: NCT03356028.

Childhood neurodivergent traits, inflammation and chronic disabling fatigue in adolescence: a longitudinal case–control study

ObjectivesTo test whether inflammatory processes link the expression of childhood neurodivergent traits to chronic disabling fatigue in adolescence.DesignLongitudinal case–control study.SettingWe analysed data from The Avon Longitudinal Study of Parents and...