Prospective Longitudinal Study Research Articles

Changes in Health-Related Quality of Life following Surgery in Patients with High-Grade Extremity Soft-Tissue Sarcoma: A Prospective Longitudinal Study

Introduction: Changes in health-related quality of life (HRQoL) during the diagnostic and treatment trajectory of high-grade extremity soft-tissue sarcoma (eSTS) has rarely been investigated for adults (18–65 y) and the elderly (aged ≥65 y), despite a potential variation in challenges from diverse levels of physical, social, or work-related activities. This study assesses HRQoL from time of diagnosis to one year thereafter among adults and the elderly with eSTS. Methods: HRQoL of participants from the VALUE-PERSARC trial (n = 97) was assessed at diagnosis and 3, 6 and 12 months thereafter, utilizing the PROMIS Global Health (GH), PROMIS Physical Function (PF) and EQ-5D-5L. Results: Over time, similar patterns were observed in all HRQoL measures, i.e., lower HRQoL scores than the Dutch population at baseline (PROMIS-PF:46.8, PROMIS GH-Mental:47.3, GH-Physical:46.2, EQ-5D-5L:0.76, EQ-VAS:72.6), a decrease at 3 months, followed by an upward trend to reach similar scores as the general population at 12 months (PROMIS-PF:49.9, PROMIS GH-Physical:50.1, EQ-5D-5L:0.84, EQ-VAS:81.5), except for the PROMIS GH-Mental (47.5), where scores remained lower than the general population mean (T = 50). Except for the PROMIS-PF, no age-related differences were observed. Conclusions: On average, eSTS patients recover well physically from surgery, yet the mental component demonstrates no progression, irrespective of age. These results underscore the importance of comprehensive care addressing both physical and mental health.

Effect of body mass index on survival after spinal cord injury.

Increased mortality after acute and chronic spinal cord injury (SCI) remains a challenge and mandates a better understanding of the factors contributing to survival in these patients. This study investigated whether body mass index (BMI) measured after acute traumatic SCI is associated with a change in mortality. A prospective longitudinal cohort study was conducted with 742 patients who were admitted to the Acute Spine Unit of the Vancouver General Hospital between 2004 and 2016 with a traumatic SCI. An investigation of the association between BMI on admission and long-term mortality was conducted using classification and regression tree (CART) and generalized additive models (spline curves) from acute care up to 7.7 years after SCI (chronic phase). Multivariable models were adjusted for (i) demographic factors (e.g., age, sex, and Charlson Comorbidity Index) and (ii) injury characteristics (e.g., neurological level and severity and Injury Severity Score). After the exclusion of incomplete datasets (n = 602), 643 patients were analyzed, of whom 102 (18.5%) died during a period up to 7.7 years after SCI. CART identified three distinct mortality risk groups: (i) BMI: > 30.5 kg/m2, (ii) 17.5-30.5 kg/m2, and (iii) < 17.5 kg/m2. Mortality was lowest in the high BMI group (BMI > 30.5 kg/m2), followed by the middle-weight group (17.5-30.5 kg/m2), and was highest in the underweight group (BMI < 17.5 kg/m2). High BMI had a mild protective effect against mortality after SCI (hazard ratio 0.28, 95% CI: 0.09-0.88, p = 0.029), concordant with a modest "obesity paradox". Moreover, being underweight at admission was a significant risk factor for mortality up to 7.7 years after SCI (hazard ratio 5.5, 95% CI: 2.34-13.17, p < 0.001). Mortality risk (1 month to 7.7 years after SCI) was associated with differences in BMI at admission. Further research is needed to better understand the underlying mechanisms. Given an established association of BMI with metabolic determinants, these results may suggest unknown neuro-metabolic pathways that are crucial for patient survival.

Assessment of perinatal anxiety: diagnostic accuracy of five measures.

Anxiety in pregnancy and after giving birth (the perinatal period) is highly prevalent but under-recognised. Robust methods of assessing perinatal anxiety are essential for services to identify and treat women appropriately. To determine which assessment measures are most psychometrically robust and effective at identifying women with perinatal anxiety (primary objective) and depression (secondary objective). We conducted a prospective longitudinal cohort study of 2243 women who completed five measures of anxiety and depression (Generalized Anxiety Disorder scale (GAD) two- and seven-item versions; Whooley questions; Clinical Outcomes in Routine Evaluation (CORE-10); and Stirling Antenatal Anxiety Scale (SAAS)) during pregnancy (15 weeks, 22 weeks and 31 weeks) and after birth (6 weeks). To assess diagnostic accuracy a sample of 403 participants completed modules of the Mini-International Neuropsychiatric Interview (MINI). The best diagnostic accuracy for anxiety was shown by the CORE-10 and SAAS. The best diagnostic accuracy for depression was shown by the CORE-10, SAAS and Whooley questions, although the SAAS had lower specificity. The same cut-off scores for each measure were optimal for identifying anxiety or depression (SAAS ≥9; CORE-10 ≥9; Whooley ≥1). All measures were psychometrically robust, with good internal consistency, convergent validity and unidimensional factor structure. This study identified robust and effective methods of assessing perinatal anxiety and depression. We recommend using the CORE-10 or SAAS to assess perinatal anxiety and the CORE-10 or Whooley questions to assess depression. The GAD-2 and GAD-7 did not perform as well as other measures and optimal cut-offs were lower than currently recommended.

Men, mindsets and birth: results of a prospective longitudinal study

ABSTRACT Aims/Background In recent years, there has been an increased interested in the contribution of fathers to childbirth. In the present paper we explore whether the father’s birth-related mindset (being either more natural or more medical) can predict the mother’s labour and birth outcomes and whether the father’s experience and evaluation of the birth can predict his psychological well-being after the birth. Design/Methods We conducted a longitudinal study (N = 304 expecting fathers) spanning the first trimester of pregnancy up to six months after birth. Results The study results could be integrated into a Single Indicator Model. They indicated that a father’s more natural birth-related mindset predicted low-intervention birth for the mother. A low-intervention birth led to a more positive birth experience for the father, and in turn to better postpartum adjustment, fewer symptoms of postpartum paternal depression eight weeks after birth, and more secure bonding to the infant six months after birth Conclusion The study results indicate that fathers do not take a merely passive role in childbirth. On the contrary, analogous to pregnant mothers, fathers’ views about childbirth might contribute to the course of birth, and their own postpartum psychological well-being. The results of the present study, thus, highlight the importance of fathers for childbirth and in a broader sense, the results also contribute to a better understanding of the psychological framework of birth and represents a valuable starting point for further research.

P1232 Alterations in microbial composition in patients with newly diagnosed Crohn's disease over a course of one year: data from a prospective longitudinal real-world study

Abstract Background Gut microbial composition in Crohn's disease (CD) is variable, changing with specific interventions. We aimed to explore the dynamics in microbial alterations in a cohort of patients with newly diagnosed Crohn's disease (ndCD) over one year. Methods This was a prospective longitudinal real-world study of patients with ndCD1 naïve to therapy who were treated at the physician's discretion. Clinical outcomes at one year were corticosteroid-free clinical remission (CSFR) and biochemical remission ([BR], CRP&amp;lt;1mg/dL and FC&amp;lt;150ug/g). We sequenced paired stool samples from diagnosis and after one year using 16S rRNA gene (V4) and analyzed changes in diversity and dysbiosis indices. A linear mixed-effect model was constructed to identify factors associated with microbial alterations and to identify specific genera that drove the alterations while controlling for confounders. Results Seventy-five patients completed one-year follow-up (49.3% female, median age 27 years [IQR 22-38.5], therapeutic interventions: 45 patients on biological therapies [43 anti-TNF], 26 antibiotics, 10 corticosteroids, 5 underwent surgery, and 59 various nutritional interventions). Rates of CSFR, BR, and conjoined CSFR-BR at one-year post-diagnosis were 64%, 56%, and 45.3%, respectively. We observed an overall significant increase in microbial Shannon diversity (H index), p&amp;lt;0.001, and decreased microbial dysbiosis index (MDI), p=0.007, from baseline to one year. On subgroup analysis, these alterations were significant among patients who achieved the clinical outcomes (all p&amp;lt;0.05) and even more prominent among patients who were on biological therapies (both indices p&amp;lt;0.001). Notably, in the biological therapy subgroup, the microbial composition at diagnosis was less diverse and more dysbiotic than in the non-biological subgroup. In the latter, microbial composition at diagnosis was less disrupted and remained relatively stable over time. Linear mixed model analysis corroborated a positive association between biological therapy and the positive dynamics in microbial indices (H-index, p=0.020 and MDI, p=0.040). Fifteen specific genera drove the microbial alterations over time (Table 1), while alterations in the relative abundance of some genera correlated with changes in clinical biomarkers and clinical indices (Figure 1). Conclusion The microbial composition of this real-world cohort of patients with ndCD improved over the course of one year, which was significant for patients who achieved clinical outcomes and was more prominent for patients requiring biological therapy. In this subgroup, the microbial signature was less diverse and more dysbiotic when diagnosed; this likely led the significant improvement over time. 1 Yanai H,et al. Crohns Colitis 360 2023;5:otad064

High magnitude exposure to repetitive head impacts alters female adolescent brain activity for lower extremity motor control

Contact and collision sport participation among adolescent athletes has raised concerns about the potential negative effects of cumulative repetitive head impacts (RHIs) on brain function. Impairments from RHIs and sports-related concussions (SRC) may propagate into lingering neuromuscular control. However, the neural mechanisms that link RHIs to altered motor control processes remain unknown. The purpose of this study was to isolate changes in neural activity for a lower extremity motor control task associated with the frequency and magnitude of RHI exposure. A cohort of fifteen high school female soccer players participated in a prospective longitudinal study and underwent pre- and post-season functional magnetic resonance imaging (fMRI). During fMRI, athletes completed simultaneous bilateral ankle, knee, and hip flexion/extension movements against resistance (bilateral leg press) to characterize neural activity associated with lower extremity motor control. RHI data were binned into continuous categories between 20 g − 120 g (defined by progressively greater intervals), with the number of impacts independently modeled within the fMRI analyses. Results revealed that differential exposure to high magnitude RHIs (≥90 g - < 110 g and ≥ 110 g) was associated with acute changes in neural activity for the bilateral leg press (broadly inclusive of motor, visual, and cognitive regions; all p < 0.05 & z > 3.1). Greater exposure to high magnitude RHIs may impair lower extremity motor control through maladaptive neural mechanisms. Future work is warranted to extend these mechanistic findings and examine the linkages between RHI exposure and neural activity as it relates to subsequent neuromuscular control deficits.

P817 Incidence and risk factors of infection in patients with inflammatory bowel disease: longitudinal prospective INFEII registry of GETECCU

Abstract Background The true effect of having IBD in the development of infections has not been studied in depth since cohort studies are scarce and the results of studies are sometimes contradictory. Especially, this complication has not been addressed prospectively in an incident cohort of patients with IBD. Aims To assess, regarding infections in IBD: 1) incidence and type, 2) risk factors, 3) effect of type and the duration of IBD treatment, 4) impact in mortality 5) effect of IBD activity. Methods The INFEII registry (ClinicalTrials.gov: NCT02904590) is a prospective study promoted by GETECCU to determine the incidence and risk factors of infection in an inception cohort of patients with IBD and follow-up of at least 5 years. This longitudinal prospective study within the ENEIDA registry was conducted including incident cases with IBD. Patients were recruited between 2016 and 2020 with a planned follow-up of 5 years. All infections were detailed analysed. An infection was considered relevant when: 1) required hospital admission, 2) led to death or endangered the patient’s life, 3) was treated with specific antibiotics,4) occurred recurrently, and/or 5) required change/withdrawal of immunosuppressive treatment. Results The INFEII registry recruited 1456 patients from 28 centres throughout Spain. The median follow-up was 71 months (IQR 60-79 months). The description of the cohort is presented in Table 1. Of the 1456 patients included, 580 (40%) presented at least one relevant infection. In total, 1321 infections were collected. One-hundred and seven infections (8%) required hospitalisation and four patients died (0.3%) over infection. Ninety-nine patients were lost to follow-up (22 died and 34 changed hospitals). The most prevalent infections were: ear-nose-throat in 238 cases, urinary tract infections in 237, respiratory in 234, COVID-19 in 133, skin infections in 127, dental in 64 and colitis/enteritis in 64 (Figure 1). From the whole cohort and at some point, in time, 756 (52%) patients received 5ASA, 481 (33%) steroids (369 (25%) oral, 112 (7.7%) intravenous), 568 (39%) azathioprine, 72 (4.9%) methotrexate, 21 (1.4%) tofacitinib, 533 (37%) antiTNF, 141 (9.9%) ustekinumab and 77 (5.3%) vedolizumab. The effect of treatment and IBD activity in each infection is being analysed. Conclusion Infections are frequent complications in patients with IBD, presented in 40% of them. Being a woman, having a history of past serious infections or occupational risk may be associated with infection occurrence. It has to be determined if IBD activity and treatment suppose a greater risk for infections. This is a paradigmatic study that implies the first use of the ENEIDA registry in prospective research.

The association between neuroendocrine/glucose metabolism and clinical outcomes and disease course in different clinical states of bipolar disorders.

The treatment of bipolar disorder (BD) remains challenging. The study evaluated the impact of the hypothalamic-pituitary-adrenal (HPA) axis/hypothalamic-pituitary-thyroid (HPT) axis and glucose metabolism on the clinical outcomes in patients with bipolar depression (BD-D) and manic bipolar (BD-M) disorders. The research design involved a longitudinal prospective study. A total of 500 BD patients aged between 18 and 65 years treated in 15 hospitals located in Western China were enrolled in the study. The Young Mania Rating Scale (YMRS) and Montgomery and Asberg Depression Rating Scale (MADRS) were used to assess the BD symptoms. An effective treatment response was defined as a reduction in the symptom score of more than 25% after 12 weeks of treatment. The score of symptoms was correlated with the homeostatic model assessment of insulin resistance (HOMA-IR) index, the HPA axis hormone levels (adrenocorticotropic hormone (ACTH) and cortisol), and the HPT axis hormone levels (thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free triiodothyronine (fT3), and free thyroxine (fT4)). In the BD-M group, the YMRS was positively correlated with baseline T4 (r = 0.349, p = 0.010) and fT4 (r = 0.335, p = 0.013) and negatively correlated with fasting insulin (r = -0.289, p = 0.013). The pre-treatment HOMA-IR was significantly correlated with adverse course (p = 0.045, OR = 0.728). In the BD-D group, the baseline MADRS was significantly positively correlated with baseline fT3 (r = 0.223, p = 0.032) and fT4 (r = 0.315, p = 0.002), while baseline T3 (p = 0.032, OR = 5.071) was significantly positively related to treatment response. The HPT axis and glucose metabolism were closely associated with clinical outcomes at 12 weeks in both BD-D and BD-M groups. If confirmed in further longitudinal studies, monitoring T3 in BD-D patients and HOMA-IR for BD-M could be used as potential treatment response biomarkers.

Association of retinal neurodegeneration with the progression of cognitive decline in Parkinson’s disease

Retinal thickness may serve as a biomarker in Parkinson’s disease (PD). In this prospective longitudinal study, we aimed to determine if PD patients present accelerated thinning rate in the parafoveal ganglion cell-inner plexiform layer (pfGCIPL) and peripapillary retinal nerve fiber layer (pRNFL) compared to controls. Additionally, we evaluated the relationship between retinal neurodegeneration and clinical progression in PD. A cohort of 156 PD patients and 72 controls underwent retinal optical coherence tomography, visual, and cognitive assessments between February 2015 and December 2021 in two Spanish tertiary hospitals. The pfGCIPL thinning rate was twice as high in PD (β [SE] = −0.58 [0.06]) than in controls (β [SE] = −0.29 [0.06], p < 0.001). In PD, the progression pattern of pfGCIPL atrophy depended on baseline thickness, with slower thinning rates observed in PD patients with pfGCIPL below 89.8 µm. This result was validated with an external dataset from Moorfields Eye Hospital NHS Foundation Trust (AlzEye study). Slow pfGCIPL progressors, characterized by older at baseline, longer disease duration, and worse cognitive and disease stage scores, showed a threefold increase in the rate of cognitive decline (β [SE] = −0.45 [0.19] points/year, p = 0.021) compared to faster progressors. Furthermore, temporal sector pRNFL thinning was accelerated in PD (βtime x group [SE] = −0.67 [0.26] μm/year, p = 0.009), demonstrating a close association with cognitive score changes (β [SE] = 0.11 [0.05], p = 0.052). This study suggests that a slower pattern of pfGCIPL tissue loss in PD is linked to more rapid cognitive decline, whereas changes in temporal pRNFL could track cognitive deterioration.

Predictive role of NICU-related stress, postpartum depression trajectory and family coping on growth trajectory of moderate-to-late preterm infants: A longitudinal study.

To describe the changes in moderate-to-late preterm infants' (MLPIs) growth during 12 months of corrected age (CA) and to examine the predictive role of NICU-related stress, postpartum depression trajectory and family coping ability on the physical developmental trajectory of MLPIs. A prospective longitudinal study. There were 237 mother-infant dyads with at least two follow-up data records included. General characteristics and NICU-related stress were recorded from medical records at baseline. Infants' physical growth was measured at 40 weeks, 1, 3, 6, 9 and 12 months CA during outpatient follow-up. Maternal postpartum depressive symptoms and family coping ability were assessed by questionnaires at 1, 3, 6, 9 and 12 months CA and 1 month CA respectively. We investigated the modifiable factors inside and outside of NICU on the trajectories of physical growth in the first year in MLPIs, mainly by using latent growth curve models with time-varying covariates. The curved trajectories of weight, length and head circumference in the first year in MLPIs demonstrated gradually slowed growth rates and these infants were above the WHO growth standards for the same age and sex. The latent growth curve models indicated that more NICU-related stress was negatively associated with the weight and length at 40 weeks CA, and family coping ability (parent-child relationship) at 1 month CA was associated with the growth rate of weight. Besides, more NICU-related stress predicted faster length growth rate. The infants of mothers who were in the group of high-level postpartum depression trajectory had a slower growth rate of head circumference. Our study identified the modifiable factors along the care continuum influencing the trajectory of MLPIs' physical growth. Nurses should receive more training about infant stress measurement and family-centred care to work in partnership with parents so that MLPIs can reach their full developmental potential. Also, multidisciplinary interventions including stress reduction strategies, close psychological monitoring and education improving parent-infant relationships should be further developed to achieve optimizing growth in the first year of MLPIs. It is recommended that nurses pay attention to the long-term physical growth status of MLPIs, and closely support their families. Quantifying NICU-related stress and developing reduction strategies should be the priority for clinical staff during hospitalization. After discharge, persistent screening of depressive symptoms, psychological intervention and education about the parent-child relationship need to be included in the follow-up visits. No patient or public contribution. The study only included patients who were research participants.

Iron deficiency in healthy, term infants aged five months, in a pediatric outpatient clinic: a prospective study

BackgroundIron deficiency (ID) is prevalent in Malaysian children. The incidence of ID in infants under 6 months of age is unknown. Our aim was to determine the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) in healthy, term infants aged below 6 months in our hospital population.MethodsA prospective longitudinal pilot study of mother-infant pairs was conducted on infants receiving routine immunizations in a mother and child clinic at a university hospital, in Kuala Lumpur, Malaysia. Mothers completed standardized questionnaires at 3- and 5-month postnatal visits. Maternal and infant full blood count, ferritin, and C-reactive protein (CRP) levels were measured at 3 months and for the infants repeated at 5 months. Infant anthropometric measurements were obtained at both visits. We conducted a univariate analysis to identify factors associated with ID and IDA.ResultsAltogether, 91 mother-infant pairs were enrolled, with 88 completing the study. No infant had ID or IDA at 3 months; the lowest ferritin level was 16.6 µg/L. At 5 months, 5.9% (5/85) of infants had ID, and 2.4% (2/85) had IDA. Median (interquartile range) infant ferritin levels significantly declined from 113.4 (65.0–183.6) µg/L at 3 months to 50.9 (29.2–70.4) µg/L at 5 months, p < 0.001. Exclusive breastfeeding until 3 or 5 months was significantly associated with ID at 5 months (p = 0.020, and p = 0.008, respectively) on univariate analysis. The drop in ferritin between 3–5 months was significantly associated with weight and length gains between 0–3 months (p = 0.018, p = 0.009, respectively). Altogether, 14.3% of infants exclusively breastfed until 5 months developed ID. At 5 months, 3.4% of infants were underweight, 1.1% stunted, and 10.2% wasted.ConclusionsIn exclusively breastfed term infants, ID occurred by 5 months. Early introduction of iron-rich foods should be considered in exclusively breastfed babies. A high prevalence of wasting suggests a calorie deficit in this population and will lead to stunting if not addressed.

Longitudinal motor system changes from acute to chronic spinal cord injury.

In acute spinal cord injury (SCI), magnetic resonance imaging (MRI) reveals tissue bridges and neurodegeneration for 2 years. This 5-year study aims to track initial lesion changes, subsequent neurodegeneration, and their impact on recovery. This prospective longitudinal study enrolled acute SCI patients and healthy controls who were assessed clinically-and by MRI-regularly from 3 days postinjury up to 60 months. We employed histologically cross-validated quantitative MRI sequences sensitive to volume, myelin, and iron changes, thereby reflecting indirectly processes of neurodegeneration and neuroinflammation. General linear models tracked lesion and remote changes in volume, myelin- and iron-sensitive magnetic resonance indices over 5 years. Associations between lesion, degeneration, and recovery (using the Spinal Cord Independence Measure [SCIM] questionnaire and the International Standards for Neurological Classification of Spinal Cord Injury total motor score) were assessed. Patients' motor scores improved by an average of 12.86 (95% confidence interval [CI] = 6.70-19.00) points, and SCIM by 26.08 (95% CI = 17.00-35.20) points. Within 3-28 days post-SCI, lesion size decreased by more than two-thirds (3 days: 302.52 ± 185.80 mm2 , 28 days: 76.77 ± 88.62 mm2 ), revealing tissue bridges. Cervical cord and corticospinal tract volumes transiently increased in SCI patients by 5% and 3%, respectively, accompanied by cervical myelin decreases and iron increases. Over time, progressive atrophy was observed in both regions, which was linked to early lesion dynamics. Tissue bridges, reduced swelling, and myelin content decreases were predictive of long-term motor score recovery and improved SCIM score. Studying acute changes and their impact on longer follow-up provides insights into SCI trajectory, highlighting the importance of acute intervention while indicating the potential to influence outcomes in the later stages.

Does visuospatial neglect contribute to standing balance within the first 12 weeks post-stroke? A prospective longitudinal cohort study.

Visuospatial neglect (VSN) has been suggested to limit standing balance improvement post-stroke. However, studies investigating this association longitudinally by means of repeated within-subject measurements early post-stroke are lacking. This prospective longitudinal cohort study evaluates the longitudinal association of egocentric and allocentric VSN severity with 1) standing balance independence and 2) postural control and weight-bearing asymmetry (WBA) during quiet standing, in the first 12 weeks post-stroke. Thirty-six hemiplegic individuals after a first-ever unilateral stroke were evaluated at weeks 3, 5, 8 and 12 post-stroke. Egocentric and allocentric VSN severity were evaluated using the Broken Hearts Test. The standing unperturbed item of the Berg Balance Scale (BBS-s) was used to clinically evaluate standing independence. Posturographic measures included measures of postural control (mediolateral (ML)/anteroposterior (AP) net center-of-pressure velocities (COPvel)) and WBA during quiet standing. A linear mixed model was used to examine longitudinal associations between egocentric and allocentric VSN, and BBS-s, COPvel-ML, COPvel-AP and WBA within the first 12 weeks post-stroke. Egocentric (β = -0.08, 95%CI[-0.15;-0.01], P = .029) and allocentric VSN severity (β = -0.09, 95%CI[-0.15; -0.04], P = .002) were significant independent factors for BBS-s scores in the first 12 weeks post-stroke. Egocentric and allocentric VSN were no significant independent factors for COPvel-ML, COPvel-AP and WBA in the first 12 weeks post-stroke. Allocentric and egocentric VSN severity were significantly associated with decreased standing independence, but not impaired postural control or greater asymmetric weight-bearing, in the early subacute post-stroke phase. This may involve traditional VSN measures being not sensitive enough to detect fine-grained VSN deficits due to a ceiling effect between 5 and 8 weeks post-stroke, once the individual regains standing ability. Future studies may require more sensitive VSN measurements to detect such deficits. Trial registration Clinicaltrials.gov. unique identifier NCT05060458.

The Relationship Between Choroidal Abnormalities and Visual Outcomes in Pediatric Patients With NF1-Associated Optic Pathway Gliomas.

Choroidal abnormalities (CAs) visualized on near-infrared reflectance (NIR) imaging are a new diagnostic criterion for neurofibromatosis type 1 (NF1), but the association between the presence of CAs and visual function remains unknown. This study evaluated the relationship between visual acuity (VA) with the presence, number, or total area of CAs visualized by NIR in children with NF1-associated optic pathway gliomas (NF1-OPGs). Patients (<18 years) enrolled in a prospective longitudinal study of children with NF1-associated OPGs from 3 institutions were eligible if they had optical coherence tomography (OCT) of the macula (Heidelberg Spectralis) with ≥1 year of follow-up. The central 30° NIR images were reviewed by 2 neuro-ophthalmologists who manually calculated the number and total area of CAs. VA (logMAR) was measured using a standardized protocol. Cross-sectional associations of presence, number, and total area of CAs with VA, retinal nerve fiber layer thickness (RNFL), and ganglion cell-inner plexiform layer thickness were evaluated at the first and most recent visits using regression models. Intereye correlation was accounted for using generalized estimating equations. Eighty-two eyes of 41 children (56% female) were included. The mean ± SD age at the first OCT was 10.1 ± 3.3 years, with a mean follow-up of 20.4 ± 7.2 months. At study entry, CAs were present in 46% of eyes with a mean number of 2.1 ± 1.7 and a mean total area of 2.0 ± 1.7 mm 2 per eye. At the most recent follow-up, CAs were present in 48% of eyes with a mean number of 2.2 ± 1.8 lesions and a mean total area of 2.3 ± 2.1 mm 2 per eye. Neither VA nor OCT parameters at first and follow-up visits were associated with the presence, number, or total area of CAs (all P > 0.05). CAs are prevalent but not ubiquitous, in children with NF1-OPGs. Although CAs are a diagnostic criterion for NF1, their presence and size do not appear to be associated with visual function.

Changes in foot posture evaluated with dynamic pedobarography over the course of childhood in ambulatory youth with cerebral palsy.

Foot deformities are prevalent in children with cerebral palsy, but there is limited research on the progression of foot posture during growth. Our study aimed to evaluate the change in dynamic foot posture in children with cerebral palsy. Children with cerebral palsy, aged 17-40 months, were recruited to participate in this Institutional Review Board-approved prospective longitudinal study by having serial foot posture evaluations. The coronal plane index and foot segmental impulses were measured with dynamic pedobarography. Data were compared between children stratified by Gross Motor Function Classification System level and typically developing children using serial Welch's t-tests across time with Holm correction for multiple comparisons. In total, 33 children (54 limbs) were included in the analysis (21 bilateral and 12 unilateral; Gross Motor Function Classification System: I-13, II-14, III-4, IV-2. Children completed 16.9 (± 4.4) evaluations (initial age 2.9 (± 0.7) and final age 18.6 (± 1.7) years)). Early valgus foot posture normalizes in children at Gross Motor Function Classification System levels I/II and persists in children at levels III/IV who do not have foot surgery. For most young children, foot posture development is variable. Foot posture in young children with cerebral palsy begins in valgus and tends to normalize in youth who walk without an assistive device. Conservative management of foot deformity is recommended in early childhood. Level II, prognostic study.

Clozapine metabolism and cardiotoxicity: A prospective longitudinal study

BackgroundClozapine-induced myocarditis and cardiomyopathy are difficult to detect clinically and may be fatal if not detected early. The current/routine biomarkers for clozapine-induced myocarditis are non-specific indicators of inflammation (C-reactive protein) or cardiomyocyte damage (troponins I and T) that lack sensitivity, and for which changes often arise too late to be clinically useful. MethodsThe Clozapine Safety Study was a prospective, longitudinal, observational study to determine what, if any, the plasma concentrations of clozapine, N-desmethylclozapine, and clozapine-N-oxide in patients contribute to cardiotoxicity. Samples were collected and analysed using liquid chromatography mass spectrometry over a 41-month period from patients in the Auckland District Health Board. ResultsSixty-seven patients were included. Six patients were diagnosed with myocarditis; none were diagnosed with cardiomyopathy in the study period. In patients not undergoing dose titration, clozapine biotransformation may shift to the N-oxide pathway rather than the N-desmethyl pathway with increasing dose. During dose titration, the timeframe in which myocarditis occurs, the rate of increase in the plasma concentration of clozapine-N-oxide, as well as the ratio of N-oxidation relative to N-desmethylation, were significantly higher in patients diagnosed with myocarditis. ConclusionsThe assessment of clozapine-N-oxide formation, and N-oxidation relative to N-desmethylation ratios during treatment, may help identify a biomarker to aid the early detection of patients at risk of developing clozapine-induced cardiotoxicity.

Multimorbidity-associated emergency hospital admissions: a “screen and link” strategy to improve outcomes for high-risk patients in sub-Saharan Africa: a prospective multicentre cohort study protocol

Background The prevalence of multimorbidity (the presence of two or more chronic health conditions) is rapidly increasing in sub–Saharan Africa. Hospital care pathways that focus on single presenting complaints do not address this pressing problem. This has the potential to precipitate frequent hospital readmissions, increase health system and out-of-pocket expenses, and may lead to premature disability and death. We aim to present a description of inpatient multimorbidity in a multicentre prospective cohort study in Malawi and Tanzania. Primary objectives Clinical: Determine prevalence of multimorbid disease among adult medical admissions and measure patient outcomes. Health Economic: Measure economic costs incurred and changes in health-related quality of life (HRQoL) at 90 days post-admission. Situation analysis: Qualitatively describe pathways of patients with multimorbidity through the health system. Secondary objectives Clinical: Determine hospital readmission free survival and markers of disease control 90 days after admission. Health Economic: Present economic costs from patient and health system perspective, sub-analyse costs and HRQoL according to presence of different diseases. Situation analysis: Understand health literacy related to their own diseases and experience of care for patients with multimorbidity and their caregivers. Methods This is a prospective longitudinal cohort study of adult (≥18 years) acute medical hospital admissions with nested health economic and situation analysis in four hospitals: 1) Queen Elizabeth Central Hospital, Blantyre, Malawi; 2) Chiradzulu District Hospital, Malawi; 3) Hai District Hospital, Boma Ng’ombe, Tanzania; 4) Muhimbili National Hospital, Dar-es-Salaam, Tanzania. Follow-up duration will be 90 days from hospital admission. We will use consecutive recruitment within 24 hours of emergency presentation and stratified recruitment across four sites. We will use point-of-care tests to refine estimates of disease pathology. We will conduct qualitative interviews with patients, caregivers, healthcare providers and policymakers; focus group discussions with patients and caregivers, and observations of hospital care pathways.

Motor difficulties from childhood to midlife: A 40-year cohort study

BackgroundThere are few studies of the persistence of childhood motor difficulties (MD) into adulthood. AimsTo investigate the association of childhood MD with motor skills and body mass index (BMI) in midlife. Methods and proceduresWe studied 324 adults aged 40 from a cohort born in 1971–1974. At age 9, they had undergone the Test of Motor Impairment, used to classify them into groups: childhood MD (cMD), borderline cMD (bcMD), or no cMD. At age 40, participants comprised 23 with cMD, 47 with bcMD, and 254 with no cMD. Participants completed motor tests of balance, manual dexterity, and visuomotor speed, followed by recording of their BMI. Outcomes and resultsAt age 40, the cMD group performed worse than the no-cMD group on all motor tests (p < .001–.008). The bcMD group had slower visuomotor speed than the no-cMD group (p = .025). The groups differed in BMI (p = .002). Having cMD was associated with obesity in midlife (p < .001). After adjusting for sex, childhood socioeconomic status, and BMI at age 9, both cMD and bcMD were associated with obesity in midlife (p = .015). Conclusions and implicationsChildhood MD are associated with poor motor skills, overweight, and obesity in midlife. This emphasises the importance of early intervention and follow-up when a child exhibits MD. What this paper addsThis prospective longitudinal study presents novel evidence that individuals with a history of comprehensively and objectively assessed childhood motor difficulties (MD) have worse motor skills and a higher risk of obesity in midlife than do those with no childhood MD. There is a growing literature on adults with developmental coordination disorder or a history of MD. There is, however, a scarcity of longitudinal studies of childhood MD that continue beyond early adulthood, into midlife. In a systematic search, we could identify only one longitudinal study of objectively measured childhood MD with a reassessment of motor skills in those same participants in adulthood, and no study with a reassessment after age 20. Furthermore, longitudinal studies of the association of comprehensively and objectively assessed childhood MD with BMI in midlife have been lacking.

Long-Term Risk of Reduced Cognitive Performance and Associated Factors in Discharged Older Adults with COVID-19: A Longitudinal Prospective Study.

Increasing numbers of reports have suggested a deterioration in cognitive performance after recovery from coronavirus disease 2019 (COVID-19), however insufficient information is available regarding long-term brain health and risk factors related to reduced cognitive performance in advanced age. We investigated the prevalence of reduced cognitive performance and its associated factors among older adults after COVID-19. This prospective observational study enrolled older individuals (aged ≥65 years) hospitalized for COVID-19. Discharged patients were contacted after an average of 15 months and a brief battery was administered during telephone interviews to assess their mental status. Among the 174 patients, 77 (44.3%) showed reduced cognitive performance at follow-up. Multivariate analysis revealed that female sex, education level, and increased Deyo/Charlson Comorbidity Index score, which is an objective indicator of chronic disease burden, were independent risk factors for long-term cognitive performance. Depression and anxiety symptoms, assessed using the Patient Health Questionnaire-2 and Generalized Anxiety Disorder 2-item questionnaire at the end of the study, were not associated with reduced cognitive performance. Our findings provide key insights into discharged older adults with COVID-19 at risk of long-term cognitive impairment, and help to ascertain the factors associated with this problem.

A longitudinal prospective cohort study of health-related quality of life assessment in outpatient adults with post-COVID-19 conditions.

Few studies have reported the long-term effects of post-COVID-19 condition (PCC) on health-related quality of life (HRQoL). We aim to assess HRQoL in outpatient adults with PCC over a 2-year period. This prospective longitudinal cohort study compared 413 PCC participants (cases) to 520 COVID-19-positive participants who recovered (controls). HRQoL was assessed with the EuroQol 5-Dimension 5-Level preference-based questionnaire (EQ-5D-5L) and fitness and frailty with the Clinical Frailty Scale (CFS) at each visit for up to 24 months. Among a total of 933 participants, 413 (42.3%) met the definition of PCC (cases) and 520 (55.7%) did not (controls). Overall, there was a significant difference in EQ-5D-5L index score from 3 months post-infection up to 18 months between cases and controls (p < 0.001). This score continued to decline up to 18 months in the PCC group only. Most impaired EQ-5D-5L dimensions at 12 months in the PCC group included pain/discomfort, anxiety/depression, and usual activities. This is one of the first studies to report 2-year alterations of HRQoL in outpatients with PCC. Our study highlights the need for continued monitoring for PCC long-term consequences. Given the high proportion of PCC participants experiencing anxiety/depression problems, further studies are needed to specifically address mental health in this population.