Retrospective Longitudinal Study Research Articles

Exploring the Multifactorial Landscape: Risk Factors for Dementia in a Tertiary Care Setting in Thailand.

Dementia poses a significant public health challenge worldwide, necessitating a deeper understanding of its risk factors to inform preventive strategies. This retrospective longitudinal study leveraged clinical data from a tertiary care database to investigate the risk factors associated with an incident dementia diagnosis. The study cohort comprised individuals aged 50 years and older. Key variables including age, income, comorbidities such as depressive disorder, osteoporosis, stroke, and metabolic conditions like type 2 diabetes and hypertension were analyzed by using Cox regression analysis. The study cohort included 127,016 adults 50 years and older. The results revealed that advancing age, with individuals aged 70-79 years having ahazard ratio (HR) of 3.9 (95% confidence interval (CI), 2.6-5.8), and those aged 80 years and above having an HR of 11.6 (95% CI, 7.7-17.3), lower income status (patients with no income or occupation had a notably higher risk of dementia diagnosis, with an HR of 2.0 (95% CI, 1.4-2.8)), depressive disorder (HR of 3.3 (95% CI, 3.3-3.7)), osteoporosis (HR of 1.2 (95% CI, 1.1-1.4)), and stroke (HR of 2.5 (95% CI, 2.3-2.7)) were significantly associated with an increased risk of incident dementia. However, no significant associations were observed for type 2 diabetes, hypertension, obesity, or underweight status managed in tertiary care. The findings underscore the importance of considering a wide range of factors in understanding dementia risk and highlight the potential utility of routinely collected clinical data for comprehensive risk assessment. Further investigation into additional variables and multi-center studies may provide deeper insights into the complex interplay of risk factors contributing to dementia onset.

A retrospective study of the relationship between the presence of complaints and the identified pathological changes in the temporomandibular joint

Introduction. In the practice of an orthodontist, diseases of the temporomandibular joint (TMJ) are an urgent problem due to their widespread, diverse clinical manifestations.Goal. To study the relationship between the identified anatomical and functional disorders of the TMJ, as risk factors for complications during orthodontic treatment, and the presence of characteristic complaints in the structure of pathological changes in the TMJ.Materials and methods. According to the type of organization and the ratio of data collection time, the scientific study belonged to a longitudinal retrospective study, according to the type of observation: case-control. A retrospective analysis of 102 outpatient medical records of patients who sought medical help from an orthodontist at a dental clinic was carried out. The criterion for inclusion in the study was the presence of a newly diagnosed disease of the temporomandibular joint, mandatory radiological diagnostic methods. Magnetic resonance imaging (MRI) of the TMJ in the patient who sought medical help was used as a radiation diagnosis. As part of the scientific study, the structure of pathological changes in the TMJ was analyzed, the relationship between the presence of complaints and the revealed pathology was studied.Results. The analysis of the data showed that the MR examination of the TMJ reveals pathological changes in patients who sought orthodontic care, both with complaints and with an asymptomatic course of diseases. Data analysis did not show a statistically significant relationship between the presence of complaints and the revealed pathology in the case of degenerative (χ2 = 0.123; p > 0.05), inflammatory changes in the TMJ (χ2 = 0.123; p > 0.05) and pathological disorders of the masticatory muscles (F = 0.704; p > 0.05). The relationship is statistically significant, but weak for ventral dislocation without reposition (p < 0.05; φ = 0.107) and the dorsal arrangement of the disc (p < 0.05; φ = 0.101). In the case of ventral dislocation of the articular disc with the reposition, the relationship is statistically significant, of medium strength (p < 0.05; φ = 0.284).Conclusions. The results of a retrospective analysis of medical documentation confirm the need for instrumental research methods for all patients, regardless of whether they have any complaints at the stage of determining the optimal tactics of orthodontic intervention to obtain diagnostic information on the state of the TMJ in order to prevent the risks of complications during orthodontic treatment.

Elevated risk of sexually transmitted infections among adolescents and young adults with borderline personality disorder: a retrospective longitudinal nationwide population-based study.

In this study, we examined the risk of sexually transmitted infections (STIs) among adolescents and young adults (AYAs) with borderline personality disorder (BPD). A total of 4649 AYAs with BPD and 46,490 age-, sex-, and socioeconomic-matched controls without BPD were enrolled from the National Health Insurance Research Database of Taiwan from 2001 to 2009 and were followed up until the end of 2011. Participants who contracted any STI during the follow-up period were identified. Cox regression analysis was conducted to examine the risk of contracting any STI among both patients and controls. A total of 4649 AYAs with BPD and 46,490 age-, sex-, and socioeconomic-matched controls without BPD were enrolled from the National Health Insurance Research Database of Taiwan from 2001 to 2009 and were followed up until the end of 2011. Participants who contracted any STI (ICD-9-CM code 042, 091-097, 087.11, 078.8, 078.88, 131, and 054.1) during the follow-up period were identified. Cox regression and sub-analyses stratified by sex, age, psychiatric comorbidity subgroups, and psychotropic medication usage were conducted to assess STI risk. AYAs with BPD were at a higher risk of contracting any STI (hazard ratio [HR] = 50.79, 95% confidence interval [CI] = 33.45-77.11) in comparison with controls, including HIV, syphilis, genital warts, gonorrhea, chlamydia, trichomoniasis, and genital herpes. The association of BPD with an increased risk of any STI was prevalent in both sexes, adolescents, and young adult patients. BPD with or without psychiatric comorbid subgroup were all associated with an elevated risk of contracting any STI relative to the control group. AYAs with BPD are highly susceptible to contracting STIs. Future studies should examine the role of the core symptoms of BPD, sexual orientation, risky sex behaviors, depressive and anxiety symptoms, and substance use before sex in the risk of STIs among AYAs with BPD.

Impact of comorbidities on relapsing rates of Neuromyelitis Optica Spectrum Disorders: Insights from a longitudinal study in Taiwan

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease characterized by relapsing clinical episodes and the presence of autoantibodies. The impact of comorbidities on relapsing rate of NMOSD patients in Taiwan remains unclear. Methods: We conducted a longitudinal retrospective study using the largest hospital system in Taiwan from 2006 to 2021. Demographic characteristics, annualized relapse rates (ARR), and comorbidities were examined. Results: We identified 485 NMOSD patients from 2006 to 2021. Of these, 466 had the adult form and 19 (3.9 %) had the pediatric form of NMOSD. The median ARR was 0.51 (interquartile range (IQR): 0.26–1.11) for adults and 0.39 (IQR: 0.21–0.77) for pediatric patients. Comorbidities included malignancy (6.7 %) and autoimmune diseases (21.7 %). The recommended age for malignancy surveillance in NMOSD patients was 43.3 years. Neither malignancy nor autoimmune disease increased the ARR within 3 years post diagnosis in NMOSD patients with comorbidities compared with those without comorbidities. Conclusions: Our study revealed the ARR within the initial three years after diagnosis was significantly higher, emphasizing the importance of early treatment. We also observed an association between malignancy and NMOSD, and a significantly higher risk of malignancy in adult patients with NMOSD than in the general population (the relative risk was 5.99) that requiring further investigations into the underlying mechanisms. These findings contribute to a better understanding of NMOSD and its comorbidities in Taiwan.

Bone health and skeletal fragility in second- and third-line medical therapies for acromegaly: preliminary results from a pilot single center experience.

Skeletal fragility is a clinically relevant and not-reversible complication of acromegaly, involving around 30-40% of patients since the disease diagnosis. Few studies have investigated the effects on skeletal health of medical therapies for acromegaly. In this retrospective longitudinal monocentre study, we investigated the outcome of skeletal fragility in patients treated with Pasireotide Lar in combination with Pegvisomant (Pasi-Lar + Peg-V), also comparing those observed in patients treated with conventional therapies. We included 6 patients treated with Pasi-Lar + Peg-V, 5 patients treated with Peg-V in monotherapy (m-Peg-V), 16 patients treated with Peg-V plus first-generation somatostatin receptor ligands (fg-SRLs + Peg-V), 9 patients treated with Pasi-Lar. None of the patients treated with Pasi-Lar + Peg-V experienced worsening of spine and femoral bone mineral density (BMD) and incident vertebral fractures (i-VFs). Eight patients experienced i-VFs. The frequency of i-VFs was significantly lower in patients treated with the Pasi-Lar + Peg-V (0/8; 0%), as compared to those observed in m-Peg-V treated patients (4/8; 50%, p = 0.02). The frequency of i-VFs was slightly but not significantly higher in Pasi-Lar treated patients (1/8; 12.5% p = 0.6) and in fg-SRLs + Peg-V treated patients (3/8; 37.5% p = 0.364), concerning those treated with Pasi-Lar + Peg-V (0/8; 0%). I-VFs occurred more frequently in patients with higher GH levels at acromegaly diagnosis (p < 0.001), and in patients who experienced a BMD worsening (p = 0.005). Our preliminary data suggested that in conventional and multi-drug resistant acromegaly, the combination therapy Pasi-Lar + Peg-V may prevent the worsening of BMD and the occurrence of i-VFs. Prospective and translational studies should further validate these results and ascertain underlying physiopathology mechanisms.

Risk of Dementia in Korean Vietnam War Veterans

BackgroundThe number of cases of all types of dementia is increasing, and a significant increase in prevalence has been noted among veterans. Evidence of an association between dementia and exposure to chemicals such as Agent Orange from the Vietnam War is still limited, and there is a reported lack of awareness.ObjectiveThis study aimed to investigate the risk of dementia among Vietnam War veterans in Korea.DesignThis retrospective longitudinal study compared the incidence of dementia between Vietnam War veterans and the general population.SettingThis study used data from the nationally representative Korean Vietnam War Veterans’ Health Study Cohort, a combined dataset sourced from the Ministry of Patriots and Veterans Affairs in Korea and the National Health Insurance Sharing Service database.ParticipantsThere were 191,272 Vietnam War veterans and 1,000,320 people of different ages, sexes, and residences. matched control in 2002. The total number of person-years were 18,543,181.MeasurementsThe dementia group included participants who had visited a medical facility with any of the following ICD-10 codes in the follow-up periods: “F00 Dementia in Alzheimer’s disease,” “F01 Vascular dementia,” “F02 Dementia in other diseases classified elsewhere,” or “F03 Unspecified dementia.”ResultsThe incidence rate ratio for all types of dementia was 1.16, with higher ratios observed for vascular and unspecified dementia, particularly in the younger age groups. There was a significant increase in the risk of dementia, Alzheimer’s disease, vascular dementia, and unspecified dementia.ConclusionVietnam War veterans showed an increased risk for all types of dementia. These findings are hypothesized to be due to the effects of the chemicals used during the Vietnam War, which can cause a variety of neurodegenerative diseases. Further studies are warranted to investigate the potential health determinants related to the Vietnam War, focusing on the neurodegenerative effects.

Time to severe chronic kidney disease and nephrolithiasis in hypoparathyroidism: results from a large longitudinal retrospective study

Time to severe chronic kidney disease and nephrolithiasis in hypoparathyroidism: results from a large longitudinal retrospective study

Human cat borne rabies as the new epidemiology of the disease in the Andes mountains.

Rabies virus (RABV) is the etiologic agent of rabies, a fatal brain disease in mammals. Rabies circulation has historically involved the dog has the main source of human rabies worldwide. Nevertheless, in Colombia, cats (Felis catus) have become a relevant species in the epidemiology of rabies. To characterize rabies cases in humans in Colombia in the last three decades in the context of the epidemiology of the aggressor animal. We conducted a retrospective longitudinal epidemiological study of human rabies caused by cats' aggression, collecting primary and secondary information. Variables considered included the demography of the patient, symptoms, information about the aggressor animal as the source of infection and the viral variant identified. We found that the distribution of rabies incidence over the years has been constant in Colombia. Nevertheless, between 2003 and 2012 a peak of cases occurred in rural Colombia where cats were the most frequent aggressor animal reported. Most cats involved in aggression were unvaccinated against rabies. Cat's clinical signs at the time of the report of the human cases included hypersalivation and changes in behaviour. Human patients were mostly children and female and the exposure primarily corresponded to bite and puncture lacerations in hands. The RABV lineage detected in most cases corresponded to variant 3, linked to the common vampire bat (Desmodus rotundus). The geographical presentation of cat borne RABV in humans occurred along the Andes mountains, epidemiologically known as the rabies red Andean corridor. By finding cats as the primary source of rabies spillover transmission in Colombia, this report highlights the importance of revising national rabies control and prevention protocol in countries in the Andes region. Our results demonstrate that rabies vaccination for outdoor cats needs to prioritize to reduce the number of rabies-related human deaths.

Effects of Once-Weekly Semaglutide on Cardiovascular Risk Factors and Metabolic Dysfunction-Associated Steatotic Liver Disease in Japanese Patients with Type 2 Diabetes: A Retrospective Longitudinal Study Based on Real-World Data.

Once-weekly semaglutide is a widely used glucagon-like peptide-1 receptor agonist (GLP-1RA) used for the treatment of type 2 diabetes (T2D). In clinical trials, semaglutide improved glycemic control and obesity, and reduced major cardiovascular events. However, the reports are limited on its real-world efficacy relating to various metabolic factors such as dyslipidemia or metabolic dysfunction-associated steatotic liver disease (MASLD) in Asian patients with T2D. In our retrospective longitudinal study, we selected patients with T2D who were given once-weekly semaglutide and compared metabolic parameters before and after the start of semaglutide. Seventy-five patients were eligible. HbA1c decreased significantly, by 0.7-0.9%, and body weight by 1.4-1.7 kg during the semaglutide treatment. Non-HDL cholesterol decreased significantly at 3, 6 and 12 months after the initiation of semaglutide; LDL cholesterol decreased at 3 and 6 months; and HDL cholesterol increased at 12 months. The effects on body weight, HbA1c and lipid profile were pronounced in patients who were given semaglutide as a first GLP-1RA (GLP-1R naïve), whereas improvements in HbA1c were also observed in patients who were given semaglutide after being switched from other GLP-1RAs. During a 12-month semaglutide treatment, the hepatic steatosis index (HSI) tended to decrease. Moreover, a significant decrease in the AST-to-platelet ratio index (APRI) was observed in GLP-1RA naïve patients. Our real-world study confirmed the beneficial effects of once-weekly semaglutide, namely, improved body weight, glycemic control and atherogenic lipid profile. The beneficial effects on MASLD were also suggested.

Healthcare resource utilization and costs among patients with alpha-1 antitrypsin deficiency with liver and/or lung disease: a longitudinal retrospective study in the USA.

Aim: To evaluate all-cause and liver-associated healthcare resource utilization (HCRU) and costs among patients with alpha-1 antitrypsin deficiency (AATD) with liver disease (LD) and/or lung disease (LgD). Materials & methods: This was a retrospective analysis of linked administrative claims data from the IQVIA PharMetrics® Plus and the IQVIA Ambulatory Electronic Medical Records (AEMR) databases from 1July2021 to 31January 2022. Patients with AATD in the IQVIA PharMetrics Plus database were included with ≥1 inpatient or ≥2 outpatient medical claims ≥90days apart with a diagnosis of AATD, or with records indicating a protease inhibitor (Pi)*ZZ/Pi*MZ genotype in the IQVIA AEMR database with linkage to IQVIA PharMetrics Plus. For a patient's identified continuous enrollment period, patient time was assigned to health states based on the initial encounter with an LD/LgD diagnosis. A unique index date was defined for each health state, and HCRU and costs were calculated per person-year (PPY). Results: Overall, 5136 adult and pediatric patients from the IQVIA PharMetrics Plus and IQVIA AEMR databases were analyzed. All-cause and liver-associated HCRU and costs were substantially higher following onset of LD/LgD. All-cause cost PPY ranged from US $11,877 in the absence of either LD/LgD to US $74,015 in the presence of both LD and LgD. Among liver transplant recipients in the AATD with LD health state, liver-associated total costs PPY were US $87,329 1-year pre-transplantation and US $461,752 1-year post-transplantation. In the AATD with LgD and AATD with LD and LgD health states, patients who received augmentation therapy were associated with higher all-cause total costs PPY and lower liver-associated total costs PPY than their counterparts who did not receive augmentation therapy. Conclusion: Patients with AATD had increased HCRU and healthcare costs in the presence of LD and/or LgD. HCRU and healthcare costs were highest in the AATD with LD and LgD health state.

COVID-19 transmission between the community and meat processing plants in Ireland: A retrospective modelling study

Outbreaks of COVID-19 in meat processing plants (MPPs) were recorded globally throughout the pandemic. There was speculation these outbreaks resulted in dissemination of COVID-19 throughout the surrounding county leading to high incidence rates. We aimed to investigate the dynamics of spread between MPPs and their surrounding counties. In this retrospective longitudinal study, data were collected on the number and size of outbreaks in 33 MPPs and county infections in Ireland between March 2020 and May 2021. These data were used to investigate the relationship between outbreaks in MPPs and county infection rates through statistical analysis, and the development of a novel SEIR model. We found an association between the number of MPPs present in a county and county incidence rates, however, incidence rates in the counties did not increase as a consequence of an outbreak in an MPP. The model results indicate that county incidence rates in the weeks prior to an MPP outbreak could reliably predict the size of that outbreak in a plant, r(49) = 0·62, p < 0·0001, RMSD = 5·6. In Ireland, outbreaks in MPPs were strongly correlated with high levels of infection in the surrounding county, rather than being a driver of infection in the county. The modified SEIR model described here can provide an explanation of the generative process required to cause outbreaks of the size and scale that occur in MPPs.

A retrospective study of congenital anomalies and associated risk factors among children admitted at a tertiary hospital in northwestern Tanzania.

Congenital anomalies in Sub-Sahara Africa (SSA) are understudied despite the significant pediatric health burden. This retrospective longitudinal hospital-based study evaluated the records of 326 inpatient children under the age of two years with congenital anomalies at Bugando Medical Centre, a tertiary referral hospital in northwestern Tanzania. Classical logistic regression was used in the analysis of congenital malformation of muscles, gastrointestinal malformation, oral facial clefts, neural tube defects, and skeletal malformations. A modified poisson regression was used to model risk factors for Central Nervous System (CNS) hydrocephalus and congenital heart disease (CHD). A majority (78.8%) of children included in the study were less than six months of age. Nearly half (48.8%) were diagnosed with CHD followed by CNS hydrocephalus (10.4%) and congenital malformation of muscles (8.9%). Babies whose mothers missed periconceptual folic acid supplementation had 83% higher risk of hydrocephalus (aPR = 1.83, 95% CI = 1.11-1.96) and 78% higher for CHD (aPR = 1.78, 95% CI = 1.31-1.94). Male children had 1.67 higher odds of muscular congenital malformations (aOR = 1.67, 95% CI = 1.23-1.89). Less than 37 gestational age had a 1.86 higher odds of muscular congenital malformations (aOR = 1.86, 95% CI = 1.53-3.66). Our study highlights the critical need for folic acid supplementation and establishes a need for a registry and the potential for mapping.

Dynamics and patterns of recurrence in neovascular AMD during real-world management using automated fluid monitoring

In this retrospective longitudinal observational study, data from one site of the Fight Retinal Blindness! Registry (University of Zurich, Switzerland) was used to investigate the quantity and distribution of recurrent fluid in neovascular age-related macular degeneration (nAMD). Study eye eligibility required treatment-naïve nAMD, receiving at least three anti-vascular endothelial growth factor injections, followed by a treatment discontinuation of at least six months and subsequence fluid recurrence. To quantify fluid, a regulatory approved deep learning algorithm (Vienna Fluid Monitor, RetInSight, Vienna, Austria) was used. Fifty-six eyes of 56 patients with a mean age of 76.29 ± 6.58 years at baseline fulfilled the inclusion criteria. From baseline to the end of the first treatment-free interval, SRF volume had decreased significantly (58.0 nl (IQR 10–257 nl) to 8.73 nl (IQR 1–100 nl), p < 0.01). The quantitative increase in IRF volume from baseline to the end of the first treatment-free interval was not statistically significant (1.35 nl (IQR 0–107 nl) to 5.18 nl (IQR 0–24 nl), p = 0.13). PED also did not reach statistical significance (p = 0.71). At the end of the second treatment discontinuation there was quantitatively more IRF (17.3 nl) than SRF (3.74 nl). In conclusion, discontinuation of treatment with anti-VEGF therapy may change the fluid pattern in nAMD.

The Prognostic Value of D-Dimer in Patients with Acute Myocardial Infarction: A Retrospective Longitudinal Cohort Study in Taiwan.

Serum D-dimer level has been associated with worsening outcomes in patients with acute myocardial infarction. This study aimed to explore the association between serum D-dimer level and clinical outcomes in Taiwanese patients with acute myocardial infarction. We analyzed Tri-Service General Hospital-Coronary Heart Disease registry data related to patients with acute myocardial infarction who were admitted between January 2014 and December 2018. A total of 748 patients were enrolled and categorized into high (≥ 495 ng/ml) and low (< 495 ng/ml) D-dimer groups. The primary endpoint was in-hospital mortality, and secondary endpoints were post-discharge mortality and post-discharge major adverse cardiovascular events. Overall, 139 patients died, with 77 from cardiovascular causes and 62 from non-cardiovascular causes. In-hospital mortality was higher in the high D-dimer group than in the low D-dimer group. Among the patients alive at discharge, those with a high D-dimer level had higher cardiovascular mortality and future major adverse cardiovascular events than those with a low D-dimer level. Multivariate Cox regression analysis revealed that higher serum D-dimer levels were significantly associated with higher risks of in-hospital mortality [hazard ratio (HR) = 1.11; 95% confidence interval (CI), 1.06-1.16, p < 0.001], subsequent cardiovascular mortality after discharge (HR = 1.15; 95% CI, 1.08-1.22, p < 0.001), and major adverse cardiovascular events (HR = 1.10; 95% CI, 1.04-1.16, p < 0.001). This is the first study in Taiwan to demonstrate that a higher baseline serum D-dimer level was independently associated with higher risks of in-hospital mortality, post-discharge mortality, and major adverse cardiovascular events in patients with acute myocardial infarction.

EFFECTS OF A PRESCRIBED, SUPERVISED EXERCISE PROGRAMME ON HEALTH-RELATED QUALITY OF LIFE IN ONCOLOGY PATIENTS: A RETROSPECTIVE OBSERVATIONAL COHORT STUDY

INTRODUCTION &amp; AIMS Individuals diagnosed with cancer experience significant physical and psychosocial consequences from oncological treatment. Based on current research, exercise therapy may be a valuable non-pharmacological approach to improve health-related quality of life (HRQoL). However, the effectiveness of individually tailored exercise programs to improve quality of life in real-world settings is understudied. The current study aims to analyse preliminary clinical data regarding the impact of tailored exercise supervised within an Australian private day hospital (LIFT) on HRQoL in individuals diagnosed with cancer. METHODS A retrospective longitudinal cohort study was conducted on adults diagnosed with cancer who attended the LIFT clinical service for at least 12 months between 2020 and 2023. QoL and symptoms were assessed using the Functional Assessment of Cancer Treatment – General Questionnaire (FACT-G). Data collected included diagnosis (type and stage), medical treatment, session frequency, and demographic data. RESULTS Overall, 40 patients (age=67.0±16.8 years) met the inclusion criteria. A within-group analysis demonstrated significant findings in the subscales of emotional wellbeing (p = 0.008) and functional wellbeing (p = 0.003), and significance was also found in the total FACT-G score (p = 0.0019). Interestingly, while not statistically significant, a clinically significant difference in HRQoL was found between individuals completing ≤1 or ≥ 2 supervised exercise sessions per week at LIFT cancer care centre, favouring those completing ≥ 2 sessions. CONCLUSION Preliminary analysis indicated that a “real-world” individualised supervised moderate-vigorous exercise within a day hospital has the potential to significantly improve HRQoL outcomes in individuals diagnosed with cancer.

Physical performance strongly predicts all-cause mortality risk in a real-world population of older diabetic patients: machine learning approach for mortality risk stratification.

Prognostic risk stratification in older adults with type 2 diabetes (T2D) is important for guiding decisions concerning advance care planning. A retrospective longitudinal study was conducted in a real-world sample of older diabetic patients afferent to the outpatient facilities of the Diabetology Unit of the IRCCS INRCA Hospital of Ancona (Italy). A total of 1,001 T2D patients aged more than 70 years were consecutively evaluated by a multidimensional geriatric assessment, including physical performance evaluated using the Short Physical Performance Battery (SPPB). The mortality was assessed during a 5-year follow-up. We used the automatic machine-learning (AutoML) JADBio platform to identify parsimonious mathematical models for risk stratification. Of 977 subjects included in the T2D cohort, the mean age was 76.5 (SD: 4.5) years and 454 (46.5%) were men. The mean follow-up time was 53.3 (SD:15.8) months, and 209 (21.4%) patients died by the end of the follow-up. The JADBio AutoML final model included age, sex, SPPB, chronic kidney disease, myocardial ischemia, peripheral artery disease, neuropathy, and myocardial infarction. The bootstrap-corrected concordance index (c-index) for the final model was 0.726 (95% CI: 0.687-0.763) with SPPB ranked as the most important predictor. Based on the penalized Cox regression model, the risk of death per unit of time for a subject with an SPPB score lower than five points was 3.35 times that for a subject with a score higher than eight points (P-value <0.001). Assessment of physical performance needs to be implemented in clinical practice for risk stratification of T2D older patients.

Human regulatory memory B cells defined by expression of TIM-1 and TIGIT are dysfunctional in multiple sclerosis.

Regulatory B cells (Bregs) play a pivotal role in suppressing immune responses, yet there is still a lack of cell surface markers that can rigorously identify them. In mouse models for multiple sclerosis (MS), TIM-1 or TIGIT expression on B cells is required for maintaining self-tolerance and regulating autoimmunity to the central nervous system. Here we investigated the activities of human memory B cells that differentially express TIM-1 and TIGIT to determine their potential regulatory function in healthy donors and patients with relapsing-remitting (RR) MS. FACS-sorted TIM-1+/-TIGIT+/- memory B (memB) cells co-cultured with allogenic CD4+ T cells were analyzed for proliferation and induction of inflammatory markers using flow cytometry and cytokine quantification, to determine Th1/Th17 cell differentiation. Transcriptional differences were assessed by SMARTSeq2 RNA sequencing analysis. TIM-1-TIGIT- double negative (DN) memB cells strongly induce T cell proliferation and pro-inflammatory cytokine expression. The TIM-1+ memB cells enabled low levels of CD4+ T cell activation and gave rise to T cells that co-express IL-10 with IFNγ and IL-17A or FoxP3. T cells cultured with the TIM-1+TIGIT+ double positive (DP) memB cells exhibited reduced proliferation and IFNγ, IL-17A, TNFα, and GM-CSF expression, and exhibited strong regulation in Breg suppression assays. The functional activity suggests the DP memB cells are a bonafide Breg population. However, MS DP memB cells were less inhibitory than HC DP memB cells. A retrospective longitudinal study of anti-CD20 treated patients found that post-treatment DP memB cell frequency and absolute number were associated with response to therapy. Transcriptomic analyses indicated that the dysfunctional MS-derived DP memB/Breg population exhibited increased expression of genes associated with T cell activation and survival (CD80, ZNF10, PIK3CA), and had distinct gene expression compared to the TIGIT+ or TIM-1+ memB cells. These findings demonstrate that TIM-1/TIGIT expressing memory B cell subsets have distinct functionalities. Co-expression of TIM-1 and TIGIT defines a regulatory memory B cell subset that is functionally impaired in MS.

Virtual insulin pump initiation is safe effective in children adolescents with type 1 diabetes.

There is no head-to-head comparison of the safety and efficacy of virtual versus in-office insulin pump initiation for youth with type 1 diabetes in the US. The study's aim was to determine the safety and efficacy of virtual versus in-office pump initiation in pediatric type 1 diabetes. A longitudinal retrospective study of 112 subjects: 65% (n=73), ages 11.2 ± 3.8 years(y), received in-office training; and 35% (n=39), ages 12.0 ± 4.0y, received virtual training. The number of White subjects was 40 (55%) in the in-office group, and 25 (66%) in the remote group; while Black subjects were 11 (15%) in the in-office group and 4 (10%) in the virtual group. Data were collected at pump initiation, 3 and 6 months. There were no significant differences in sex, race, height, weight, BMI, and the duration of diabetes between the groups at baseline. There was no significant difference in A1c between the groups at 0, 3, and 6 months. A1c correlated significantly with the glucose management indicator at 0, 3, and 6 months: baseline: r=0.49, p<0.0001; 3 months: r=0.77, p<0.0001; and 6 months: r=0.71, p<0.0001. There was no relationship between A1c or TIR and pubertal status, BMI, sex, or race. A1c was significantly elevated in the non-White individuals at 6 months only: 57.9 mmol/mol (50.8-69.4) versus 51.9 mmol/mol (46.5-59.6)], p=0.007. Virtual insulin pump initiation is safe and effective in children with type 1 diabetes. This approach could accelerate the adoption of the use of diabetes technology in minority populations in the US.

Underweight in young Japanese women over time: a longitudinal retrospective study of the change in body mass index from ages 6 to 20 years

Background The high prevalence of underweight in young women has become a serious health problem in Japan. When and how young women reach a low body mass index (BMI) has not been clarified. Aim To clarify the characteristics of BMI standard deviation scores (BMI SDS) trajectory of young Japanese women with underweight. Subjects and methods A total of 601 Japanese female university students aged 20 years were classified into underweight and healthy weight groups. Their school health check-up data were available from the ages of 6 to 20 years. We evaluated the estimated mean values of BMI SDS at each age and differences in BMI SDS (ΔBMI SDS) from 6 years to each age using a mixed-effects model and compared between the two groups at each age. Results In the underweight group, the BMI SDS at every age (−1.67 to −0.91) and the ΔBMI SDS after 16 years of age (−0.76 to −0.38) were significantly lower than those in the healthy weight group (−0.41 to −0.13, −0.07 to 0.04), respectively. Conclusion Young Japanese women with underweight have at least two characteristics of BMI SDS trajectory: being constitutionally underweight and shifting their weight status from baseline towards underweight in their late teens.

Predicting lung function decline in cystic fibrosis: the impact of initiating ivacaftor therapy

BackgroundModulator therapies that seek to correct the underlying defect in cystic fibrosis (CF) have revolutionized the clinical landscape. Given the heterogeneous nature of lung disease progression in the post-modulator era, there is a need to develop prediction models that are robust to modulator uptake.MethodsWe conducted a retrospective longitudinal cohort study of the CF Foundation Patient Registry (N = 867 patients carrying the G551D mutation who were treated with ivacaftor from 2003 to 2018). The primary outcome was lung function (percent predicted forced expiratory volume in 1 s or FEV1pp). To characterize the association between ivacaftor initiation and lung function, we developed a dynamic prediction model through covariate selection of demographic and clinical characteristics. The ability of the selected model to predict a decline in lung function, clinically known as an FEV1-indicated exacerbation signal (FIES), was evaluated both at the population level and individual level.ResultsBased on the final model, the estimated improvement in FEV1pp after ivacaftor initiation was 4.89% predicted (95% confidence interval [CI]: 3.90 to 5.89). The rate of decline was reduced with ivacaftor initiation by 0.14% predicted/year (95% CI: 0.01 to 0.27). More frequent outpatient visits prior to study entry and being male corresponded to a higher overall FEV1pp. Pancreatic insufficiency, older age at study entry, a history of more frequent pulmonary exacerbations, lung infections, CF-related diabetes, and use of Medicaid insurance corresponded to lower FEV1pp. The model had excellent predictive accuracy for FIES events with an area under the receiver operating characteristic curve of 0.83 (95% CI: 0.83 to 0.84) for the independent testing cohort and 0.90 (95% CI: 0.89 to 0.90) for 6-month forecasting with the masked cohort. The root-mean-square errors of the FEV1pp predictions for these cohorts were 7.31% and 6.78% predicted, respectively, with standard deviations of 0.29 and 0.20. The predictive accuracy was robust across different covariate specifications.ConclusionsThe methods and applications of dynamic prediction models developed using data prior to modulator uptake have the potential to inform post-modulator projections of lung function and enhance clinical surveillance in the new era of CF care.