Long-term Observational Studies Research Articles

Long-term clinical observation of patients with heterozygous KIF1A variants.

KIF1A-related disorders (KRDs) encompass recessive and dominant variants with wide clinical variability. Recent genetic investigations have expanded the clinical phenotypes of heterozygous KIF1A variants. However, there have been a few long-term observational studies of patients with heterozygous KIF1A variants. A retrospective chart review of consecutive patients diagnosed with spastic paraplegia at Miyagi Children's Hospital from 2016 to 2020 identified six patients with heterozygous KIF1A variants. To understand the long-term changes in clinical symptoms, we examined these patients in terms of their characteristics, clinical symptoms, results of electrophysiological and neuroimaging studies, and genetic testing. The median follow-up period was 30 years (4-44 years). This long-term observational study showed that early developmental delay and equinus gait, or unsteady gait, are the first signs of disease onset, appearing with the commencement of independent walking. In addition, later age-related progression was observed in spastic paraplegia, and the appearance of axonal neuropathy and reduced visual acuity were characteristic features of the late disease phenotype. Brain imaging showed age-related progression of cerebellar atrophy and the appearance of hyperintensity of optic radiation on T2WI and FLAIR imaging. Long-term follow-up revealed a pattern of steady progression and a variety of clinical symptoms, including spastic paraplegia, peripheral neuropathy, reduced visual acuity, and some degree of cerebellar ataxia. Clinical variability between patients was observed to some extent, and therefore, further studies are required to determine the phenotype-genotype correlation.

Low Rate of AVN and Complications in Unstable SCFE With Epiphyseal-metaphyseal Discontinuity After Treatment With a Modified Dunn Procedure

Background The risk of developing avascular necrosis (AVN) in the setting of an unstable slipped capital femoral epiphysis (SCFE) that is undergoing treatment with the modified Dunn procedure is not well understood. In addition, since the Loder classification of unstable is reportedly different than actual intraoperatively observed instability (that is, discontinuity between the femoral head epiphysis and proximal femoral metaphysis), the overall risk of developing AVN, as well as the potential complications of treatment of these patients with the modified Dunn procedure, are unknown. Questions/purposes To evaluate the modified Dunn procedure for the treatment of patients with epiphyseal-metaphyseal discontinuity, we asked: (1) What was the survivorship free from AVN at 10 years? (2) What was the survivorship free from subsequent surgery and/or complications at 10 years? (3) What were the clinical and patient-reported outcome scores? Methods In a retrospective analysis, we identified 159 patients (159 hips) treated with a modified Dunn procedure for SCFE between 1998 and 2020, of whom 97% (155 of 159) had documentation about intraoperatively observed epiphyseal-metaphyseal stability. Of those, 37% (58 of 155) of patients were documented to have intraoperatively observed epiphyseal-metaphyseal discontinuity and were considered eligible for inclusion, whereas 63% (97 of 155) had documented epiphyseal-metaphyseal stability and were excluded. No patients were lost to follow-up before the 2-year minimum. All patients were assessed for survival, but 7% (4 of 58) did not fill out our outcomes score questionnaire. This resulted in 93% (54 of 58) of patients who were available for outcome score assessment. Additionally, 50% (29 of 58) of patients had not been seen within the last 5 years; they are included, but we note that there is uncertainty about their status. The median (range) age at surgery was 13 years (10 to 16), and the sex ratio was 60% (35 of 58) male and 40% (23 of 58) female patients. Sixty-four percent (37 of 58) of patients were classified as acute-on-chronic, and 17% (10 of 58) of patients were classified as acute. Forty-seven percent (27 of 58) of patients presented with severe slips and 43% (25 of 58) of patients with moderate slips based on radiographic classification. All patients underwent surgical hip dislocation with the modified Dunn procedure to correct the slip deformity and provide stabilization. Complications and reoperations were assessed from a review of electronic medical records, and a Kaplan-Meier estimator was used to estimate survivorship free from complications and reoperations at 10 years. Clinical examination results and questionnaire responses were evaluated at minimum 2-year follow-up. Results Kaplan-Meier survivorship free from AVN was 93% (95% CI 87% to 100%) at 10 years. Survivorship free from any reoperation was 75% (95% CI 64% to 88%) at 10 years. In addition, survivorship free from complications, defined as development of AVN, reoperation, or a Sink Grade II complication or higher, was 57% (95% CI 45% to 73%) at 10 years. The median (range) Merle D’Aubigne Postel score was 18 (14 to 18) for the patients who did not develop AVN, and 12 (6 to 16) for the four patients who developed AVN (p < 0.001). The median modified Harris hip score was 100 (74 to 100) in the non-AVN cohort and 65 (37 to 82) in the AVN cohort (p = 0.001). Median HOOS total score was 95 (50 to 100) in the non-AVN cohort and 53 (40 to 82) in the AVN cohort (p = 0.002). Conclusion Although the modified Dunn procedure is technically challenging, this study shows that in experienced hands, patients with who have demonstrated epiphyseal-metaphyseal discontinuity can be treated with a low risk of AVN and subsequent surgery. Referral of these patients to specialists who have substantial expertise in this procedure is recommended to improve patient outcomes. Prospective, long-term observational studies will help us identify these high-risk patients preoperatively and determine the long-term success of this procedure. Level of Evidence Level IV, therapeutic study.

Incidence and outcomes of subsequent malignancy after allogeneic hematopoietic stem cell transplantation in adult patients with severe aplastic anemia

The allogeneic hematopoietic stem cell transplantation (HSCT) is widely performed for the curative treatment of severe aplastic anemia (SAA). After HSCT, the long-term survival rates of SAA patients have substantially improved, with reported over 80%. However, as the post-HSCT survival period extends, there is a risk of exposure to long-term complications associated with HSCT. One such complication is the development of subsequent malignancies (SNs), which has observed to occur 2-5 times more frequently in HSCT recipients compared to age-matched controls. Although SN can have a critical impact on the survival of patients with SAA post-HSCT, there has been a lack of large-scale, long-term observational studies on the occurrence of SNs after HSCT in a disease of SAA. In this background, we investigated the incidence of SNs after HSCT in adult patients with SAA. This study is a single-center retrospective cohort study conducted on adult patients with SAA who received HSCT from 2002 to 2021. We analyzed the frequency of SN that occurred after HSCT, and the SN types were denominated according to the Surveillance, Epidemiology, and End Results (SEER) database classification. In addition, the cumulative incidence of SNs were analyzed considering death as a competing risk, and the risk factors influencing the occurrence of SN after HSCT were examined using the Fine-Gray model. Total 376 patients were included, and their median age at the time of HSCT was 35 (interquartile range, IQR: 27-46). Of them, 52.9% had received immunosuppressive treatment (ATG+CsA or CsA) before HSCT. HLA-matched sibling, unrelated, haplo-identical donors compromised of 48.7%, 31.6%, and 19.7%, respectively. During the observation period, 30 cases (7.2%) of SN were observed. one patient diagnosed with primary malignancies three times, and another patient having two primary malignancies. Among subsequent malignancies, 33.3% were hematologic malignancies, and 66.7% were solid malignancies. The frequencies of hematologic malignancies were as follows: Post-transplant lymphoproliferative disorder (23.3%), myelodysplastic neoplasm (6.7%), and acute myeloid leukemia (3.3%). The most common solid malignancies were thyroid cancer (26.7%), followed by stomach cancer (13.3%), oral cavity & pharyngeal cancer (10.0%), esophageal cancer (6.7%), bladder cancer, skin cancer, and cervical cancer (3.3% of each). The 15-year cumulative incidence of all malignancies was 13.4% (95% confidence interval [CI]: 7.3%-23.9%) (Figure A). After SN diagnosis, the overall survival rate from the diagnosis of SN (n=27) was 72.3% (95% CI: 55.0%-95.2%) at 12 years (Figure B). The 15-year post-HSCT survival rate for SN patients from the date of HSCT was 74.6% (95% CI: 85.6%-94.9%), which was significantly lower than the survival rate of patients who did not develop SN (n=334, 92.4% [95% CI: 89.6-95.2]) (Log-rank test p = 0.03). Factors identified to have significant impact to the occurrence of SN were the use of Total body irradiation (HR 7.58 [95% CI: 1.07-53.83]) and ATG usage of more than 5mg/kg (HR 7.97 [95% CI: 1.22-52.23]) during HSCT (Table A). We observed occurrences of SN in a considerable proportion of SAA patients after HSCT. Our finding highlights that SN adversely affects survival, and the use of TBI and high dose of ATG were found to be significantly associated with SN occurrence. Therefore, SAA patients having these factors during conditioning regimen should be carefully monitored after HSCT.

Real-world use of ofatumumab to treat multiple sclerosis 9 months post-FDA approval during COVID-19 pandemic.

Relapsing multiple sclerosis (MS) is an inflammatory, demyelinating, neurodegenerative disease of the central nervous system that causes episodes of neurological dysfunction (relapse) alternating with variable intervals of stability. Disease-modifying therapies (DMTs) aim to reduce the rate of relapse and slow disease progression in people with MS, particularly in those with relapsing MS. Ofatumumab is a fully human anti-CD20 monoclonal antibody approved to treat patients with relapsing forms of MS. This study describes the demographics, clinical characteristics, and prior DMT use of patients with at least one ofatumumab prescription claim following approval by the United States (US) Food and Drug Administration (FDA). Understanding ofatumumab utilization patterns and patient characteristics can help define the journey of patients with MS and aid future clinical decision-making. This retrospective study is based on data from IQVIA's Longitudinal Prescription Data (LRx) and Medical Claims (Dx) databases in the US, collected between August 01, 2019 and May 31, 2021. The index date was defined as the date of the first ofatumumab prescription. The pre-index period was defined as the 12 months prior to the index date. Adult patients (aged ≥18 years) with a diagnosis of MS and at least one prescription for ofatumumab between August 2020 and May 2021 in the LRx database were included. Only patients with at least one medical claim in the Dx database and a diagnosis of MS 24 months prior to the index date were included. Descriptive analyses were conducted 3, 6, and 9 months after FDA approval. Overall, 3,600 patients with a prescription for ofatumumab were identified in the LRx claims database, and 2,101 patients remained in the study after inclusion and exclusion criteria had been applied. At the 9-month post-approval time point, patients with ofatumumab claims were characterized as primarily female (74%) and middle-aged (median age: 48 years); two-thirds (64.7%) had a mild MS disability level. Patients were otherwise generally healthy with limited comorbid conditions. Most patients (81.7%) in the study did not experience relapse during the pre-index period. DMT-naïve patients who were prescribed ofatumumab at 3, 6, and 9 months post-approval accounted for 46.9%, 54.8%, and 58.4% of the study population, respectively. Over time, this increase in DMT-naïve ofatumumab initiators was statistically significant (p=0.0003). Among patients who had been treated with DMTs during the previous year, most had taken them orally (50.6%), some had received them via intravenous infusion (32.2%), and some via subcutaneous/intramuscular injection (21.1%). Intravenous ocrelizumab was the most common DMT switch observed (n=205, 23.4%) among these patients. This real-world study is the first to describe patients treated with ofatumumab since FDA approval during the COVID-19 pandemic. The majority of patients in this study were middle-aged women with mild MS symptoms. Ofatumumab was increasingly used as a first-line DMT. Additionally, a number of patients aged ≥55 years (beyond the trial population) used ofatumumab, which may suggest expanding clinician confidence in the safety and clinical utility of ofatumumab therapy. However, future long-term observational studies are needed to confirm these results.

Long-Term Observational Characteristics of Different Severe Convective Wind Types around Australia

Abstract Regional understanding of severe surface winds produced by convective processes [severe convective winds (SCWs)] is important for decision-making in several areas of society, including weather forecasting and engineering design. Meteorological studies have demonstrated that SCWs can occur due to a number of different mesoscale and microscale processes, in a range of large-scale atmospheric environments. However, long-term observational studies of SCW characteristics often have not considered this diversity in physical processes, particularly in Australia. Here, a statistical clustering method is used to separate a large dataset of SCW events, measured by automatic weather stations around Australia, into three types, associated with strong background wind, steep lapse rate, and high moisture environments. These different types of SCWs are shown to have different seasonal and spatial variations in their occurrence, as well as different measured wind gust, lightning, and parent-storm characteristics. In addition, various convective diagnostics are tested in their ability to discriminate between measured SCW events and nonsevere events, with significant variations in skill between event types. Differences in environmental conditions and wind gust characteristics between event types suggests potentially different physical processes for SCW production. These findings are intended to improve regional understanding of severe wind characteristics, as well as environmental prediction of SCWs in weather and climate applications, by considering different event types. Significance Statement The purpose of this study is to improve regional understanding of different types of severe wind events in Australia, specifically those associated with atmospheric convection. We did this by constructing a dataset of 413 severe convective wind events, using weather station and radar data within 20 regions around Australia. We then split those events into three different types, based on the environmental conditions that they occur within. We found that each event type tends to occur at different times of the year and in different regions, while also having different wind gust and lightning characteristics. In addition, the atmospheric conditions that are helpful for prediction of severe wind events differs between each type. These results are intended to be useful for prediction of severe wind events associated with convection and assessing their variability, characteristics, and impacts, in both weather forecasting and climate analysis.

Objective sleep was longitudinally associated with brain amyloid burden in mild cognitive impairment.

Understanding the longitudinal association of objective sleep and physical activity with brain amyloid burden and cortical glucose metabolism has critical clinical and public health implications for dementia prevention in later life. We enrolled 118 individuals aged ≥65 years with mild cognitive impairment, who were followed up on from August 2015 to September 2019. All participants continuously wore an accelerometer sensor for 7 consecutive days every 3 months and received annual 11 C-Pittsburgh compound-B and 18 F-fluorodeoxyglucose positron emission tomography (PET). Sleep and physical activity parameters were assessed using accelerometer sensor data andPET imaging was quantified using a standardized uptake-value ratio. Fifty-seven participants (48.3%) completed a lifestyle factor assessment and PET imaging over the 3-year period. A linear mixed-effects model was applied to examine the longitudinal association of sleep and physical activity parameters with PET imaging over the 3-year period, controlling for potential confounders. Sleep efficiency was inversely associated with amyloid uptake in the frontal lobe. Although sleep duration was positively associated with global amyloid uptake, particularly in the frontal lobe, their impact was extremely small. However, physical activity parameters were not significantly associated with the 11 C-Pittsburgh compound-B-uptake. Furthermore, sleep and physical activity parameters were not significantly associated with cortical glucose metabolism. Lower sleep efficiency could be an early symptom of greater brain amyloid burden at the mild cognitive impairment stage. Therefore, the assessment of sleep may be useful for identifying individuals at higher risk for brain amyloid burden. Future longer term observational studies are required to confirm these findings.

The safety of systemic Janus kinase inhibitors in atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials.

Janus kinase (JAK) inhibitors have been recently approved by the FDA and are widely used in the treatment of patients with atopic dermatitis. However, a comprehensive safety profile of JAK inhibitors in patients with atopic dermatitis has not been analysed. This study aimed to establish clinical evidence for the safety of systemic JAK inhibitors in patients with atopic dermatitis. Medline, Embase, Clinicaltrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL) and International Clinical Trials Registry Platform (ICTRP) were considered for search databases. Randomized controlled trials reporting the adverse events of systemic therapy in patients with atopic dermatitis were included. The risk of 11 adverse events was compared between the JAK inhibitors and placebo groups. Fourteen randomized controlled trials were analysed published between 2019 and 2022. The JAK inhibitors included in the analysis were abrocitinib (10, 30, 100 and 200 mg), baricitinib (1, 2 and 4 mg) and upadacitinib (7.5, 15 and 30 mg). The risk of herpes zoster, headache, acne, elevated blood creatinine phosphokinase and nausea was significantly increased, but the risk of serious infection, non-melanoma skin cancer (NMSC), malignancies other than NMSC, major adverse cardiovascular event, venous thromboembolism and nasopharyngitis was not increased. This study provides comprehensive clinical evidence on the risk of various adverse events in patients with atopic dermatitis. However, since the follow-up periods of the studies analysed in this review were mostly limited to 16 weeks or less, it is recommended that comprehensive long-term observational studies be conducted to determine any potential adverse events associated with major cardiovascular events or malignancies, which typically have prolonged courses.

Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study.

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan-Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8-91.5%) at month 12, 78.8% (95% CI: 78.8-85.2%) at month 24, 63.8% (95% CI: 55.1-73.8%) at month 36, and 59.9% (95% CI: 55.1-73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results.

Association between dietary carbohydrate intake and risk of type 2 diabetes: a systematic review and meta-analysis of cohort studies.

Previous meta-analyses have assessed the relationship between carbohydrate intake and type 2 diabetes (T2D) risk; however, they included few studies of Asian populations who have a higher carbohydrate intake and lower insulin secretory capacity than non-Asians. Since the publication of the previous meta-analyses, three further studies of Asian populations have been conducted. Based on this background, the present study aimed to perform an updated systematically examine observational studies concerning the link between dietary carbohydrate intake and T2D risk. We conducted a systematic search for cohort studies that investigated the target association. For each analyzed study, parameter-adjusted risk ratios were used to compare the lowest and highest carbohydrate-intake groups in terms of their risk of incident T2D. The risk ratios were calculated using a random-effects model. Ten publications were analyzed. Overall, carbohydrate intake was found not to be associated with increased risk ratios of incident T2D (risk ratio [RR] = 1.07; 95% confidence interval [95% CI] = 0.94, 1.21; P < 0.01, I2 = 61.9%). However, studies of Asian populations reported that high carbohydrate intake is significantly associated with this risk (RR = 1.29; 95% CI 1.15, 1.45; P = 0.59, I2 = 0.0%). This updated meta-analysis showed that, overall, carbohydrate intake is not associated with the risk of T2D; nevertheless, a significant association exists among Asian populations. To confirm the association between dietary carbohydrate intake and T2D risk observed in this study, further evidence from long-term observational studies of Asian populations is required. The online version contains supplementary material available at 10.1007/s13340-023-00642-0.

Differential Effects of Anti-PD-1/PD-L1 Checkpoint Inhibitors on Adhesion Molecules and Cytokine Secretion by THP-1 Monocytes.

Immune checkpoint inhibitors have improved the treatment regimen for human cancers in recent years. Particularly, inhibitors of the checkpoint molecules PD-1/PD-L1 have emerged as promising therapeutic treatments by preventing T-cell anergy and exhaustion. However, the impact of different anti-PD-1/PD-L1 checkpoint inhibitors on human monocytes remains elusive. In this study, using the human monocyte leukemia cell line THP-1 as a model, we investigated the influence of different therapeutic anti-PD-1/PD-L1 checkpoint inhibitors on monocytic adhesion molecule expression and cytokine secretion. THP-1 monocytes were treated with the anti-PD-1 checkpoint inhibitors Nivolumab and Pembrolizumab and anti-PD-L1 checkpoint inhibitors Atezolizumab and Durvalumab. Cytokine expression patterns were evaluated using cytokine arrays and enzyme-linked immunosorbent assays (ELISA) and analysis of adhesion molecules was addressed using flow cytometry. Our data show an overall moderate apoptosis induction upon checkpoint inhibitor treatment and significantly reduced expression levels of adhesion molecules CD29, CD49d, and CX3CR1 in response to anti-PD-1 treatment. Cytokine screening revealed overall decreased secretion levels of insulin-like growth factor binding protein 2 (IGFBP2), CD147 (basigin) and CD31 (PECAM-1) as well as elevated levels of interleukin 5 (IL-5) and interferon gamma (IFNγ) in response to checkpoint inhibitor treatment. Our data indicate differential effects of anti-PD-1/PD-L1 checkpoint inhibitors on THP-1 monocytes, both by specific anti-PD-1/PD-L1 binding and unspecific antibody IgG isotype recognition. Further investigations on peripheral blood monocyte subsets in terms of their expansion and function upon checkpoint inhibitor therapy are required to better understand the individual immunological balances in cancer patients in long-term observational studies.

Efficacy of Serotonin and Dopamine Activity Modulators in the Treatment of Negative Symptoms in Schizophrenia: A Rapid Review

Schizophrenia is among the fifteen most disabling diseases worldwide. Negative symptoms (NS) are highly prevalent in schizophrenia, negatively affect the functional outcome of the disorder, and their treatment is difficult and rarely specifically investigated. Serotonin-dopamine activity modulators (SDAMs), of which aripiprazole, cariprazine, brexpiprazole, and lumateperone were approved for schizophrenia treatment, represent a possible therapy to reduce NS. The aim of this rapid review is to summarize the evidence on this topic to make it readily available for psychiatrists treating NS and for further research. We searched the PubMed database for original studies using SDAM, aripiprazole, cariprazine, brexpiprazole, lumateperone, schizophrenia, and NS as keywords. We included four mega-analyses, eight meta-analyses, two post hoc analyses, and 20 clinical trials. Aripiprazole, cariprazine, and brexpiprazole were more effective than placebo in reducing NS. Only six studies compared SDAMs with other classes of antipsychotics, demonstrating a superiority in the treatment of NS mainly for cariprazine. The lack of specific research and various methodological issues, related to the study population and the assessment of NS, may have led to these partial results. Here, we highlight the need to conduct new methodologically robust investigations with head-to-head treatment comparisons and long-term observational studies on homogeneous groups of patients evaluating persistent NS with first- and second-generation scales, namely the Brief Negative Symptom Scale and the Clinical Assessment Interview for Negative Symptoms. This rapid review can expand research on NS therapeutic strategies in schizophrenia, which is fundamental for the long-term improvement of patients' quality of life.

Nitrogen dynamics in the Critical Zones of China

Nitrogen dynamics at ecosystem levels profoundly impact the Earth’s surface system due to their environmental and ecological significance. Exploring the sources and transformation of nitrogen in various Critical Zones is vital to understanding biogeochemical cycles and sustainable development. This study summarized nitrogen characteristics in soil profiles and nitrogen dynamics in diverse terrestrial ecosystems based on data from typical Critical Zones of China. The results indicated that nitrogen accumulates in the deep soils of cropland ecosystems due to intensive fertilizer applications, which potentially harms soil functions and water quality. Therefore, it is necessary and meaningful to take adequate measures to alleviate nitrogen accumulation in deep soils. Additionally, surplus nitrogen transported into groundwater and riverine systems from soil has emerged as an important issue for environmental management. There are serious nitrogen pollution issues in many river water and groundwater areas, which could be addressed by reducing the fast leaching and considerable nitrogen accumulation in the vadose zone. Systematic and long-term observational studies are needed to achieve the ultimate goal of ecological conservation and high-quality development. Therefore, future research should consider monitoring and evaluating ecosystems based on the long-term Critical Zone Observatories networks to advance appropriate environmental management strategies that adapt to nature’s rules and strengthen the ecosystem service function for sustainable development.

A systematic literature review informing the consensus statement on efficacy and safety of pharmacological treatment with interleukin-6 pathway inhibition with biological DMARDs in immune-mediated inflammatory diseases

ObjectivesInforming an international task force updating the consensus statement on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) selectively targeting interleukin-6 (IL-6) pathway in the context of immune-mediated inflammatory...

ÇOCUK İŞÇİLERİN SAĞLIK SORUNLARININ OMAHA SİSTEMİ İLE BELİRLENMESİ: İSTANBUL'UN BİR KENAR MAHALLESİNDEN ÖRNEK

Objective: This study assessed health problems of migrant and non-migrant child workers in lower-secondary schools from suburb of Istanbul. Method: This descriptive and observational study was conducted in Istanbul. It comprised child workers. Descriptive Characteristics Assessment Form and Nightingale Notes Software based on the terminology of the Omaha System were used for data collection. Results: The participants were 81 child workers aged 10–13 years, 86% were male, and 12% were migrants from Syria. Eighty-five percent worked to contribute their family income. The most common health problems were mental health, neglect, income, oral health, nutrition, personal care, physical activity, sleep and rest patterns, and neighbourhood/workplace safety. There was an association between mental health problems and family health status;between individual health status and oral health as well as role change;between maternal education level and oral health as well as personal care and between nutrition and paternal education level (p&amp;lt;.05). Conclusion: The Omaha system was found suitable for determining health problems of migrant and non-migrant juvenile labor. However, it is necessary to prevent poverty, develop the understanding of the social state, and comply with legal norms. We recommend that researchers examine the health of child workers in long-term and mixed-method observational studies.

Impact of climate change on the epidemiology of vector-borne diseases in Pakistan

Climate change is a hard reality that has already started affecting air quality, food production, water supply, coastal settlements, and human health. There is increasing evidence about the effect of climate change on vector-borne diseases (VBDs). In this article, we have collected data from published articles, journals, reports, and books on VBDs in Pakistan and review the changing epidemiology of the most important VBDs i.e. Malaria, Dengue fever, Chikungunya, Leishmaniasis, Crimean-Congo hemorrhagic fever (CCHF), West Nile fever and Japanese encephalitis in Pakistan. We have summarized the district-wise VBDs outbreaks and developed maps. There is no proper surveillance of vectors and diseases available in Pakistan. Early warning system for preventing outbreaks are direly needed. No study has done not the effect of climate change on disease vectors in Pakistan. Long-term observational studies are needed to monitor climate-change effects on vector-borne diseases in Pakistan. A multidisciplinary effort is needed to handle the situation before the vector-borne diseases become an epidemic in non-endemic areas. It is essential to address issues related to the establishment of the vector surveillance system, integrated vector management (IVM), and climate change with the utmost priority for the prevention and control of VBDs in Pakistan.

COVID-19 and Parkinsonism: A Critical Appraisal.

A few cases of parkinsonism linked to COVID-19 infection have been reported so far, raising the possibility of a post-viral parkinsonian syndrome. The objective of this review is to summarize the clinical, biological, and neuroimaging features of published cases describing COVID-19-related parkinsonism and to discuss the possible pathophysiological mechanisms. A comprehensive literature search was performed using NCBI’s PubMed database and standardized search terms. Thirteen cases of COVID-19-related parkinsonism were included (7 males; mean age: 51 years ± 14.51, range 31–73). Patients were classified based on the possible mechanisms of post-COVID-19 parkinsonism: extensive inflammation or hypoxic brain injury within the context of encephalopathy (n = 5); unmasking of underlying still non-symptomatic Parkinson’s Disease (PD) (n = 5), and structural and functional basal ganglia damage (n = 3). The various clinical scenarios show different outcomes and responses to dopaminergic treatment. Different mechanisms may play a role, including vascular damage, neuroinflammation, SARS-CoV-2 neuroinvasive potential, and the impact of SARS-CoV-2 on α-synuclein. Our results confirm that the appearance of parkinsonism during or immediately after COVID-19 infection represents a very rare event. Future long-term observational studies are needed to evaluate the possible role of SARS-CoV-2 infection as a trigger for the development of PD in the long term.

Trends in western USA fire fuels using historical data and modeling

BackgroundRecent increases in wildfire activity in the Western USA are commonly attributed to a confluence of factors including climate change, human activity, and the accumulation of fuels due to fire suppression. However, a shortage of long-term forestry measurements makes it difficult to quantify regional changes in fuel loads over the past century. A better understanding of fuel accumulation is vital for managing forests to increase wildfire resistance and resilience. Numerical models provide one means of estimating changes in fuel loads, but validating these models over long timescales and large geographic extents is made difficult by the scarcity of sufficient data. One such model, MC2, provides estimates of multiple types of fuel loads and simulates fire activity according to fuel and climate conditions. We used the Forest Inventory and Analysis Database (FIADB) observed data to validate MC2 estimates of fuel load change over time where possible.ResultsWe found that the MC2 model’s accuracy varied geographically, but at a regional scale the distributions of changes in fuel loads were similar to distributions of FIADB values. While FIADB data provided consistent measurement types across a wide geographic area, usable data only spanned approximately 30 years. We therefore supplemented this quantitative validation with a qualitative comparison to data that covered less area, but for much longer time spans: long-term forestry plots outside of the FIA plot network and repeat photography studies. Both model results and long-term studies show increases in fuel loads over the past century across much of the western USA, with exceptions in the Pacific Northwest and other areas. Model results also suggest that not all of the increases are due to fire suppression.ConclusionsThis model validation and aggregation of information from long-term studies not only demonstrate that there have been extensive fuel increases in the western USA but also provide insights into the level of uncertainty regarding fire suppression’s impact on fuel loads. A fuller understanding of changing fuel loads and their impact on fire behavior will require an increase in the number of long-term observational forestry studies.

Allogeneic hematopoietic stem cell transplantation for inherited metabolic disorders.

Allogeneic hematopoietic stem cell transplantation (HSCT) has been used to treat patients with inherited metabolic disorders (IMDs) for more than 40years. In the first two decades, various IMDs were treated by HSCT with a wide variety of donor sources and conditioning regimens selected at the institutional level. However, HSCT was not always successful due to post-transplant complications such as graft failure. In the third decade, myeloablative conditioning with targeted busulfan-based pharmacokinetic monitoring was established as an optimal conditioning regimen, and unrelated cord blood was recognized as an excellent donor source. During the fourth decade, further improvements were made to transplant procedures, including modification of the conditioning regimen, and the survival rate after HSCT markedly improved. Simultaneously, several long-term observational studies for patients after HSCT clarified its therapeutic effects on growth and development of cognitive function, fine motor skills, and activities of daily living when compared with enzyme replacement therapy. Although immune-mediated cytopenia was newly highlighted as a problematic morbidity after HSCT for IMDs, especially in younger patients who received unrelated cord blood, a recent study with rituximab added to the conditioning raised expectations that this issue can be overcome.

How Does Deep Brain Stimulation Change the Course of Parkinson's Disease?

A robust body of evidence from randomized controlled trials has established the efficacy of deep brain stimulation (DBS) in reducing off time and dyskinesias in levodopa‐treated patients with Parkinson's disease (PD). These effects go along with improvements in on period motor function, activities of daily living, and quality of life. In addition, subthalamic DBS is effective in controlling drug‐refractory PD tremor. Here, we review the available data from long‐term observational and controlled follow‐up studies in DBS‐treated patients to re‐examine the persistence of motor and quality of life benefits and evaluate the effects on disease progression, major disability milestones, and survival. Although there is consistent evidence from observational follow‐up studies in DBS‐treated patients over 5–10 years and beyond showing sustained improvement of motor control, the long‐term impact of DBS on overall progression of disability in PD is less clear. Whether DBS reduces or delays the development of later motor and non‐motor disability milestones in comparison to best medical management strategies is difficult to answer by uncontrolled observational follow‐up, but there are signals from controlled long‐term observational studies suggesting that subthalamic DBS may delay some of the late‐stage disability milestones including psychosis, falls, and institutionalization, and also slightly prolongs survival compared with matched medically managed patients. These observations could be attributable to the sustained improvements in motor function and reduction in medication‐induced side effects, whereas there is no clinical evidence of direct effects of DBS on the underlying disease progression. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Abstract 112: Post-COVID vaccination ASIA syndrome (autoimmune/inflammatory syndrome induced by adjuvants) and thyroid dysfunction

Background: ASIA syndrome is an entity that incorporates diverse autoimmune conditions after exposure to various adjuvants in vaccines. There is limited literature available regarding development of thyroid disorders after covid 19 vaccination.Aims and Objectives: Retrospective case series of patients diagnosed with thyroid disease within 2 months of covid-19 vaccination. History, examination, relationship with covid infection and vaccination, onset of symptoms, thyroid function tests, TRAb, Anti-TPO, ESR, CRP, Tc99-thyroid scan were recorded for each of the patient.Results: We observed 9 subjects (females 5, males 4; age range 22-63 yrs) with thyrotoxicosis. The onset of symptoms after vaccination ranged from 2 days to 60 days. Six subjects had Graves’ disease (GD) while 3 had subacute thyroiditis (SAT). Two subjects had acute onset of thyroid associated opthalmopathy; one patient needed glucocorticoids (GC). All subjects with GD were treated with antithyroid drugs while subjects with SAT were treated with NSAIDS; none required GC.Conclusions: SAT and GD may develop as a manifestation of ASIA syndrome after covid 19 vaccine. Long-term multicentric observational studies are needed to establish the natural history of ASIA syndrome following covid vaccination.