Absolute Number Research Articles

Does sex influence the natural history of idiopathic adult-onset dystonia?

BackgroundSeveral earlier studies showed a female predominance in idiopathic adult-onset dystonia (IAOD) affecting the craniocervical area and a male preponderance in limb dystonia. However, sex-related differences may result from bias...

Descemet’s membrane endothelial keratoplasty is the predominant keratoplasty procedure in Germany since 2016: a report of the DOG-section cornea and its keratoplasty registry

Background/aimsThis retrospective multicentric panel study provides absolute numbers, types of and indications for corneal transplantation in Germany from 2011 to 2021 and sets them into the international context.MethodsA questionnaire was...

Progression, reliability, predicting parameters and sample size calculations for quantitative fundus autofluorescence measures in ABCA4-related retinopathy

Background/aimsTo investigate the progression of quantitative autofluorescence (qAF) measures and the potential as clinical trial endpoint in ABCA4-related retinopathy.MethodsIn this longitudinal monocentre study, 64 patients with ABCA4-related retinopathy (age (mean±SD),...

The burden of Cardiovascular diseases in Jordan: a longitudinal analysis from the global burden of disease study, 1990–2019

BackgroundCardiovascular Disease (CVD) is the leading cause of mortality worldwide. While countries in the Arab world continue to lack public health data and be severely understudied in health research, previous research has shown that compared to 1990, CVDs had a higher burden of disease in the Arab World in 2010. Jordan, a middle-income Arab country, is profiled with unique attributes such as a dual-sector healthcare system, political stability, and its role as a haven for refugees and migrants. These distinctive factors emphasize Jordan’s suitability as a case study. This investigation aims to quantify CVD burden in Jordan and identify risk factors, contributing to a broader understanding of health challenges in the Arab region and beyond.MethodsThe Global Burden of Disease (GBD) dataset was used to estimate prevalence, death, and disability-adjusted life-years (DALYs) as age-standardized rates from 1990 to 2019. We calculated percentage change for nine specific CVDs and reported trends by gender and age groups. Additionally, data on twelve a priori selected behavioral, clinical, and environmental risk factors attributing to overall age-standardized CVDs DALY were reported per 100,00 population.ResultsIn 2019, the age-standardized CVD prevalence, death, and DALYs rates in Jordan were 7980 (95% uncertainty interval [UI] 7629, 8360), 248 (95% UI 211, 288), and 4647 (95% UI 4028, 5388), respectively. Despite an increase in the absolute number of mortality and prevalence, between 1990 and 2019, the age-standardized prevalence, death, and DALYs rates all decreased by 5.5%, 45.1%, and 46.7%, respectively. In 2019, the leading risk factors contributing to overall age-standardized CVDs DALY per 100,000 population were high systolic blood pressure, high BMI, dietary risks, and high LDL cholesterol.ConclusionDespite decreasing burden rate of CVDs in Jordan between 1990 and 2019, CVDs remain the leading cause of mortality in Jordan, with an increase in the total number of prevalence and mortality. Overall, this contributes to increased healthcare costs. Further research is required to quantify the burden of CVDs and understand it better. Intervention measures and policies tailored to specific CVDs should be designed to reduce the burden of CVDs in Jordan.

Id1 expression in CD4 T cells promotes differentiation and function of follicular helper T cells and upregulation of related functional molecules.

Although the roles of E proteins and inhibitors of DNA-binding (Id) in T follicular helper (TFH) and T follicular regulatory (TFR) cells have been previously reported, direct models demonstrating the impact of multiple E protein members have been lacking. To suppress all E proteins including E2A, HEB and E2-2, we overexpressed Id1 in CD4 cells using a CD4-Id1 mouse model, to observe any changes in TFH and TFR cell differentiation. Our objective was to gain better understanding of the roles that E proteins and Id molecules play in the differentiation of TFH and TFR cells. The CD4-Id1 transgenic (TG) mice that we constructed overexpressed Id1 in CD4 cells, inhibiting E protein function. Our results showed an increase in the proportion and absolute numbers of Treg, TFH and TFR cells in the spleen of TG mice. Additionally, the expression of surface characterisation molecules PD-1 and ICOS was significantly upregulated in TFH and TFR cells. The study also revealed a downregulation of the marginal zone B cell precursor and an increase in the activation and secretion of IgG1 in spleen B cells. Furthermore, the peripheral TFH cells of TG mice enhanced the function of assisting B cells. RNA sequencing results indicated that a variety of TFH-related functional molecules were upregulated in TFH cells of Id1 TG mice. In conclusion, E proteins play a crucial role in regulating TFH/TFR cell differentiation and function and suppressing E protein activity promotes germinal centre humoral immunity, which has important implications for immune regulation and treating related diseases.

Global disease burden linked to diet high in red meat and colorectal cancer from 1990 to 2019 and its prediction up to 2030.

Numerous studies have already identified an association between excessive consumption of red meat and colorectal cancer (CRC). However, there has been a lack of detailed understanding regarding the disease burden linked to diet high in red meat and CRC. We aim to offer evidence-based guidance for developing effective strategies that can mitigate the elevated CRC burden in certain countries. We used the data from the Global Burden of Disease (GBD) Study 2019 to evaluate global, regional, and national mortality rates and disability-adjusted Life years (DALYs) related to diet high in red meat. We also considered factors such as sex, age, the socio-demographic index (SDI), and evaluated the cross-national inequalities. Furthermore, we utilized DALYs data from 204 countries and regions to measure cross-country inequalities of CRC by calculating the slope index of inequality and concentration index as standard indicators of absolute and relative inequalities. The results show that globally, the age-standardized mortality rate (ASMR) and age-standardized disability adjusted life year rate (ASDR) related to CRC due to diet high in red meat have decreased, with estimated annual percent change (EAPCs) of -0.32% (95% CI -0.37 to -0.28) and-0.18% (95% CI -0.25 to -0.11). Notably, the burden was higher among males and the elderly. The slope index of inequality rose from 22.0 (95% CI 18.1 to 25.9) in 1990 to 32.9 (95% CI 28.3 to 37.5) in 2019 and the concentration index fell from 59.5 (95% CI 46.4 to 72.6) in 1990 to 48.9 (95% CI 34.6 to 63.1) in 2019. Also, according to our projections, global ASDR and ASMR might tend to increase up to 2030. ASMR and ASDR for CRC associated with high red meat diets declined globally from 1990 to 2019, but the absolute number of cases is still rising, with men and the elderly being more affected. CRC associated with diets high in red meat exhibits significant income inequality, placing a disproportionate burden on wealthier countries. Moreover, according to our projections, ASMR and ASDR are likely to increase globally by 2030. In order to address this intractable disease problem, understanding changes in global and regional epidemiologic trends is critical for policy makers and others.

Clinicodemographic profile of orbital exenteration in a tertiary eye care center - A 20-year experience.

This study aimed to determine the clinical indications for orbital exenteration, demographic profile of these patients, and clinicopathologic correlations in the current times and to compare these results with previous published data. It was a retrospective study. All exenterations performed at a tertiary eye care center over a period of 20 years (from January 2001 to June 2020) were retrospectively evaluated. Patient records were reviewed to obtain demographic data, presenting symptoms and their duration, laterality, and clinical and histopathologic diagnosis. A total of 352 cases (males:females = 222:130) who underwent exenteration were identified. Patients age ranged from 11 months to 87 years (mean: 43.86 years, median: 50 years). The most common indication for exenteration was found to be eyelid malignancy in 54.36%, followed by retinoblastoma in 18.75% and primary orbital tumors in 14.49%. Out of 156 cases of eyelid malignancies requiring exenteration, squamous cell carcinoma (SCC) was the most common histologic subtype ( n = 94, 60.26%), followed by sebaceous gland carcinoma ( n = 40, 25.64%) and basal cell carcinoma ( n = 20, 12.82%). The most common primary orbital tumors requiring exenteration were adenocystic carcinoma of the lacrimal gland in adults and rhabdomyosarcoma in the pediatric age group. Benign conditions requiring exenteration included fulminant fungal orbital infections and lymphangioma among others. The number of exenterations performed have significantly increased in terms of absolute numbers. However, the ratio of exenteration to other tumor-related surgeries, mainly excision biopsy, has reduced compared to that reported from a previous study. The most common indication in our study remains eyelid malignancy followed by intraocular malignancy. However, SCC has emerged as the most common tumor histologic subtype requiring exenterations.

Health impacts of new-onset diabetes in women post-gestational diabetes mellitus: Insights from Hong Kong's territory-wide data.

To determine the population health burden attributable to the development of diabetes among women with a history of gestational diabetes mellitus (GDM). We conducted a retrospective analysis of women with a history of GDM attending the Hong Kong Hospital Authority between 2000 and 2019. The time-varying population attributable fraction was calculated. A total of 76,181 women with a history of gestational diabetes mellitus were included, 6,606 of them developed diabetes during a median follow-up of 8.6 years. The respective hazard ratios (95% confidence interval) among women with GDM who developed diabetes vs those with GDM only were 2.8 (2.2, 3.7) for cardiovascular disease (CVD), 4.8 (3.0, 7.7) for end-stage kidney disease (ESKD), 2.2 (1.9, 2.6) for infection-related hospitalization, and 1.8 (1.3, 2.4) for all-cause mortality. The development of diabetes was associated with 1.3 (0.8, 1.7), 0.6 (0.3, 0.8), 3.2 (2.4, 4.0), and 0.5 (0.2, 0.9) additional incident cases per 1,000 person-years, accounting for 24.0% (13.2%, 35.9%), 42.0% (22.5%, 58.8%), 10.8% (7.1%, 14.9%), and 6.0% (-3.1%, 16.1%) of absolute number of CVD, ESKD, infection-related hospitalization, and all-cause mortality over 20 years after GDM, respectively. Diabetes is a significant contributor to the population health burden of some clinical outcomes in women with a history of gestational diabetes mellitus, but other risk factors need to be considered.

Progress in site-specific cancer mortality in Canada over the last 70 years

In Canada, the absolute number of cancer deaths has been steadily increasing, however, age-standardized cancer mortality rates peaked decades ago for most cancers. The objective of this study was to estimate the reduction in deaths for each cancer type under the scenario where peak mortality rates had remained stable in Canada. Data for this study were obtained the Global Cancer Observatory and Statistics Canada. We estimated age-standardized mortality rates (ASMR, per 100,000) from 1950 to 2022, standardized to the 2011 Canadian standard population. We identified peak mortality rates and applied the age-specific mortality rates from the peak year to the age-specific Canadian population estimates for subsequent years (up to 2022) to estimate the number of expected deaths. Avoided cancer deaths were the difference between the observed and expected number of cancer deaths. There have been major reductions in deaths among cancers related to tobacco consumption and other modifiable lifestyle habits (417,561 stomach; 218,244 colorectal; 186,553 lung; 66,281 cervix; 32,732 head and neck; 27,713 bladder; 22,464 leukemia; 20,428 pancreas; 8863 kidney; 3876 esophagus; 290 liver). There have been 201,979 deaths avoided for female-specific cancers (breast, cervix, ovary, uterus). Overall, there has been a 34% reduction in mortality for lung cancer among males and a 9% reduction among females. There has been a significant reduction in cancer mortality in Canada since site-specific cancer mortality rates peaked decades ago for many cancers. This shows the exceptional progress made in cancer control in Canada due to substantial improvements in prevention, screening, and treatment. This study highlights priority areas where more attention and investment are needed to achieve progress.

Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy.

Natural killer (NK) cells have gained attention as a promising adoptive cell therapy platform for their potential to improve cancer treatments. NK cells offer distinct advantages over T-cells, including major histocompatibility complex class I (MHC-I)-independent tumor recognition and low risk of toxicity, even in an allogeneic setting. Despite this tremendous potential, challenges persist, such as limited in vivo persistence, reduced tumor infiltration, and low absolute NK cell numbers. This review outlines several strategies aiming to overcome these challenges. The developed strategies include optimizing NK cell expansion methods and improving NK cell antitumor responses by cytokine stimulation and genetic manipulations. Using K562 cells expressing membrane IL-15 or IL-21 with or without additional activating ligands like 4-1BBL allows "massive" NK cell expansion and makes multiple cell dosing and "off-the-shelf" efforts feasible. Further improvements in NK cell function can be reached by inducing memory-like NK cells, developing chimeric antigen receptor (CAR)-NK cells, or isolating NK-cell-based tumor-infiltrating lymphocytes (TILs). Memory-like NK cells demonstrate higher in vivo persistence and cytotoxicity, with early clinical trials demonstrating safety and promising efficacy. Recent trials using CAR-NK cells have also demonstrated a lack of any major toxicity, including cytokine release syndrome, and, yet, promising clinical activity. Recent data support that the presence of TIL-NK cells is associated with improved overall patient survival in different types of solid tumors such as head and neck, colorectal, breast, and gastric carcinomas, among the most significant. In conclusion, this review presents insights into the diverse strategies available for NK cell expansion, including the roles played by various cytokines, feeder cells, and culture material in influencing the activation phenotype, telomere length, and cytotoxic potential of expanded NK cells. Notably, genetically modified K562 cells have demonstrated significant efficacy in promoting NK cell expansion. Furthermore, culturing NK cells with IL-2 and IL-15 has been shown to improve expansion rates, while the presence of IL-12 and IL-21 has been linked to enhanced cytotoxic function. Overall, this review provides an overview of NK cell expansion methodologies, highlighting the current landscape of clinical trials and the key advancements to enhance NK-cell-based adoptive cell therapy.

Nuclear imaging to visualize periodontal inflammation: Findings of a randomized controlled trial.

To investigate non-surgical periodontal therapy by 18F-fluorodeoxyglucose (2-[18F]FDG) uptake using positron emission tomography (PET) integrated with computed tomography (CT). Eighty-five patients with peripheral artery disease and severe periodontitis-randomized into three groups receiving therapy with (PT1; n = 29) or without (PT2; n = 28) systemic antibiotics or no treatment (controls: n = 28)-underwent nuclear imaging at baseline and at 3 months. Clinical inflammation (periodontal inflamed surface area; PISA) did not significantly differ across the groups at baseline (p = 0.395) but was significantly reduced at 3 months (p < 0.001), and significantly more so in the PT1/PT2 groups than in the control group (p < 0.001/=0.025) and in the PT1 than in the P2 group (p = 0.001). Radiotracer uptake was measured in both jaws using maximum and mean 'standardized uptake values' (SUVmax, SUVmean) and 'target-to-background ratios' (TBRmax, TBRmean). At 3 months, reductions were relatively small in absolute numbers and fell short of revealing correlations with PISA or significant differences across the groups. Still, they were very consistent in both treatment groups, whereas reductions were not consistently seen in the control group. 2-[18F]FDG PET/CT scans did reflect the clinical effects of periodontal treatment very consistently but, for reasons yet to be clarified, less closely than expected.

Abstract A076: T-cell exhaustion is an independent predictive biomarker of clinical outcome in high grade serous ovarian cancer regardless of homologous recombination deficiency status

Abstract Epithelial ovarian cancer is the most lethal gynecologic malignancy, with 5-year survival rates of 46%. High grade serous carcinoma (HGSC) is the most frequent subtype of epithelial ovarian cancer. Approximately 50% of cases are homologous recombination deficient (HRD). Whereas maintenance treatment by PARP inhibitors has significantly improved the prognosis of patients with HRD tumors, clinical outcome in this malignancy is still poor. Despite the immunogenic nature of HGSC, in which T-cell infiltration correlates to improved clinical outcome following surgery and chemotherapy, the disease exhibits low response rates to immune checkpoint blockade (ICB) monotherapy in advanced line settings. We have previously identified epithelial malignancies including HGSC, CD4 and CD8 populations of tumor-infiltrating and antigen-specific T cells that display features of terminal exhaustion. These populations were key players in the response to anti-PD-1 in patients with epithelial tumors. Here, we set out to characterize tumor-infiltrating T cells in a cohort of 80 HGSC patients treated at our institution from whom we collected tumor samples prior to therapy in which HRD status was assessed. We used multiplex immunofluorescence of FFPE tumor samples to assess infiltration by CD4 and CD8 T cells and multiparametric flow cytometry of frozen viable cell suspensions to assess CD4 and CD8 T-cell exhaustion. The link between biological parameters and clinical outcome was assessed by univariable and multivariable analyses. Assessment of the T-cell infiltrate by immunofluorescence showed no difference in the absolute numbers, per tumor or stroma mm2, of CD8 or CD4 T cells between HRD and homologous recombination proficient (HRP) tumors. Instead, analysis of exhausted CD8 and CD4 T cells showed an increased frequency of terminally exhausted PD-1HighTIM-3+ CD8 T cells in HRD tumors. This population, which expresses the ectonucleotidase CD39, was significantly correlated to the presence of T regulatory cells (Treg), which agreed with previous studies showing comigration of effector and regulatory T cells in ovarian cancer. In addition, terminally exhausted CD4 T cells, expressing the immune checkpoints PD-1 and TIM-3 as well as CD39, were enriched in HRD tumors. Among HRD tumors, no difference was observed between the exhaustion profile in tumors presenting deleterious BRCA1/2 mutations compared to those with other mutations in the homologous recombination pathway. Univariable analyses showed exhaustion parameters to be significant predictors of progression-free survival (PFS). The frequencies of exhausted CD4 and CD8 T cells stood out as predictors of PFS in multivariable analyses. Altogether, these results provide the first evidence of a link between T-cell exhaustion and HRD status and reveal T-cell exhaustion as an independent predictor of disease outcome. They also underline the major role played by the antitumor immune response in HGSC and warrant the development of combination immunotherapies despite the lack of response to ICB monotherapy. Citation Format: Anna Salvioni, Mathilde Del, Marie Michelas, Pierre Vuattoux, Clara-Maria Scarlata, Carlos Martinez-Gomez, Nathalie Van Acker, François-Xavier Frenois, Guillaume Bataillon, Jean-Pierre Delord, Alejandra Martinez, Maha Ayyoub. T-cell exhaustion is an independent predictive biomarker of clinical outcome in high grade serous ovarian cancer regardless of homologous recombination deficiency status [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A076.

Burden of Ischemic and Hemorrhagic Stroke Across the US From 1990 to 2019

Stroke is a leading cause of death and disability in the US. Accurate and updated measures of stroke burden are needed to guide public health policies. To present burden estimates of ischemic and hemorrhagic stroke in the US in 2019 and describe trends from 1990 to 2019 by age, sex, and geographic location. An in-depth cross-sectional analysis of the 2019 Global Burden of Disease study was conducted. The setting included the time period of 1990 to 2019 in the US. The study encompassed estimates for various types of strokes, including all strokes, ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs). The 2019 Global Burden of Disease results were released on October 20, 2020. In this study, no particular exposure was specifically targeted. The primary focus of this analysis centered on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100 000 individuals. In 2019, the US recorded 7.09 million prevalent strokes (4.07 million women [57.4%]; 3.02 million men [42.6%]), with 5.87 million being ischemic strokes (82.7%). Prevalence also included 0.66 million ICHs and 0.85 million SAHs. Although the absolute numbers of stroke cases, mortality, and DALYs surged from 1990 to 2019, the age-standardized rates either declined or remained steady. Notably, hemorrhagic strokes manifested a substantial increase, especially in mortality, compared with ischemic strokes (incidence of ischemic stroke increased by 13% [95% uncertainty interval (UI), 14.2%-11.9%]; incidence of ICH increased by 39.8% [95% UI, 38.9%-39.7%]; incidence of SAH increased by 50.9% [95% UI, 49.2%-52.6%]). The downturn in stroke mortality plateaued in the recent decade. There was a discernible heterogeneity in stroke burden trends, with older adults (50-74 years) experiencing a decrease in incidence in coastal areas (decreases up to 3.9% in Vermont), in contrast to an uptick observed in younger demographics (15-49 years) in the South and Midwest US (with increases up to 8.4% in Minnesota). In this cross-sectional study, the declining age-standardized stroke rates over the past 3 decades suggest progress in managing stroke-related outcomes. However, the increasing absolute burden of stroke, coupled with a notable rise in hemorrhagic stroke, suggests an evolving and substantial public health challenge in the US. Moreover, the significant disparities in stroke burden trends across different age groups and geographic locations underscore the necessity for region- and demography-specific interventions and policies to effectively mitigate the multifaceted and escalating burden of stroke in the country.

Main circulating CD8&lt;sup&gt;+&lt;/sup&gt; T cell subsets in patients with systemic lupus erythematosus

Relevance. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of immune tolerance and sustained production of autoantibodies.The aim of the study – to compare composition of peripheral blood cytotoxic CD8+ T lymphocytes (Tc) subsets and assess the clinical significance of them in systemic lupus erythematosus. Materials and methods. A total of 35 SLE patients and 49 healthy volunteers were included in the study. Phenotyping of peripheral blood T cell subpopulations was carried out by means of flow cytometry. T lymphocytes were determined using CD3+, CD4+, CD8+ antibodies. Tc were identified by using CD45RA and CD62L antibodies. Also the expression of chemokine receptors (CCR4, CCR6, CXCR3 and CXCR5) on Tc cells was assessed and the main Tc subpopulations were determined: Type 1 (Tc1), type 2 (Tc2), type 17 (Tc17), type 17/1 (Tc17.1), type 17/22 (Tc17.22) cytotoxic cells and T follicular cytotoxic cells (Tfc).Results. The absolute and relative number of Tc was significantly higher in the group of patients with SLE compared with the control group. Additionally, there was a significant decrease in the relative number of Tc1, Tc 17.1 and Tfc1 and a significant increase in the relative number of Tc2, Tfc 17 and Tfc17.1 within the SLE group when compared to the control group. There were significant positive correlationfor Tc1 and levels of C3 and C4 complement components (r=0.404, p&lt;0.05).Conclusions. The absolute and relative number of peripheral blood Tc subsets is altered in SLE patients compared with the control group. It was found that patients with SLE contained increased number of Tc2 cells, which seems to be associated with markers of disease activity. These results demonstrate a prominent pathological role of Tc2 in SLE. While Tc1, Tc17, Tc17.1, Tfc subsets probably have regulatory functions

Exploiting Natural Language Processing to Unveil Topics and Trends of Traumatic Brain Injury Research.

Traumatic brain injury (TBI) has evolved from a topic of relative obscurity to one of widespread scientific and lay interest. The scope and focus of TBI research have shifted, and research trends have changed in response to public and scientific interest. This study has two primary goals: first, to identify the predominant themes in TBI research; and second, to delineate "hot" and "cold" areas of interest by evaluating the current popularity or decline of these topics. Hot topics may be dwarfed in absolute numbers by other, larger TBI research areas but are rapidly gaining interest. Likewise, cold topics may present opportunities for researchers to revisit unanswered questions. We utilized BERTopic, an advanced natural language processing (NLP)-based technique, to analyze TBI research articles published since 1990. This approach facilitated the identification of key topics by extracting sets of distinctive keywords representative of each article's core themes. Using these topics' probabilities, we trained linear regression models to detect trends over time, recognizing topics that were gaining (hot) or losing (cold) relevance. Additionally, we conducted a specific analysis focusing on the trends observed in TBI research in the current decade (the 2020s). Our topic modeling analysis categorized 42,422 articles into 27 distinct topics. The 10 most frequently occurring topics were: "Rehabilitation," "Molecular Mechanisms of TBI," "Concussion," "Repetitive Head Impacts," "Surgical Interventions," "Biomarkers," "Intracranial Pressure," "Posttraumatic Neurodegeneration," "Chronic Traumatic Encephalopathy," and "Blast Induced TBI," while our trend analysis indicated that the hottest topics of the current decade were "Genomics," "Sex Hormones," and "Diffusion Tensor Imaging," while the cooling topics were "Posttraumatic Sleep," "Sensory Functions," and "Hyperosmolar Therapies." This study highlights the dynamic nature of TBI research and underscores the shifting emphasis within the field. The findings from our analysis can aid in the identification of emerging topics of interest and areas where there is little new research reported. By utilizing NLP to effectively synthesize and analyze an extensive collection of TBI-related scholarly literature, we demonstrate the potential of machine learning techniques in understanding and guiding future research prospects. This approach sets the stage for similar analyses in other medical disciplines, offering profound insights and opportunities for further exploration.

Hoarding of insulin and oral antidiabetics in the first phase oftheCOVID-19 pandemic: Regulatory actions taken to avoid shortage.

To report on hoarding of prescribed medicines, with focus on insulins, in the early phase of the COVID-19 pandemic and on regulatory actions taken to avoid shortage. The National Prescribed Drug Register which utilizes the Anatomic Therapeutic Chemical (ATC) Classification System and covers the total Swedish population was used. We calculated the number of packages of insulins (ATC code A10A), oral anti-diabetics (A10B), and all medicines across all ATC codes combined (A-S) dispensed per week in 2019 and 2020. Correspondingly, the number of packages of glucose test strips dispensed was calculated using the data source Concise held by the Swedish eHealth Agency. Prompt increases in numbers of dispensed packages were observed in March, peaking at week 11/2020. The absolute numbers of packages dispensed in week 11/2019 and week 11/2020 were: insulin, 49,694 and 95,767, an increase by +92.7%; oral antidiabetics, 55,478 and 82,684, +47.1%; glucose test strips, 18,119 and 23,476, +29:6%; and all medicines across all ATC codes combined, 1,988,456 and 2,659,421, +33.7%. Voluntary restriction of dispensing and a rapid change to applicable regulation were implemented within 2 weeks. A steep decline occurred, which became more pronounced after temporary regulation came in force from April 1, then leveling out during the following months. A signal of insulin hoarding was detected early in the COVID-19 pandemic. A temporary regulation, reducing dispensing to a maximum supply of 3 months was rapidly implemented. A shortage of vitally important prescribed medicines was avoided.

Sex-specific Impact of the first COVID-19 Lockdown on Age Structure and Case Acuity at Admission in a Patient Population in southwestern Germany: a retrospective comparative Study in Neuroradiology

ObjectivesA hard lockdown was presumed to lead to delayed diagnosis and treatment of serious diseases, resulting in higher acuity at admission. This should be elaborated based on the estimated acuity...

Change in injury pattern with mandatory, referred access compared to open access in an emergency department.

This retrospective cohort study aimed to examine whether implementing mandatory referral changed the composition of patients visiting the Accident and Emergency (A and E) Department in relation to severity, demographics and activity at injury. Patients visiting the A and E Department at Odense University Hospital, Denmark, in 2008-2019, were divided into three time periods: before (four years before any changes in the operation of the A and E), transition period (the four years during which mandatory referral and the centralised emergency medical service were implemented) and after (the four years after these changes had been implemented). The incidence rate ratios and odds were calculated. The absolute number of severe injuries declined, but to a lesser extent than the number of minor injuries. The incidence rate ratios throughout all subcategories, including severity, fracture, sex, age and activity at injury, indicate a smaller risk of visiting the A and E Department in the after period than in the before period, with a total lower (0.82 times; 95% confidence interval: 0.82-0.83 times) risk of visiting the A and E Department in the after period than in the before period. Changing from open to referred access altered the composition of injuries for patients seen in the A and E Department, indicating a smaller risk of a visit with referred access than with open access. The odds of a visit being due to a major injury increased after implementing referred access, and the number of visits decreased. The Nordentoft Fund TRIAL REGISTRATION. Not relevant.

Climate Change Implications for Agricultural Productivity: A Comprehensive Analysis

The impact of climate change on global agriculture has been noticeable in recent decades, with rapid trends affecting various agricultural regions. As we look to the future, concerns about food security arise, prompting questions about the potential effects on aggregate productivity. Numerous factors, such as population growth, income disparities, dietary preferences, disease incidence, and competing demands for land and water resources, will influence global food security in the coming decades. While studies indicate that the overall food supply worldwide may not be seriously jeopardized by projected climate changes, there is a growing consensus that food insecurity in Africa will intensify. The risk of hunger is expected to increase both in terms of percentage and absolute numbers throughout the century. Despite projections suggesting a relatively minimal impact on the global average supply of calories in the next few decades, ranging from close to zero to potentially 20% to 30% of overall yield trends, the complexity of the issue is underscored by significant regional variations. The global perspective on food security conceals nuanced changes at smaller scales, which could have substantial implications even if overall production is maintained. To mitigate uncertainties in understanding global impacts, this paper recommends improving estimates of global warming rates and the responsiveness of crop yields to both warming and increased carbon dioxide levels. The responsiveness of yields is intricately linked to various factors, including genetic improvements made to crops, making it essential to address these variables for a more accurate assessment of future scenarios. Keywords: Climate Change, Agricultural Productivity, Food Security, Global Warming, Crop Yield Responsiveness

Risk of malignancy in a high-incidence population-based cohort of Faroese patients with inflammatory bowel disease from 1960 to 2020 – a Faroese IBD cohort study

Background The association between inflammatory bowel disease (IBD) and malignancy remains disputed despite many observational studies. The Faroese population exhibits the highest occurrence of IBD in the world. This study aimed to investigate the cancer risk in Faroese IBD patients in a nationwide IBD cohort. Methods This study included all IBD patients diagnosed in the Faroe Islands between 1960 and 2020. Clinical demographics and cancer diagnoses were retrieved from patient files and the Faroese cancer registry. Cancer risk in IBD patients was calculated as standardized incidence ratios (SIRs) based on the Faroese background population’s age- and sex-specific cancer incidence rates, retrievable from NORDCAN. Results The cohort consisted of 699 patients with a total follow-up time of 9,629 person-years. Overall, the risk of cancer was not statistically significantly increased compared to the background population. Patients diagnosed with cancer at age 50–59 years had higher overall cancer risk (SIR 1.8; 95% CI, 1.02–2.99) as did UC patients diagnosed with IBD at 50–59 (SIR 2.1; 95% CI, 1.10–3.54). Absolute numbers were small and no estimates for site-specific cancers reached statistical significance, though lung, breast, and cancer of the female reproductive organs were elevated among IBD and UC patients, and colorectal cancer in CD patients. Conclusions This nationwide study found no statistically significantly increased risk of cancer among Faroese patients with CD or UC, except from age 50 to 59 years. While the incidence of IBD is significantly higher in the Faroe Islands than in other countries, risk estimates of cancers are comparable.