Effect of Peroxisome Proliferator-Activated Receptor Gamma Agonist (Pioglitazone) and Methotrexate on Disease Activity in Rheumatoid Arthritis (Experimental and Clinical Study)

Objective To investigate the combined effect of both pioglitazone and methotrexate on disease activity of rheumatoid arthritis in a biphasic study; experimental and clinical. Methods Experimentally: 50 rats were divided into 5 equal groups; controls, experimental arthritis, methorexate treated (0.1 mg/Kg daily), pioglitazone-treated (10 mg/kg daily), and methotrexate and pioglitazone treated. Clinically: forty-nine diabetic rheumatoid arthritis patients were included. Patients group consisted of 28 patients and they received pioglitazone 30 mg orally beside their usual treatment. Control group consisted of 21 patients and they continued their usual treatment plus placebo. Disease activity was assessed using DAS28 score. Patients were followed up for 3 months. Results Pioglitazone produced a significant improvement of serum oxidative stress parameters ( P < 0.05), and inflammatory cytokines in the treated arthritic group ( P < 0.05). Clinically, the pioglitazone treated group showed significant improvement in DAS28 ( P = 0.001) and C-reactive protein ( P < 0.0001) compared to placebo group. Conclusion The concomitant use of the PPAR γ agonist pioglitazone and methotrexate appears to be promising therapeutic strategy for rheumatoid arthritis patients

Serum interferon-alpha level in first degree relatives of systemic lupus erythematosus patients: Correlation with autoantibodies titers

AbstractBackground and objectivesInterferon-α (IFN-α), a cytokine with both antiviral and immune-regulatory functions, was suggested as a useful tool which can evaluate current systemic lupus erythematosus (SLE) disease activity and identify patients who are at risk of future disease flares. In the current study, serum IFN-α levels and associated demographic, and serological features in Egyptian SLE patients and their first degree relatives (FDRs) in comparison to unrelated healthy controls (UHCs) were examined, in order to identify individuals at the greatest risk for clinical illness.MethodsIn a cross-sectional study, blood samples were drawn from 54 SLE patients, 93 of their FDRs who consented to enroll into the study and 76 UHCs. Measurement of serum IFN-α by a modified ELISA was carried out. Data were analyzed for associations of serum IFN-α levels with autoantibodies titer.ResultsMean serum IFN-α in FDRs was statistically higher than the UHCs and lower than in SLE patients (P<0.0001) and it was correlated with ANA titer (r=0.6, P<0.0001) and anti ds DNA titer (r=0.62, P<0.0001).ConclusionIFN-α is a crucial player in the complicated autoimmune changes that occur in SLE and serum IFN-α can be a useful marker identifying persons who are at risk of future disease development

Cystic Fibrosis in Egyptian Children: Achievements and Future Directions

Cystic fibrosis (CF) is the most common potentially lethal and life-shortening genetic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Clinical consequences of the CFTR defect are site-specific and range from severe (lungs, pancreas, male reproductive tract) to mild (intestine) to asymptomatic (sweat glands). In many developing countries CF has remained largely unrecognized, and inadequately managed, resulting in avoidable death or suffering in infancy, childhood, and adulthood. Delivering adequate CF services is met by substantial difficulties as the spectrum and distribution of CF in Egypt are still not well known. Against this background, the aim of this work is to emphasize the challenges facing initiation of a CF center in low privileged settings with the objectives of improving diagnosis, survival, and to eventually provide optimum management. Strategies for the implementation and development of CF services, as well as proper collection and documentation of patient data are therefore of vital importance. The characterization of the prevalence and molecular genetics of CF in Egypt is of utmost importance so that appropriate genetic counseling to CF patients and their families can be achieved and to pave the way for new treatment modalities

Evaluation of the role of perceived quality and satisfaction of beneficiaries about the health care services and benefits of community clinics in Bangladesh

Introduction Bangladesh provides free healthcare to its citizens through 10,723 community clinics which provide one-stop healthcare services that is vital in ensuring primary healthcare. Measuring beneficiary' contentment is crucial to improve the quality of care and the perceived service quality have a significant impact on how often people use those health services. This study focuses on perceived quality and satisfaction of beneficiaries about the primary health care services and benefits of community clinics in Bangladesh. Methods A quantitative descriptive survey was conducted from March 2019 to April 2019 in the catchment area of 80 community clinics located at 16 Upazila under eight districts of eight divisions in Bangladesh. The survey compiled local data on client’s experience on health care service of community clinics. Besides, Sixteen Upazilas from eight districts were randomly selected for conducting interviews. Results Data was provided by a total of 760 female participants, among them majority (41%) belonged to the age group of 18-24 years old, and this very group showed more satisfaction than others (Odds Ratio 1.44). Besides, childless married women were also found to be content with the community clinic services compared to the remaining types of clients (Odds Ratio 1.64). However, gender, education, and economic perspective were positive aspects of getting service from community clinics. Conclusions Although there is a challenge balancing psychosocial and medical care, promoting client-oriented care with a focus on the cultural factors of the area is vital. This can be done through community-focused training together with explaining written prescriptions to the beneficiary, including the signs, symptoms, treatment, and referral points. The study findings will enable responsible authority to improve quality of primary health care services, realizing beneficiary’ ideas of community clinic service quality

Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-Adjusted life-years for 29 cancer groups, 1990 to 2017 : A systematic analysis for the global burden of disease study

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-Adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care. © 2019 American Medical Association. All rights reserved.Peer reviewe

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Characteristics of incidentally found thyroid nodules in computed tomography: comparison with thyroid scintigraphy

Background In our daily experience, the differentiation between a cold and hot nodule is a very important factor for further clinical management of the patient. In this study, we compared the characteristics of incidentally found thyroid nodules detected on computed tomography (CT) to thyroid scintigraphy (TS). Methods Diagnostic reports from chest CT with intravenous contrast and TS examinations performed from January 2013 to January 2016 were analyzed retrospectively. We identified 70 subjects: 50 with thyroid nodules and 20 control subjects without thyroid nodules. The examination time of the TS was a minimum of two to four months after a chest CT. Chest CTs were performed in the arterial phase after the application of contrast media. Results Patients with a cold nodule had a significantly lower Hounsfield Unit (HU) Nodule(N)/Parenchyma (P) ratio values than the patients with a hot or warm nodule (P<0.05). The cut-off HU N/P ratio value with the highest sum of sensitivity and specificity for the prediction of a functioning nodule was 69 (95% CI: 0.790.95). Conclusions Our results imply that the HU N/P ratio of the thyroid nodule on the chest CT should be taken into account to assess the functionality of the nodule. A lower HU N/P ratio should alert the radiologist or nuclear medicine physician to the possibility that the nodule might be cold and thus more prone to malignancy.(VLID)484430