Optimizing Clinical Benefits of Bisphosphonates in Cancer Patients with Bone Metastases

Malignant bone disease is common in patients with advanced solid tumors or multiple myeloma. Bisphosphonates have been found to be important treatments for bone metastases. A positive benefit-risk ratio for bisphosphonates has been established, and ongoing clinical trials will determine whether individualized therapy is possible

Количественная характеристика клеток Лангерганса в слое нервных волокон роговицы при первичной открытоугольной глаукоме

Purpose: To estimate the number of Langerhans cells (LC) in the cornea in primary open-angle glaucoma (POAG) at various stages of the disease.Methods: The study included 129 patients. The main group — 102 patients (204 eyes) aged from 42 to 83 years (62.5±2.4 years) — diagnosed with POAG stage I-IV. The control group consisted of 27 ophthalmologically healthy volunteers (54 eyes) with a normal level of IOP and no signs of POAG aged 54 to 76 years (65.9±1.4 years). The patients underwent visometry, biomicroscopy of the anterior segment of the eye, ophthalmoscopy, gonioscopy, Pascal contour tonometry, optical coherence tomography (OCT) (Zeiss Stratus 3000) and corneal confocal microscopy (CMR) (HRT III, with Rostock Cornea Modul).Results: The average number of LC in patients with glaucoma amounted to 144±21 cells/mm2. It was higher than in the norm group, the difference was statistically significant (p=0.0002). The study revealed an increase in the number of LC associated with the development of glaucoma. A significant positive correlation of the amount of LC in the nerve fiber layer with the stage of the disease (R=0.23, p<0.05) was also found, as well as a negative correlation with the anisotropy coefficient of the directivity of the corneal nerve fibers in the POAG group (R= -0.29, p<0.001). Intereye asymmetry was investigated, which was found to be the higher, the greater the difference in the stages of POAG between paired eyes. With the value of the indicator of interocular asymmetry LC, equal to 19.68%, the sensitivity and specificity of the proposed indicator for the diagnosis of POAG were 94.1 and 66.6%, respectively. Thus, the values of the interocular asymmetry LC indicator above 19.68% are considered pathological.Conclusion: The detected increase in the number of LC in the nerve fiber layer indicates the presence of an inflammatory process in the eye, which may well be autoimmune. And it may be the root cause of open-angle glaucoma, lead to pathological glaucomatous scleropathy with damage to the drainage apparatus of the eye and a corresponding increase in IOP level. It also causes a characteristic clinical course in the form of a chronic, bilateral, low-intensity process. In this sense, the neurodegenerative processes in the anterior and posterior segments of the eye are pathogenetically uniform.Цель. Оценить количество клеток Лангерганса (КЛ) в роговице при первичной открытоугольной глаукоме (ПОУГ) в различных стадиях заболевания.Методы. В исследование вошли 129 пациентов. Основная группа — 102 пациента (204 глаза) в возрасте от 42 до 83 лет (62,5±2,4 года) — с диагнозом ПОУГ I-IV стадий. Контрольная группа — 27 пациентов (54 глаза) — офтальмологически здоровые добровольцы в возрасте от 54 до 76 лет (65,9±1,4 года) с нормальным уровнем внутриглазного давления (ВГД) и без признаков ПОУГ. Были проведены: визометрия, биомикроскопия переднего отрезка глаза, офтальмоскопия, гониоскопия, контурная тонометрия по методу Pascal, оптическая когерентная томография (ОКТ) дисков зрительных нервов (Zeiss Stratus 3000) и конфокальная микроскопия роговицы (КМР) (HRT III, с Rostock Cornea Modul).Результаты. При ПОУГ среднее количество КЛ оказалось выше, чем в группе нормы, и составило 144±21 кл./мм2, что достоверно отличается от группы нормы (р=0,0002). Обнаружено возрастание количества КЛ по мере развития заболевания, увеличение количества КЛ от начальной глаукомы к терминальной. Выявлены достоверная положительная связь количества КЛ в слое суббазальных нервных волокон (НВР) со стадией заболевания (R=0,23, p<0,05), достоверная отрицательная корреляционная связь с коэффициентом анизотропии направленности НВР в группе ПОУГ (R=-0,29, р<0,001). Исследована межокулярная асимметрия посредством вычисления показателя межокулярной асимметрии (ПМА). ПМА количества КЛ в слое НВР тем выше, чем больше рас- хождение по стадиям ПОУГ между парными глазами. При значении ПМА КЛ 19,68% чувствительность и специфичность предлагаемого показателя для диагностики ПОУГ составили 94,1 и 66,6% соответственно. Таким образом, значения ПМА КЛ выше 19,68% принимаются как патологические.Заключение. Обнаруженное увеличение количества КЛ в слое НВР указывает на присутствие воспалительного процесса в глазу, который вполне может быть аутоиммунным. И может претендовать на первопричинность открытоугольной глаукомы, приводить к патологической глаукомной склеропатии с повреждением дренажного аппарата глаза и соответствующим повышением ВГД, а также диктовать характерное клиническое течение в виде хронического двухстороннего вялотекущего процесса. В этом смысле нейродегенеративные процессы в переднем и заднем сегментах глаза патогенетически едины

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016

Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. FINDINGS: The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. INTERPRETATION: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. FUNDING: Bill & Melinda Gates Foundation

Tick-borne Encephalitis in the Yaroslavl Region in the Context of Planned Vaccine Prevention

Relevance. In the Yaroslavl region, the Central Federal District of Russia, endemic for tick-borne encephalitis (TBE), specific TBE vaccination has been routinely carried out for more than 20 years. Therefore, the evaluation of the results of long-term universal immunoprophylaxis the population has a practical and scientific interest. Purpose: To study the epidemiology of tick-borne encephalitis in the context universal vaccine in 2008-2019. Results and discussion. According to the results of long-term immunization, by 2019 19.1% of the population was vaccinated, while vaccine coverage for the children living in endemic areas of the region reaches 68-83%. The article noted a 2.9-fold decrease in the incidence of TBE in 2013-2018 compared with 2008-2012. The average long-term level was 0.69 per 100 ths people. TBE was recorded among the unvaccinated population, mild febrile forms prevailed - 56.8%, however, the proportion of focal forms of the disease remained high (36.3%). Deaths from TBE in the period from 2013-2018 did not have. Thus, in the absence of specific treatment for TBE, vaccine prophylaxis is of great medical and social importance for the Yaroslavl region endemic for TBE. Conclusion. Vaccine coverage in the population of Yaroslavl region, children living in endemic areas and natural immunization in natural foci of TBE contributed to the formation of a significant level of collective immunity of the population to TBE, reducing the incidence of in the last 5 years

Effect of zoledronic acid (Z) treatment based on serum parathyroid hormone (PTH) levels in patients (pts) with malignant bone disease.

Background: Z prevents skeletal-related events (SREs) in pts with bone metastases or multiple myeloma. However, secondary hyperparathyroidism and increased PTH may stimulate osteoclast activity and tumor growth, thus potentially limiting the efficacy of Z. Methods: Serum PTH was assessed at baseline and every 3 months in 1,068 pts enrolled in 3 randomized trials: 547 received Z, and 521 received placebo or pamidronate. Results: 213 (20%) pts had elevated PTH at baseline, and 105 of 547 (19%) pts had elevated PTH during Z treatment. In patients with normal baseline PTH, Z significantly reduced the incidence of SREs and delayed time to first SRE compared with control, whereas the risk of SREs was not reduced in patients with elevated baseline PTH. In prostate cancer patients, Z significantly decreased the risk of death compared with placebo in pts with normal baseline PTH (relative risk [RR] = 0.72; 95% confidence interval [CI]: 0.55, 0.94; P = .015). No survival advantage was observed in this subpopulation among pts with lung cancer or other solid tumors. In the small subset of pts with elevated PTH during Z treatment, there was an increased risk of death (for breast cancer pts, RR = 1.68 [95% CI: 1.10, 2.56]; P = .016; for prostate cancer pts, RR = 2.92 [95% CI: 1.83, 4.67]; P < .001). Additionally, elevated PTH during Z treatment in prostate cancer pts also significantly correlated with an increased risk of bone lesion progression (RR = 1.54 [95% CI: 1.09, 2.17]; P = .015). Elevated PTH during treatment did not affect the incidence or time to onset of SREs. Among pts with lung cancer or other solid tumors, elevated PTH during Z treatment did not provide any predictive or prognostic information. Conclusions: PTH levels either at baseline or during Z treatment appear to correlate with disease progression and the clinical benefit of Z in pts with bone metastases from certain types of cancer. This retrospective analysis suggests the importance of PTH status in patients undergoing Z treatment. Normalization of PTH levels may increase the benefit of Z

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016. Methods We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57.6 million (95% uncertainty interval [UI] 40.8-75.9 million [7.2%, 6.0-8.3]), 45.1 million (29.0-62.8 million [5.6%, 4.0-7.2]), 36.3 million (25.3-50.9 million [4.5%, 3.8-5.3]), 34.7 million (23.0-49.6 million [4.3%, 3.5-5.2]), and 34.1 million (23.5-46.0 million [4.2%, 3.2-5.3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2.7% (95% UI 2.3-3.1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10.4% (95% UI 9.0-11.8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862-11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018-19 228). Interpretation The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-todate information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe