HIV disease metrics and COVID-19 infection severity and outcomes in people living with HIV in central and eastern Europe.

BACKGROUND: To date there remains much ambiguity in the literature regarding the immunological interplay between SARS-CoV-2 and HIV and the true risk posed to coinfected individuals. There has been little conclusive data regarding the use of CD4 cell count and HIV viral load stratification as predictors of COVID-19 severity in this cohort. METHODS: We performed a retrospective, observational cohort study on people living with HIV (PLWH) who contracted COVID-19 in central and eastern Europe. We enrolled 536 patients from 16 countries using an online survey. We evaluated patient demographics, HIV characteristics and COVID-19 presentation and outcomes. Statistical analysis was performed using SPSS 20.1. RESULTS: The majority of the study cohort were male (76.4%) and 152 (28.3%) had a significant medical comorbidity. Median CD4 cell count at COVID-19 diagnosis was 605 cells/µL [interquartile range (IQR) 409-824]. The majority of patients on antiretroviral therapy (ART) were virally suppressed (92%). In univariate analysis, CD4 cell count <350 cells/µL was associated with higher rates of hospitalization (p < 0.0001) and respiratory failure (p < 0.0001). Univariate and multivariate analyses found that an undetectable HIV VL was associated with a lower rate of hospitalization (p < 0.0001), respiratory failure (p < 0.0001), ICU admission or death (p < 0.0001), and with a higher chance of full recovery (p < 0.0001). CONCLUSION: We can conclude that detectable HIV viral load was an independent risk factor for severe COVID-19 illness and can be used as a prognostic indicator in this cohort.

Correlation between high-risk HPV infection and p16/Ki-67 abnormalities in Pap samples in a South Eastern Europe cohort.

Cervical cancer (CC) is the fourth most common cause of cancer-related deaths amongst women worldwide. CC represents a major global healthcare issue, and Romania ranks the worst in mortality rates amongst EU countries. However, the early detection of CC can be lifesaving. To understand the testing process undergone by women in Romania, we performed a retrospective study, and investigated a cohort of 83 785 cervical cases from Romanian women aged 15-70, obtained in private-based opportunistic screening. We examined the correlation between Pap smear results, human papilloma virus (HPV) genotyping, and the expression of cell cycle markers p16 and Ki-67. Analysis of Pap results revealed approximately 10% abnormal cases, of which high-grade squamous intraepithelial lesions constituted 4.9%. HPV genotyping of 12 185 cases with available Pap results unveiled a range of high-risk HPV (hrHPV) types associated with cervical abnormalities. Notably, 26% of hrHPV-positive cases showed no observable abnormalities. In a subset of cases with abnormal Pap and a type of hrHPV, P16/Ki-67 double-staining was also positive. This study suggests the importance of an integrated diagnostic algorithm that should consider the HPV genotype, Pap smear, and p16/Ki-67 staining. This algorithm should enhance the CC screening accuracy and its management strategies, particularly in those regions with a high disease burden, such as Romania.

Disentangling the roles of age and knowledge in early language acquisition: A fine-grained analysis of the vocabularies of infant and child language learners.

The words that children learn change over time in predictable ways. The first words that infants acquire are generally ones that are both frequent and highly imageable. Older infants also learn words that are more abstract and some that are less common. It is unclear whether this pattern is attributable to maturational factors (i.e., younger children lack sufficiently developed cognitive faculties needed to learn abstract words) or linguistic factors (i.e., younger children lack sufficient knowledge of their language to use grammatical or contextual cues needed to figure out the meaning of more abstract words). The present study explores this question by comparing vocabulary acquisition in 53 preschool-aged children (M = 51 months, range = 30-76 months) who were adopted from China and Eastern Europe after two and half years of age and 53 vocabulary-matched infant controls born and raised in English speaking families in North America (M = 24 months, range = 16-33 months). Vocabulary was assessed using the MB-CDI Words and Sentences form, word frequency was estimated from the CHILDES database, and imageability was measured using adult ratings of how easily words could be pictured mentally. Both groups were more likely to know words that were both highly frequent and imageable (resulting in an over-additive interaction). Knowledge of a word was also independently affected by the syntactic category that it belongs to. Adopted preschoolers' vocabulary was slightly less affected by imageability. These findings were replicated in a comparison with a larger sample of vocabulary-matched controls drawn from the MB-CDI norming study (M = 22 months, range = 16-30 months; 33 girls). These results suggest that the patterns of acquisition in children's early vocabulary are primarily driven by the accrual of linguistic knowledge, but that vocabulary may also be affected by differences in early life experiences or conceptual knowledge.

The role of ataluren in the treatment of ambulatory and non-ambulatory children with nonsense mutation duchenne muscular dystrophy - a consensus derived using a modified Delphi methodology in Eastern Europe, Greece, Israel and Sweden.

BACKGROUND: This paper details the results of an evaluation of the level of consensus amongst clinicians on the use of ataluren in both ambulatory and non-ambulatory patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). The consensus was derived using a modified Delphi methodology that involved an exploration phase and then an evaluation phase. METHODS: The exploration phase involved 90-minute virtual 1:1 interviews of 12 paediatric neurologists who cared for 30-120 DMD patients each and had patient contact every one or two weeks. The respondents managed one to ten nmDMD patients taking ataluren. The Discussion Guide for the interviews can be viewed as Appendix A. Following the exploration phase interviews, the interview transcripts were analysed by an independent party to identify common themes, views and opinions and developed 43 draft statements that the Steering Group (authors) reviewed, refined and endorsed a final list of 42 statements. Details of the recruitment of participants for the exploration and evaluation phases can be found under the Methods section. RESULTS: A consensus was agreed (> 66% of respondents agreeing) for 41 of the 42 statements using results from a consensus survey of healthcare professionals (n = 20) experienced in the treatment of nmDMD. CONCLUSIONS: The statements with a high consensus suggest that treatment with ataluren should be initiated as soon as possible to delay disease progression and allow patients to remain ambulatory for as long as possible. Ataluren is indicated for the treatment of Duchenne muscular dystrophy that results from a nonsense mutation in the dystrophin gene, in ambulatory patients aged 2 years and older (see Summary of Product Characteristics for each country).

Antithrombotic Usage, Including Three-Year Outcomes With Dabigatran and Vitamin K Antagonists for Atrial Fibrillation, in Eastern Europe: A Descriptive Analysis From Phase 3 of the GLORIA-AF Registry.

BACKGROUND: Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) is a prospective registry of outcomes from patients with newly diagnosed AF at risk of stroke. In the propensity score (PS)-matched global population of phase 3 GLORIA-AF, at 3 years, dabigatran-treated patients experienced reduced risk for major bleeding, and similar risk for stroke and myocardial infarction, compared with vitamin K antagonist (VKA)-treated patients. STUDY QUESTION: Do patients in Eastern Europe benefit from treatment with dabigatran versus VKA? STUDY DESIGN: Descriptive analysis, without PS matching. To contextualize the Eastern Europe results of GLORIA-AF phase 3, we also descriptively analyzed the global population without PS matching. Consecutive patients with newly diagnosed AF and CHA2DS2-VASc-score ≥1 were enrolled until December 2016 in 38 countries (9 in Eastern Europe). MEASURES AND OUTCOMES: Three-year outcomes with dabigatran and VKA. RESULTS: In Eastern Europe, 1341 patients were eligible (6% of patients globally), and incidence rates (per 100 patient-years) for the following outcomes were numerically lower with dabigatran (N = 498) versus VKA (N = 466): major bleeding (0.26 vs. 0.90), all-cause death (2.04 vs. 3.50), and a composite of stroke, systemic embolism, myocardial infarction, life-threatening bleeding, and vascular death (1.37 vs. 1.92); stroke was comparable (0.51 vs. 0.50). All incidence rates were numerically lower in Eastern Europe versus the global population for both treatments. Chronic concomitant use of high bleeding risk medications (eg, nonsteroidal anti-inflammatories) was lower in Eastern Europe (dabigatran 3.8%, VKA 9.3%) than globally (dabigatran 14.8%, VKA 20.6%) and persistence with dabigatran was higher in Eastern Europe (76%) than globally (64%). CONCLUSIONS: Dabigatran was associated with numerically reduced major bleeding, all-cause death, and cardiovascular (CV) composite, with comparable risk of stroke versus VKA, in Eastern Europe. Limitations of this descriptive analysis include few CV events (n = 11 for stroke, in the dabigatran and VKA groups combined) and a lack of statistical analysis and PS matching, which precludes definitive conclusions; however, the CV outcomes in Eastern Europe were consistent with the beneficial impact of dabigatran versus VKA in the statistically analyzed global population with PS matching.

The Importance of Early Diagnosis and Intervention in Chronic Kidney Disease: Calls-to-Action from Nephrologists Based Mainly in Central/Eastern Europe.

BACKGROUND: Chronic kidney disease (CKD) has a global prevalence of 9.1-13.4%. Comorbidities are abundant and may cause and affect CKD. Cardiovascular disease strongly correlates with CKD, increasing the burden of both diseases. SUMMARY: As a group of 15 clinical nephrologists primarily practicing in 12 Central/Eastern European countries, as well as Israel and Kazakhstan, herein we review the significant unmet needs for patients with CKD and recommend several key calls-to-action. Early diagnosis and treatment are imperative to ensure optimal outcomes for patients with CKD, with the potential to greatly reduce both morbidity and mortality. Lack of awareness of CKD, substandard indicators of kidney function, suboptimal screening rates, and geographical disparities in reimbursement often hamper access to effective care. KEY MESSAGES: Our key calls-to-action to address these unmet needs, thus improving the standard of care for patients with CKD, are the following: increase disease awareness, such as through education; encourage provision of financial support for patients; develop screening algorithms; revisit primary care physician referral practices; and create epidemiological databases that rectify the paucity of data on early-stage disease. By focusing attention on early detection, diagnosis, and treatment of high-risk and early-stage CKD populations, we aim to reduce the burdens, progression, and mortality of CKD.

Central and Eastern European Migrants in the United Kingdom: A Scoping Review of the Reasons for Utilisation of Transnational Healthcare.

BACKGROUND: An estimated 2.2 million people from Central and Eastern Europe (CEE) live in the United Kingdom. It has been documented that CEE migrants underutilise health services in the United Kingdom and, as an alternative, seek healthcare in their home country. However, reasons for seeking healthcare abroad are not always clear. This review aims to identify the reasons for the uptake of transnational healthcare among CEE migrants resident in the United Kingdom. METHODS: Informed by discussions with community members, medical stakeholders and academics, a systematic scoping review was undertaken following the nine-stage Joanna Briggs Institute framework for scoping reviews. A search strategy with MeSH terms, where relevant, was used and adapted in five academic databases, two grey literature databases and Google Scholar. Included records encompassed four concepts: migration, CEE nationalities, UK nations and healthcare utilisation, which were written in English and published between May 2004 and 2022. Data from the literature were coded, grouped and organised into themes. RESULTS: A total of 16 publications fulfilled the inclusion criteria. There is evidence that some CEE migrants exclusively use healthcare services in the United Kingdom. However, many CEE migrants utilise healthcare both in the United Kingdom and their country of origin. Four themes were identified from the literature as to why migrants travelled to their country of origin for healthcare: cultural expectations of medical services, distrust in the UK NHS, barriers and transnational ties. CONCLUSION: Push factors led CEE migrants to seek healthcare in their country of origin, facilitated by ongoing transnational ties. CEE migrants frequently combine visits to their country of origin with medical appointments. Utilising healthcare in their country of origin as opposed to the United Kingdom can result in fragmented and incomplete records of medications, medical tests and surgeries and risk of unnecessary treatments and complications. This review highlights the need for more targeted health outreach with CEE groups within the United Kingdom, as well as the need for further research on the impact of national events, for example, COVID-19 and Brexit, on transnational healthcare-seeking behaviours. PATIENT OR PUBLIC CONTRIBUTION: The concept for this scoping review was informed by discussions with community members, medical professionals and academics, who identified it as a current issue. The results of this scoping review were discussed with healthcare stakeholders.

How likely are Eastern European and central Asian countries to achieve global NCD targets: multi-country analysis.

BACKGROUND: In Europe, mortality rates from noncommunicable diseases (NCDs) among persons 30-69 years of age ("NCD premature mortality rates") have declined significantly, except in twelve countries of Eastern Europe and Central Asia, namely Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Turkmenistan, Ukraine and Uzbekistan. Data on long-term trends in NCD mortality in these countries are limited. We analyzed NCD premature mortality rates, identified change points in NCD mortality trends and forecasted how likely countries are to achieve the global NCD targets, stratified by gender and NCD type. METHODS: We used the 1990-2019 Global Burden of Disease database to analyze NCD trends and identified country-specific change points by using piecewise linear regression. We assessed the likelihood of achieving the global targets for reducing NCD premature mortality rates among persons 30-69 years of age from four NCDs: cancers, diabetes, cardiovascular and chronic respiratory diseases. The global NCD targets are 25% reduction in mortality from 2010 to 2025 (WHO 25X25 target) and 33%-from 2015 to 2030 (SDG 3.4.1). We applied the analysis to both genders and four NCDs. RESULTS: Only Kazakhstan and Russia are likely to achieve the global NCD targets. For Kazakhstan, WHO 25X25 and SDG 3.4.1 global targets for mortality rates were 494.3 and 374.8 per 100,000 population respectively; the corresponding predicted values (PVs) were 360.6 [CI 260.1-461.1] and 245.1 [CI 113.4-376.8]. For Russia, WHO 25X25 and SDG 3.4.1 global targets were 560.5 and 442.8 per 100,000 population respectively; the corresponding PVs were 427.7 [CI 270.3-585.1] and 311.0 [CI 102.8-519.1]. Achieving NCD global targets is less likely for Kyrgyzstan, while it is unlikely for the rest of countries. Most countries had higher mortality rates and slower progress among men compared with women. The likelihood of achieving overall global NCD targets was mainly explained by reduction in cardiovascular mortality. CONCLUSIONS: In most Eastern Europe and Central Asia countries, progress towards achieving NCD global targets is slow, or there's a reverse trend. Further quantitative and qualitative research is needed to understand the underlying reasons. Separate indicators are needed to monitor trends for cancers, diabetes and chronic respiratory diseases.

Characteristics and management of generalized pustular psoriasis (GPP): Experience from the Central and Eastern Europe (CEE) GPP Expert Network.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, inflammatory skin disease characterized by widespread eruption of sterile pustules with or without systemic symptoms. OBJECTIVES: This study aimed to describe the demographics of patients with GPP in Central and Eastern Europe (CEE), present the clinical characteristics of individual GPP flares and explore the current treatment landscape. METHODS: Patient demographics were collected at the times of last observation and previous treatment. Characteristics of a patient's last (most recent) and most severe (from all documented episodes) flare were provided at clinician's discretion. RESULTS: Fifty-eight patients were recruited from 12 centres in nine CEE countries; median (range) age was 61 (16-92) years and 60.3% (35 out of 58) were female. The most common comorbidities were hypertension (43.1% [25 out of 58]) and hyperlipidaemia (32.8% [19 out of 58]). Thirty-four patients (58.6%) presented with concomitant plaque psoriasis before or during the course of GPP. Data from two separate flares were recorded in 26 individuals; in 32 patients, the most recent flare was reported as the most severe. Over 90% of patients with a flare episode classified as most severe by clinicians were hospitalized, with >75% of these individuals having a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score of 3 or 4. Systemic symptoms were more common in patients with a GPPGA score of 3 or 4 but were also manifest in individuals with a GPPGA score ≤2. A significant correlation was observed between a combined systemic disease score of clinical and laboratory features and both GPPGA total score (r = 0.385, p < 0.001) and GPPGA pustulation subscore (r = 0.305, p < 0.05). CONCLUSIONS: Considerable heterogeneity in the presentation of GPP flares was observed, both between patients and within-patient. All GPP flares were associated with a significant clinical burden, highlighting the unmet need for accurate and early diagnosis.

Impact of transnational land acquisitions on local food security and dietary diversity.

Foreign investors have acquired approximately 90 million hectares of land for agriculture over the past two decades. The effects of these investments on local food security remain unknown. While additional cropland and intensified agriculture could potentially increase crop production, preferential targeting of prime agricultural land and transitions toward export-bound crops might affect local access to nutritious foods. We test these hypotheses in a global systematic analysis of the food security implications of existing land concessions. We combine agricultural, remote sensing, and household survey data (available in 11 sub-Saharan African countries) with georeferenced information on 160 land acquisitions in 39 countries. We find that the intended changes in cultivated crop types generally imply transitions toward energy-rich, but nutrient-poor, crops that are predominantly destined for export markets. Specific impacts on food production and access vary substantially across regions. Deals likely have little effect on food security in eastern Europe and Latin America, where they predominantly occur within agricultural areas with current export-oriented crops, and where agriculture would have both expanded and intensified regardless of the land deals. This contrasts with Asia and sub-Saharan Africa, where deals are associated with both an expansion and intensification (in Asia) of crop production. Deals in these regions also shift production away from local staples and coincide with a gradually decreasing dietary diversity among the surveyed households in sub-Saharan Africa. Together, these findings point to a paradox, where land deals can simultaneously increase crop production and threaten local food security.

Mental health effects of adult children's outmigration on older parents in Central and Eastern Europe.

OBJECTIVE: To examine the association between adult children's migration and depression among older parents in Central and Eastern Europe (CEE) and explore the role of intergenerational support in contributing to their depression. METHODS: Data are from the eighth wave of the Survey of Health, Ageing and Retirement in Europe (SHARE), pooling a study sample of 11 CEE countries, with a cross-sectional design. Analysis of covariance (ANCOVA) and hierarchical linear regression were conducted using a study sample of 9133 respondents. RESULTS: Older adults whose children migrated over 500 km were more likely to experience depression compared to those with no migrant child or all children within 500 km. Among intergenerational support, frequent parent-child contact mitigated the effects of migration on depression in older parents with all their children who migrated over 500 km. CONCLUSION: This study suggests that older parents with migrant children over 500 km away should be considered a vulnerable population at risk for mental health in CEE countries. It is crucial for local governments and policymakers to address these challenges through improving integrated mental health and social programs for better mental health outcomes among older adults in CEE countries.

An Eastern Europe and Middle East multinational expert Delphi consensus study on the prevention, diagnosis, and treatment of developmental dysplasia of the hip before walking age.

PURPOSE: The incidence of developmental dysplasia of the hip (DDH) is higher in Eastern Europeans and Middle Easterners. This study aimed to establish consensus among experts in this geographical area on the management of DDH before walking age. METHODS: Fourteen experienced orthopedic surgeons agreed to participate in a four-round online consensus panel by the Delphi method. The questionnaire included 31 statements concerning the prevention, diagnosis, and treatment of DDH before walking age. RESULTS: Consensus was established for 26 (84%) of 31 statements. Hip ultrasonography is the proper diagnostic tool under six months in DDH; universal newborn hip screening between three and six weeks is necessary; positive family history, breech presentation, female gender, and postnatal swaddling are the most important risk factors; Ortolani, Barlow tests, and limitation of abduction are the most important clinical findings; Pavlik harness is the first bracing preference; some Graf type IIa hips and all Graf type IIb and worse hips need abduction bracing treatment; the uppermost age limit for closed and open reductions is 12 months and 12-24 months, respectively; anatomic reduction is essential in closed and open reductions, postoperative MRI or CT is not always indicated; anterior approach open reduction is better than medial approach open reduction; forceful reduction and extreme positioning of the hips (> 60° hip abduction) are the two significant risk factors for osteonecrosis of the femoral head. CONCLUSION: The findings of the present study may be useful for clinicians because a practical reference, based on the opinions of the multinational expert panel, but may not be applicable to all settings is provided.

Raising the Jewish nation: prescriptions of modern motherhood in folksgeszunt to Jews in interwar Eastern Europe.

The Society for the Preservation of the Health of the Jewish Population (OZE) was an organisation dedicated to providing medical aid to Eastern European Jews ravaged by war, revolution, poverty and disease during and after World War I. The OZE's top priority was addressing the health needs of Jewish children and teaching mothers how to 'properly' raise their infants, as children were believed to be the backbone and future of the Jewish nation. Analysing the OZE's public-facing newspaper Folksgezunt (People's Health), this paper examines how the OZE used reigning ideas in the Western European and North American scientific community around race and hygiene packaged in Yiddish to transform Jewish women into 'modern mothers'. Modernising maternity required Jewish women to be completely reliant on medical authority and relinquish traditional forms of childcare. At a time when Jews lived in different newly established nation-states of Eastern Europe, transforming maternity practices was part of a larger project started by Jewish physicians in the Russian Empire to unite Jews by defining them in national terms, replacing religious and parochial definitions. This paper uses discursive and gender analysis to explore how the OZE saw women's abilities (or not) to raise a healthy Jewish nation as a crucial part of Jewish national diaspora politics. Hence, this paper emphasises the political nature of a seemingly apolitical humanitarian project by uncovering how the image of a modern Jewish mother facilitated a vision of Jewish cohesion and perseverance through health.

Infectious risk profile and strategies for prevention and control of outbreaks in refugee, asylum seekers and migrant populations in EU/EEA countries: a systematic narrative review of evidence.

Introduction: The recent surge in migration to and within the European Union and European Economic Area has brought the development of migration policy, including health policy, to the forefront of regional priorities. While migrants, in general, do not pose a health threat to the host population, specific subgroups of migrants, including refugees, asylum seekers, and irregular migrants, are particularly vulnerable to infectious diseases. To support public health policies in this area, the Emergency Preparedness and Management' working group of the Italian Society of Hygiene, Preventive Medicine and Public Health has conducted a systematic narrative review with the aim to comprehensively analyze the infectious disease risk within the refugee and asylum seeker populations in EU, EEA, and EU-applicant countries. Methods: Forty-two studies were systematically selected from scientific articles in the MEDLINE/PubMed database from January 1, 2008, to June 1, 2023. The infectious risk associated with each infectious disease among refugees and asylum seekers, as well as the strategies to prevent and control outbreaks, was collected from all available studies. Results: The congregate living conditions in refugee camps, transit centers, and temporary housing facilities make this population particularly vulnerable to infectious diseases. As such, implementing stringent hygiene and preventive measures is critical to safeguarding the health of refugees and reducing the risk of outbreaks that may affect both the refugee population and the host communities. Conclusion: Effective vaccination and preventive strategies for migrants, refugees, and asylum seekers are vital for public health and the well-being of these populations. They should be delivered as part of universal health care. By addressing barriers and implementing tailored programs, we can ensure equitable access to vaccines and protect the health of these vulnerable individuals.

[The participation of the USSR in development of penicillin industry in the Eastern Europe].

The article considers on the basis of analysis of archival documents issue of rendering assistance by the Soviet Union to the countries of Eastern Europe to organize production of penicillin. It is established that by the mid of 1950s, modern powerful plants were launched in Bulgaria, Romania and Czechoslovakia by the forces of Soviet engineers . Their construction was carried out on preferential terms for countries-customers. The mutually beneficial cooperation in sphere of production of antibiotics carried out and with other countries of this region. It is demonstrated that the USSR, performing task of enormous humanitarian significance in conditions of the Cold War, simultaneously implemented another goal - formation of loyalty of population of these countries and organization of coalition of friendly states on its Western borders.

Global variations in lung cancer incidence by histological subtype in 2020: a population-based study.

BACKGROUND: Lung cancer is the second most common cancer worldwide, yet the distribution by histological subtype remains unknown. We aimed to quantify the global, regional, and national burden of lung cancer incidence for the four main subtypes in 185 countries and territories. METHODS: In this population-based study, we used data from Cancer Incidence in Five Continents Volume XI and the African Cancer Registry Network to assess the proportions of adenocarcinoma, squamous cell carcinoma, small-cell carcinoma, and large-cell carcinoma among all lung cancers by country, sex, and age group and subsequently applied these data to corresponding national (GLOBOCAN) estimates of lung cancer incidence in 2020. Unspecified morphologies were reallocated to specified subtypes. Age-standardised incidence rates were calculated using the world standard population to compare subtype risks worldwide, adjusted for differences in age composition between populations by country. FINDINGS: In 2020, there were an estimated 2 206 771 new cases of lung cancer, with 1 435 943 in males and 770 828 in females worldwide. In males, 560 108 (39%) of all lung cancer cases were adenocarcinoma, 351 807 (25%) were squamous cell carcinoma, 163 862 (11%) were small-cell carcinoma, and 115 322 (8%) were large-cell carcinoma cases. In females, 440 510 (57%) of all lung cancer cases were adenocarcinoma, 91 070 (12%) were squamous cell carcinoma, 68 224 (9%) were small-cell carcinoma, and 49 246 (6%) were large-cell carcinoma cases. Age-standardised incidence rates for adenocarcinoma, squamous cell carcinoma, small-cell carcinoma, and large-cell carcinoma, respectively, were estimated to be 12·4, 7·7, 3·6, and 2·6 per 100 000 person-years in males and 8·3, 1·6, 1·3, and 0·9 per 100 000 person-years in females worldwide. The incidence rates of adenocarcinoma exceeded those of squamous cell carcinoma in 150 of 185 countries in males and in all 185 countries in females. The highest age-standardised incidence rates per 100 000 person-years for adenocarcinoma, squamous cell carcinoma, small-cell carcinoma, and large-cell carcinoma, respectively, for males occurred in eastern Asia (23·5), central and eastern Europe (17·5), western Asia (7·2), and south-eastern Asia (11·0); and for females occurred in eastern Asia (16·0), northern America (5·4), northern America (4·7), and south-eastern Asia (3·4). The incidence of each subtype showed a clear gradient according to the Human Development Index for male and female individuals, with increased rates in high and very high Human Development Index countries. INTERPRETATION: Adenocarcinoma has become the most common subtype of lung cancer globally in 2020, with incidence rates in males exceeding those of squamous cell carcinoma in most countries, and in females in all countries. Our findings provide new insights into the nature of the global lung cancer burden and facilitates tailored national preventive actions within each world region. FUNDING: None.

European Groundshot-addressing Europe's cancer research challenges: a Lancet Oncology Commission.

Cancer research is a crucial pillar for countries to deliver more affordable, higher quality, and more equitable cancer care. Patients treated in research-active hospitals have better outcomes than patients who are not treated in these settings. However, cancer in Europe is at a crossroads. Cancer was already a leading cause of premature death before the COVID-19 pandemic, and the disastrous effects of the pandemic on early diagnosis and treatment will probably set back cancer outcomes in Europe by almost a decade. Recognising the pivotal importance of research not just to mitigate the pandemic today, but to build better European cancer services and systems for patients tomorrow, the Lancet Oncology European Groundshot Commission on cancer research brings together a wide range of experts, together with detailed new data on cancer research activity across Europe during the past 12 years. We have deployed this knowledge to help inform Europe's Beating Cancer Plan and the EU Cancer Mission, and to set out an evidence-driven, patient-centred cancer research roadmap for Europe. The high-resolution cancer research data we have generated show current activities, captured through different metrics, including by region, disease burden, research domain, and effect on outcomes. We have also included granular data on research collaboration, gender of researchers, and research funding. The inclusion of granular data has facilitated the identification of areas that are perhaps overemphasised in current cancer research in Europe, while also highlighting domains that are underserved. Our detailed data emphasise the need for more information-driven and data-driven cancer research strategies and planning going forward. A particular focus must be on central and eastern Europe, because our findings emphasise the widening gap in cancer research activity, and capacity and outcomes, compared with the rest of Europe. Citizens and patients, no matter where they are, must benefit from advances in cancer research. This Commission also highlights that the narrow focus on discovery science and biopharmaceutical research in Europe needs to be widened to include such areas as prevention and early diagnosis; treatment modalities such as radiotherapy and surgery; and a larger concentration on developing a research and innovation strategy for the 20 million Europeans living beyond a cancer diagnosis. Our data highlight the important role of comprehensive cancer centres in driving the European cancer research agenda. Crucial to a functioning cancer research strategy and its translation into patient benefit is the need for a greater emphasis on health policy and systems research, including implementation science, so that the innovative technological outputs from cancer research have a clear pathway to delivery. This European cancer research Commission has identified 12 key recommendations within a call to action to reimagine cancer research and its implementation in Europe. We hope this call to action will help to achieve our ambitious 70:35 target: 70% average 10-year survival for all European cancer patients by 2035.

A Phase I, Double-blind, Randomized, Placebo-controlled, Single Dose-escalation Study to Evaluate the Tolerability, and Safety of Cytisinicline in Adult Smokers.

INTRODUCTION: Cytisinicline is a nicotinic acetylcholine receptor partial agonist marketed historically as oral tablets in Central and Eastern Europe as an aid to smoking cessation. Dosing and scheduled regimen for cytisinicline treatment is currently being redeveloped for market approval in the United States and elsewhere. AIMS AND METHODS: A phase 1, double-blind, randomized, placebo-controlled, single-ascending dose clinical trial was conducted under fasting conditions in healthy adults who were current daily (>10 cigarettes) smokers. Safety parameters for the identification of a maximum tolerated dose (MTD) and limited supportive pharmacokinetic assessments were evaluated. Ascending single oral doses of cytisinicline or placebo were administered to 9 cohorts, each comprised of eight unique participants (randomization: 6 cytisinicline; 2 placebo). Dose escalation to the next cohort was dependent upon the safety review of preceding cohorts. Dose levels tested were 6, 9, 12, 15, 18, 21, 24, 27, and 30 mg. Treatment-emergent adverse events (TEAEs) and clinically relevant changes in laboratory blood tests, vital signs, and 12-lead electrocardiograms were evaluated. RESULTS: Seventy-two participants completed the study (54 cytisinicline; 18 placebo). Nausea was the most common TEAE (10 participants [19%]). The MTD was defined as cytisinicline 30 mg based on gastrointestinal symptoms, predominantly vomiting (2 of 6 subjects, 33%). Maximum plasma concentration (observed Cmax) values appeared to plateau at higher dose levels (beyond 24 mg). CONCLUSIONS: Single cytisinicline doses up to 30 mg were well tolerated and raised no new safety concerns in fasting adult smokers. An increased frequency of gastrointestinal symptoms defined the MTD at 30 mg. IMPLICATIONS: The cytisinicline therapeutic dose being evaluated in phase 3 clinical trials is 3 mg, which is a 10-fold lower dose than the 30 mg MTD level for cytisinicline, resulting in an excellent safety margin.

Addressing HIV stigma in healthcare, community, and legislative settings in Central and Eastern Europe.

INTRODUCTION: Surging HIV prevalence across countries of Central and Eastern Europe (CEE) is largely a result of poor HIV care engagement and a lack of comprehensive support for key populations. This is fostered by widespread stigma across healthcare, community, and legislative settings. DISCUSSION: Throughout CEE, HIV stigma and intersectional stigma are serious obstacles to providing adequate medical care to people living with HIV. Anticipated and enacted (experienced) stigma from healthcare professionals, and fears of breaches in confidentiality, deter individuals from having an HIV test and engaging in HIV care. Furthermore, negative connotations surrounding HIV infection can lead to discrimination from family, friends, colleagues, and the public, leading to internalized stigma and depression. Key populations that have higher HIV prevalence, such as men who have sex with men, people who inject drugs, transgender individuals, and sex workers, experience additional stigma and discrimination based on their behaviour and identities. This contributes to the concentrated HIV epidemics seen in these populations in many CEE countries. The stigma is exacerbated by punitive legislation that criminalizes HIV transmission and penalizes sexual orientation, drug use, gender identities, and sex work. Despite high levels of HIV stigma and intersectional stigma, there are many evidence-based interventions that have reduced stigma in other parts of the world. Here, we discuss the interventions that are currently being enacted in various countries of CEE, and we suggest additional effective, evidence-based interventions that will tackle stigma and lead to increased HIV care engagement and higher rates of viral suppression. We cover the promotion of the undetectable = untransmittable (U = U) message, stigma-reduction education and training for healthcare professionals, patient-centric approaches for testing and treatment, and advocacy for non-discriminatory legislation, policies, and practices. We also consider targeted stigma-reduction interventions that acknowledge the wider challenges faced by marginalized populations. CONCLUSIONS: HIV stigma and intersectional stigma in CEE drive poor engagement with HIV testing services and care. Widespread adoption of evidence-based interventions to tackle stigma highlighted in this review will improve the quality of life of people living with HIV, improve HIV care engagement, and ultimately slow the surging HIV prevalence and concentrated epidemics occurring throughout CEE.

Global, regional and national burden of male infertility in 204 countries and territories between 1990 and 2019: an analysis of global burden of disease study.

BACKGROUND: Many countries and regions have experienced male fertility problems due to various influencing factors, especially in less developed countries. Unlike female infertility, male infertility receives insufficient attention. Understanding the changing patterns of male infertility in the world, different regions and different countries is crucial for assessing the global male fertility and reproductive health. METHODS: We obtained data on prevalence, years of life lived with disability (YLD), age-standardized rates of prevalence (ASPR) and age-standardized YLD rate (ASYR) from the Global Burden of Disease Study 2019. We analyzed the burden of male infertility at all levels, including global, regional, national, age stratification and Socio-demographic Index (SDI). RESULTS: In 2019, the global prevalence of male infertility was estimated to be 56,530.4 thousand (95% UI: 31,861.5-90,211.7), reflecting a substantial 76.9% increase since 1990. Furthermore, the global ASPR stood at 1,402.98 (95% UI: 792.24-2,242.45) per 100,000 population in 2019, representing a 19% increase compared to 1990. The regions with the highest ASPR and ASYR for male infertility in 2019 were Western Sub-Saharan Africa, Eastern Europe, and East Asia. Notably, the prevalence and YLD related to male infertility peaked in the 30-34 year age group worldwide. Additionally, the burden of male infertility in the High-middle SDI and Middle SDI regions exceeded the global average in terms of both ASPR and ASYR. CONCLUSION: The global burden of male infertility has exhibited a steady increase from 1990 to 2019, as evidenced by the rising trends in ASPR and ASYR, particularly in the High-middle and Middle SDI regions. Notably, the burden of male infertility in these regions far exceeds the global average. Additionally, since 2010, there has been a notable upward trend in the burden of male infertility in Low and Middle-low SDI regions. Given these findings, it is imperative to prioritize efforts aimed at improving male fertility and reproductive health.