Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization.

BACKGROUND: WHO, as requested by its member states, launched the Expanded Programme on Immunization (EPI) in 1974 to make life-saving vaccines available to all globally. To mark the 50-year anniversary of EPI, we sought to quantify the public health impact of vaccination globally since the programme's inception. METHODS: In this modelling study, we used a suite of mathematical and statistical models to estimate the global and regional public health impact of 50 years of vaccination against 14 pathogens in EPI. For the modelled pathogens, we considered coverage of all routine and supplementary vaccines delivered since 1974 and estimated the mortality and morbidity averted for each age cohort relative to a hypothetical scenario of no historical vaccination. We then used these modelled outcomes to estimate the contribution of vaccination to globally declining infant and child mortality rates over this period. FINDINGS: Since 1974, vaccination has averted 154 million deaths, including 146 million among children younger than 5 years of whom 101 million were infants younger than 1 year. For every death averted, 66 years of full health were gained on average, translating to 10·2 billion years of full health gained. We estimate that vaccination has accounted for 40% of the observed decline in global infant mortality, 52% in the African region. In 2024, a child younger than 10 years is 40% more likely to survive to their next birthday relative to a hypothetical scenario of no historical vaccination. Increased survival probability is observed even well into late adulthood. INTERPRETATION: Since 1974 substantial gains in childhood survival have occurred in every global region. We estimate that EPI has provided the single greatest contribution to improved infant survival over the past 50 years. In the context of strengthening primary health care, our results show that equitable universal access to immunisation remains crucial to sustain health gains and continue to save future lives from preventable infectious mortality. FUNDING: WHO.

Lactation Education for Surgeons: American Society of Breast Surgeons (ASBrS) Survey Demonstrates Strong Member Interest in Expanded Training.

BACKGROUND: The availability and extent of breastfeeding-specific surgical training has not been previously described. We aimed to survey breast surgeons on their lactation education and desire for additional knowledge. METHODS: Members of the American Society of Breast Surgeons were invited via email to anonymously complete an electronic survey from 27 October 2021 to 23 January 2022. The survey content included demographic information, sources of lactation education, and desired topics and methods for further training. Descriptive statistics were used to analyze the data. RESULTS: A total of 2698 surveys were delivered and 542 (20.1%) completed. While nearly all respondents (99%) reported treating lactating patients at least once or twice per year, 78% reported that their training was inadequate. The most frequently cited sources of lactation information were peer-to-peer informal knowledge sharing (50%) and personal experience with breastfeeding (44%). Nearly all respondents (99%) agreed that formal lactation education would benefit breast surgeons. Specific topics of interest included management of patients with complications of lactation (48%), management of lactating patients with a new diagnosis of breast cancer (47%), and counseling patients with pregnancy-associated breast cancer who desire to breastfeed (46%). The most frequently recommended educational formats included presentation at a national conference (60%), evidence-based management guidelines (58%), webinar (55%), and workshop/course (47%). CONCLUSION: Breast surgeons self-report minimal formal training in the management of benign and malignant breast disease in lactating patients and strong desire for expanded education. Development of clinical practice guidelines and additional educational content for surgeons should be considered to meet the needs of this patient population.

Social contact patterns during the COVID-19 pandemic in 21 European countries - evidence from a two-year study.

BACKGROUND: Most countries have enacted some restrictions to reduce social contacts to slow down disease transmission during the COVID-19 pandemic. For nearly two years, individuals likely also adopted new behaviours to avoid pathogen exposure based on personal circumstances. We aimed to understand the way in which different factors affect social contacts - a critical step to improving future pandemic responses. METHODS: The analysis was based on repeated cross-sectional contact survey data collected in a standardized international study from 21 European countries between March 2020 and March 2022. We calculated the mean daily contacts reported using a clustered bootstrap by country and by settings (at home, at work, or in other settings). Where data were available, contact rates during the study period were compared with rates recorded prior to the pandemic. We fitted censored individual-level generalized additive mixed models to examine the effects of various factors on the number of social contacts. RESULTS: The survey recorded 463,336 observations from 96,456 participants. In all countries where comparison data were available, contact rates over the previous two years were substantially lower than those seen prior to the pandemic (approximately from over 10 to < 5), predominantly due to fewer contacts outside the home. Government restrictions imposed immediate effect on contacts, and these effects lingered after the restrictions were lifted. Across countries, the relationships between national policy, individual perceptions, or personal circumstances determining contacts varied. CONCLUSIONS: Our study, coordinated at the regional level, provides important insights into the understanding of the factors associated with social contacts to support future infectious disease outbreak responses.

The influence of COVID-19 risk perception and vaccination status on the number of social contacts across Europe: insights from the CoMix study.

BACKGROUND: The SARS-CoV-2 transmission dynamics have been greatly modulated by human contact behaviour. To curb the spread of the virus, global efforts focused on implementing both Non-Pharmaceutical Interventions (NPIs) and pharmaceutical interventions such as vaccination. This study was conducted to explore the influence of COVID-19 vaccination status and risk perceptions related to SARS-CoV-2 on the number of social contacts of individuals in 16 European countries. METHODS: We used data from longitudinal surveys conducted in the 16 European countries to measure social contact behaviour in the course of the pandemic. The data consisted of representative panels of participants in terms of gender, age and region of residence in each country. The surveys were conducted in several rounds between December 2020 and September 2021 and comprised of 29,292 participants providing a total of 111,103 completed surveys. We employed a multilevel generalized linear mixed effects model to explore the influence of risk perceptions and COVID-19 vaccination status on the number of social contacts of individuals. RESULTS: The results indicated that perceived severity played a significant role in social contact behaviour during the pandemic after controlling for other variables (p-value < 0.001). More specifically, participants who had low or neutral levels of perceived severity reported 1.25 (95% Confidence intervals (CI) 1.13 - 1.37) and 1.10 (95% CI 1.00 - 1.21) times more contacts compared to those who perceived COVID-19 to be a serious illness, respectively. Additionally, vaccination status was also a significant predictor of contacts (p-value < 0.001), with vaccinated individuals reporting 1.31 (95% CI 1.23 - 1.39) times higher number of contacts than the non-vaccinated. Furthermore, individual-level factors played a more substantial role in influencing contact behaviour than country-level factors. CONCLUSION: Our multi-country study yields significant insights on the importance of risk perceptions and vaccination in behavioral changes during a pandemic emergency. The apparent increase in social contact behaviour following vaccination would require urgent intervention in the event of emergence of an immune escaping variant.

Estimates of hepatitis B virus prevalence among general population and key risk groups in EU/EEA/UK countries: a systematic review.

BackgroundThe burden of chronic hepatitis B virus (HBV) varies across the European Union (EU) and European Economic Area (EEA).AimWe aimed to update the 2017 HBV prevalence estimates in EU/EEA countries and the United Kingdom for 2018 to 2021.MethodsWe undertook a systematic review, adding to HBV prevalence estimates from an existing (2005-2017) database. Databases were searched for original English-language research articles including HBV surface antigen prevalence estimates among the general population, pregnant women, first-time blood donors (FTB), men who have sex with men (MSM), migrants and people in prison. Country experts contributed grey literature data. Risk of bias was assessed using a quality assessment framework.FindingsThe update provided 147 new prevalence estimates across the region (updated total n = 579). Median HBV prevalence in the general population was 0.5% and the highest was 3.8% (Greece). Among FTB, the highest prevalence was 0.8% (Lithuania). Estimates among pregnant women were highest in Romania and Italy (5.1%). Among migrants, the highest estimate was 31.7% (Spain). Relative to 2017 estimates, median prevalence among pregnant women decreased by 0.5% (to 0.3%) and increased by 0.9% (to 5.8%) among migrants. Among MSM, the highest estimate was 3.4% (Croatia). Prevalence among people in prison was highest in Greece (8.3%) and the median prevalence increased by 0.6% (to 2.1%).ConclusionsThe HBV prevalence is low in the general population and confined to risk populations in most European countries with some exceptions. Screening and treatment should be targeted to people in prison and migrants.

Refining breast cancer prognosis by incorporating age at diagnosis into clinical prognostic staging: introduction of a novel online calculator.

PURPOSE: American Joint Committee on Cancer (AJCC) clinical staging is used to estimate breast cancer prognosis, but individual patient survival within each stage varies considerably by age at diagnosis. We hypothesized that the addition of age at diagnosis to the staging schema will enable more refined risk stratification. METHODS: We performed a retrospective population analysis of adult women diagnosed with invasive breast cancer between 2010 and 2015 registered in SEER. Multivariable Cox hazards models were used to evaluate the association of AJCC 8th edition clinical prognostic stage (CPS) and age with risk of overall mortality. Separate hierarchical models were fit to the data: Model 1: CPS alone; Model 2: CPS + age + age2; and Model 3: CPS + age + age2 + CPS x age + CPS x age2. Models were compared by the Akaike information criterion (AIC), the c-statistic for time-dependent receiver operator characteristic curves, and category-free net reclassification improvement (NRI). Internal validation was performed using bootstrapping samples. RESULTS: Among 86,637 women, the median follow-up was 36 months and 3-year overall survival was 91.9% ± 0.1%. Age significantly modified the effect of CPS on survival (p < 0.0001). Model 3 was the most precise, with the lowest AIC (126,619.63), the highest c-statistic (0.8212, standard error 0.0187), and superior NRI indices. CONCLUSION: Age at diagnosis is a highly prognostic variable that warrants consideration for inclusion in future editions of the AJCC Breast Cancer Staging Manual.

Evaluation of the safety and effectiveness of prostate-specific antigen (PSA) monitoring in primary care after discharge from hospital-based follow-up following prostate cancer treatment.

OBJECTIVE: To examine follow-up procedures after men are discharged into primary care following prostate cancer and highlight any areas for service improvement. METHODS: Patient record data from two Greater Manchester boroughs were retrieved retrospectively to investigate discharge instructions and monitoring adherence. Questionnaires were sent to patients exploring their understanding of the follow-up process. RESULTS: A total of 300 records were accessed. Prostate-specific antigen (PSA) re-referral level was provided to GPs in 39% of cases. Forty- six percent of men were not tested frequently enough, and 6% had no PSA testing recorded post-discharge. A total of 222 patient questionnaires were returned. Sixty-seven percent felt GPs should be responsible for PSA monitoring, and 60% felt confident that their GP was doing so effectively. Conversely, 12% felt their PSA monitoring had been neglected. CONCLUSION: The findings highlight the complex nature of the follow-up and monitoring processes for prostate cancer patients. There is an urgent need for consensus in terms of monitoring frequency and referral pathways. Many patients do not engage in accurate monitoring post-treatment which has implications for early diagnosis of recurrence. Findings will be used to create an evidence-based, uniform Greater Manchester PSA monitoring service which is safe, acceptable and effective for all.

Human papillomavirus vaccination in the European Union/European Economic Area and globally: a moral dilemma.

While many European Union/European Economic Area (EU/EEA) countries recently expanded human papillomavirus (HPV) vaccination to boys, HPV vaccine supply is currently limited for girls in low- and middle-income countries (LMIC) that are severely affected by HPV.Globally, about 50% of countries have introduced HPV vaccination. Some LMIC with high burden of cervical cancer have not yet introduced HPV vaccination, or are reaching suboptimal vaccination coverage. While WHO issued a call for cervical cancer elimination in 2018, a global shortage of HPV vaccines is currently predicted to last at least until 2024.We reviewed national policies of EU/EEA countries and recommendations of the World Health Organization (WHO) Strategic Advisory Group of Experts on immunisation to discuss current challenges and dose-sparing options. Several EU/EEA countries have extended HPV vaccination to boys and the European Cancer Organisation has issued a resolution for elimination of all HPV-associated cancers in both sexes. The European Centre for Disease Prevention and Control concluded in its 2020 guidance that cost-effectiveness of extending routine vaccination to boys depends on several context-specific factors. The extension of HPV vaccination to boys in EU/EEA countries may affect global availability of vaccines. Temporary dose-sparing options could be considered during the COVID-19 post-pandemic period.

Breast Pathology That Contributes to Dysfunction of Human Lactation: a Spotlight on Nipple Blebs.

Nipple blebs are blister-like fibrinous lesions that form on the surface of the nipple during lactation, and can result in orifice obstruction and mastitis. They likely result from superficial extension of underlying ductal plugging, and can present concurrently with hyperlactation and mammary dysbiosis. Despite their prevalence, few formal reports on nipple blebs exist. In this perspective, we review the experience of a breastfeeding medicine practice that receives referrals for patients with nipple blebs, and provide preliminary insight into etiology, management, and outcomes of these lesions.

Lactational phlegmon: A distinct clinical entity affecting breastfeeding women within the mastitis-abscess spectrum.

We aimed to describe the presentation and treatment of lactational phlegmon, a unique complication of mastitis in breastfeeding women that may require surgical management. We retrospectively analyzed medical charts of breastfeeding women treated by a single breast surgeon for lactational phlegmon or the related conditions of abscess or uncomplicated mastitis (UM) from July 2016 to October 2018. Demographic variables and treatment details were analyzed using ANOVA and Pearson's Chi-square test. Ten women with lactational phlegmon (19.2%), 15 women with abscess (28.8%), and 27 women with UM (51.9%) were identified. Phlegmon presented as a tender, erythematous, and nonfluctuant mass in a ductal distribution. Ultrasonography demonstrated an ill-defined, complex fluid collection. Epidemiologically, women with phlegmon were similar to patients with abscess and UM. Women with phlegmon reported more intense deep breast massage than patients in the other two groups, but significantly lower rates of breast pump use than women with abscess (30.0% vs 80.0%, P < .05). Relative to women with UM, patients with complicated mastitis (CM, defined as phlegmon or abscess) reported greater utilization of nipple shields (36.0% vs 11.1%, P < .05). Treatment of phlegmon entailed effective milk removal, antibiotics (range 10-30 days), and close follow-up until both clinical and radiographic resolution (range 8 days to >3 months), with biopsy of persistent masses. Antibiotic duration was significantly longer for patients with phlegmon compared to those with UM (mean 15.0 days vs 9.7 days, P < .05). Two phlegmons coalesced into abscesses within 1 week of diagnosis. Lactational phlegmon is a complication of mastitis in breastfeeding women that is distinct from abscess and UM. Optimal treatment consists of an extended course of antibiotics and close follow-up to monitor for coalescence into a drainable fluid collection and/or persistence of mass requiring biopsy.

Potential scenarios for the progression of a COVID-19 epidemic in the European Union and the European Economic Area, March 2020.

Two months after the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the possibility of established and widespread community transmission in the European Union and European Economic Area (EU/EEA) is becoming more likely. We provide scenarios for use in preparedness for a possible widespread epidemic. The EU/EEA is moving towards the 'limited sustained transmission' phase. We propose actions to prepare for potential mitigation phases and coordinate efforts to protect the health of citizens.

The effect of local therapy on breast cancer-specific mortality of women with occult breast cancer and advanced nodal disease (N2/N3): a population analysis.

PURPOSE: Current NCCN guidelines for occult breast cancer (OBC) recommend modified radical mastectomy, with the option for breast preservation with radiation instead of mastectomy for N1 patients. Our aim was to compare the effect of local therapy-mastectomy versus breast radiation-on breast cancer-specific mortality (BCSM) in a contemporary cohort of OBC patients of all nodal stages. METHODS: Competing risk analyses were performed to evaluate the effect of local therapy, nodal stage, and other demographic and clinical prognostic variables on risk of BCSM for women registered in the SEER database with T0N+M0 breast cancer from 2004 to 2015. RESULTS: Of the 353 women with OBC who underwent axillary nodal dissection, 152 received breast radiation and 201 underwent mastectomy. Overall, 57.5% had N1 disease, 54.4% had estrogen receptor (ER) positive tumors, 80.7% were white, and 88.1% received chemotherapy. Women treated with radiation were older (p < 0.001). The two groups were comparable with respect to all other variables analyzed. During a median follow-up of 66 months, 32 women died from breast cancer (radiation: 11, mastectomy: 21). Five-year cumulative incidence of BCSM was 8.0% ± 2.6% with radiation versus 10.9% ± 2.6% with mastectomy (p = 0.309). On multivariate analysis, independent predictors of BCSM included older age, higher N stage, and ER negativity, but the type of local therapy was not significantly associated with outcome. CONCLUSIONS: These results suggest that breast preservation is a reasonable alternative to mastectomy for OBC patients, regardless of nodal stage.

Quantifying the relationship between age at diagnosis and breast cancer-specific mortality.

PURPOSE: The relationship between age at diagnosis and breast cancer-specific mortality (BCSM) is unclear. The aim of this study was to examine the nature of this relationship using rigorous statistical methodology. METHODS: A historical cohort study of adult women with invasive breast cancer in the SEER database from 2000 to 2015 was conducted. Multivariable Cox's cause-specific hazards model was used to evaluate the association of age at diagnosis with risk of BCSM. Functional relationship of age was assessed using cumulative sums of Martingale residuals and the Kolmogorov-type supremum test. RESULTS: A total of 206,332 women were eligible for study. Mean age at diagnosis was 59.7 ± 13.8 years. Median follow-up was 80 months. During the study period, 21,771 women (10.6%) died from breast cancer and 18,566 (9.0%) died from other causes. Cumulative incidence of BCSM at 120 months post-diagnosis was 14.4% (95% CI 14.2-14.6%). Age was found to be quadratically related to the risk of BCSM (p < 0.001), with a nadir at 45 years of age. The final Cox model suggests that a 30-year-old woman has approximately the same adjusted BCSM risk (HR 1.187, 95% CI 1.187-1.188) as a 60-year-old woman (HR 1.174, 95% CI 1.174-1.175). CONCLUSIONS: Women diagnosed with breast cancer at the extremes of age suffer disproportionate rates of cancer-specific mortality. The relationship between age at diagnosis and adjusted risk of BCSM is complex, consistent with a quadratic function. With the growing appreciation for breast cancer as a heterogeneous disease, it is essential to accurately address age as a prognostic risk factor in predictive models.

Breastfeeding and Breast Cancer: Managing Lactation in Survivors and Women with a New Diagnosis.

BACKGROUND: Supporting breastfeeding is a global health priority, yet few clinical guidelines exist to guide surgical oncologists in managing lactation during or after breast cancer treatment. METHODS: The literature was reviewed to identify evidence-based strategies for managing lactation during multidisciplinary breast cancer treatment or among breast cancer survivors. RESULTS: The majority of the evidence is from observational studies, with some higher levels of evidence, including systematic reviews and meta-analyses. Several significant gaps in knowledge remain. CONCLUSIONS: This review serves as a comprehensive resource of evidence-based recommendations for managing lactation in breast cancer survivors and breastfeeding women with a new breast cancer diagnosis.

Esophageal perforation secondary to malignant gastric outlet obstruction: a case report.

BACKGROUND: Esophageal perforation is a rare presenting sign of gastric cancer. To date, only nine case reports of this phenomenon have been previously published. CASE PRESENTATION: Esophageal perforation was diagnosed radiographically during workup for acute chest pain in a 67-year-old man. Emergent endoscopy confirmed esophageal perforation and biopsied a pre-pyloric mass confirmed to be adenocarcinoma. The perforation was managed with endoscopically placed transluminal pleural and mediastinal drains and esophageal stenting. The gastric outlet obstruction was temporized with a transpyloric stent. After the patient recovered from sepsis, distal gastrectomy was performed and he made a full recovery. CONCLUSIONS: Rarely, pre-pyloric gastric cancer can present with Boerhaave syndrome, spontaneous esophageal perforation associated with forceful vomiting. We present the tenth report in the literature of this phenomenon and the first to be initially treated with endoscopic stenting and transluminal thoracoscopic drainage. When endoscopic management is used to treat patients with Boerhaave syndrome, it may be beneficial to examine the entire stomach to evaluate for malignant etiology.

Clinical Outcomes for BRCA Pathogenic Variant Carriers With Breast Cancer Undergoing Breast Conservation.

Importance: Although most women with BRCA-associated breast cancer choose bilateral mastectomy, current guidelines support breast-conserving therapy as an option. As the indications for genetic testing expand and targeted therapies emerge, understanding the outcomes of breast-conserving therapy in the population of patients choosing breast conservation is important. Objective: To describe the clinical outcomes of women with BRCA-associated breast cancer who were treated with breast-conserving therapy, including the risks of ipsilateral and contralateral cancer events and bilateral mastectomy-free survival. Design, Setting, and Participants: This cohort study conducted at a single-institution academic national comprehensive cancer center included 172 women identified from a prospectively maintained database who had pathogenic BRCA1/2 variants and were treated with breast-conserving therapy from January 1, 1977, to December 31, 2021. Main Outcomes and Measures: Clinical and pathologic characteristics for patients with BRCA1 and BRCA2 were compared, and estimates of overall survival, bilateral mastectomy-free survival, distant disease-free survival, risk of ipsilateral breast cancer, and risk of contralateral cancer were computed. Results: The cohort included 172 women (mean [SD] age, 47.1 [11.7] years), with 42 (24.4%) receiving a diagnosis of breast cancer prior to 40 years of age. Compared with BRCA2 variant carriers (80 [46.5%]), women with BRCA1 variants (92 [53.5%]) were younger at breast cancer diagnosis and tended to have more advanced tumors, which were more likely to be hormone receptor negative and higher grade. At a median follow-up of 11.8 years (IQR, 5.7-18.2 years), estimates of 10-year survival and risk were: overall survival, 88.5% (95% CI, 83.1%-94.2%); bilateral mastectomy-free survival, 70.7% (95% CI, 63.3%-78.9%); risk of an ipsilateral breast cancer event, 12.2% (95% CI, 5.8%-18.2%); and risk of contralateral cancer, 21.3% (95% CI, 13.3%-28.6%). Risks continued to increase after 10 years of follow-up. Conclusions and Relevance: In this cohort study, although women with breast cancer and pathogenic BRCA1/2 variants treated with breast-conserving therapy had above-average risks of ipsilateral and contralateral breast cancer events, most did not have another cancer event and remained bilateral mastectomy free. These findings may be useful for informing patients with BRCA variants choosing breast conservation.

Integration of population genetics with oceanographic models reveals strong connectivity among coral reefs across Seychelles.

Many countries with tropical reef systems face hard choices preserving coral reefs in the face of climate change on limited budgets. One approach to maximising regional reef resilience is targeting management efforts and resources at reefs that export large numbers of larvae to other reefs. However, this requires reef connectivity to be quantified. To map coral connectivity in the Seychelles reef system we carried out a population genomic study of the Porites lutea species complex using 241 sequenced colonies from multiple islands. To identify oceanographic drivers of this connectivity and quantify variability, we further used a 2 km resolution regional ocean simulation coupled with a larval dispersal model to predict the flow of coral larvae between reef sites. Patterns of admixture and gene flow are broadly supported by model predictions, but the realised connectivity is greater than that predicted from model simulations. Both methods detected a biogeographic dispersal barrier between the Inner and Outer Islands of Seychelles. However, this barrier is permeable and substantial larval transport is possible across Seychelles, particularly for one of two putative species found in our genomic study. The broad agreement between predicted connectivity and observed genetic patterns supports the use of such larval dispersal simulations in reef system management in Seychelles and the wider region.

Carbapenem-resistant Acinetobacter baumannii complex in the United States-An epidemiological and molecular description of isolates collected through the Emerging Infections Program, 2019.

BACKGROUND: Understanding the epidemiology of carbapenem-resistant A. baumannii complex (CRAB) and the patients impacted is an important step toward informing better infection prevention and control practices and improving public health response. METHODS: Active, population-based surveillance was conducted for CRAB in 9 U.S. sites from January 1 to December 31, 2019. Medical records were reviewed, isolates were collected and characterized including antimicrobial susceptibility testing and whole genome sequencing. RESULTS: Among 136 incident cases in 2019, 66 isolates were collected and characterized; 56.5% were from cases who were male, 54.5% were from persons of Black or African American race with non-Hispanic ethnicity, and the median age was 63.5 years. Most isolates, 77.2%, were isolated from urine, and 50.0% were collected in the outpatient setting; 72.7% of isolates harbored an acquired carbapenemase gene (aCP), predominantly blaOXA-23 or blaOXA-24/40; however, an isolate with blaNDM was identified. The antimicrobial agent with the most in vitro activity was cefiderocol (96.9% of isolates were susceptible). CONCLUSIONS: Our surveillance found that CRAB isolates in the U.S. commonly harbor an aCP, have an antimicrobial susceptibility profile that is defined as difficult-to-treat resistance, and epidemiologically are similar regardless of the presence of an aCP.