Summary Background In 2009, on the basis of promising evidence from trials in south Asia, WHO and UNICEF issued a joint statement about home visits as a strategy to improve newborn survival. In the ...Newhints trial, we aimed to test this home-visits strategy in sub-Saharan Africa by assessing the effect on all-cause neonatal mortality rate (NMR) and essential newborn-care practices. Methods The Newhints cluster randomised trial was undertaken in 98 zones in seven districts in the Brong Ahafo Region, Ghana. 49 zones were randomly assigned to the Newhints intervention and 49 to the control intervention by use of restricted randomisation with stratification to ensure comparability between interventions. Community-based surveillance volunteers (CBSVs) in Newhints zones were trained to identify pregnant women in their community and to make two home visits during pregnancy and three in the first week of life to promote essential newborn-care practices, weigh and assess babies for danger signs, and refer as necessary. Primary outcomes were NMR and coverage of key essential newborn-care practices. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00623337. Findings 16 168 (99%) of 16 329 deliveries between November, 2008, and December, 2009, were livebirths; the status at 1 month was known for 15 619 (97%) livebirths. 482 neonatal deaths were recorded. Coverage data were available from 6029 women in Newhints zones; of these 4358 (72%) reported having CBSV visits during pregnancy and 3815 (63%) reported having postnatal visits. This coverage increased substantially from June, 2009, after the introduction of new implementation strategies and reached almost 90% for pregnancy visits by the end of the trial and 75% for postnatal visits. The Newhints intervention significantly increased coverage of key essential newborn-care behaviours, except for four or more antenatal-care visits (5975 76% of 7859 vs 5988 74% of 8121, respectively; relative risk 1·02, 95% CI 0·96–1·09; p=0·52) and baby delivered in a facility (5373 68% vs 5539 68%, respectively; 0·97, 0·81–1·14; p=0·69). The largest increase was for care-seeking, with 102 (77%) of 132 sick babies in Newhints zones taken to a hospital or clinic compared with 77 (55%) of 139 in control zones (1·43, 1·17–1·76; p=0·001). Increases were also noted in bednet use during pregnancy (5398 69% of 7859 vs 5135 63% of 8121, respectively; 1·12, 1·03–1·21; p=0·005), money saved for delivery or emergency (5730 86% of 6681 vs 5525 80% of 6941, respectively; 1·09, 1·05–1·12; p<0·0001), transport arranged in advance for facility (2496 37% vs 2061 30%, respectively; 1·30, 1·12–1·49; p=0·0004), birth assistant for home delivery washed hands with soap (1853 93% of 1992 vs 1817 87% of 2091, respectively; 1·05, 1·02–1·09; p=0·001), initiation of breastfeeding in less than 1 h of birth (3743 49% of 7673 vs 3280 41% of 7921, respectively; 1·22, 1·07–1·40; p=0·004), skin to skin contact (3355 44% vs 1931 24%, respectively; 2·30, 1·85–2·87; p=0·0002), first bath delayed for longer than 6 h (3131 41% vs 2269 29%, respectively; 1·65, 1·27–2·13; p<0·0001), exclusive breastfeeding for 26–32 days (1217 86% of 1414 vs 1091 80% of 1371; 1·10, 1·04–1·16; p=0·001), and baby sleeping under bednet for 8–56 days (4548 79% of 5756 vs 4291 73% of 5846; 1·09, 1·03–1·15; p=0·002). There were 230 neonatal deaths in the Newhints zones compared with 252 in the control zones. The overall NMRs per 1000 livebirths were 29·8 and 31·9, respectively (0·92, 0·75–1·12; p=0·405). Interpretation The reduction in NMR with Newhints is consistent with the reductions achieved in three trials undertaken in programme settings in south Asia. Because there is no suggestion of any heterogeneity (p=0·850) between these trials and Newhints, the meta-analysis summary estimate of a reduction of 12% (95% CI 5–18) provides the best evidence for the likely effect of the home-visits strategy delivered within programmes in sub-Saharan Africa and in south Asia. Improvements in the quality of delivery and neonatal care in health facilities and development of innovative, effective strategies to increase coverage of home visits on the day of birth could lead to the achievement of more substantial reductions. Funding WHO, Bill & Melinda Gates Foundation, and UK Department for International Development.
We assessed cardiovascular disease (CVD) incidence in 1474 survivors of Hodgkin lymphoma (HL) younger than 41 years at treatment (1965-1995). Multivariable Cox regression and competing risk analyses ...were used to quantify treatment effects on CVD risk. After a median follow-up of 18.7 years, risks of myocardial infarction (MI) and congestive heart failure (CHF) were strongly increased compared with the general population (standardized incidence ratios SIRs = 3.6 and 4.9, respectively), resulting in 35.7 excess cases of MI and 25.6 excess cases of CHF per 10 000 patients/year. SIRs of all CVDs combined remained increased for at least 25 years and were more strongly elevated in younger patients. Mediastinal radiotherapy significantly increased the risks of MI, angina pectoris, CHF, and valvular disorders (2- to 7-fold). Anthracyclines significantly added to the elevated risks of CHF and valvular disorders from mediastinal RT (hazard ratios HRs were 2.81 and 2.10, respectively). The 25-year cumulative incidence of CHF after mediastinal radiotherapy and anthracyclines in competing risk analyses was 7.9%. In conclusion, risks of several CVDs are 3- to 5-fold increased in survivors of HL compared with the general population, even after prolonged follow-up, leading to increasing absolute excess risks over time. Anthracyclines further increase the elevated risks of CHF and valvular disorders from mediastinal radiotherapy.
Improved survival of children with cancer has been accompanied by multiple treatment-related complications. However, most studies in survivors of childhood cancer focused on only 1 late effect.
To ...assess the total burden of adverse health outcomes (clinical or subclinical disorders "adverse events") following childhood cancer in a large cohort of childhood cancer survivors with long-term and complete medical follow-up.
Retrospective cohort study of 1362 five-year survivors of childhood cancer treated in a single institution in the Netherlands between 1966 and 1996. All survivors were invited to a late-effects clinic for medical assessment of adverse events. Adverse events occurring before January 2004 were graded for severity in a standardized manner.
Treatment-specific prevalence of adverse events (according to severity) at end of follow-up and relative risk of high or severe burden of disease (> or =2 severe or > or =1 life-threatening or disabling adverse events) associated with various treatments.
Medical follow-up was complete for 94.3% of survivors (median follow-up, 17.0 years). The median attained age at end of follow-up was 24.4 years. Almost 75% of survivors had 1 or more adverse events, and 24.6% had 5 or more adverse events. Furthermore, 40% of survivors had at least 1 severe or life-threatening or disabling adverse event. A high or severe burden of adverse events was observed in 55% of survivors who received radiotherapy only and 15% of survivors treated with chemotherapy only, compared with 25% of survivors who had surgery only (adjusted relative risks, 2.18 95% confidence interval, 1.62-2.95 and 0.65 95% confidence interval, 0.46-0.90, respectively). A high or severe burden of adverse events was most often observed in survivors of bone tumors (64%) and least often in survivors of leukemia or Wilms tumor (12% each).
In young adulthood, a substantial proportion of childhood cancer survivors already has a high or severe burden of disease, particularly after radiotherapy. This underscores the need for lifelong risk-stratified medical surveillance of childhood cancer survivors.
Invasive alien species (IAS) can substantially affect ecosystem services and human well-being. However, quantitative assessments of their impact on human health are rare and the benefits of ...implementing IAS management likely to be underestimated. Here we report the effects of the allergenic plant Ambrosia artemisiifolia on public health in Europe and the potential impact of the accidentally introduced leaf beetle Ophraella communa on the number of patients and healthcare costs. We find that, prior to the establishment of O. communa, some 13.5 million persons suffered from Ambrosia-induced allergies in Europe, causing costs of Euro 7.4 billion annually. Our projections reveal that biological control of A. artemisiifolia will reduce the number of patients by approximately 2.3 million and the health costs by Euro 1.1 billion per year. Our conservative calculations indicate that the currently discussed economic costs of IAS underestimate the real costs and thus also the benefits from biological control.
Mobile health (mHealth) describes the use of portable electronic devices with software applications to provide health services and manage patient information. With approximately 5 billion mobile ...phone users globally, opportunities for mobile technologies to play a formal role in health services, particularly in low- and middle-income countries, are increasingly being recognized. mHealth can also support the performance of health care workers by the dissemination of clinical updates, learning materials, and reminders, particularly in underserved rural locations in low- and middle-income countries where community health workers deliver integrated community case management to children sick with diarrhea, pneumonia, and malaria.
Our aim was to conduct a thematic review of how mHealth projects have approached the intersection of cellular technology and public health in low- and middle-income countries and identify the promising practices and experiences learned, as well as novel and innovative approaches of how mHealth can support community health workers.
In this review, 6 themes of mHealth initiatives were examined using information from peer-reviewed journals, websites, and key reports. Primary mHealth technologies reviewed included mobile phones, personal digital assistants (PDAs) and smartphones, patient monitoring devices, and mobile telemedicine devices. We examined how these tools could be used for education and awareness, data access, and for strengthening health information systems. We also considered how mHealth may support patient monitoring, clinical decision making, and tracking of drugs and supplies. Lessons from mHealth trials and studies were summarized, focusing on low- and middle-income countries and community health workers.
The review revealed that there are very few formal outcome evaluations of mHealth in low-income countries. Although there is vast documentation of project process evaluations, there are few studies demonstrating an impact on clinical outcomes. There is also a lack of mHealth applications and services operating at scale in low- and middle-income countries. The most commonly documented use of mHealth was 1-way text-message and phone reminders to encourage follow-up appointments, healthy behaviors, and data gathering. Innovative mHealth applications for community health workers include the use of mobile phones as job aides, clinical decision support tools, and for data submission and instant feedback on performance.
With partnerships forming between governments, technologists, non-governmental organizations, academia, and industry, there is great potential to improve health services delivery by using mHealth in low- and middle-income countries. As with many other health improvement projects, a key challenge is moving mHealth approaches from pilot projects to national scalable programs while properly engaging health workers and communities in the process. By harnessing the increasing presence of mobile phones among diverse populations, there is promising evidence to suggest that mHealth can be used to deliver increased and enhanced health care services to individuals and communities, while helping to strengthen health systems.
Prototypic receptors for human influenza viruses are N-glycans carrying α2,6-linked sialosides. Due to immune pressure, A/H3N2 influenza viruses have emerged with altered receptor specificities that ...bind α2,6-linked sialosides presented on extended N-acetyl-lactosamine (LacNAc) chains. Here, binding modes of such drifted hemagglutinin's (HAs) are examined by chemoenzymatic synthesis of N-glycans having
C-labeled monosaccharides at strategic positions. The labeled glycans are employed in 2D STD-
H by
C-HSQC NMR experiments to pinpoint which monosaccharides of the extended LacNAc chain engage with evolutionarily distinct HAs. The NMR data in combination with computation and mutagenesis demonstrate that mutations distal to the receptor binding domain of recent HAs create an extended binding site that accommodates with the extended LacNAc chain. A fluorine containing sialoside is used as NMR probe to derive relative binding affinities and confirms the contribution of the extended LacNAc chain for binding.
To investigate the long-term impact of pathologic characteristics and an extra boost dose of 16 Gy on local relapse, for stage I and II invasive breast cancer patients treated with breast conserving ...therapy (BCT).
In the European Organisation for Research and Treatment of Cancer boost versus no boost trial, after whole breast irradiation, patients with microscopically complete excision of invasive tumor, were randomly assigned to receive or not an extra boost dose of 16 Gy. For a subset of 1,616 patients central pathology review was performed.
The 10-year cumulative risk of local breast cancer relapse as a first event was not significantly influenced if the margin was scored negative, close or positive for invasive tumor or ductal carcinoma in situ according to central pathology review (log-rank P = .45 and P = .57, respectively). In multivariate analysis, high-grade invasive ductal carcinoma was associated with an increased risk of local relapse (P = .026; hazard ratio HR, 1.67), as was age younger than 50 years (P < .0001; HR, 2.38). The boost dose of 16 Gy significantly reduced the local relapse rate (P = .0006; HR, 0.47). For patients younger than 50 years old and in patients with high grade invasive ductal carcinoma, the boost dose reduced the local relapse from 19.4% to 11.4% (P = .0046; HR, 0.51) and from 18.9% to 8.6% (P = .01; HR, 0.42), respectively.
Young age and high-grade invasive ductal cancer were the most important risk factors for local relapse, while margin status had no significant influence. A boost dose of 16 Gy significantly reduced the negative effects of both young age and high-grade invasive cancer.
Breast cancer patients with the same stage of disease can have markedly different treatment responses and overall outcome. The strongest predictors for metastases (for example, lymph node status and ...histological grade) fail to classify accurately breast tumours according to their clinical behaviour. Chemotherapy or hormonal therapy reduces the risk of distant metastases by approximately one-third; however, 70-80% of patients receiving this treatment would have survived without it. None of the signatures of breast cancer gene expression reported to date allow for patient-tailored therapy strategies. Here we used DNA microarray analysis on primary breast tumours of 117 young patients, and applied supervised classification to identify a gene expression signature strongly predictive of a short interval to distant metastases ('poor prognosis' signature) in patients without tumour cells in local lymph nodes at diagnosis (lymph node negative). In addition, we established a signature that identifies tumours of BRCA1 carriers. The poor prognosis signature consists of genes regulating cell cycle, invasion, metastasis and angiogenesis. This gene expression profile will outperform all currently used clinical parameters in predicting disease outcome. Our findings provide a strategy to select patients who would benefit from adjuvant therapy.
Whilst there is compelling evidence of an almost 2-fold increased risk of still births, and suggestive evidence of increased mortality among offspring of mothers with psychotic disorders, only three ...studies have addressed the role of antenatal depression (AND) on survival of the baby. We examined these associations in a large cohort of pregnant women in Ghana.
A Cohort study nested within 4-weekly surveillance of all women of reproductive age to identify pregnancies and collect data on births and deaths in the Kintampo Health Research Centre study area of Ghana. Women were screened for AND using the Patient Health Questionnaire (PHQ-9) to ascertain DSM-IV major or minor depression. Outcomes were adverse birth outcomes, maternal/infant morbidity, and uptake of key newborn care practices, examined using logistic regression; effect sizes reported as relative risks with 95% confidence intervals.
20679 (89.6%) pregnant women completed the PHQ-9. The prevalence of AND was 9.9% (n = 2032) (95% confidence interval 9.4%-10.2%). AND was associated with: prolonged labour (RR 1.25, 95% CI 1.02-1.53); peripartum complications (RR 1.11, 95% CI 1.07-1.15); postpartum complications (RR 1.27, 96% CI 1.21-1.34); non-vaginal delivery (RR 1.19, 95% CI 1.02-1.40); newborn illness (RR 1.52, 95% CI 1.16-1.99); and bed net use during pregnancy (RR 0.93, 95% CI 0.89-0.98), but not neonatal deaths, still births, low birth weight, immediate breast feeding initiation, or exclusive breastfeeding. AND was marginally associated with preterm births (RR 1.32, 95% CI 0.98-1.76).
This paper has contributed important evidence on the role of antenatal depression as a potential contributor to maternal and infant morbidity. Non-pharmacological treatments anchored on primary care delivery structures are recommended as an immediate step. We further recommend that trials are designed to assess if treating antenatal depression in conjunction with improving the quality of obstetric care results in improved maternal and newborn outcomes.
A more accurate means of prognostication in breast cancer will improve the selection of patients for adjuvant systemic therapy.
Using microarray analysis to evaluate our previously established ...70-gene prognosis profile, we classified a series of 295 consecutive patients with primary breast carcinomas as having a gene-expression signature associated with either a poor prognosis or a good prognosis. All patients had stage I or II breast cancer and were younger than 53 years old; 151 had lymph-node-negative disease, and 144 had lymph-node-positive disease. We evaluated the predictive power of the prognosis profile using univariable and multivariable statistical analyses.
Among the 295 patients, 180 had a poor-prognosis signature and 115 had a good-prognosis signature, and the mean (+/-SE) overall 10-year survival rates were 54.6+/-4.4 percent and 94.5+/-2.6 percent, respectively. At 10 years, the probability of remaining free of distant metastases was 50.6+/-4.5 percent in the group with a poor-prognosis signature and 85.2+/-4.3 percent in the group with a good-prognosis signature. The estimated hazard ratio for distant metastases in the group with a poor-prognosis signature, as compared with the group with the good-prognosis signature, was 5.1 (95 percent confidence interval, 2.9 to 9.0; P<0.001). This ratio remained significant when the groups were analyzed according to lymph-node status. Multivariable Cox regression analysis showed that the prognosis profile was a strong independent factor in predicting disease outcome.
The gene-expression profile we studied is a more powerful predictor of the outcome of disease in young patients with breast cancer than standard systems based on clinical and histologic criteria.
PDF
