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Background. Depression is a leading cause of disease burden worldwide and is especially problematic in people with chronic diseases, including cancer. Although depression can be effectively treated in the general population using antidepressant medication and psychological treatments, these treatments may have different benefits and harms in cancer patients. Previous reviews have not adequately addressed this topic. We therefore aimed to determine which, if any, treatments are effective for patients with diagnoses of both cancer and depression. Method. We conducted a systematic review of relevant randomized controlled trials identified through searches of Medline, EMBASE, PsycINFO and The Cochrane Central Register of Controlled Trials (CENTRAL). Results. Seven relatively small trials met the selection criteria. These provided some evidence that antidepressant medication, given alone or in combination with a psychological treatment, may be effective. We found no good evidence for psychological treatments given alone or for any other forms of treatment. Conclusions. There is very limited evidence from clinical trials to guide the treatment of cancer patients with a diagnosis of depression, especially for psychological treatments. High quality trials of treatments for depression in patients with cancer are urgently needed. [ABSTRACT FROM AUTHOR]

Objectives: Comorbid major depression is associated with reduced quality of life and greater use of healthcare resources. A recent randomised trial (SMaRT, Symptom Management Research Trials, Oncology-2) found that a collaborative care treatment programme (Depression Care for People with Cancer, DCPC) was highly effective in treating depression in patients with cancer. This study aims to estimate the cost-effectiveness of DCPC compared with usual care from a health service perspective.Methods: Costs were estimated using UK national unit cost estimates and health outcomes measured using quality-adjusted life-years (QALYs). Incremental cost-effectiveness of DCPC compared with usual care was calculated and scenario analyses performed to test alternative assumptions on costs and missing data. Uncertainty was characterised using cost-effectiveness acceptability curves. The probability of DCPC being cost-effective was determined using the UK National Institute for Health and Care Excellence's (NICE) cost-effectiveness threshold range of £ 20,000 to £ 30,000 per QALY gained.Results: DCPC cost on average £ 631 more than usual care per patient, and resulted in a mean gain of 0.066 QALYs, yielding an incremental cost-effectiveness ratio of £ 9549 per QALY. The probability of DCPC being cost-effective was 0.9 or greater at cost-effectiveness thresholds above £ 20,000 per QALY for the base case and scenario analyses.Conclusions: Compared with usual care, DCPC is likely to be cost-effective at the current thresholds used by NICE. This study adds to the weight of evidence that collaborative care treatment models are cost-effective for depression, and provides new evidence regarding their use in specialist medical settings. [ABSTRACT FROM AUTHOR]

Using a common protocol across seven countries in the European Union/European Economic Area, we estimated XBB.1.5 monovalent vaccine effectiveness (VE) against COVID-19 hospitalisation and death in booster-eligible ≥ 65-year-olds, during October-November 2023. We linked electronic records to construct retrospective cohorts and used Cox models to estimate adjusted hazard ratios and derive VE. VE for COVID-19 hospitalisation and death was, respectively, 67% (95%CI: 58-74) and 67% (95%CI: 42-81) in 65- to 79-year-olds and 66% (95%CI: 57-73) and 72% (95%CI: 51-85) in ≥ 80-year-olds. Results indicate that periodic vaccination of individuals ≥ 65 years has an ongoing benefit and support current vaccination strategies in the EU/EEA., (© 2024 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Importance: This study is important because it shows the potential epidemiological silence associated with the use of culture as the primary diagnostic method for the laboratory identification of human campylobacteriosis. Also, we show how polymerase chain reaction methods are associated with a systematic increase in the number of human campylobacteriosis episodes as reported by routine disease surveillance. These findings are operationally relevant and have public health implications because they tell how crucial it is to consider changes in diagnostic methods, e.g., in the epidemiological analysis of historical data and in the interpretation of future data in light of the past. We also believe that this study highlights how the synergy between microbiology and epidemiology is essential for disease surveillance., Competing Interests: The authors declare no conflict of interest.

To monitor relative vaccine effectiveness (rVE) against COVID-19-related hospitalisation of the first, second and third COVID-19 booster (vs complete primary vaccination), we performed monthly Cox regression models using retrospective cohorts constructed from electronic health registries in eight European countries, October 2021-July 2023. Within 12 weeks of administration, each booster showed high rVE (≥ 70% for second and third boosters). However, as of July 2023, most of the relative benefit has waned, particularly in persons ≥ 80-years-old, while some protection remained in 65-79-year-olds.

Schools offer an advantageous setting for the prevention, early identification, and treatment of mental health problems for youth. However, school mental health (SMH) services are typically not based on evidence for effectiveness, nor are they efficiently delivered, with SMH practitioners (SMHPs) able to only treat a small number of students in need. The current study evaluated the feasibility, acceptability, efficiency, and outcomes of a four-session assessment, engagement, problem-solving, and triage strategy for SMHPs that aimed to improve efficiency while being based on elements of evidence-based care. The study, conducted in 15 US school districts in three states, used stratified random assignment to assign 49 high schools and their participating SMHP(s) to either the Brief Intervention for School Clinicians (BRISC; N = 259 students) or services as usual (SAU; N = 198 students). SMHPs implemented BRISC elements with adequate to excellent fidelity and reported the strategy was feasible and well-aligned with presenting problems. Students assigned to BRISC reported significantly greater engagement in SMH at 2 months and completion of SMH treatment by 6 months. BRISC-assigned SMHPs reported significantly greater treatment completion after four sessions (53.4%) compared to SAU (15.4%). Students in the BRISC condition also reported significantly greater reduction in problem severity as evaluated by the Youth Top Problems Assessment. No differences were found for anxiety or depression symptoms or overall functioning. Results indicate that BRISC is a feasible early intervention and triage strategy that may aid in more efficient provision of SMH services with no compromise to SMH effectiveness., (© 2023. The Author(s).)

Background: High-quality essential newborn care (ENC) can improve newborn health and reduce preventable newborn mortality. The World Health Organization recommends specific ENC interventions. Video recordings have potential as a tool for assessment of clinical care also in low and middle-income countries., Objective: To use video observations of healthy newborns to describe ENC practices in a low-income setting and compare actual clinical practice with WHO recommendations., Method: This is a cross-sectional observational study. Video records of neonatal interventions to 324 healthy newborns were assessed. They were obtained at baseline of a pre-post intervention study during a 10-week study period in Pemba, Tanzania. Data also included postnatal structured questionnaires. Eight ENC interventions and quality indicators were defined as per the WHO recommendations. Descriptive statistics were used to summarize ENC practices and maternal and neonatal characteristics., Results: None of the newborns received all eight recommended ENC interventions. The median duration of separation from the mother was 25 minutes and 15 seconds (ranging from 22 seconds to 3 hours and 36 minutes), 51% of the newborns received proper thermal care during the separation. Twenty-one percent had sufficient umbilical cord care, 8% were stimulated for breathing, 69% were observed at least once by healthcare staff and 9% did undergo suctioning. None of the newborns received antibiotic ointments or vitamin K., Conclusion: Video recording of healthy newborns was feasible. The study identified omission of key ENC practices including proper thermal care, skin-to-skin contact and establishment of breastfeeding within the first hour of life, vitamin K administration as well as application of unnecessary practices such as excessive suctioning of breathing newborns.

Objectives: To identify the risk factors for neonatal sepsis in Sub-Saharan Africa., Design: Systematic review and meta-analysis., Data Sources: PubMed, Embase, Web of Science, African Index Medicus and ClinicalTrials.gov were searched for observational studies from January 2010 to August 2020., Setting: Sub-Saharan Africa, at all levels of healthcare facilities., Participants: 'Neonates' (<28 days of age) at risk of developing either clinical and/or laboratory-dependent diagnosis of sepsis., Outcome Measures: Identification of any risk factors for neonatal sepsis., Results: A total of 36 studies with 23 605 patients from secondary or tertiary level of care facilities in 10 countries were included. Six studies were rated as good quality, 8 as fair and 22 as poor. Four studies were omitted in the meta-analysis due to insufficient data. The significant risk factors were resuscitation (OR 2.70, 95% CI 1.36 to 5.35), low birth weight <1.5 kg (OR 3.37, 95% CI 1.59 to 7.13) and 1.5-2.5 kg (OR 1.36, 95% CI 1.01 to 1.83), low Apgar score at the first minute (OR 3.69, 95% CI 2.34 to 5.81) and fifth minute (OR 2.55, 95% CI 1.46 to 4.45), prematurity <37 weeks (OR 1.91, 95% CI 1.27 to 2.86), no crying at birth (OR 3.49, 95% CI 1.42 to 8.55), male sex (OR 1.30, 95% CI 1.01 to 1.67), prolonged labour (OR 1.57, 95% CI 1.08 to 2.27), premature rupture of membranes (OR 2.15, 95% CI 1.34 to 3.47), multiple digital vaginal examinations (OR 2.22, 95% CI 1.27 to 3.89), meconium-stained amniotic fluid (OR 2.72, 95% CI 1.58 to 4.69), intrapartum maternal fever (OR 2.28, 95% CI 1.18 to 4.39), foul-smelling vaginal discharge (OR 3.31, 95% CI 2.16 to 5.09) and low socioeconomic status (OR 1.93, 95% CI 1.11 to 3.35). We found considerable heterogeneity in the meta-analysis of 11 out of 15 identified risk factors., Conclusion: Multiple risk factors for neonatal sepsis in Sub-Saharan Africa were identified. We revealed risk factors not listed by the WHO guidelines. The included studies overall had high risk of bias and high heterogeneity and thus, additional research of high quality is needed., Prospero Registration Number: CRD42020191067., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Seroprevalence studies have proven an important tool to monitor the progression of the coronavirus disease 2019 (COVID-19) pandemic. We present results of consecutive population-based seroprevalence surveys performed in Denmark in 2020. In spring, late summer and autumn/winter of 2020, invitation letters including a questionnaire covering symptoms were sent to representative samples of the population above 12 years and to parents of children below 18 years in the sample. Blood samples were analysed for total Ig and seroprevalence estimates per population segment were calculated and compared to other surveillance parameters. Based on 34 081 participants (participation rate 33%), seroprevalence estimates increased from 1.2% (95%CI: 0.3-1.9%) in May to 4.1% (95%CI: 3.1-4.9%) in December 2020. Seroprevalence estimates were roughly three times higher in those aged 12-29 years compared to 65 + and higher in metropolitan municipalities. By December 2020, 1.5% of the population had tested positive by RT-PCR. Infected individuals in older age groups were hospitalised several fold more often than in younger. Amongst seropositives, loss of taste/smell were the more specific symptoms, 32-56% did not report any symptoms. In more than half of seroconverted families, we did not see evidence of transmission between generations. Seroprevalence increased during 2020; adolescents were primarily infected in the autumn/winter. Denmark has a high per capita test rate; roughly one undiagnosed infection of SARS-CoV-2 were estimated to occur for each diagnosed case. Approximately half were asymptomatically infected. The epidemic appears to have progressed relatively modestly during 2020 in Denmark., (© 2021. The Author(s).)

Despite the discovery of the tubercle bacillus more than 130 years ago, its physiology and the mechanisms of virulence are still not fully understood. A comprehensive analysis of the proteomes of members of the human-adapted Mycobacterium tuberculosis complex (MTBC) lineages 3, 4, 5, and 7 was conducted to better understand the evolution of virulence and other physiological characteristics. Unique and shared proteomic signatures in these modern, pre-modern and ancient MTBC lineages, as deduced from quantitative bioinformatics analyses of high-resolution mass spectrometry data, were delineated. The main proteomic findings were verified by using immunoblotting. In addition, analysis of multiple genome alignment of members of the same lineages was performed. Label-free peptide quantification of whole cells from MTBC lineages 3, 4, 5, and 7 yielded a total of 38,346 unique peptides derived from 3092 proteins, representing 77% coverage of the predicted proteome. MTBC lineage-specific differential expression was observed for 539 proteins. Lineage 7 exhibited a markedly reduced abundance of proteins involved in DNA repair, type VII ESX-3 and ESX-1 secretion systems, lipid metabolism and inorganic phosphate uptake, and an increased abundance of proteins involved in alternative pathways of the TCA cycle and the CRISPR-Cas system as compared to the other lineages. Lineages 3 and 4 exhibited a higher abundance of proteins involved in virulence, DNA repair, drug resistance and other metabolic pathways. The high throughput analysis of the MTBC proteome by super-resolution mass spectrometry provided an insight into the differential expression of proteins between MTBC lineages 3, 4, 5, and 7 that may explain the slow growth and reduced virulence, metabolic flexibility, and the ability to survive under adverse growth conditions of lineage 7., (Copyright © 2020 Yimer, Kalayou, Homberset, Birhanu, Riaz, Zegeye, Lutter, Abebe, Holm-Hansen, Aseffa and Tønjum.)

Background: The long-term clinical course of patients with an enterovirus central nervous system infection (ECI) is poorly understood., Methods: We performed a nationwide population-based cohort study of all Danish patients with ECI diagnosed 1997-2016 (n = 1745) and a comparison cohort from the general population individually matched on date of birth and sex (n = 17 450). Outcomes were categorized into mortality and risk of cancer and likely measures of neurological sequelae: neuropsychiatric morbidities, educational landmarks, use of hospital services, employment, receipt of disability pension, income, number of sick leave days, and nursing home residency., Results: Mortality in the first year was higher among patients with ECI (mortality rate ratio [MRR] = 10.0; 95% confidence interval [CI], 4.17-24.1), but thereafter mortality was not higher (MMR = 0.94; 95% CI, 0.47-1.86). Long-term outcomes for patients with ECI were not inferior to those of the comparison cohort for risk of cancer, epilepsy, mental and behavioral disorders, dementia, depression, school start, school marks, high school education, use of hospital services, employment, receipt of disability pension, income, days of sick leave, or nursing home residency., Conclusions: Diagnosis of an ECI had no substantial impact on long-term survival, health, or social/educational functioning., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: Cervical cancer is the leading cause of cancer-related mortality among women in sub-Saharan Africa (SSA). Data on human papillomavirus (HPV) epidemiology in adolescent girls in SSA are essential to inform HPV vaccine policy recommendations for cervical cancer prevention. We assessed the burden of HPV infection, and risk factors for infection, among adolescent girls around the time of sexual debut., Methods: Cross-sectional study of secondary school girls aged 17-18 years in Tanzania. Consenting participants provided samples for HPV and STI testing. Vaginal swabs were tested for 37 HPV genotypes by Roche Linear Array. Logistic regression was used to identify factors associated with HPV infection. Y chromosome was tested as a marker of recent condomless sex., Results: 163/385 girls (42.3%) reported previous penetrative sex. HPV was detected in 125/385 (32.5%) girls, including 84/163 (51.5%) girls reporting previous sex and 41/222 (18.5%) reporting no previous sex. High-risk (HR) genotypes were detected in 70/125 (56.0%) girls with HPV infection. The most common HR genotype was HPV-16 (15/385; 3.9%). The prevalence of other HR HPV vaccine genotypes was between 0.8% and 3.1%. Among 186 girls who reported no previous sex, were negative for Y chromosome, and had no STI, 32 (17%) had detectable HPV. Lactobacillus sp and bacterial vaginosis-associated bacteria were negatively and positively associated, respectively, with HPV., Conclusions: HPV prevalence among adolescent girls around the time of sexual debut was high. However, prevalence of most vaccine genotypes was low, indicating that extending the age range of HPV vaccination in this region may be cost-effective., Competing Interests: Competing interests: DWJ has received research grants from GSK Biologicals for HPV vaccine-related research., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Bacterial vaginosis (BV) increases women's susceptibility to sexually transmitted infections (STIs) and HIV and may partly explain the high incidence of STI/HIV among girls and young women in East and southern Africa. The objectives of this study were to investigate the association between BV and sexual debut, to investigate other potential risk factors of BV and to estimate associations between BV and STIs., Methods: Secondary school girls in Mwanza, aged 17 and 18 years, were invited to join a cross-sectional study. Consenting participants were interviewed and samples were obtained for STI and BV testing. Factors associated with prevalent BV were analysed using multivariable logistic regression. Y-chromosome was tested as a biomarker for unprotected penile-vaginal sex., Results: Of the 386 girls who were enrolled, 163 (42%) reported having ever had penile-vaginal sex. Ninety-five (25%) girls had BV. The prevalence of BV was 33% and 19% among girls who reported or did not report having ever had penile-vaginal sex, respectively. BV was weakly associated with having ever had one sex partner (adjusted odds ratio (aOR) 1.59;95% CI 0.93 to 2.71) and strongly associated with two or more partners (aOR = 3.67; 95% CI 1.75 to 7.72), receptive oral sex (aOR 6.38; 95% CI 1.22 to 33.4) and having prevalent human papillomavirus infection (aOR = 1.73; 95% CI 1.02 to 2.95). Of the 223 girls who reported no penile-vaginal sex, 12 (5%) tested positive for an STI and 7 (3%) tested positive for Y-chromosome. Reclassifying these positive participants as having ever had sex did not change the key results., Conclusions: Tanzanian girls attending school had a high prevalence of BV. Increasing number of sex partner was associated with BV; however, 19% of girls who reported no penile-vaginal sex had BV. This suggests that penile-vaginal sexual exposure may not be a prerequisite for BV. There was evidence of under-reporting of sexual debut., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Preschool children in Addis Ababa, Ethiopia, are highly exposed to influenza viruses. Factors related to infections, nutrition, and environmental conditions that might explain the burden of influenza among these children were investigated. Ninety-five preschool children, 48 girls and 47 boys, were followed clinically for 12 months. Illness and immune responses to influenza; three other respiratory viruses; five airway pathogenic bacteria; and levels of vitamins D, A, and B12 were assessed. Most of the children had antibodies to numerous respiratory viral and bacterial agents at study start, and many were infected during follow-up. Twenty-five girls and 25 boys fell ill during the study, and were treated with one or more courses of systemic antimicrobials. Ninety percent of both girls and boys had 25-hydroxyvitamin D [25(OH)D] levels below the recommended levels. While there was no overall difference in the levels of vitamins D, A, and B12 between girls and boys, treated girls had significantly lower 25(OH)D levels than non-treated girls and treated boys. There was a considerable number of short for age children, but only the short treated girls had significantly lower 25(OH)D levels than the non-treated children. Preschool girls with low 25(OH)D levels were more vulnerable to pathogenic microbes than boys.

Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb). PTMs such as glycosylation play a significant role in Mtb adaptive processes. The glycoproteomic patterns of clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7 were characterized by mass spectrometry. A total of 2944 glycosylation events were discovered in 1325 proteins. This data set represents the highest number of glycosylated proteins identified in Mtb to date. O-glycosylation constituted 83% of the events identified, while 17% of the sites were N-glycosylated. This is the first report on N-linked protein glycosylation in Mtb and in Gram-positive bacteria. Collectively, the bulk of Mtb glycoproteins are involved in cell envelope biosynthesis, fatty acid and lipid metabolism, two-component systems, and pathogen-host interaction that are either surface exposed or located in the cell wall. Quantitative glycoproteomic analysis revealed that 101 sites on 67 proteins involved in Mtb fitness and survival were differentially glycosylated between the four lineages, among which 64% were cell envelope and membrane proteins. The differential glycosylation pattern may contribute to phenotypic variabilities across Mtb lineages. The study identified several clinically important membrane-associated glycolipoproteins that are relevant for diagnostics as well as for drug and vaccine discovery.

It is often unclear what specific adaptive trial design features lead to an efficient design which is also feasible to implement. This article describes the preparatory simulation study for a Bayesian response-adaptive dose-finding trial design. Dexamethasone for Excessive Menstruation aims to assess the efficacy of Dexamethasone in reducing excessive menstrual bleeding and to determine the best dose for further study. To maximise learning about the dose response, patients receive placebo or an active dose with randomisation probabilities adapting based on evidence from patients already recruited. The dose-response relationship is estimated using a flexible Bayesian Normal Dynamic Linear Model. Several competing design options were considered including: number of doses, proportion assigned to placebo, adaptation criterion, and number and timing of adaptations. We performed a fractional factorial study using SAS software to simulate virtual trial data for candidate adaptive designs under a variety of scenarios and to invoke WinBUGS for Bayesian model estimation. We analysed the simulated trial results using Normal linear models to estimate the effects of each design feature on empirical type I error and statistical power. Our readily-implemented approach using widely available statistical software identified a final design which performed robustly across a range of potential trial scenarios.

Increasing evidence demonstrates that lysine acetylation is involved in Mycobacterium tuberculosis (Mtb) virulence and pathogenesis. However, previous investigations in Mtb have only monitored acetylation at lysine residues using selected reference strains. We analyzed the global N ε - and O-acetylation of three Mtb isolates: two lineage 7 clinical isolates and the lineage 4 H37Rv reference strain. Quantitative acetylome analysis resulted in identification of 2490 class-I acetylation sites, 2349 O-acetylation and 141 N ε -acetylation sites, derived from 953 unique proteins. Mtb O-acetylation was thereby significantly more abundant than N ε -acetylation. The acetylated proteins were found to be involved in central metabolism, translation, stress responses, and antimicrobial drug resistance. Notably, 261 acetylation sites on 165 proteins were differentially regulated between lineage 7 and lineage 4 strains. A total of 257 acetylation sites on 161 proteins were hypoacetylated in lineage 7 strains. These proteins are involved in Mtb growth, virulence, bioenergetics, host-pathogen interactions, and stress responses. This study provides the first global analysis of O-acetylated proteins in Mtb. This quantitative acetylome data expand the current understanding regarding the nature and diversity of acetylated proteins in Mtb and open a new avenue of research for exploring the role of protein acetylation in Mtb physiology.

In order to decipher the nature of the slowly growing Mycobacterium tuberculosis (M .tuberculosis) lineage 7, the differentially abundant proteins in strains of M. tuberculosis lineage 7 and lineage 4 were defined. Comparative proteomic analysis by mass spectrometry was employed to identify, quantitate and compare the protein profiles of strains from the two M. tuberculosis lineages. Label-free peptide quantification of whole cells from M. tuberculosis lineage 7 and 4 yielded the identification of 2825 and 2541 proteins, respectively. A combined total of 2867 protein groups covering 71% of the predicted M. tuberculosis proteome were identified. The abundance of 125 proteins in M. tuberculosis lineage 7 and 4 strains was significantly altered. Notably, the analysis showed that a number of M. tuberculosis proteins involved in growth and virulence were less abundant in lineage 7 strains compared to lineage 4. Five ABC transporter proteins, three phosphate binding proteins essential for inorganic phosphate uptake, and six components of the type 7 secretion system ESX-3 involved in iron acquisition were less abundant in M. tuberculosis lineage 7. This proteogenomic analysis provided an insight into the lineage 7-specific protein profile which may provide clues to understanding the differential properties of lineage 7 strains in terms of slow growth, survival fitness, and pathogenesis.

Background: A deeply rooted phylogenetic lineage of Mycobacterium tuberculosis (M. tuberculosis) termed lineage 7 was discovered in Ethiopia. Whole genome sequencing of 30 lineage 7 strains from patients in Ethiopia was performed. Intra-lineage genome variation was defined and unique characteristics identified with a focus on genes involved in DNA repair, recombination and replication (3R genes)., Results: More than 800 mutations specific to M. tuberculosis lineage 7 strains were identified. The proportion of non-synonymous single nucleotide polymorphisms (nsSNPs) in 3R genes was higher after the recent expansion of M. tuberculosis lineage 7 strain started. The proportion of nsSNPs in genes involved in inorganic ion transport and metabolism was significantly higher before the expansion began. A total of 22346 bp deletions were observed. Lineage 7 strains also exhibited a high number of mutations in genes involved in carbohydrate transport and metabolism, transcription, energy production and conversion., Conclusions: We have identified unique genomic signatures of the lineage 7 strains. The high frequency of nsSNP in 3R genes after the phylogenetic expansion may have contributed to recent variability and adaptation. The abundance of mutations in genes involved in inorganic ion transport and metabolism before the expansion period may indicate an adaptive response of lineage 7 strains to enable survival, potentially under environmental stress exposure. As lineage 7 strains originally were phylogenetically deeply rooted, this may indicate fundamental adaptive genomic pathways affecting the fitness of M. tuberculosis as a species.

Lineage 7 of the Mycobacterium tuberculosis complex has recently been identified among strains originating from Ethiopia. Using different DNA typing techniques, this study provides additional information on the genetic heterogeneity of five lineage 7 strains collected in the Amhara Region of Ethiopia. It also confirms the phylogenetic positioning of these strains between the ancient lineage 1 and TbD1-deleted, modern lineages 2, 3 and 4 of Mycobacterium tuberculosis . Four newly identified large sequence polymorphisms characteristic of the Amhara Region lineage 7 strains are described. While lineage 7 strains have been previously identified in the Woldiya area, we show that lineage 7 strains circulate in other parts of the Amhara Region and also among foreign-born individuals from Eritrea and Somalia in The Netherlands. For ease of documenting future identification of these strains in other geographical locations and recognizing the place of origin, we propose to assign lineage 7 strains the lineage name ' Aethiops vetus ' .

Hypertension control rates are low in sub-Saharan Africa. Population-specific determinants of blood pressure (BP) control have not been adequately described. The authors measured BP and conducted interviews to determine factors associated with BP control among adults attending a hypertension clinic in Tanzania. Three hundred adults were enrolled. BP was controlled in 47.7% of patients at the study visit but only 28.3% over three consecutive visits. Demographic and socioeconomic factors were not associated with control. Obesity and higher medication cost were associated with decreased control. Their effect was mediated through adherence. Good knowledge of (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.0-6.1; P=.047), attitudes towards (OR, 2.7; 95% CI, 1.0-7.1; P=.04), and practices concerning (OR, 5.4; 95% CI, 2.3-13.0; P<.001) hypertension were independently associated with increased control, even after adjusting for mediation through adherence. Good adherence had the strongest association with control (OR, 14.6; 95% CI, 5.8-37.0; P<.001). Strategies to reduce hypertension-related morbidity and mortality in sub-Saharan Africa should target these factors. Interventional studies of such strategies are needed., (© 2015 Wiley Periodicals, Inc.)

Recent genotyping studies of Mycobacterium tuberculosis in Ethiopia have reported the identification of a new phylogenetically distinct M. tuberculosis lineage, lineage 7. We therefore investigated the genetic diversity and association of specific M. tuberculosis lineages with sociodemographic and clinical parameters among pulmonary TB patients in the Amhara Region, Ethiopia. DNA was isolated from M. tuberculosis-positive sputum specimens (n=240) and analyzed by PCR and 24-locus mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) analysis and spoligotyping. Bioinformatic analysis assigned the M. tuberculosis genotypes to global lineages, and associations between patient characteristics and genotype were evaluated using logistic regression analysis. The study revealed a high diversity of modern and premodern M. tuberculosis lineages, among which approximately 25% were not previously reported. Among the M. tuberculosis strains (n=138) assigned to seven subgroups, the largest cluster belonged to the lineage Central Asian (CAS) (n=60; 26.0%), the second largest to lineage 7 (n=36; 15.6%), and the third largest to the lineage Haarlem (n=35; 15.2%). Four sublineages were new in the MIRU-VNTRplus database, designated NW-ETH3, NW-ETH1, NW-ETH2, and NW-ETH4, which included 24 (10.4%), 18 (7.8%), 8 (3.5%), and 5 (2.2%) isolates, respectively. Notably, patient delay in seeking treatment was significantly longer among patients infected with lineage 7 strains (Mann-Whitney test, P<0.008) than in patients infected with CAS strains (adjusted odds ratio [AOR], 4.7; 95% confidence interval [CI], 1.6 to 13.5). Lineage 7 strains also grew more slowly than other M. tuberculosis strains. Cases of Haarlem (OR, 2.8; 95% CI, 1.2 to 6.6) and NW-ETH3 (OR, 2.8; 95% CI, 1.0 to 7.3) infection appeared in defined clusters. Intensified active case finding and contact tracing activities in the study region are needed to expedite diagnosis and treatment of TB., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: Vacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to reduce viral load set-points after intradermal administration. In this randomized controlled pilot study we investigate intranasal administration of Vacc-4x with Endocine as adjuvant., Methods: Safety and immunogenicity were tested in patients on effective ART. They were randomized to low, medium or high dose Vacc-4x or adjuvant alone, administered four times at weekly intervals with no booster. Vacc-4x-specific T cell responses were measured in vitro by proliferation and in vivo by a single DTH skin test at the end of study. Nasal and rectal mucosal secretions were analyzed for Vacc-4x-specific antibodies by ELISA. Immune regulation induced by Vacc-4x was assessed by functional blockade of the regulatory cytokines IL-10 and TGF-β., Results: Vacc-4x proliferative T cell responses increased only among the vaccinated (p ≤ 0.031). The low dose group showed the greatest increase in Vacc-4x CD8+T cell responses (p = 0.037) and developed larger DTH (p = 0.005) than the adjuvant group. Rectal (distal) Vacc-4x IgA and IgG antibodies also increased (p = 0.043) in this group. In contrast, the high dose generated higher nasal (local) Vacc-4x IgA (p = 0.028) and serum IgG (p = 0.030) antibodies than the adjuvant. Irrespective of dose, increased Vacc-4x CD4+T cell responses were associated with low proliferation (r = -0.82, p < 0.001) and high regulation (r = 0.61, p = 0.010) at baseline., Conclusion: Intranasal administration of Vacc-4x with Endocine was safe and induced dose-dependent vaccine-specific T cell responses and both mucosal and systemic humoral responses. The clinical significance of dose, immune regulation and mucosal immunity warrants further investigation., Trial Registration: ClinicalTrials.gov NCT01473810.

Background: Medical conditions are often complicated by major depression, with consequent additional impairment of quality of life. We aimed to compare the effectiveness of an integrated treatment programme for major depression in patients with cancer (depression care for people with cancer) with usual care., Methods: SMaRT Oncology-2 is a parallel-group, multicentre, randomised controlled effectiveness trial. We enrolled outpatients with major depression from three cancer centres and their associated clinics in Scotland, UK. Participants were randomly assigned in a 1:1 ratio to the depression care for people with cancer intervention or usual care, with stratification (by trial centre) and minimisation (by age, primary cancer, and sex) with allocation concealment. Depression care for people with cancer is a manualised, multicomponent collaborative care treatment that is delivered systematically by a team of cancer nurses and psychiatrists in collaboration with primary care physicians. Usual care is provided by primary care physicians. Outcome data were collected up until 48 weeks. The primary outcome was treatment response (≥50% reduction in Symptom Checklist Depression Scale [SCL-20] score, range 0-4) at 24 weeks. Trial statisticians and data collection staff were masked to treatment allocation, but participants could not be masked to the allocations. Analyses were by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN40568538., Findings: 500 participants were enrolled between May 12, 2008, and May 13, 2011; 253 were randomly allocated to depression care for people with cancer and 247 to usual care. 143 (62%) of 231 participants in the depression care for people with cancer group and 40 (17%) of 231 in the usual care group responded to treatment: absolute difference 45% (95% CI 37-53), adjusted odds ratio 8·5 (95% CI 5·5-13·4), p<0·0001. Compared with patients in the usual care group, participants allocated to the depression care for people with cancer programme also had less depression, anxiety, pain, and fatigue; and better functioning, health, quality of life, and perceived quality of depression care at all timepoints (all p<0·05). During the study, 34 cancer-related deaths occurred (19 in the depression care for people with cancer group, 15 in the usual care group), one patient in the depression care for people with cancer group was admitted to a psychiatric ward, and one patient in this group attempted suicide. None of these events were judged to be related to the trial treatments or procedures., Interpretation: Our findings suggest that depression care for people with cancer is an effective treatment for major depression in patients with cancer. It offers a model for the treatment of depression comorbid with other medical conditions., Funding: Cancer Research UK and Chief Scientist Office of the Scottish Government., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To demonstrate the application of TB management time as an alternative parameter to estimate the size of the tuberculosis infectious pool in West Gojjam Zone of Amhara Region, Ethiopia., Methods: In this study, we used the TB management time, i.e. the number of days from start of cough until start of treatment, to determine the infectious period. Patients with sputum smear-positive and smear-negative pulmonary TB, retreatment and an estimated number of undetected cases were included. The infectious pool was then estimated as the annual number of infectious person days in a defined population., Results: The TB management time of presently undiagnosed TB cases and sputum smear-positive patients contributed significantly to the infectious pool with 151,840 and 128,750 infectious person days per year, respectively. The total infectious pool including sputum smear-negative TB cases and retreatment patients in the study area was estimated at 325,410 person days or 15,447 person days per 100,000 population during the study year., Conclusion: Recording TB management time may be used to estimate the infectious pool of TB and to monitor programme performance in the community., (© 2014 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Background: Early detection and treatment of TB is essential for the success of TB control program performance. The aim of this study was to determine the length and analyze predictors of patients', health systems' and total delays among patients attending a referral hospital in Bahir Dar, Ethiopia., Methods: A cross-sectional study was conducted among newly diagnosed TB cases ≥ 15 years of age. Delay was analyzed at three levels: the periods between 1) onset of TB symptoms and first visit to medical provider, i.e. patients' delay, 2) the first visit to a medical provider and the initiation of treatment i.e. health systems' delay and 3) onset of TB symptoms and initiation of treatment i.e. total delay. Uni- and multi-variate logistic regression analyses were performed to investigate predictors of patients', health systems' and total delays., Results: The median time of patients' delay was 21 days [(interquartile range (IQR) (7 days, 60 days)]. The median health systems' delay was 27 days (IQR 8 days, 60 days) and the median total delay was 60 days (IQR 30 days, 121 days). Patients residing in rural areas had a three-fold increase in patients' delay compared to those from urban areas [Adjusted Odds Ratio (AOR) 3.4; 95% (CI 1.3, 8.9)]. Extra-pulmonary TB (EPTB) cases were more likely to experience delay in seeking treatment compared to pulmonary (PTB) cases [(AOR 2.6; 95% (CI 1.3, 5.4)]. Study subjects who first visited health centres [(AOR) 5.1; 95% (CI 2.1, 12.5)], private facilities [(AOR) 3.5; 95% (CI 1.3, 9.7] and health posts [(AOR) 109; 95% (CI 12, 958], were more likely to experience an increase in health systems' delay compared to those who visited hospitals., Conclusions: The majority of TB patients reported to medical providers within an acceptable time after the onset of symptoms. Rural residence was associated with patients' and total delays. Providing the population with information about TB symptoms and the importance of early health seeking may be an efficient way to decrease TB transmission, morbidity and mortality. Establishing efficient TB diagnostic and treatment facilities at the periphery level is imperative to reduce diagnostic delay and expedite TB treatment.

The aim of this study was to characterize Mycobacterium tuberculosis isolates circulating in the Amhara Region of Ethiopia. Sputum samples were collected from new pulmonary tuberculosis (TB) patients in the Region. Genotyping of mycobacterial DNA was performed by spoligotyping and isolates were assigned to families using the SpolDB4 and the model-based program 'Spotclust'. A high level of diversity was found among the 237 isolates. Sixty-five different spoligopatterns were obtained. The T (30.8%), Central Asian (CAS; 21.1%) and U (17.7%) families were the predominant isolates comprising 69.6% of the total strains. Eighty-five per cent of the U lineage belonged to Spoligo-International-Type (SIT) 910 and SIT 1729. Only a few of these strains are included in SpolDB4 to date. Of the total strains, 41 (17.3%) were unique and have not been described in SpolDB4 to date. This study indicated that the TB epidemic in Amhara Region, Ethiopia, is characterized by the circulation of numerous M. tuberculosis strain families. The high proportion of SIT 910 and SIT 1729 strains may indicate an increase in the importance of these lineages in the transmission of TB in the study region., (© 2013 APMIS. Published by John Wiley & Sons Ltd.)