Emergence of Canonical and Noncanonical Genomic Variants following In Vitro Exposure of Clinical Mycobacterium tuberculosis Strains to Bedaquiline or Clofazimine.

In Mycobacterium tuberculosis, bedaquiline and clofazimine resistance occurs primarily through Rv0678 variants, a gene encoding a repressor protein that regulates mmpS5/mmpL5 efflux pump gene expression. Despite the shared effect of both drugs on efflux, little else is known about other pathways affected. We hypothesized that in vitro generation of bedaquiline- or clofazimine-resistant mutants could provide insight into additional mechanisms of action. We performed whole-genome sequencing and determined phenotypic MICs for both drugs on progenitor and mutant progenies. Mutants were induced through serial passage on increasing concentrations of bedaquiline or clofazimine. Rv0678 variants were identified in both clofazimine- and bedaquiline-resistant mutants, with concurrent atpE SNPs occurring in the latter. Of concern was the acquisition of variants in the F420 biosynthesis pathway in clofazimine-resistant mutants obtained from either a fully susceptible (fbiD: del555GCT) or rifampicin mono-resistant (fbiA: 283delTG and T862C) progenitor. The acquisition of these variants possibly implicates a shared pathway between clofazimine and nitroimidazoles. Pathways associated with drug tolerance and persistence, F420 biosynthesis, glycerol uptake and metabolism, efflux, and NADH homeostasis appear to be affected following exposure to these drugs. Shared genes affected by both drugs include Rv0678, glpK, nuoG, and uvrD1. Genes with variants in the bedaquiline resistant mutants included atpE, fadE28, truA, mmpL5, glnH, and pks8, while clofazimine-resistant mutants displayed ppsD, fbiA, fbiD, mutT3, fadE18, Rv0988, and Rv2082 variants. These results show the importance of epistatic mechanisms as a means of responding to drug pressure and highlight the complexity of resistance acquisition in M. tuberculosis.

Target Organ Toxicity in Rats After Subchronic Oral Exposure to Soil Extracts Containing a Complex Mixture of Contaminants.

Complex mixtures of unknown contaminants present a challenge to identify toxicological risks without using large numbers of animals and labor-intensive screens of all organs. This study examined soil extracts from a legacy-contaminated pesticide packaging and blending site. HepG2 cytotoxicity was used as an initial screen of 18 soil samples; then, three extracts (A, B and C) from different locations at the study site were used for testing in animals. The first two extracts were identified as the most toxic in vitro, and the latter extract obtained from a location further from these two toxic sampling sites. Then, target organ toxicities were identified following biweekly oral gavage for one month of three soil extracts (0.1% in polyethylene glycol or PEG) compared to vehicle control in male Sprague-Dawley rats (n = 9-10/group). Exposure to extract A significantly increased neutrophils and lymphocytes compared to control. In contrast, all extracts increased plasma α-2 macroglobulin and caused mild-to-moderate lymphocytic proliferation within the spleen white pulp, all indicative of inflammation. Rats exposed to all soil extracts exhibited acute tubular necrosis. Cholinesterase activity was significantly reduced in plasma, but not brain, after exposure to extract A compared to control. Increased hepatic ethoxyresorufin-o-deethylase activity compared to control was observed following exposure to extracts A and B. Exposure to soil extract C in rats showed a prolonged QTc interval in electrocardiography as well as increased brain lipid peroxidation. Candidate contaminants are organochlorine, organophosphate/carbamate pesticides or metabolites. Overall, HepG2 cytotoxicity did not successfully predict the neurotoxicity and cardiotoxicity observed with extract C but was more successful with suspected hydrocarbon toxicities in extracts A and B. Caution should be taken when extrapolating the observation of no effects from in vitro cell culture to in vivo toxicity, and better cell culture lines or assays should be explored.

An appeal to our government for nationwide policies in the prevention of cardiovascular disease.

The high prevalence and burden of cardiovascular diseases (CVD) is largely attributable to unhealthy lifestyle factors such as smoking, alcohol consumption, physical inactivity and unhealthy food habits. Prevention of CVD, through the promotion of healthy lifestyles, appears to be a Sisyphean task for healthcare professionals, as the root causes of an unhealthy lifestyle lie largely outside their scope. Since most lifestyle choices are habitual and a response to environmental cues, rather than rational and deliberate choices, nationwide policies targeting the context in which lifestyle behaviours occur may be highly effective in the prevention of CVD. In this point-of-view article, we emphasise the need for government policies beyond those mentioned in the National Prevention Agreement in the Netherlands to effectively reduce the CVD risk, and we address the commonly raised concerns regarding 'paternalism'.

Lifestyle management to prevent atherosclerotic cardiovascular disease: evidence and challenges.

Lifestyle management is the cornerstone of both primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) and the importance of lifestyle management is emphasised by all major guidelines. Despite this, actual implementation of lifestyle management is poor. Lifestyle modification includes smoking cessation, weight loss, dietary change, increasing physical inactivity, and stress management. This review summarises evidence-based opportunities and challenges for healthcare professionals to promote healthy lifestyles at an individual level for the prevention of ASCVD.

The challenge of choosing in cardiovascular risk management.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. For many years guidelines have listed optimal preventive therapy. More recently, novel therapeutic options have broadened the options for state-of-the-art CV risk management (CVRM). In the majority of patients with CVD, risk lowering can be achieved by utilising standard preventive medication combined with lifestyle modifications. In a minority of patients, add-on therapies should be considered to further reduce the large residual CV risk. However, the choice of which drug combination to prescribe and in which patients has become increasingly complicated, and is dependent on both the absolute CV risk and the reason for the high risk. In this review, we discuss therapeutic decisions in CVRM, focusing on (1) the absolute CV risk of the patient and (2) the pros and cons of novel treatment options.

Microbial and physicochemical assessment of irrigation water treatment methods.

AIMS: The presence of foodborne pathogens in preharvest agricultural water has been identified as a potential contamination source in outbreak investigations, driving markets and auditing bodies to begin requiring water treatment for high-risk produce. Therefore, it is essential that we identify water treatment methods which are effective as well as practical in their application on farm. METHODS AND RESULTS: In this work, we evaluated two sanitizers which are most prominent in preharvest agricultural water treatment (calcium hypochlorite (free chlorine: 3-5 ppm) and peracetic acid (PAA: 5 ppm)), an EPA registered antimicrobial device (ultraviolet light (UV)), in addition to a combination approach (chlorine + UV, PAA + UV). Treatments were evaluated for their ability to inactivate total coliforms and generic Escherichia coli and consistency in treatment efficacy over 1 h of operation. Physicochemical variables were measured along with microbial populations at 0, 5, 15, 30, 45 and 60 min of operation. Escherichia coli and coliform counts showed a significant (P < 0·05) reduction after treatment, with combination and singular treatments equally effective at inactivating E. coli and coliforms. A significant increase (P < 0·05) in oxidation-reduction potential was seen during water treatment (Chlorine; UV + Chlorine), and a significant reduction (P < 0·05) in pH was seen after PAA and PAA + UV treatments (60 min). CONCLUSION: Overall, the results indicate that all treatments evaluated are equally efficacious for inactivating E. coli and coliforms present in surface agricultural water. SIGNIFICANCE AND IMPACT OF THE STUDY: This information when paired with challenge studies targeting foodborne pathogens of interest can be used to support grower decisions when selecting and validating a preharvest agricultural water treatment programme.

Multi-vendor multi-site T1ρ and T2 quantification of knee cartilage.

OBJECTIVE: To develop 3D T1ρ and T2 imaging based on the same sequence structure on MR systems from multiple vendors, and to evaluate intra-site repeatability and inter-site inter-vendor reproducibility of T1ρ and T2 measurements of knee cartilage. METHODS: 3D magnetization-prepared angle-modulated partitioned k-space spoiled gradient echo snapshots (3D MAPSS) were implemented on MR systems from Siemens, GE and Philips. Phantom and human subject data were collected at four sites using 3T MR systems from the three vendors with harmonized protocols. Phantom data were collected by means of different positioning of the coil. Volunteers were scanned and rescanned after repositioning. Two traveling volunteers were scanned at all sites. Data were transferred to one site for centralized processing. RESULTS: Intra-site average coefficient of variations (CVs) ranged from 1.09% to 3.05% for T1ρ and 1.78-3.30% for T2 in phantoms, and 1.60-3.93% for T1ρ and 1.44-4.08% for T2 in volunteers. Inter-site average CVs were 5.23% and 6.45% for MAPSS T1ρ and T2, respectively in phantoms, and 8.14% and 10.06% for MAPSS T1ρ and T2, respectively, In volunteers. CONCLUSION: This study showed promising results of multi-site, multi-vendor reproducibility of T1ρ and T2 values in knee cartilage. These quantitative measures may be applied in large-scale multi-site, multi-vendor trials with controlled sequence structure and scan parameters and centralized data processing.

Health literacy and hypertension outcomes in a multi-ethnic population: the HELIUS study.

BACKGROUND: Hypertension disproportionately affects ethnic minority groups. Although health literacy may play role in these ethnic inequalities, little is known about the extent to which health literacy affects hypertension prevalence, awareness, treatment and control in different ethnic groups. Therefore, we assessed these associations in a multi-ethnic population. METHODS: Baseline data from the HELIUS study were used including participants of Dutch (n = 1948), South-Asian Surinamese (n = 2054) and African Surinamese (n = 1932) origin aged 18-70 years, who lived in Amsterdam, the Netherlands, were fluent in Dutch and underwent health literacy assessment through the Rapid Estimate of Adult Literacy in Medicine-Dutch (REALM-D). The REALM-D was categorized either as low (<60 sumscore) or adequate (≥60 sumscore) health literacy. Participants completed questionnaires and underwent physical examination. RESULTS: After adjusting for confounding variables, Dutch [odds ratio (OR) 2.02; 95% confidence interval (CI), 1.11-3.64] and African Surinamese (OR 1.36; 1.03-1.79) with low health literacy were more likely than those with adequate health literacy to have hypertension, whereas in South-Asian Surinamese this association was not significant. No significant associations were found between health literacy and hypertension awareness, treatment and control in any of the ethnic groups. CONCLUSION: Findings indicate that health literacy is associated with hypertension prevalence in selected ethnic groups, but not with hypertension awareness, treatment and control. Targeting health literacy might be an entry point for tackling ethnic inequalities in hypertension prevalence. To substantially reduce these inequalities, further research is needed to explore other factors and pathways through which health literacy may impact hypertension outcomes in different ethnic groups.

Smartphone Application-Enabled Apple Fruit Surface Temperature Monitoring Tool for In-Field and Real-Time Sunburn Susceptibility Prediction.

Heat stress and resulting sunburn is a major abiotic stress in perineal specialty crops. For example, such stress to the maturing fruits on apple tree canopies can cause several physiological disorders that result in considerable crop losses and reduced marketability of the produce. Thus, there is a critical technological need to effectively monitor the abiotic stress under field conditions for timely actuation of remedial measures. Fruit surface temperature (FST) is one of the stress indicators that can reliably be used to predict apple fruit sunburn susceptibility. This study was therefore focused on development and in-field testing of a mobile FST monitoring tool that can be used for real-time crop stress monitoring. The tool integrates a smartphone connected thermal-Red-Green-Blue (RGB) imaging sensor and a custom developed application ('AppSense 1.0') for apple fruit sunburn prediction. This tool is configured to acquire and analyze imagery data onboard the smartphone to estimate FST. The tool also utilizes geolocation-specific weather data to estimate weather-based FST using an energy balance modeling approach. The 'AppSense 1.0' application, developed to work in the Android operating system, allows visual display, annotation and real-time sharing of the imagery, weather data and pertinent FST estimates. The developed tool was evaluated in orchard conditions during the 2019 crop production season on the Gala, Fuji, Red delicious and Honeycrisp apple cultivars. Overall, results showed no significant difference (t110 = 0.51, p = 0.6) between the mobile FST monitoring tool outputs, and ground truth FST data collected using a thermal probe which had accuracy of ±0.4 °C. Upon further refinements, such tool could aid growers in real-time apple fruit sunburn susceptibility prediction and assist in more effective actuation of apple fruit sunburn preventative measures. This tool also has the potential to be customized for in-field monitoring of the heat stressors in some of the sun-exposed perennial and annual specialty crops at produce maturation.

The scientific basis for secondary prevention of coronary artery disease: recent contributions from the Netherlands.

While the beneficial effects of secondary prevention of cardiovascular disease are undisputed, implementation remains challenging. A gap between guideline-mandated risk factor targets and clinical reality was documented as early as the 1990s. To address this issue, research groups in the Netherlands have performed several major projects. These projects address innovative, multidisciplinary strategies to improve medication adherence and to stimulate healthy lifestyles, both in the setting of cardiac rehabilitation and at dedicated outpatient clinics. The findings of these projects have led to changes in prevention and rehabilitation guidelines.

Provision of HIV services by community health workers should be strengthened to achieve full programme potential: a cross-sectional analysis in rural South Africa.

OBJECTIVE: South Africa's community health workers (CHWs) provide a bridge between the primary healthcare (PHC) facility and its community. We conducted a cross-sectional analysis to determine the contribution of the community-based HIV programme (CBHP) to the overall HIV programme. METHODS: We collected service provision data from the daily activity register of CHWs attached to 12 PHC facilities in rural Mopani District, South Africa. Personal identifiers of individuals referred to the facility for HIV services were recorded and verified against facility routine patient registers to determine the effectiveness of referral. RESULTS: HIV services were provided on 18 927 occasions; 30% of the total activities performed by CHWs during the study period. CHWs assessed 12 159 individuals for HIV risk (13% coverage of the study population); only 290 (2%) were referred for HIV testing services. Referral was effective in 213 (73%) individuals; evidence of an HIV-positive status was found for 38 (18%) individuals. However, 30 (79%) of these individuals were referred by CHWs despite being on ART. Adherence support was provided during 5657 visits; only one individual was referred for complications. Finally, of the 864 individuals lost to the ART programme, CHWs managed to find 452 (52%) for referral back to the facility; only 241 (53%) of these were (re)initiated on ART. CONCLUSIONS: Provision of HIV services by CHWs should be strengthened to fully deliver on the programme's potential. Human resource investment, home-based HIV testing and improved tracing models constitute potential strategies to enhance CHWs impact on the HIV programme.

OBJECTIF: Les agents de santé communautaires (ASC) d'Afrique du Sud constituent un pont entre les établissements de soins de santé primaires et leur communauté. Nous avons effectué une analyse transversale pour déterminer la contribution du programme VIH basé sur la communauté (PVBC) au programme global de lutte contre le VIH. MÉTHODES: Nous avons collecté des données sur la prestation de services à partir du registre des activités quotidiennes des ASC rattachés à 12 établissements de soins de santé primaires dans le district rural de Mopani, en Afrique du Sud. Les identifiants individuels des personnes référées vers l'établissement pour des services VIH ont été enregistrés et vérifiés par rapport aux registres de routine des patients de l'établissement afin de déterminer l'efficacité de l'aiguillage. RÉSULTATS: Les services VIH ont été fournis dans 18.927 occasions; 30% du total des activités réalisées par les ASC au cours de la période d'étude. Les ASC ont évalué 12.159 personnes pour les risques du VIH (couverture de 13% de la population étudiée); seuls 290 (2%) ont été référés pour des services de dépistage du VIH. L'aiguillage a été efficace chez 213 personnes (73%). L'évidence de séropositivité a été trouvée chez 38 personnes (18%). Cependant, 30 (79%) de ces personnes ont été référées par des ASC alors qu'elles étaient sous ART. Un soutien à la compliance a été fourni au cours de 5.657 visites; un seul individu a été référé pour des complications. Enfin, sur 864 personnes perdues du programme ART, les ASC ont réussi à retrouver 452 (52%) pour les référer de nouveau à l'établissement; seuls 241 (53%) de celles-ci ont été (ré) initiées sous ART. CONCLUSIONS: La fourniture de services VIH par les ASC devrait être renforcée pour exploiter pleinement le potentiel du programme. Les investissements dans les ressources humaines, le dépistage du VIH à domicile et les modèles de traçage améliorés constituent des stratégies potentielles pour améliorer l'impact des ASC sur le programme VIH.

Subjective memory complaints and incident dementia in a high risk older adult hypertensive population.

BACKGROUND: there is a growing body of evidence demonstrating an association between subjective memory complaints (SMC) and an increased risk of incident cognitive decline or dementia. To date this has not been examined in hypertensive older adults, a prevalent and growing population group at high risk of cognitive decline. METHODS: using data from participants in the Hypertension in the Very Elderly Trial cohort the association between baseline SMC and incident cognitive decline and dementia was examined using Cox proportional hazard regression. Cognitive function was assessed using the Mini-Mental State Exam and diagnoses of dementia were made using standard diagnostic criteria. SMC was assessed by the question 'do you feel that you have more problems with memory than most?' Analyses were rerun to examine the associations by level of baseline cognitive function, to evaluate the role of SMC by dementia type and by sex. RESULTS: baseline SMC were associated with an increased risk of developing any dementia (hazard ratio (HR)1.63 (95% confidence intervals (CI): 1.18:2.25)), Alzheimer's disease (HR1.59 (95% CI: 1.08:2.34)) and vascular dementia (HR2.05 (95% CI: 1.19:3.54)). Similar patterns were seen across all levels of baseline MMSE but were strongest in those with scores of 25-27. There were no clear differences by sex. DISCUSSION: a positive report of SMC assessed by a single question in an older adult with hypertension raises the possibility of increased risk of incident dementia. As such its use may be a useful addition to the repertoire of the general practitioner and geriatrician when assessing older adults.

Ethnic differences in metabolic cardiovascular risk among normal weight individuals: Implications for cardiovascular risk screening. The HELIUS study.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) risk factors may occur among a substantial proportion of normal weight individuals, particularly among some ethnic minorities. It is unknown how many of these individuals would be missed by commonly applied eligibility criteria for cardiovascular risk screening. Thus, we aim to determine cardiovascular risk and eligibility for cardiovascular risk screening among normal weight individuals of different ethnic backgrounds. METHODS AND RESULTS: Using the HELIUS study (Amsterdam, The Netherlands), we determined cardiovascular risk among 6910 normal weight individuals of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Moroccan and Turkish background. High cardiovascular risk was approximated by high metabolic risk based on blood pressure, HDL, triglycerides and fasting glucose. Eligibility criteria for screening were derived from Dutch CVD prevention guidelines and include age ≥ 50 y, family history of CVD, or current smoking. Ethnic group comparisons were made using logistic regression. Age-adjusted proportions of high metabolic risk ranged from 12.6% to 38.4% (men) and from 2.7% to 11.5% (women). This prevalence was higher among most ethnic minorities than the Dutch, especially among women. For most ethnic groups, 79.9%-86.7% of individuals with high metabolic risk were eligible for cardiovascular risk screening. Exceptions were Ghanaian women (58.8%), Moroccan men (70.9%) and Moroccan women (45.0%), although age-adjusted proportions did not differ between groups. CONCLUSION: Even among normal weight individuals, high cardiovascular metabolic risk is more common among ethnic minorities than among the majority population. Regardless of ethnicity, most normal weight individuals with increased risk are eligible for cardiovascular risk screening.

Readmission and mortality in patients ≥70 years with acute myocardial infarction or heart failure in the Netherlands: a retrospective cohort study of incidences and changes in risk factors over time.

OBJECTIVES: To determine the risk of first unplanned all-cause readmission and mortality of patients ≥70 years with acute myocardial infarction (AMI) or heart failure (HF) and to explore which effects of baseline risk factors vary over time. METHODS: A retrospective cohort study was performed on hospital and mortality data (2008) from Statistics Netherlands including 5,175 (AMI) and 9,837 (HF) patients. We calculated cumulative weekly incidences for first unplanned all-cause readmission and mortality during 6 months post-discharge and explored patient characteristics associated with these events. RESULTS: At 6 months, 20.4% and 9.9% (AMI) and 24.6% and 22.4% (HF) of patients had been readmitted or had died, respectively. The highest incidences were found in week 1. An increased risk for 14-day mortality after AMI was observed in patients who lived alone (hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.01-2.44) and within 30 and 42 days in patients with a Charlson Comorbidity Index ≥3. In HF patients, increased risks for readmissions within 7, 30 and 42 days were found for a Charlson Comorbidity Index ≥3 and within 42 days for patients with an admission in the previous 6 months (HR 1.42, 95% CI 1.12-1.80). Non-native Dutch HF patients had an increased risk of 14-day mortality (HR 1.74, 95% CI 1.09-2.78). CONCLUSION: The risk of unplanned readmission and mortality in older AMI and HF patients was highest in the 1st week post-discharge, and the effect of some risk factors changed over time. Transitional care interventions need to be provided as soon as possible to prevent early readmission and mortality.

Magnetic conjugated polymer nanoparticles doped with a europium complex for biomedical imaging.

Self-assembling conjugated polymer nanoparticles containing PVK and PLGA-PEG as a matrix polymer were doped with both a luminescent rare-earth complex and magnetic nanoparticles (SPIONs), giving rise to materials that are both luminescent and magnetic. Nanoparticle sizes ranged from 80-110 nm without SPIONs and showed an increase in size (200-1000 nm) with additional SPION content (11-54%). Quantum yields (QYs) of 24% and 18% were measured for systems without and with 11% SPIONs, respectively. Optical properties were stable and suitable for biological imaging applications.

The impact of implementing a Xpert MTB/RIF algorithm on drug-sensitive pulmonary tuberculosis: a retrospective analysis.

Xpert MTB/RIF (Xpert) is the preferred first-line test for all persons with tuberculosis (TB) symptoms in South Africa in line with a diagnostic algorithm. This study evaluates pre- and post-implementation trends in diagnostic practices for drug-sensitive, pulmonary TB in adults in an operational setting, following the introduction of the Xpert-based algorithm. We retrospectively analysed data from the national TB database for Greater Tzaneen sub-district, Limpopo Province. Trends in a number of cases, diagnosis and outcome and characteristics associated with death are reported. A total of 8407 cases were treated from 2008 until 2015, with annual cases registered decreasing by 31·7% over that time period (from 1251 to 855 per year). After implementation of Xpert, 69·9% of cases were diagnosed by Xpert, 29·4% clinically, 0·6% by smear microscopy and 0·1% by culture. Cases with a recorded microbiological test increased from 76·2% to 96·4%. Cases started on treatment without confirmation, but with a negative microbiological test increased from 7·1% to 25·7%. Case fatality decreased from 15·0% to 9·8%, remaining consistently higher in empirically treated groups, regardless of HIV status. Implementation of the algorithm coincided with a reduced number of TB cases treated and improved coverage of microbiological testing; however, a substantial proportion of cases continued to start treatment empirically.

Detection of titanium particles in human liver and spleen and possible health implications.

BACKGROUND: Titanium dioxide (TiO2) is produced at high volumes and applied in many consumer and food products. Recent toxicokinetic modelling indicated the potential of TiO2 to accumulate in human liver and spleen upon daily oral exposure, which is not routinely investigated in chronic animal studies. A health risk from nanosized TiO2 particle consumption could not be excluded then. RESULTS: Here we show the first quantification of both total titanium (Ti) and TiO2 particles in 15 post-mortem human livers and spleens. These low-level analyses were enabled by the use of fully validated (single particle) inductively coupled plasma high resolution mass spectrometry ((sp)ICP-HRMS) detection methods for total Ti and TiO2 particles. The presence of TiO2 in the particles in tissues was confirmed by Scanning Electron Microscopy with energy dispersive X-ray spectrometry. CONCLUSIONS: These results prove that TiO2 particles are present in human liver and spleen, with ≥24% of nanosize (< 100 nm). The levels are below the doses regarded as safe in animals, but half are above the dose that is deemed safe for liver damage in humans when taking into account several commonly applied uncertainty factors. With these new and unique human data, we remain with the conclusion that health risks due to oral exposure to TiO2 cannot be excluded.

The cardiac care bridge program: design of a randomized trial of nurse-coordinated transitional care in older hospitalized cardiac patients at high risk of readmission and mortality.

BACKGROUND: After hospitalization for cardiac disease, older patients are at high risk of readmission and death. Although geriatric conditions increase this risk, treatment of older cardiac patients is limited to the management of cardiac diseases. The aim of this study is to investigate if unplanned hospital readmission and mortality can be reduced by the Cardiac Care Bridge transitional care program (CCB program) that integrates case management, disease management and home-based cardiac rehabilitation. METHODS: In a randomized trial on patient level, 500 eligible patients ≥ 70 years and at high risk of readmission and mortality will be enrolled in six hospitals in the Netherlands. Included patients will receive a Comprehensive Geriatric Assessment (CGA) at admission. Randomization with stratified blocks will be used with pre-stratification by study site and cognitive status based on the Mini-Mental State Examination (15-23 vs ≥ 24). Patients enrolled in the intervention group will receive a CGA-based integrated care plan, a face-to-face handover with the community care registered nurse (CCRN) before discharge and four home visits post-discharge. The CCRNs collaborate with physical therapists, who will perform home-based cardiac rehabilitation and with a pharmacist who advices the CCRNs in medication management The control group will receive care as usual. The primary outcome is the incidence of first all-cause unplanned readmission or mortality within 6 months post-randomization. Secondary outcomes at three, six and 12 months after randomization are physical functioning, functional capacity, depression, anxiety, medication adherence, health-related quality of life, healthcare utilization and care giver burden. DISCUSSION: This study will provide new knowledge on the effectiveness of the integration of geriatric and cardiac care. TRIAL REGISTRATION: NTR6316 . Date of registration: April 6, 2017.

Hot topic: Management of cull dairy cows-Consensus of an expert consultation in Canada.

Many cull dairy cows enter the marketing system and travel to widely dispersed and specialized slaughter plants, and they may experience multiple handling events (e.g., loading, unloading, mixing), change of ownership among dealers, and feed and water deprivation during transport and at livestock markets. The objectives of this study were to describe the diverse management of cull dairy cows in Canada and establish consensus on ways to achieve improvements. A 2-day expert consultation meeting was convened, involving farmers, veterinarians, regulators, and experts in animal transport, livestock auction, and slaughter. The 15 participants, recruited from across Canada, discussed regional management practices for cull cattle, related risk factors, animal welfare problems, and recommendations. An audio recording of the meeting was used to extract descriptive data on cull cattle management and identify points of agreement. Eight consensus points were reached: (1) to assemble information on travel times and delays from farm to slaughter; (2) to increase awareness among producers and herd veterinarians of potential travel distances and delays; (3) to promote pro-active culling; (4) to improve the ability of personnel to assess animal condition before loading; (5) to identify local options for slaughter of cull dairy cows; (6) to investigate different management options such as emergency slaughter and mobile slaughter; (7) to ensure that all farms and auctions have, or can access, personnel trained and equipped for euthanasia; and (8) to promote cooperation among enforcement agencies and wider adoption of beneficial regulatory options.

Acceptability and Feasibility of Integrating Point-of-Care Diagnostic Testing of Sexually Transmitted Infections into a South African Antenatal Care Program for HIV-Infected Pregnant Women.

Background: Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) infections may increase the risk of vertical transmission of the human immunodeficiency virus (HIV). In resource-limited settings, symptomatic screening, and syndromic management of sexually transmitted infections (STIs) during pregnancy continue to be the standard of care. In the absence of diagnostic testing, asymptomatic infections in pregnant women go untreated. Objective: To describe the acceptability and feasibility of integrating diagnostic STI screening into first antenatal care visits for HIV-infected pregnant women. Methods: HIV-infected pregnant women were recruited during their first antenatal care visit from three antenatal care clinics in Tshwane District, South Africa, between June 2016 and October 2017. Self-collected vaginal swabs were used to screen for CT, NG, and TV with a diagnostic point-of-care (POC) nucleic acid amplification test. Those with STIs were provided treatment per South African national guidelines. Results: Of 442 eligible women, 430 (97.3%) agreed to participate and were tested. Of those with a positive STI test result (n = 173; 40.2%), 159 (91.9%) received same-day results and treatment; 100% of STI-infected women were treated within seven days. Conclusions: Integration of POC diagnostic STI screening into first-visit antenatal care services was feasible and highly acceptable for HIV-infected pregnant women.