Loss of hepatocyte cell division leads to liver inflammation and fibrosis.

The liver possesses a remarkable regenerative capacity based partly on the ability of hepatocytes to re-enter the cell cycle and divide to replace damaged cells. This capability is substantially reduced upon chronic damage, but it is not clear if this is a cause or consequence of liver disease. Here, we investigate whether blocking hepatocyte division using two different mouse models affects physiology as well as clinical liver manifestations like fibrosis and inflammation. We find that in P14 Cdk1Liv-/- mice, where the division of hepatocytes is abolished, polyploidy, DNA damage, and increased p53 signaling are prevalent. Cdk1Liv-/- mice display classical markers of liver damage two weeks after birth, including elevated ALT, ALP, and bilirubin levels, despite the lack of exogenous liver injury. Inflammation was further studied using cytokine arrays, unveiling elevated levels of CCL2, TIMP1, CXCL10, and IL1-Rn in Cdk1Liv-/- liver, which resulted in increased numbers of monocytes. Ablation of CDK2-dependent DNA re-replication and polyploidy in Cdk1Liv-/- mice reversed most of these phenotypes. Overall, our data indicate that blocking hepatocyte division induces biological processes driving the onset of the disease phenotype. It suggests that the decrease in hepatocyte division observed in liver disease may not only be a consequence of fibrosis and inflammation, but also a pathological cue.

The three cytokines IL-1ß, IL-18, and IL-1α share related but distinct secretory routes.

Interleukin (IL)-1 family cytokines potently regulate inflammation, with the majority of the IL-1 family proteins being secreted from immune cells via unconventional pathways. In many cases, secretion of IL-1 cytokines appears to be closely coupled to cell death, yet the secretory mechanisms involved remain poorly understood. Here, we studied the secretion of the three best-characterized members of the IL-1 superfamily, IL-1α, IL-1ß, and IL-18, in a range of conditions and cell types, including murine bone marrow-derived and peritoneal macrophages, human monocyte-derived macrophages, HeLa cells, and mouse embryonic fibroblasts. We discovered that IL-1ß and IL-18 share a common secretory pathway that depends upon membrane permeability and can operate in the absence of complete cell lysis and cell death. We also found that the pathway regulating the trafficking of IL-1α is distinct from the pathway regulating IL-1ß and IL-18. Although the release of IL-1α could also be dissociated from cell death, it was independent of the effects of the membrane-stabilizing agent punicalagin, which inhibited both IL-1ß and IL-18 release. These results reveal that in addition to their role as danger signals released from dead cells, IL-1 family cytokines can be secreted in the absence of cell death. We propose that models used in the study of IL-1 release should be considered context-dependently.

Identifying Frailty and its Outcomes in Older People in Rural Tanzania.

Background/Study Context: Interest in frailty is growing in low- and middle-income countries, due to demographic aging and resource limitations. However, there is a paucity of data on the nature of frailty in Africa. METHODS: The study collected frailty data from people aged 70 years and over living in six villages in the rural Hai District of northern Tanzania. At baseline, a limited data set was collected for 1198 people and a more comprehensive data set for a stratified sample of 296 people. A 40-item frailty index was constructed. Data regarding mortality and dependency were collected at 3-year follow-up. RESULTS: A higher frailty index score was significantly correlated with greater age, never having attended school, falls, mortality, and dependency in activities of daily living. Logistic regression modeling revealed functional disability and cognitive function to be significant independent predictors of the outcome "mortality or dependency." CONCLUSIONS: In resource-poor settings, brief frailty screening assessments may be a useful way of identifying those most in need of support.

Levels of functional disability in elderly people in Tanzania with dementia, stroke and Parkinson's disease.

BACKGROUND: Disability is associated with increasing age and poverty, yet there are few reliable data regarding disability amongst the elderly in low-income countries. The aim of this study was to compare disability levels for three of the most common neurological, non-communicable diseases: dementia, stroke and Parkinson's disease (PD). METHODS: We performed a community-based study of people aged 70 years and over in 12 randomly selected villages in the rural Hai district of Tanzania. Participants underwent disability assessment using the Barthel Index, and clinical assessment for dementia, stroke and PD. RESULTS: In a representative cohort of 2232 people aged 70 years and over, there were 54 cases of stroke, 12 cases of PD and estimated (by extrapolation from a sub-sample of 1198 people) to be 112 cases of dementia. People with stroke were the most disabled, with 62.9% having moderate or severe disability. Levels of moderate or severe disability were 41.2% in people with dementia and 50.0% in people with PD. However, the higher prevalence of dementia meant that, at a population level, it was associated with similar levels of disability as stroke, with 18.5% of 249 people identified as having moderate or severe disability having dementia, compared to 13.7% for stroke and 2.4% for PD. CONCLUSIONS: Levels of disability from these conditions is high and is likely to increase with demographic ageing. Innovative, community-based strategies to reduce disability levels should be investigated.

Electrocardiographic reference values for a population of older adults in sub-Saharan Africa.

BACKGROUND/OBJECTIVES: Older adults in sub-Saharan Africa (SSA) are at greatest risk of an impending noncommunicable diseases epidemic, of which cardiac disease is the most prevalent contributor. Thus, it is essential to establish electrocardiographic reference values for a population that is likely to differ genetically and environmentally from others where reference values are established. METHODS: Two thousand two hundred thirty-two apparently healthy community-based participants without known cardiac disease aged 70+ in rural Tanzania underwent 12-lead electrocardiography. Electrocardiograms were digitally analyzed and gender-specific reference values for P duration (PD), P amplitude (PAMP), P area (PAREA), P terminal negative force (V1) (PTNF), PR interval, QRS duration (QRSD), QT/QTc, R amplitude (II, V5) (RAMP) LVH index (LVHI), R axis and R/S ratio (V1) reported, following univariate analysis of covariance using a multiple linear regression model, adjusting for age, systolic blood pressure (SBP), body mass index (BMI), and RR interval. RESULTS: Data from 1824 subjects were suitable for analysis. Adjusted mean values for men/women were: PD 115/110 ms, PAMP (avg) 123/114 µV, PAMP (II) 203/190 µV, PAREA (avg) 5.3/4.6 mV*s, PAREA (II) 9.3/8.1 mV*s, PTNF 1.7/1.4 mV*s, PR 158/152 ms, QRSD 89/84 ms, QT 370/375 ms, QTc 421/427 ms, RAMP (II) 805/854 µV, (V5) 2022/1742 µV, LVHI 3.0/2.8 mV (Sokolow-Lyon), 1.293/1.146 mV (Cornell), R axis 51/49°, R/S 0.2/0.2. Excluding PTNF , R axis and R/S ratio, all gender differences were significant (P < 0.001 apart from LVHI [Sokolow-Lyon; P < 0.005)] and RAMP (II) [P < 0.05]) following adjustment for age, SBP, BMI, and RR interval. CONCLUSIONS: Our description of comprehensive electrocardiographic parameters establishes reference values in this genetically and environmentally diverse SSA population thereby allowing identification of "outliers" with potential cardiac disease.

Electrocardiographic assessment of coronary artery disease and stroke risk factors in rural and urban Tanzania: a case-control study.

BACKGROUND: Although the association between cerebrovascular and coronary artery disease (CAD) is well known in high-income countries, this association is not well documented in black Africans. AIMS: The aim of this study was to document electrocardiographic (ECG) evidence of CAD in stroke cases and controls and to identify other common ECG abnormalities related to known stroke risk factors in a community-based population of incident stroke cases in Tanzania, East Africa. METHODS: This was a case-control study. Incident stroke cases were identified by the Tanzanian Stroke Incidence Project. Age- and sex-matched controls were randomly selected from the background population. Electrocardiograms were manually analyzed using the Minnesota Coding System, looking for evidence of previous myocardial infarction (MI), atrial fibrillation (AF) or atrial flutter (AFl), and left ventricular hypertrophy (LVH). RESULTS: In Hai, there were 93 cases and 241 controls with codable electrocardiograms, and in Dar-es-Salaam, there were 39 cases and 72 controls with codable electrocardiograms. Comparing cases and controls, there was a higher prevalence of MI and AF or AFl (but not LVH) in cases compared with controls. CONCLUSIONS: This is the first published study of ECG assessment of CAD and other stroke risk factors in an incident population of stroke cases in sub-Saharan Africa. It suggests that concomitant CAD in black African stroke cases is more common than previously suggested.

The prevalence of dementia in rural Tanzania: a cross-sectional community-based study.

OBJECTIVES: Despite the growing burden of dementia in low-income countries, there are few previous data on the prevalence of dementia in sub-Saharan Africa. The aim of this study was to estimate the prevalence of dementia in those who are 70 years and older in the rural Hai District of Tanzania. METHODS: This was a two-phase cross-sectional survey. Using census data, we screened individuals aged 70 years and older from six rural villages using the Community Screening Instrument for Dementia in Phase I. In Phase II, a stratified sample of those identified in Phase I were clinically assessed using the DSM-IV criteria. RESULTS: Of 1198 people who fulfilled the inclusion criteria, 184 screened positive for probable dementia, and 104 screened positive for possible dementia using the Community Screening Instrument for Dementia. During clinical assessment in Phase II, 78 cases of dementia were identified according to the DSM-IV criteria. The age-standardised prevalence of dementia was 6.4% (95% confidence interval: 4.9 to 7.9). Prevalence rates increased significantly with increasing age. CONCLUSIONS: The prevalence of dementia in this rural Tanzanian population is similar to that reported in high-income countries. Dementia is likely to become a significant health burden in this population as demographic transition continues. Further research on risk factors for dementia in sub-Saharan Africa is needed to inform policy makers and plan local health services.

Assessment of left ventricular geometrical patterns and function among hypertensive patients at a tertiary hospital, Northern Tanzania.

BACKGROUND: With hypertension, the cardiovascular system changes to adapt to the varying neuro-humoral and hemodynamic changes and this may lead to the development of different left ventricular geometric patterns, each carrying a different risk profile for major adverse cardiovascular events. METHODS: Using a consecutive sampling technique, a cross-sectional, prospective, hospital based study was done and two hundred and twenty seven (227) hypertensive patients were studied. RESULTS: The distribution of different abnormal LV geometrical patterns was 19.8%, 28.2%, 22% for concentric remodelling, concentric hypertrophy and eccentric hypertrophy respectively. With echocardiographic criteria, the proportion of patients with left ventricular hypertrophy (LVH) was higher when left ventricular mass (LVM) was indexed to height(2.7) than to body surface area (70.0% vs. 52.9%). Duration of hypertension markedly influenced the type of LV geometry with normal LV geometry predominating in early hypertension and abnormal geometrical patterns predominating in late hypertension. The left ventricular fractional shortening decreased with duration of hypertension and was common in patients with eccentric hypertrophy. Age of the patient, systolic blood pressure, duration of hypertension and body mass index were found to be independent predictors left ventricular hypertrophy. CONCLUSION: About 70% of hypertensive patients had abnormal geometry existing in different patterns. Eccentric hypertrophy had more of clinical and echocardiographic features suggestive of reduced left ventricular systolic function. Hypertensive patients should be recognized as a heterogeneous population and therefore stratifying them into their respective LV geometrical patterns is useful as way of assessing their risk profile as well as instituting appropriate management.

The prevalence of disability in older people in Hai, Tanzania.

BACKGROUND: the World Health Organization estimates that more than one billion of the world's population are disabled. Disability is associated with increasing age and poverty, yet there are few reliable data regarding disability among the elderly in low-income countries. The aim of this study was to accurately document the prevalence of disability in those aged 70 years and over in a community-based setting in sub-Saharan Africa. METHODS: we performed a community-based study of people aged 70 years and over in Hai, Tanzania. Participants underwent disability assessment using the culturally non-specific Barthel index (BI), and also clinical assessment for neurological disorders and memory problems. RESULTS: in 2,232 participants, the age-adjusted prevalence of severe disability (BI<15) was 3.7% (95% CI: 2.9-4.5) and the age-adjusted prevalence of moderate disability (BI: 15-18) was 6.2% [95% confidence interval (CI): 5.2-7.2]. Increasing age, female gender, memory problems and the presence of neurological disorders were all independent predictors of the presence of disability. CONCLUSION: in this study, the average disability level was lower than seen in most high-income countries. This may reflect increased mortality from disabling disease in low-income countries. Disability is likely to increase as the population of low-income countries ages and disease survival improves.

A Novel Quadripolar Active Fixation Left-Ventricular Pacing Lead for Cardiac Resynchronization Therapy: Initial United Kingdom Experience.

OBJECTIVES: This study sought to assess immediate and short-term performance of the Medtronic Attain Stability Quadripolar 4798 lead (Medtronic, Dublin, Ireland). BACKGROUND: Cardiac resynchronization therapy (CRT) is an established treatment for appropriately selected patients with left ventricular (LV) systolic dysfunction. The most common reason for failure to implant a lead is the lack of a suitable epicardial vein, due either to an absent vessel in the target site, an unacceptably high threshold, lead instability, phrenic nerve stimulation, or a combination of reasons. In August 2017, a novel quadripolar active fixation LV lead (Medtronic) was released. This paper reports the initial clinical experience with lead implantation and specifically immediate and short-term pacing parameters across 3 United Kingdom centers. METHODS: Consecutive patients eligible for CRT were deemed suitable for this lead. Immediate and short-term lead performance data regarding LV threshold, impedance, and displacement rates were collected at standard pacing checks (1 day, 5 weeks, 3 months, and 9 months post-implantation). RESULTS: CRT using this lead was attempted in 82 cases and was successful in 81 cases (98.8%). LV thresholds and impedance levels were 1.22 ± 0.75 V and 737 ± 319 Ω at implantation; 1.16 ± 0.71 V and 597 ± 218 Ω at day 1; 1.02 ± 0.48 V and 579 ± 148 Ω at week 6; 0.98 ± 0.49 V and 569 ± 133 Ω at 3 months; and 1.06 ± 0.48 V and 570 ± 140 Ω at 9 months. As of the publication of this paper, no LV lead has been displaced. CONCLUSIONS: CRT using the Medtronic lead was successful in more than 98% of the patients. Short-to-medium-term data regarding lead performance and stability were excellent, with zero displacements as of the publication of this paper.

Hypertension in a resource-limited setting: Is it associated with end organ damage in older adults in rural Tanzania?

Few data from sub-Saharan Africa exist on the effects of hypertension on the organs of the human body. We aimed to establish the prevalence of hypertensive end organ damage (EOD) in an elderly cohort of Tanzanians. The population aged 70 years and over of 2 villages in northern Tanzania (n = 246), had blood pressure (BP) data available from 2010 and 2013, and underwent in-depth follow-up for markers of hypertensive EOD in 2016. Assessment included ankle-brachial pressure index, lying-standing BP, electrocardiogram, and mid-stream urine dip. Sustained hypertension (those with hypertension at all 3 assessments) was found in 129 (52.4% subjects). Of the entire cohort, 13.9% had left ventricular hypertrophy and 26.4% had peripheral arterial disease, both of which were associated with sustained hypertension, although orthostatic hypotension, stroke, proteinuria, and arterial stiffening were not. Further investigation, particularly in younger age groups, is merited if hypertension-associated morbidity is to be controlled.

Metabolic Remodeling during Liver Regeneration.

Liver disease is linked to a decreased capacity of hepatocytes to divide. In addition, cellular metabolism is important for tissue homeostasis and regeneration. Since metabolic changes are a hallmark of liver disease, we investigated the connections between metabolism and cell division. We determined global metabolic changes at different stages of liver regeneration using a combination of integrated transcriptomic and metabolomic analyses with advanced functional redox in vivo imaging. Our data indicate that blocking hepatocyte division during regeneration leads to mitochondrial dysfunction and downregulation of oxidative pathways. This resulted in an increased redox ratio and hyperactivity of alanine transaminase allowing the production of alanine and α-ketoglutarate from pyruvate when mitochondrial functions are impaired. Our data suggests that during liver regeneration, cell division leads to hepatic metabolic remodeling. Moreover, we demonstrate that hepatocytes are equipped with a flexible metabolic machinery able to adapt dynamically to changes during tissue regeneration.

Undiagnosed and diagnosed diabetes mellitus among hospitalised acute heart failure patients in Botswana.

OBJECTIVE: The objective of this study was to determine the burden of diagnosed and undiagnosed type 2 diabetes mellitus among patients hospitalised with acute heart failure in Botswana. METHODS: The study enrolled 193 consecutive patients admitted with acute heart failure to the medical wards at Princess Marina Hospital in Gaborone. Patients were classified as previously known diabetics, undiagnosed diabetics (glycated haemoglobin ≥ 6.5%) or as non-diabetics (glycated haemoglobin < 6.5%). Data on other comorbid conditions such as hypertension, atrial fibrillation, ischaemic heart disease, stroke, and renal failure were also collected. RESULTS: The mean (SD) age of the participants was 54.2 (17.1) years and 53.9% were men. The percentage of known and undiagnosed diabetes mellitus was 15.5% and 12.4%, respectively. Diabetic patients were significantly more likely to have hypertension (77.8% vs 46.0%, p < 0.001), ischaemic heart disease (20.4% vs 5.0%, p < 0.001), chronic kidney disease (51.3% vs 23.0%, p < 0.001), and stroke (20.4% vs 5.8%, p < 0.01). In addition, diabetics were older than non-diabetics (61.0 years vs 51.6 years, p < 0.001). CONCLUSION: About 27.9% of patients admitted with acute heart failure in Botswana had diabetes, and almost half of them presented with undiagnosed diabetes. These findings indicate that all hospitalised patients should be screened for diabetes.

Presentation and mortality of patients hospitalised with acute heart failure in Botswana.

INTRODUCTION: Heart failure is a common cause of hospitalisation and therefore contributes to in-hospital outcomes such as mortality. In this study we describe patient characteristics and outcomes of acute heart failure (AHF) in Botswana. METHODS: Socio-demographic, clinical and laboratory data were collected from 193 consecutive patients admitted with AHF at Princess Marina Hospital in Gaborone between February 2014 and February 2015. The length of hospital stay and 30-, 90- and 180-day in-hospital mortality rates were assessed. RESULTS: The mean age was 54 ± 17.1 years, and 53.9% of the patients were male. All patients were symptomatic (77.5% in NYHA functional class III or IV) and the majority (64.8%) presented with significant left ventricular dysfunction. The most common concomitant medical conditions were hypertension (54.9%), human immuno-deficiency virus (HIV) (33.9%), anaemia (23.3%) and prior diabetes mellitus (15.5%). Moderate to severe renal dysfunction was detected in 60 (31.1%) patients. Peripartum cardiomyopathy was one of the important causes of heart failure in female patients. The most commonly used treatment included furosemide (86%), beta-blockers (72.1%), angiotensin converting enzyme inhibitors (67.4%), spironolactone (59.9%), digoxin (22.1%), angiotensin receptor blockers (5.8%), nitrates (4.7%) and hydralazine (1.7%). The median length of stay was nine days, and the in-hospital mortality rate was 10.9%. Thirty-, 90- and 180-day case fatality rates were 14.7, 25.8 and 30.8%, respectively. Mortality at 180 days was significantly associated with increasing age, lower haemoglobin level, lower glomerular filtration rate, hyponatraemia, higher N-terminal pro-brain natriuretic peptide levels, and prolonged hospital stay. CONCLUSIONS: AHF is a major public health problem in Botswana, with high in-hospital and post-discharge mortality rates and prolonged hospital stays. Late and symptomatic presentation is common, and the most common aetiologies are preventable and/or treatable co-morbidities, including hypertension, diabetes mellitus, renal failure and HIV.

Rates and predictors of three-year mortality in older people in rural Tanzania.

BACKGROUND: There are few data on mortality rates in the general elderly living in sub-Saharan Africa. We aimed to detail three-year mortality rates in a population of rural community-dwelling older adults in northern Tanzania. METHODS: We performed a community-based study of 2232 people aged 70 years and over living in Hai district, Tanzania. At baseline, participants underwent clinical assessment for disability, neurological disorders, hypertension, atrial fibrillation and memory problems. At three-year follow-up mortality data were collected. Mortality rates were compared to UK estimates. RESULTS: At follow-up, data were available for 1873 subjects (83.9%). Of those, 208 (11.1%, 95% CI 9.7-12.5) had died. The age-standardised mortality rate was 10.2% (95% CI 8.8-11.6). Age-standardised mortality rates were lower than estimated for the UK (13.9%). In Cox regression analysis, greater age, higher levels of functional disability, use of a walking aid, subjective report of memory problems, being severely underweight and being normotensive were significant predictors of mortality. CONCLUSIONS: Those who survive to old age in Tanzania appear to have relatively low mortality rates. Physical and cognitive disabilities were strongly associated with mortality risk in this elderly community-dwelling population. The association between blood pressure and mortality merits further study.

High EMT Signature Score of Invasive Non-Small Cell Lung Cancer (NSCLC) Cells Correlates with NFκB Driven Colony-Stimulating Factor 2 (CSF2/GM-CSF) Secretion by Neighboring Stromal Fibroblasts.

We established co-cultures of invasive or non-invasive NSCLC cell lines and various types of fibroblasts (FBs) to more precisely characterize the molecular mechanism of tumor-stroma crosstalk in lung cancer. The HGF-MET-ERK1/2-CREB-axis was shown to contribute to the onset of the invasive phenotype of Calu-1 with HGF being secreted by FBs. Differential expression analysis of the respective mono- and co-cultures revealed an upregulation of NFκB-related genes exclusively in co-cultures with Calu-1. Cytokine Array- and ELISA-based characterization of the "cytokine fingerprints" identified CSF2 (GM-CSF), CXCL1, CXCL6, VEGF, IL6, RANTES and IL8 as being specifically upregulated in various co-cultures. Whilst CXCL6 exhibited a strictly FB-type-specific induction profile regardless of the invasiveness of the tumor cell line, CSF2 was only induced in co-cultures of invasive cell lines regardless of the partnered FB type. These cultures revealed a clear link between the induction of CSF2 and the EMT signature of the cancer cell line. The canonical NFκB signaling in FBs, but not in tumor cells, was shown to be responsible for the induced and constitutive CSF2 expression. In addition to CSF2, cytokine IL6, IL8 and IL1B, and chemokine CXCL1 and CXCL6 transcripts were also shown to be increased in co-cultured FBs. In contrast, their induction was not strictly dependent on the invasiveness of the co-cultured tumor cell. In a multi-reporter assay, additional signaling pathways (AP-1, HIF1-α, KLF4, SP-1 and ELK-1) were found to be induced in FBs co-cultured with Calu-1. Most importantly, no difference was observed in the level of inducibility of these six signaling pathways with regard to the type of FBs used. Finally, upon tumor fibroblast interaction the massive induction of chemokines such as CXCL1 and CXCL6 in FBs might be responsible for increased recruitment of a monocytic cell line (THP-1) in a transwell assay.

The association between disability and cognitive impairment in an elderly Tanzanian population.

Cognitive impairment is thought to be a major cause of disability worldwide, though data from sub-Saharan Africa (SSA) are sparse. This study aimed to investigate the association between cognitive impairment and disability in a cohort of community-dwelling older adults living in Tanzania. The study cohort of 296 people aged 70years and over was recruited as part of a dementia prevalence study. Subjects were diagnosed as having dementia or mild cognitive impairment according to the DSM-IV criteria. Disability level was assessed according to the WHO Disability Assessment Schedule, version 2.0 (WHODAS). A higher WHODAS score indicates greater disability. The median WHODAS in the background population was 25.0; in those with dementia and in those with mild cognitive impairment, 72 of 78 (92.3%) and 41 of 46 (89.1%), respectively, had a WHODAS score above this level. The presence of dementia, mild cognitive impairment, hearing impairment, being unable to walk without an aid and not having attended school were independent predictors of having a WHODAS score above 25.0, though age and gender were not. In summary, cognitive impairment is a significant predictor of disability in elderly Tanzanians. Screening for early signs of cognitive decline would allow management strategies to be put in place that may reduce the associated disability burden.

Ambulatory blood pressure monitoring to assess the white-coat effect in an elderly East African population.

The authors hypothesized that published hypertension rates in Tanzania were influenced by the physiological response of individuals to blood pressure (BP) testing, known as the white-coat effect (WCE). To test this, a representative sample of 79 participants from a baseline cohort of 2322 people aged 70 years and older were followed to assess BP using conventional BP measurement (CBPM) and ambulatory BP monitoring (ABPM). There was a significant difference between daytime ABPM and CBPM for both systolic BP (mean difference 29.7 mm Hg) and diastolic BP (mean difference 7.4 mm Hg). Rates of hypertension were significantly lower when measured by 24-hour ABPM (55.7%) than by CBPM (78.4%). The WCE was observed in 54 participants (68.4%). The WCE was responsible for an increase in recorded BP. Accurate identification of individuals in need of antihypertensive medication is important if resources are to be used efficiently, especially in resource-poor settings.

Current Evidence and Recommendations for Cardiac Resynchronisation Therapy.

The number of people in Europe living with symptomatic heart failure is increasing. Since its advent in the 1990s, cardiac resynchronisation therapy (CRT) has proven beneficial in terms of morbidity and mortality in selected heart failure (HF) patient populations, when combined with optimal pharmacological therapy. We review the evidence for CRT and the populations of HF patients it is currently shown to benefit, and those in which more research needs to be performed.

Rates of diagnosis and treatment of neurological disorders within a prevalent population of community-dwelling elderly people in sub-Saharan Africa.

BACKGROUND: The prevalence of neurological disorders in those aged 70years and over in the Hai district of Tanzania has been previously reported. The following research reports rates of patient's: treatment seeking, diagnosis and treatment within this prevalent population. METHODS: All people identified as having at least one neurological disorder in the prevalence study were questioned regarding whether they had sought treatment for their disorder, whether they had had a previous correct diagnosis and whether they were being currently treated. RESULTS: From a background population of 2232 people, 349 people had neurological disorders, of whom 225 (64.5%) had sought treatment for their symptoms. Of the 384 disorders identified in these 349 people, only 14.6% had been diagnosed and only 9.9% were receiving appropriate treatment. Males were significantly more likely to have been diagnosed and were more likely to have been treated appropriately. CONCLUSIONS: Levels of diagnosis and treatment were low, with some gender inequality. Reasons for this may include a lack of recognition of the condition within the local population and lack of access to appropriate services. In the absence of effective primary and secondary preventative measures, and effective treatment, the burden of neurological disorders is likely to increase with further demographic ageing.