Although renal impairment has been described in COPD, there is opportunity to evaluate further to determine nature and consider optimal management. Increased aortic stiffness, as seen in COPD, leads to reduced buffering of pulsatile flow. We hypothesised that urinary albumin creatinine ratio (UACR) would reflect glomerular damage related to aortic stiffness.
Patients with COPD and controls underwent spirometry, blood pressure, arterial stiffness - aortic pulse wave velocity (PWV) and provided a spot urine sample for UACR, with other renal biomarkers measured.
The UACR was increased in patients (n = 52): 0.80 mg/mmol compared to controls (n = 34): 0.46 mg/mmol, p < 0.05. Aortic PWV was related to log10 UACR in all subjects (r = 0.426, p < 0.001) and COPD patients alone. Aortic PWV was a significant variable for UACR with oxygen saturations, after accounting for potential confounders. Eight subjects (7 patients) reached a defined clinical microalbuminuria threshold, with aortic PWV greater in these patients compared to those patients without, although albuminuria is a continuum. Proximal tubular damage biomarkers, unlike the glomerular marker, were not different between patients and controls.
There is glomerular damage in patients with COPD evidenced by increased UACR, related to increased aortic stiffness. Besides the macrovascular prognostic implications of increased aortic stiffness, the microvascular state in COPD management should be considered.
Arterial stiffness; Biomarkers; Haemodynamics; Kidney; Renal; Microvascular
Carotid-femoral pulse wave velocity (CFPWV) is a heritable measure of aortic stiffness that is strongly associated with increased risk for major cardiovascular disease events.
Methods and Results
We conducted a meta-analysis of genome-wide association data in 9 community-based European ancestry cohorts consisting of 20,634 participants. Results were replicated in 2 additional European ancestry cohorts involving 5,306 participants. Based on a preliminary analysis of 6 cohorts, we identified a locus on chromosome 14 in the 3′-BCL11B gene desert that is associated with CFPWV (rs7152623, minor allele frequency = 0.42, beta=−0.075±0.012 SD/allele, P = 2.8 x 10−10; replication beta=−0.086±0.020 SD/allele, P = 1.4 x 10−6). Combined results for rs7152623 from 11 cohorts gave beta=−0.076±0.010 SD/allele, P=3.1x10−15. The association persisted when adjusted for mean arterial pressure (beta=−0.060±0.009 SD/allele, P = 1.0 x 10−11). Results were consistent in younger (<55 years, 6 cohorts, N=13,914, beta=−0.081±0.014 SD/allele, P = 2.3 x 10−9) and older (9 cohorts, N=12,026, beta=−0.061±0.014 SD/allele, P=9.4x10−6) participants. In separate meta-analyses, the locus was associated with increased risk for coronary artery disease (hazard ratio [HR]=1.05, confidence interval [CI]=1.02 to 1.08, P=0.0013) and heart failure (HR=1.10, CI=1.03 to 1.16, P=0.004).
Common genetic variation in a locus in the BCL11B gene desert that is thought to harbor one or more gene enhancers is associated with higher CFPWV and increased risk for cardiovascular disease. Elucidation of the role this novel locus plays in aortic stiffness may facilitate development of therapeutic interventions that limit aortic stiffening and related cardiovascular disease events.
aorta; arterial stiffness; pulse wave velocity; genetics; cardiovascular disease
Pulmonary function tests in patients with idiopathic pulmonary fibrosis characteristically show a restrictive pattern including small lung volumes and increased expiratory flow rates resulting from a reduction in pulmonary compliance due to diffuse fibrosis. Conversely, an obstructive pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. When the diseases coexist, pulmonary volumes are compensated, and a smaller than expected reduction or even normal lung volumes can be found. The present report describes 10 patients with progressive breathlessness, three of whom experienced severe limitation in their quality of life. All patients showed lung interstitial involvement and emphysema on computed tomography scan of the chest. The 10 patients showed normal spirometry and lung volumes with severe compromise of gas exchange. Normal lung volumes do not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.
Emphysema; Expiratory flow rates; Intersitial lung disease; Lung volumes
In efficacy trials male circumcision (MC) protected men against HIV infection. Planners need information relevant to MC programmes in practice. In 2008, we interviewed 2915 men and 4549 women aged 15–29 years in representative cluster samples in Botswana, Namibia and Swaziland, asking about socio-economic characteristics, knowledge and attitudes about HIV and MC and MC history. We tested finger prick blood samples for HIV. We calculated weighted frequencies of MC knowledge and attitudes, and MC history and HIV status. Multivariate analysis examined associations between MC and other variables and HIV status. In Botswana, 11% of young men reported MC, 28% in Namibia and 8% in Swaziland; mostly (75% in Botswana, 94% – mostly Herero – in Namibia and 68% in Swaziland) as infants or children. Overall, 6.5% were HIV positive (8.3% Botswana, 2.6% Namibia and 9.1% Swaziland). Taking other variables into account, circumcised men were as likely as uncircumcised men to be HIV positive. Nearly half of the uncircumcised young men planned to be circumcised; two-thirds of young men and women planned to have their sons circumcised. Some respondents had inaccurate beliefs and unhelpful views about MC and HIV, with variation between countries. Between 9 and 15% believed a circumcised man is fully protected against HIV; 20–26% believed men need not be tested for HIV before MC; 14–26% believed HIV-positive men who are circumcised cannot transmit the virus; and 8–34% thought it was “okay for a circumcised man to expect sex without a condom”. Inaccurate perceptions about protection from MC could lead to risk compensation and reduce women's ability to negotiate safer sex. More efforts are needed to raise awareness about the limitations of MC protection, especially for women, and to study the interactions between MC roll out programmes and primary HIV prevention programmes.
male circumcision (MC); HIV status; HIV attitudes; Southern Africa
Data regarding ethnic differences in wave reflections, which markedly affect the central pressure profile, are very limited. Furthermore, because age, heart rate and body height are strong determinants of augmentation index, relating single measurements to normative data (in which augmentation index values correspond to average population values of its determinants) is challenging. We studied subject-level data from 10,550 adults enrolled in large population-based studies. In a healthy reference sample (n=3,497), we assessed ethnic differences in augmentation index (ratio of second/first systolic peaks) and generated equations for adjusted z-scores, allowing for a standardized comparison between individual augmentation index measurements and the normative population mean from subjects of the same age, gender, ethnic population, body height and heart rate. After adjustment for age, body height, heart rate and mean arterial pressure, African blacks (women:154%; men:138%) and Andean-Hispanics (women:152%; men:133%) demonstrated higher central (aortic) augmentation index values than British whites (women:140%; men:128%); whereas American Indians (women:133%; men:122%) demonstrated lower augmentation index (all P<0.0001), without significant differences between Chinese and British whites. Similar results were found for radial augmentation index. Non-linear ethnic/gender-specific equations for z-scores were successfully generated to adjust individual augmentation index values for age, body height and heart rate. Marked ethnic differences in augmentation index exist, which may contribute to ethnic differences in hypertensive organ damage. Our study provides normative data that can be used to complement the interpretation of individual hemodynamic assessments among men and women of various ethnic populations, after removing the effect of various physiologic determinants.
wave reflections; augmentation index; ethnicity
To study prevalence at two time points and risk factors for experience of forced or coerced sex among school-going youth in 10 southern African countries.
Cross-sectional surveys, by facilitated self-administered questionnaire, of in-school youth in 2003 and 2007.
Schools serving representative communities in eight countries (Botswana, Lesotho, Malawi, Mozambique, Namibia, Swaziland, Zambia and Zimbabwe) in 2003 and with Tanzania and South Africa added in 2007.
Students aged 11–16 years present in the school classes.
Main outcome measures
Experience of forced or coerced sex, perpetration of forced sex.
In 2007, 19.6% (4432/25 840) of female students and 21.1% (4080/21 613) of male students aged 11–16 years reported they had experienced forced or coerced sex. Rates among 16-year-olds were 28.8% in females and 25.4% in males. Comparing the same schools in eight countries, in an analysis age standardised on the 2007 Botswana male sample, there was no significant decrease between 2003 and 2007 among females in any country and inconsistent changes among males. In multilevel analysis using generalised linear mixed model, individual-level risk factors for forced sex among female students were age over 13 years and insufficient food in the household; school-level factors were a lower proportion of students knowing about child rights and higher proportions experiencing or perpetrating forced sex; and community-level factors were a higher proportion of adults in favour of transactional sex and a higher rate of intimate partner violence. Male risk factors were similar. Some 4.7% of female students and 11.7% of male students reported they had perpetrated forced sex. Experience of forced sex was strongly associated with perpetration and other risk factors for perpetration were similar to those for victimisation.
Forced or coerced sex remained common among female and male youth in 2007. Experience of sexual abuse in childhood is recognised to increase the risk of HIV infection. The association the authors found between forced sex and school-level factors suggests preventive interventions in schools could help to tackle the HIV epidemic in southern Africa.
Cross-sectional studies 2003 and 2007.
History of coerced sex and its perpetration.
Individual, school and community risk factors.
No evidence of decline 2003–2007.
Community factors include views of transactional sex.
School factors show clustering.
Strengths and limitations of this study
Cross-sectional study limits causal inferences.
School base excludes out of school youth.
The Bangladesh government implemented a pilot Hospital Improvement Initiative (HII) in five hospitals in Sylhet division between 1998 and 2003. This included management and behaviour change training for staff, waste disposal and procurement, and referral arrangements. Two linked cross-sectional surveys in 2000 and 2003 assessed the impact of the HII, assessing both patients' experience and satisfaction and public views and use of the hospitals.
In each survey we asked 300 consecutive outpatients and a stratified random sample of 300 inpatients in the five hospitals about waiting and consultation time, use of an agent for admission, and satisfaction with privacy, cleanliness, and staff behaviour. The field teams observed cleanliness and privacy arrangements, and visited a sample of households in communities near the hospitals to ask about their opinions and use of the hospital services. Analysis examined changes over time in patients' experience and views. Multivariate analysis took account of other variables potentially associated with the outcomes. Survey managers discussed the survey findings with gender stratified focus groups in each sample community.
Compared with 2000, an outpatient in three of the hospitals in 2003 was more likely to be seen within 10 minutes and for at least five minutes by the doctor, but outpatients were less likely to report receiving all the prescribed medicines from the hospital. In 2003, inpatients were more likely to have secured admission without using an agent. Although patients’ satisfaction with several aspects of care improved, most changes were not statistically significant. Households in 2003 were significantly more likely to rate the hospitals as good than in 2000. Use of the hospitals did not change, except that more households used the medical college hospital for inpatient care in 2003. Focus groups confirmed criticisms of services and suggested improvements.
Improvements in some aspects of patients' experience may have been due to the programme, but the decreased availability of medicines in government facilities across the country over the period also occurred in these hospitals. Monitoring patients’ experience and satisfaction as well as public views and use of hospital services is feasible and useful for assessing service interventions.
In rebuilding devastated health services, the government of Afghanistan has provided access to basic services mainly by contracting with non-government organisations (NGOs), and more recently the Strengthening Mechanism (SM) of contracting with Provincial Health Offices. Community-based information about the public's views and experience of health services is scarce.
Field teams visited households in a stratified random sample of 30 communities in two districts in Kabul province, with health services mainly provided either by an NGO or through the SM and administered a questionnaire about household views, use, and experience of health services, including payments for services and corruption. They later discussed the findings with separate community focus groups of men and women. We calculated weighted frequencies of views and experience of services and multivariate analysis examined the related factors.
The survey covered 3283 households including 2845 recent health service users. Some 42% of households in the SM district and 57% in the NGO district rated available health services as good. Some 63% of households in the SM district (adjacent to Kabul) and 93% in the NGO district ordinarily used government health facilities. Service users rated private facilities more positively than government facilities. Government service users were more satisfied in urban facilities, if the household head was not educated, if they had enough food in the last week, and if they waited less than 30 minutes. Many households were unwilling to comment on corruption in health services; 15% in the SM district and 26% in the NGO district reported having been asked for an unofficial payment. Despite a policy of free services, one in seven users paid for treatment in government facilities, and three in four paid for medicine outside the facilities. Focus groups confirmed people knew payments were unofficial; they were afraid to talk about corruption.
Households used government health services but preferred private services. The experience of service users was similar in the SM and NGO districts. People made unofficial payments in government facilities, whether SM or NGO run. Tackling corruption in health services is an important part of anti-corruption measures in Afghanistan.
Unofficial payments in health services around the world are widespread and as varied as the health systems in which they occur. We reviewed the main lessons from social audits of petty corruption in health services in South Asia (Bangladesh, Pakistan), Africa (Uganda and South Africa) and Europe (Baltic States).
The social audits varied in purpose and scope. All covered representative sample communities and involved household interviews, focus group discussions, institutional reviews of health facilities, interviews with service providers and discussions with health authorities. Most audits questioned households about views on health services, perceived corruption in the services, and use of government and other health services. Questions to service users asked about making official and unofficial payments, amounts paid, service delivery indicators, and satisfaction with the service.
Contextual differences between the countries affected the forms of petty corruption and factors related to it. Most households in all countries held negative views about government health services and many perceived these services as corrupt. There was little evidence that better off service users were more likely to make an unofficial payment, or that making such a payment was associated with better or quicker service; those who paid unofficially to health care workers were not more satisfied with the service. In South Asia, where we conducted repeated social audits, only a minority of households chose to use government health services and their use declined over time in favour of other providers. Focus groups indicated that reasons for avoiding government health services included the need to pay for supposedly free services and the non-availability of medicines in facilities, often perceived as due to diversion of the supplied medicines.
Unofficial expenses for medical care represent a disproportionate cost for vulnerable families; the very people who need to make use of supposedly free government services, and are a barrier to the use of these services. Patient dissatisfaction due to petty corruption may contribute to abandonment of government health services. The social audits informed plans for tackling corruption in health services.
Corruption pervades educational and other institutions worldwide and medical schools are not exempt. Empirical evidence about levels and types of corruption in medical schools is sparse. We conducted surveys in 2000 and 2007 in the medical school of the Autonomous University of Guerrero in Mexico to document student perceptions and experience of corruption and to support the medical school to take actions to tackle corruption.
In both 2000 and 2007 medical students completed a self-administered questionnaire in the classroom without the teacher present. The questionnaire asked about unofficial payments for admission to medical school, for passing an examination and for administrative procedures. We examined factors related to the experience of corruption in multivariate analysis. Focus groups of students discussed the quantitative findings.
In 2000, 6% of 725 responding students had paid unofficially to obtain entry into the medical school; this proportion fell to 1.6% of the 436 respondents in 2007. In 2000, 15% of students reported having paid a bribe to pass an examination, not significantly different from the 18% who reported this in 2007. In 2007, students were significantly more likely to have bribed a teacher to pass an examination if they were in the fourth year, if they had been subjected to sexual harassment or political pressure, and if they had been in the university for five years or more. Students resented the need to make unofficial payments and suggested tackling the problem by disciplining corrupt teachers. The university administration made several changes to the system of admissions and examinations in the medical school, based on the findings of the 2000 survey.
The fall in the rate of bribery to enter the medical school was probably the result of the new admissions system instituted after the first survey. Further actions will be necessary to tackle the continuing presence of bribery to pass examinations and for administrative procedures. The social audit helped to draw attention to corruption and to stimulate actions to tackle it.
Maps can portray trends, patterns, and spatial differences that might be overlooked in tabular data and are now widely used in health research. Little has been reported about the process of using maps to communicate epidemiological findings.
Population weighted raster maps show colour changes over the study area. Similar to the rasters of barometric pressure in a weather map, data are the health occurrence – a peak on the map represents a higher value of the indicator in question. The population relevance of each sentinel site, as determined in the stratified last stage random sample, combines with geography (inverse-distance weighting) to provide a population-weighted extension of each colour. This transforms the map to show population space rather than simply geographic space.
Maps allowed discussion of strategies to reduce violence against women in a context of political sensitivity about quoting summary indicator figures. Time-series maps showed planners how experiences of health services had deteriorated despite a reform programme; where in a country HIV risk behaviours were improving; and how knowledge of an economic development programme quickly fell off across a region. Change maps highlighted where indicators were improving and where they were deteriorating. Maps of potential impact of interventions, based on multivariate modelling, displayed how partial and full implementation of programmes could improve outcomes across a country. Scale depends on context. To support local planning, district maps or local government authority maps of health indicators were more useful than national maps; but multinational maps of outcomes were more useful for regional institutions. Mapping was useful to illustrate in which districts enrolment in religious schools – a rare occurrence - was more prevalent.
Population weighted raster maps can present social audit findings in an accessible and compelling way, increasing the use of evidence by planners with limited numeracy skills or little time to look at evidence. Maps complement epidemiological analysis, but they are not a substitute. Much less do they substitute for rigorous epidemiological designs, like randomised controlled trials.
The government of Pakistan introduced devolution in 2001. Responsibility for delivery of most health services passed from provincial to district governments. Two national surveys examined public opinions, use, and experience of health services in 2001 and 2004, to assess the impact of devolution on these services from the point of view of the public.
A stratified random cluster sample drawn in 2001 and revisited in 2004 included households in all districts. Field teams administered a questionnaire covering views about available health services, use of government and private health services, and experience and satisfaction with the service. Focus groups in each community discussed reasons behind the findings, and district nazims (elected mayors) and administrators commented about implementation of devolution. Multivariate analysis, with an adjustment for clustering, examined changes over time, and associations with use and satisfaction with services in 2004.
Few of 57,321 households interviewed in 2002 were satisfied with available government health services (23%), with a similar satisfaction (27%) among 53,960 households in 2004. Less households used government health services in 2004 (24%) than in 2002 (29%); the decrease was significant in the most populous province. In 2004, households were more likely to use government services if they were satisfied with the services, poorer, or less educated. The majority of users of government health services were satisfied; the increase from 63% to 67% between 2002 and 2004 was significant in two provinces. Satisfaction in 2004 was higher among users of private services (87%) or private unqualified practitioners (78%). Users of government services who received all medicines from the facility or who were given an explanation of their condition were more likely to be satisfied. Focus groups explained that people avoid government health services particularly because of bad treatment from staff, and unavailable or poor quality medicines. District nazims and administrators cited problems with implementation of devolution, especially with transfer of funds.
Under devolution, the public did not experience improved government health services, but devolution was not fully implemented as intended. An ongoing social audit process could provide a basis for local and national accountability of health services.
The Maldives faces challenges in the provision of health services to its population scattered across many small islands. The government commissioned two separate reproductive health surveys, in 1999 and 2004, to inform their efforts to improve reproductive and sexual health services.
A stratified random sample of islands provided the study base for a cluster survey in 1999 and a follow-up of the same clusters in 2004. In 1999 the household survey enquired about relevant knowledge, attitudes and practices and views and experience of available reproductive health services, with a focus on women aged 15-49 years. The 2004 household survey included some of the same questions as in 1999, and also sought views of men aged 15-64 years. A separate survey about sexual and reproductive health covered 1141 unmarried youth aged 15-24 years.
There were 4087 household respondents in 1999 and 4102 in 2004. The contraceptive prevalence rate (CPR) for modern methods was 33% in 1999 and 34% in 2004. Antenatal care improved: more women in 2004 than in 1999 had at least four antenatal care visits (90.0% v 65.1%) and took iron supplements (86.7% v 49.6%) during their last pregnancy. The response rate for the youth survey was only 42% (varying from 100% in some islands to 12% in sites in the capital). The youth respondents had some knowledge gaps (one third did not know if people with HIV could look healthy and less than half thought condoms could protect against HIV), and some unhelpful attitudes about gender and reproductive health.
The two household surveys were commissioned as separate entities, with different priorities and data capture methods, rather than being undertaken as a specific research study. The direct comparisons we could make indicated an unchanged CPR and improvements in antenatal care, with the Maldives ahead of the South Asia region for antenatal care. The low response rate in the youth survey limited interpretation of the findings. But the survey highlighted areas requiring attention. Surveys not undertaken primarily for research purposes have important limitations but can provide useful information.
In Bangladesh, widespread dissatisfaction with government health services did not improve during the Health and Population Sector Programme (HPSP) reforms from 1998-2003. A 2003 national household survey documented public and health service users' views and experience. Attitudes and behaviour of health workers are central to quality of health services. To investigate whether the views of health workers influenced the reforms, we surveyed local health workers and held evidence-based discussions with local service managers and professional bodies.
Some 1866 government health workers in facilities serving the household survey clusters completed a questionnaire about their views, experience, and problems as workers. Field teams discussed the findings from the household and health workers' surveys with local health service managers in five upazilas (administrative sub-districts) and with the Bangladesh Medical Association (BMA) and Bangladesh Nurses Association (BNA).
Nearly one half of the health workers (45%) reported difficulties fulfilling their duties, especially doctors, women, and younger workers. They cited inadequate supplies and infrastructure, bad behaviour of patients, and administrative problems. Many, especially doctors (74%), considered they were badly treated as employees. Nearly all said lack of medicines in government facilities was due to inadequate supply, not improved during the HPSP. Two thirds of doctors and nurses complained of bad behaviour of patients. A quarter of respondents thought quality of service had improved as a result of the HPSP.
Local service managers and the BMA and BNA accepted patients had negative views and experiences, blaming inadequate resources, high patient loads, and patients' unrealistic expectations. They said doctors and nurses were demotivated by poor working conditions, unfair treatment, and lack of career progression; private and unqualified practitioners sought to please patients instead of giving medically appropriate care. The BMA considered it would be dangerous to attempt to train and register unqualified practitioners.
The continuing dissatisfaction of health workers may have undermined the effectiveness of the HPSP. Presenting the views of the public and service users to health managers helped to focus discussions about quality of services. It is important to involve health workers in health services reforms.
A large kindred of familial pulmonary fibrosis is reported. Six members from the first two generations of this particular kindred were described more than 40 years previously; six more individuals from the third and fourth generations have also been evaluated. The proband, now 23 years of age, has mild disease; the other 11 documented affected family members all died from their disease at an average age of 37 years (range 25 to 50 years). The pathology was that of usual interstitial pneumonia, as is typical in idiopathic pulmonary fibrosis. However, the initial radiographic pattern in many of these individuals was upper lobe and nodular and, along with the young age, was atypical for idiopathic pulmonary fibrosis. Several genetic abnormalities have been associated with familial pulmonary fibrosis. The present study examined the genes coding for surfactant protein-C, ATP-binding cassette protein A3 and telomerase, and found no abnormalities.
ABCA3; Idiopathic pulmonary fibrosis; Familial pulmonary fibrosis; Surfactant protein-C; Telomerase; Usual interstitial pneumonia
Patients with COPD have an increased risk of cardiovascular disease. Whilst pulmonary rehabilitation has proven benefit for exercise tolerance and quality of life, any effect on cardiovascular risk has not been fully investigated. We hypothesised that pulmonary rehabilitation, through the exercise and nutritional intervention, would address these factors.
Thirty-two stable patients with COPD commenced rehabilitation, and were compared with 20 age and gender matched controls at baseline assessment. In all subjects, aortic pulse wave velocity (PWV) an independent non-invasive predictor of cardiovascular risk, blood pressure (BP), interleukin-6 (IL-6) and fasting glucose and lipids were determined. These measures, and the incremental shuttle walk test (ISWT) were repeated in the patients who completed pulmonary rehabilitation.
On commencement of rehabilitation aortic PWV was increased in patients compared with controls (p < 0.05), despite mean BP, age and gender being similar. The IL-6 was also increased (p < 0.05). Twenty-two patients completed study assessments. In these subjects, rehabilitation reduced mean (SD) aortic PWV (9.8 (3.0) to 9.3 (2.7) m/s (p < 0.05)), and systolic and diastolic BP by 10 mmHg and 5 mmHg respectively (p < 0.01). Total cholesterol and ISWT also improved (p < 0.05). On linear regression analysis, the reduction in aortic PWV was attributed to reducing the BP.
Cardiovascular risk factors including blood pressure and thereby aortic stiffness were improved following a course of standard multidisciplinary pulmonary rehabilitation in patients with COPD.
COPD; pulmonary rehabilitation; arterial stiffness
Interpersonal power gradients may prevent people implementing HIV prevention decisions. Among 7,464 youth aged 15–29 years in Botswana, Namibia and Swaziland we documented indicators of choice-disability (low education, educational disparity with partner, experience of sexual violence, experience of intimate partner violence (IPV), poverty, partner income disparity, willingness to have sex without a condom despite believing partner at risk of HIV), and risk behaviours like inconsistent use of condoms and multiple partners. In Botswana, Namibia and Swaziland, 22.9, 9.1, and 26.1% women, and 8.3, 2.8, and 9.3% men, were HIV positive. Among both women and men, experience of IPV, IPV interacted with age, and partner income disparity interacted with age were associated with HIV positivity in multivariate analysis. Additional factors were low education (for women) and poverty (for men). Choice disability may be an important driver of the AIDS epidemic. New strategies are needed that favour the choice-disabled.
HIV; Choice-disability; Risk factors; Intimate partner violence
Determining the presence and extent of co-morbidities is fundamental in assessing patients with chronic respiratory disease, where increased cardiovascular risk, presence of osteoporosis and low muscle mass have been recognised in several disease states. We hypothesised that the systemic consequences are evident in a further group of subjects with COPD due to Alpha-1 Antitrypsin Deficiency (A1ATD), yet are currently under-recognised.
We studied 19 patients with PiZZ A1ATD COPD and 20 age, sex and smoking matched controls, all subjects free from known cardiovascular disease. They underwent spirometry, haemodynamic measurements including aortic pulse wave velocity (aPWV), an independent predictor or cardiovascular risk, dual energy X-ray absorptiometry to determine body composition and bone mineral density.
The aPWV was greater in patients: 9.9(2.1) m/s than controls: 8.5(1.6) m/s, p = 0.03, despite similar mean arterial pressure (MAP). The strongest predictors of aPWV were age, FEV1% predicted and MAP (all p < 0.01). Osteoporosis was present in 8/19 patients (2/20 controls) and was previously unsuspected in 7 patients. The fat free mass and bone mineral density were lower in patients than controls (p < 0.001).
Patients with A1ATD related COPD have increased aortic stiffness suggesting increased risk of cardiovascular disease and evidence of occult musculoskeletal changes, all likely to contribute hugely to overall morbidity and mortality.
Ataxia telangiectasia (A-T) mutated (ATM) is critical for cell cycle checkpoints and DNA repair. Thus, specific small molecule inhibitors targeting ATM could perhaps be developed into efficient radiosensitizers. Recently, a specific inhibitor of the ATM kinase, KU-55933, was shown to radiosensitize human cancer cells. Herein, we report on an improved analogue of KU-55933 (KU-60019) with Ki and IC50 values half of those of KU-55933. KU-60019 is 10-fold more effective than KU-55933 at blocking radiation-induced phosphorylation of key ATM targets in human glioma cells. As expected, KU-60019 is a highly effective radiosensitizer of human glioma cells. A-T fibroblasts were not radiosensitized by KU-60019 strongly suggesting that the ATM kinase is specifically targeted. Furthermore, KU-60019 reduced basal S473 AKT phosphorylation, suggesting that the ATM kinase might regulate a protein phosphatase acting on AKT. In line with this finding, the effect of KU-60019 on AKT phosphorylation was countered by low levels of okadaic acid, a phosphatase inhibitor, and A-T cells were impaired in S473 AKT phosphorylation in response to radiation and insulin, and unresponsive to KU-60019. We also show that KU-60019 inhibits glioma cell migration and invasion in vitro, suggesting that glioma growth and motility might be controlled by ATM via AKT. Inhibitors of MEK and AKT did not further radiosensitize cells treated with KU-60019 supporting the idea that KU-60019 interferes with prosurvival signaling separate from its radiosensitizing properties. Altogether, KU-60019 inhibits the DNA damage response, reduces AKT phosphorylation and prosurvival signaling, inhibits migration and invasion, and effectively radiosensitizes human glioma cells.
DNA repair; radiosurvival; KU-55933
HIV testing with counseling is an integral component of most national HIV and AIDS prevention strategies in southern Africa. Equity in testing implies that people at higher risk for HIV such as women; those who do not use condoms consistently; those with multiple partners; those who have suffered gender based violence; and those who are unable to implement prevention choices (the choice-disabled) are tested and can have access to treatment.
We conducted a household survey of 24,069 people in nationally stratified random samples of communities in Botswana, Lesotho, Malawi, Mozambique, Namibia, South Africa, Swaziland, Tanzania, Zambia, and Zimbabwe. We asked about testing for HIV in the last 12 months, intention to test, and about HIV risk behaviour, socioeconomic indicators, access to information, and attitudes related to stigma.
Across the ten countries, seven out of every ten people said they planned to have an HIV test but the actual proportion tested in the last 12 months varied from 24% in Mozambique to 64% in Botswana. Generally, people at higher risk of HIV were not more likely to have been tested in the last year than those at lower risk, although women were more likely than men to have been tested in six of the ten countries. In Swaziland, those who experienced partner violence were more likely to test, but in Botswana those who were choice-disabled for condom use were less likely to be tested. The two most consistent factors associated with HIV testing across the countries were having heard about HIV/AIDS from a clinic or health centre, and having talked to someone about HIV and AIDS.
HIV testing programmes need to encourage people at higher risk of HIV to get tested, particularly those who do not interact regularly with the health system. Service providers need to recognise that some people are not able to implement HIV preventive actions and may not feel empowered to get themselves tested.
We visualized insulin uptake in vivo across the apical membrane of the rat proximal tubule (PT) by confocal microscopy; we compared it with in vitro findings in a rat PT cell line (WKPT) using fluorescence microscopy and flow cytometry. Surface tubules were observed in vivo with a 633-nm single laser-illuminated real-time video-rate confocal scanning microscope in upright configuration for optical sectioning below the renal capsule. Fields were selected containing proximal and distal tubules; Cy5-labeled insulin was injected twice (the second time after ∼140 min) into the right jugular vein, and the fluorescence signal (at 650–670 nm) was recorded. Fluorescence was detected almost immediately at the brush-border membrane (BBM) of PT cells only, moving inside cells within 30–40 min. As a measure of insulin uptake, the ratio of the fluorescence signal after the second injection to the first doubled (ratio: 2.11 ± 0.26, mean ± SE, n = 10), indicating a “priming,” or stimulating, effect of insulin on its uptake mechanism at the BBM. This effect did not occur after pretreatment with intravenous lysine (ratio: 1.03 ± 0.07, n = 6; P < 0.01). Cy2- or Cy3-labeled insulin uptake in a PT cell line in vitro was monitored by 488-nm excitation fluorescence microscopy using an inverted microscope. Insulin localized toward the apical membrane of these cells. Semiquantitative analysis of insulin uptake by flow cytometry also demonstrated a priming effect (upregulation) on insulin internalization in the presence of increasing amounts of insulin, as was observed in vivo; moreover, this effect was not seen with, or affected by, the similarly endocytosed ligand β2-glycoprotein.
intravital confocal microscopy; fluorescence; kidney
Rates of childhood vaccination in Pakistan remain low.There is continuing debate about the role of consumer and service factors in determining levels of vaccination in developing countries.
In a stratified random cluster sample of census enumeration areas across four districts in Pakistan, household interviews about vaccination of children and potentially related factors with 10,423 mothers of 14,542 children preceded discussion of findings in separate male and female focus groups. Logistic regression analyses helped to clarify local determinants of measles vaccination.
Across the four districts, from 17% to 61% of mothers had formal education and 50% to 86% of children aged 12-23 months had received measles vaccination. Children were more likely to receive measles vaccination if the household was less vulnerable, if their mother had any formal education, if she knew at least one vaccine preventable disease, and if she had not heard of any bad effects of vaccination. Discussing vaccinations in the family was strongly associated with vaccination. In rural areas, living within 5 km of a vaccination facility or in a community visited by a vaccination team were associated with vaccination, as was the mother receiving information about vaccinations from a visiting lady health worker. Focus groups confirmed personal and service delivery obstacles to vaccination, in particular cost and poor access to vaccination services. Despite common factors, the pattern of variables related to measles vaccination differed between and within districts.
Vaccination coverage varies from district to district in Pakistan and between urban and rural areas in any district. Common factors are associated with vaccination, but their relative importance varies between locations. Good local information about vaccination rates and associated variables is important to allow effective and equitable planning of services.
Achieving equity means increased uptake of health services for those who need it most. But the poorest families continue to have the poorest service. In Pakistan, large numbers of children do not access vaccination against measles despite the national government's effort to achieve universal coverage.
A cross-sectional study of a random sample of 23 rural and 9 urban communities in the Lasbela district of south Pakistan, explored knowledge, attitudes and discussion around measles vaccination. Several socioeconomic variables allowed examination of the role of inequities in vaccination uptake; 2479 mothers provided information about 4007 children aged 10 to 59 months. A Mantel-Haenszel stratification analysis, with and without adjustment for clustering, clarified determinants of measles vaccination in urban and rural areas.
A high proportion of mothers had appropriate knowledge of and positive attitudes to vaccination; many discussed vaccination, but only one half of children aged 10-59 months accessed vaccination. In urban areas, having an educated mother, discussing vaccinations, having correct knowledge about vaccinations, living in a community with a government vaccination facility within 5 km, and living in houses with better roofs were associated with vaccination uptake after adjusting for the effect of each of these variables and for clustering; maternal education was an equity factor even among those with good access. In rural areas, the combination of roof quality and access (vaccination post within 5 km) along with discussion about vaccines and knowledge about vaccines had an effect on uptake.
Stagnating rates of vaccination coverage may be related to increasing inequities. A hopeful finding is that discussion about vaccines and knowledge about vaccines had a positive effect that was independent of the negative effect of inequity - in both urban and rural areas. At least as a short term strategy, there seems to be reason to expect an intervention increasing knowledge and discussion about vaccination in this district might increase uptake.
Childhood vaccination rates are low in Lasbela, one of the poorest districts in Pakistan's Balochistan province. This randomised cluster controlled trial tested the effect on uptake of informed discussion of vaccination costs and benefits, without relying on improved health services.
Following a baseline survey of randomly selected representative census enumeration areas, a computer generated random number sequence assigned 18 intervention and 14 control clusters. The intervention comprised three structured discussions separately with male and female groups in each cluster. The first discussion shared findings about vaccine uptake from the baseline study; the second focussed on the costs and benefits of childhood vaccination; the third focussed on local action plans. Field teams encouraged the group participants to spread the dialogue to households in their communities. Both intervention and control clusters received a district-wide health promotion programme emphasizing household hygiene. Interviewers in the household surveys were blind of intervention status of different clusters. A follow-up survey after one year measured impact of the intervention on uptake of measles and full DPT vaccinations of children aged 12-23 months, as reported by the mother or caregiver.
In the follow-up survey, measles and DPT vaccination uptake among children aged 12-23 months (536 in intervention clusters, 422 in control clusters) was significantly higher in intervention than in control clusters, where uptake fell over the intervention period. Adjusting for baseline differences between intervention and control clusters with generalized estimating equations, the intervention doubled the odds of measles vaccination in the intervention communities (OR 2.20, 95% CI 1.24-3.88). It trebled the odds of full DPT vaccination (OR 3.36, 95% CI 2.03-5.56).
The relatively low cost knowledge translation intervention significantly increased vaccine uptake, without relying on improved services, in a poor district with limited access to services. This could have wide relevance in increasing coverage in developing countries.