Does Cataract Surgery Alleviate Poverty? Evidence from a Multi-Centre Intervention Study Conducted in Kenya,the Philippines and Bangladesh

Background

Poverty and blindness are believed to be intimately linked, but empirical data supporting this purported relationship are sparse. The objective of this study is to assess whether there is a reduction in poverty after cataract surgery among visually impaired cases.

Methodology/Principal Findings

A multi-centre intervention study was conducted in three countries (Kenya, Philippines, Bangladesh). Poverty data (household per capita expenditure – PCE, asset ownership and self-rated wealth) were collected from cases aged ≥50 years who were visually impaired due to cataract (visual acuity<6/24 in the better eye) and age-sex matched controls with normal vision. Cases were offered free/subsidised cataract surgery. Approximately one year later participants were re-interviewed about poverty. 466 cases and 436 controls were examined at both baseline and follow-up (Follow up rate: 78% for cases, 81% for controls), of which 263 cases had undergone cataract surgery (“operated cases”). At baseline, operated cases were poorer compared to controls in terms of PCE (Kenya: $22 versus £35 p = 0.02, Bangladesh: $16 vs $24 p = 0.004, Philippines: $24 vs 32 p = 0.0007), assets and self-rated wealth. By follow-up PCE had increased significantly among operated cases in each of the three settings to the level of controls (Kenya: $30 versus £36 p = 0.49, Bangladesh: $23 vs $23 p = 0.20, Philippines: $45 vs $36 p = 0.68). There were smaller increases in self-rated wealth and no changes in assets. Changes in PCE were apparent in different socio-demographic and ocular groups. The largest PCE increases were apparent among the cases that were poorest at baseline.

Conclusions/Significance

This study showed that cataract surgery can contribute to poverty alleviation, particularly among the most vulnerable members of society. This study highlights the need for increased provision of cataract surgery to poor people and shows that a focus on blindness may help to alleviate poverty and achieve the Millennium Development Goals.     

Prevalence of Diabetes and Pre-Diabetes and Associated Risk Factors among Tuberculosis Patients in India

Background

Diabetes mellitus (DM) is recognised as an important risk factor to tuberculosis (TB). India has high TB burden, along with rising DM prevalence. There are inadequate data on prevalence of DM and pre-diabetes among TB cases in India. Aim was to determine diabetes prevalence among a cohort of TB cases registered under Revised National Tuberculosis Control Program in selected TB units in Tamil Nadu, India, and assess pattern of diabetes management amongst known cases.

Methods

827 among the eligible patients (n = 904) underwent HbA1c and anthropometric measurements. OGTT was done for patients without previous history of DM and diagnosis was based on WHO criteria. Details of current treatment regimen of TB and DM and DM complications, if any, were recorded. A pretested questionnaire was used to collect information on sociodemographics, habitual risk factors, and type of TB.

Findings

DM prevalence was 25.3% (95% CI 22.6–28.5) and that of pre-diabetes 24.5% (95% CI 20.4–27.6). Risk factors associated with DM among TB patients were age (31–35, 36–40, 41–45, 46–50, >50 years vs <30 years) [OR (95% CI) 6.75 (2.36–19.3); 10.46 (3.95–27.7); 18.63 (6.58–52.7); 11.05 (4.31–28.4); 24.7 (9.73–62.7) (p<0.001)], positive family history of DM [3.08 (1.73–5.5) (p<0.001)], sedentary occupation [1.69 (1.10–2.59) (p = 0.016)], and BMI (18.5–22.9, 23–24.9 and ≥25 kg/m² vs <18.5 kg/m²) [2.03 (1.32–3.12) (p = 0.001); 0.87 (0.31–2.43) (p = 0.78); 1.44 (0.54–3.8) (p = 0.47)]; for pre-diabetes, risk factors were age (36–40, 41–45, 46–50, >50 years vs <30 years) [2.24 (1.1–4.55) (p = 0.026); 6.96 (3.3–14.7); 3.44 (1.83–6.48); 4.3 (2.25–8.2) (p<0.001)], waist circumference [<90 vs. ≥90 cm (men), <80 vs. ≥80 cm (women)] [3.05 (1.35–6.9) (p = 0.007)], smoking [1.92 (1.12–3.28) (p = 0.017)] and monthly income (5000–10,000 INR vs <5000 INR) [0.59 (0.37–0.94) (p = 0.026)]. DM risk was higher among pulmonary TB [3.06 (1.69–5.52) (p<0.001)], especially sputum positive, than non-pulmonary TB.

Interpretation

Nearly 50% of TB patients had either diabetes or pre-diabetes.     

EPHA2 polymorphisms and age-related cataract in India

Objective

We investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India.

Methods

We carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear ≥4, cortical ≥3, posterior sub-capsular (PSC) ≥2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location.

Results

7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p>0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract.

Conclusions

Our results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians.     

Mortality burden and socioeconomic status in India

Background

The dimensions along which mortality is patterned in India remains unclear. We examined the specific contribution of social castes, household income, assets, and monthly per capita consumption to mortality differentials in India.

Methods and Findings

Cross-sectional data on 217 363 individuals from 41 554 households from the 2004–2005 India Human Development Survey was analyzed using multiple logistic regressions. Mortality differentials across social castes were attenuated after adjusting for household economic factors such as income and assets. Individuals living in the lowest income and assets quintiles had an increased risk of mortality with odds ratio (OR) of 1.66 (95% CI  = 1.23–2.24) in the bottom income quintile and OR of 2.94 (95% CI  = 1.66–5.22) in the bottom asset quintile. Counter-intuitively, individuals living in households with lowest monthly consumption per capita had significantly lower probability of death (OR  = 0.27, 95% CI  = 0.20–0.38).

Conclusions

Mortality burden in India is largely patterned on economic dimensions as opposed to caste dimensions, though caste may play an important role in predicting economic opportunities.     

Adequate wound care and use of bed nets as protective factors against Buruli Ulcer: results from a case control study in Cameroon

Background

Buruli ulcer is an infectious disease involving the skin, caused by Mycobacterium ulcerans. Its exact transmission mechanism remains unknown. Several arguments indicate a possible role for insects in its transmission. A previous case-control study in the Nyong valley region in central Cameroon showed an unexpected association between bed net use and protection against Buruli ulcer. We investigated whether this association persisted in a newly discovered endemic Buruli ulcer focus in Bankim, northwestern Cameroon.

Methodology/Principal Findings

We conducted a case-control study on 77 Buruli ulcer cases and 153 age-, gender- and village-matched controls. Participants were interviewed about their activities and habits. Multivariate conditional logistic regression analysis identified systematic use of a bed net (Odds-Ratio (OR) = 0.4, 95% Confidence Interval [95%CI] = [0.2–0.9], p-value (p) = 0.04), cleansing wounds with soap (OR [95%CI] = 0.1 [0.03–0.3], p<0.0001) and growing cassava (OR [95%CI] = 0.3 [0.2–0.7], p = 0.005) as independent protective factors. Independent risk factors were bathing in the Mbam River (OR [95%CI] = 6.9 [1.4–35], p = 0.02) and reporting scratch lesions after insect bites (OR [95%CI] = 2.7 [1.4–5.4], p = 0.004). The proportion of cases that could be prevented by systematic bed net use was 32%, and by adequate wound care was 34%.

Conclusions/Significance

Our study confirms that two previously identified factors, adequate wound care and bed net use, significantly decreased the risk of Buruli ulcer. These associations withstand generalization to different geographic, climatic and epidemiologic settings. Involvement of insects in the household environment, and the relationship between wound hygiene and M. ulcerans infection should now be investigated.     

Risk factors associated with increased mortality among HIV infected children initiating antiretroviral therapy (ART) in South Africa

Objective

To identify demographic and clinical risk factors associated with mortality after initiation of antiretroviral therapy (ART) in a cohort of human immunodeficiency (HIV) infected children in KwaZulu-Natal, South Africa.

Methods

We performed a retrospective cohort study of 537 children initiating antiretroviral therapy at McCord Hospital in KwaZulu-Natal, South Africa. Data were extracted from electronic medical records and risk factors associated with mortality were assessed using Cox regression analysis.

Results

Overall there were 47 deaths from the cohort of 537 children initiating ART with over 991 child-years of follow-up (median 22 months on ART), yielding a mortality rate of 4.7 deaths per 100 child years on ART. Univariate analysis indicated that mortality was significantly associated with lower weight-for-age Z-score (p<0.0001), chronic diarrhea (p = 0.0002), lower hemoglobin (p = 0.002), age <3 years (p = 0.003), and CD4% <10% (p = 0.005). The final multivariable Cox proportional hazards mortality model found age less than 3 years (p = 0.004), CD4 <10% (p = 0.01), chronic diarrhea (p = 0.03), weight-for-age Z-score (<0.0001) and female gender as a covariate varying with time (p = 0.03) all significantly associated with mortality.

Conclusion

In addition to recognized risk factors such as young age and advanced immunosuppression, we found female gender to be significantly associated with mortality in this pediatric ART cohort. Future studies are needed to determine whether intrinsic biologic differences or socio-cultural factors place female children with HIV at increased risk of death following initiation of ART.     

Impact of migration and acculturation on prevalence of type 2 diabetes and related eye complications in Indians living in a newly urbanised society

Background

Health of migrants is a major public health challenge faced by governments and policy makers. Asian Indians are among the fastest growing migration groups across Asia and the world, but the impact of migration and acculturation on diabetes and diabetes-related eye complications among Indians living in urban Asia remains unclear.

Methodologies/Principal Findings

We evaluated the influence of migration and acculturation (i.e., migration status and length of residence) on the prevalence of type-2 diabetes mellitus (T2DM) and diabetes-related eye complications (diabetic retinopathy (DR) and cataract), among first-generation (defined as participant born in India with both parents born in India, n = 781) and second-generation (participants born in Singapore with both parents born in India, n = 1,112) Indian immigrants from a population-based study of Adult Indians in Singapore. Diabetes was defined as HbA1c≥6.5%, use of diabetic medication or a physician diagnosis of diabetes. Retinal and lens photographs were graded for the presence of DR and cataract. Compared to first generation immigrants, second generation immigrants had a higher age- and gender-standardized prevalence of T2DM (34.4% versus 29.0%, p<0.001), and, in those with T2DM, higher age- and gender-standardized prevalence of DR (31.7% versus 24.8%, p<0.001), nuclear cataract (13.6% versus 11.6%, p<0.001), and posterior sub-capsular cataract (6.4% versus 4.6%, p<0.001). Among first generation migrants, longer length of residence was associated with significantly younger age of diagnosis of diabetes and greater likelihood of having T2DM and diabetes-related eye complications.

Conclusion

Second generation immigrant Indians and longer length of residence are associated with higher prevalence of diabetes and diabetes-related complications (i.e., DR and cataract) among migrant Indians living in Singapore. These data highlight potential worldwide impacts of migration patterns on the risk and burden of diabetes.     

CCND1 as a predictive biomarker of neoadjuvant chemotherapy in patients with locally advanced head and neck squamous cell carcinoma

Background

Cyclin D1 (CCND1) has been associated with chemotherapy resistance and poor prognosis. In this study, we tested the hypothesis that CCND1 expression determines response and clinical outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC) patients treated with neoadjuvant chemotherapy followed by surgery and radiotherapy.

Methodology and Findings

224 patients with HNSCC were treated with either cisplatin-based chemotherapy followed by surgery and radiotherapy (neoadjuvant group, n = 100) or surgery and radiotherapy (non-neoadjuvant group, n = 124). CCND1 expression was assessed by immunohistochemistry. CCND1 levels were analyzed with chemotherapy response, disease-free survival (DFS) and overall survival (OS). There was no significant difference between the neoadjuvant group and non-neoadjuvant group in DFS and OS (p = 0.929 and p = 0.760) when patients treated with the indiscriminate administration of cisplatin-based chemotherapy. However, in the neoadjuvant group, patients whose tumors showed a low CCND1 expression more likely respond to chemotherapy (p<0.001) and had a significantly better OS and DFS than those whose tumors showed a high CCND1 expression (73% vs 8%, p<0.001; 63% vs 6%, p<0.001). Importantly, patients with a low CCND1 expression in neoadjuvant group received more survival benefits than those in non-neoadjuvant group (p = 0.016), however patients with a high CCND1 expression and treated with neoadjuvant chemotherapy had a significantly poor OS compared to those treated with surgery and radiotherapy (p = 0.032). A multivariate survival analysis also showed CCND1 expression was an independent predictive factor (p<0.001).

Conclusions

This study suggests that some but not all patients with HNSCC may benefit from neoadjuvant chemotherapy with cisplatin-based regimen and CCND1 expression may serve as a predictive biomarker in selecting patients undergo less than two cycles of neoadjuvant chemotherapy.     

Prevalence and Outcomes of Cataract Surgery in Adult Rural Chinese Populations of the Bai Nationality in Dali: The Yunnan Minority Eye Study

Purpose

To investigate the prevalence and visual acuity (VA) outcomes of cataract surgery in adults of the Bai Nationality populations in rural China.

Methods

We conducted a population-based cross-sectional survey (from randomly selected block groups) of Chinese Bai Nationality aged ≥50 years in southwestern China. Presenting visual acuity (PVA), best corrected visual acuity (BCVA) were recorded and a detailed eye examination was carried out. For all aphakic and pseudophakic subjects identified, information on the date, setting, type, and complications of cataract surgery were recorded. In eyes with VA <20/63, the principal cause of visual impairment was identified.

Results

Of 2133 (77.8% of 2742) subjects, 99 people (129 eyes) had undergone cataract surgery. The prevalence of cataract surgery was 4.6%. Surgical coverage among those with PVA <20/200 in both eyes because of cataract was 52.8%. Unoperated cataract was associated with older age. The main barrier to cataract surgery was lack of awareness and knowledge, cost, and fear. Among the 129 cataract-operated eyes, 22.5% had PVA of ≥20/32, 25.6% had PVA of 20/40 to 20/63, 23.3% had PVA <20/63 to 20/200, and 28.7% had PVA<20/200. With BCVA, the percentages were 42.6%, 23.3%, 10.9%, and 23.3%, respectively. Aphakia (odds ratio [OR], 8.49; P<0.001) and no education (OR, 10.18; P = 0.001) or less education (OR, 6.49; P = 0.014) were significantly associated with postoperative visual impairment defined by PVA, while aphakia (OR, 8.49; P<0.001) and female gender (OR, 4.19; P = 0.004) were significantly associated with postoperative visual impairment by BCVA. The main causes of postoperative visual impairment were refractive error, retinal disorders and glaucoma.

Conclusions

Half of those with bilateral visual impairment or blindness because of cataract remain in need of cataract surgery in Bai population. Surgical uptake and visual outcomes should be further improved in the future.     

Household tobacco smoke and admission weight predict severe bronchiolitis in infants independent of deprivation: prospective cohort study

Objectives

To examine demographic, environmental and clinical factors associated with severe bronchiolitis in infants admitted to hospital and quantify the independent effects of these factors.

Design

Prospective cohort study.

Setting

Alder Hey Children''s Hospital, Liverpool, United Kingdom.

Participants

378 infants admitted to hospital with a diagnosis of bronchiolitis, of whom 299 (79%) were antigen positive to respiratory syncytial virus (RSV).

Outcome

Severity of disease during admission, defined as “no need for supplemental oxygen” (reference group), “any need for supplemental oxygen” and “any need for mechanical ventilation”.

Results

Univariate analysis found male sex (p = 0.035) and tobacco smoking by a household member (p<0.001) were associated with need for both supplemental oxygen and mechanical ventilation. Premature birth, low gestation, low birth weight, low admission weight and low corrected age on admission were also associated with need for mechanical ventilation (all p≤0.002). Deprivation scores (IMD 2004) were significantly higher in households where a member smoked compared to non-smoking households (p<0.001). The odds of smoking predicted by deprivation were 7 times higher (95%CI (3.59, 14.03)), when comparing the least and most deprived quintiles of the study population. Family history of atopic disease and deprivation score were not associated with severe disease. Multivariate multinomial logistic regression which initially included all covariates, found household tobacco smoking (adjusted OR = 2.45, 95%CI (1.60, 3.74) predicted need for oxygen supplementation. Household tobacco smoking (adjusted OR = 5.49, (2.78, 10.83)) and weight (kg) on admission (adjusted OR = 0.51, (0.40, 0.65)) were both significant predictors in the final model for mechanical ventilation. The same associations and similar size of effects were found when only children with proven RSV infection were included in analysis.

Conclusions

Low admission weight and householder tobacco smoking increased the risk of severe bronchiolitis in infants admitted to hospital. These effects were independent of a standard deprivation measure. NIHR Study Ref. DHCS/G121/10.     

The tissue microlocalisation and cellular expression of CD163, VEGF, HLA-DR, iNOS, and MRP 8/14 is correlated to clinical outcome in NSCLC

Background

We have previously investigated the microlocalisation of M1 and M2 macrophages in NSCLC. This study investigated the non-macrophage (NM) expression of proteins associated with M1 and M2 macrophages in NSCLC.

Methods

Using immunohistochemistry, CD68⁺ macrophages and proteins associated with either a cytotoxic M1 phenotype (HLA-DR, iNOS, and MRP 8/14), or a non-cytotoxic M2 phenotype (CD163 and VEGF) were identified. NM expression of the markers was analysed in the islets and stroma of surgically resected tumours from 20 patients with extended survival (ES) (median 92.7 months) and 20 patients with poor survival (PS) (median 7.7 months).

Results

The NM expression of NM-HLA-DR (p<0.001), NM-iNOS (p = 0.02) and NM-MRP 8/14 (p = 0.02) was increased in ES compared to PS patients in the tumour islets. The tumour islet expression of NM-VEGF, was decreased in ES compared to PS patients (p<0.001). There was more NM-CD163 expression (p = 0.04) but less NM-iNOS (p = 0.002) and MRP 8/14 (p = 0.01) expression in the stroma of ES patients compared with PS patients. The 5-year survival for patients with above and below median NM expression of the markers in the islets was 74.9% versus 4.7% (NM-HLA-DR p<0.001), 65.0% versus 14.6% (NM-iNOS p = 0.003), and 54.3% versus 22.2% (NM-MRP 8/14 p = 0.04), as opposed to 34.1% versus 44.4% (NM-CD163 p = 0.41) and 19.4% versus 59.0% (NM-VEGF p = 0.001).

Conclusions

Cell proteins associated with M1 and M2 macrophages are also expressed by other cell types in the tumour islets and stroma of patients with NSCLC. Their tissue and cellular microlocalisation is associated with important differences in clinical outcome.     

Active Chronic Sarcoidosis is Characterized by Increased Transitional Blood B Cells, Increased IL-10-Producing Regulatory B Cells and High BAFF Levels

Background

Sarcoidosis is a multisystemic disease of unknown etiology characterized by a disproportionate Th1 granulomatous immune response in the organs involved. Plasmatic hypergammaglobulinemia and B cell accumulation in granulomatous lesions suggest the possible role of humoral immune responses in the pathogenesis of sarcoidosis. The purpose of this study is to describe B cell peripheral compartment in sarcoidosis.

Methodology/Principal Findings

We analyzed blood B cell subsets and BAFF levels in 33 patients with chronic sarcoidosis (active sarcoidosis n = 18; inactive sarcoidosis n = 15) and 18 healthy donors. Active chronic sarcoidosis patients had significantly less circulating memory B cells (p<0.01), more transitional (p<0.01) and increased numbers of IL-10-producing regulatory B cells (p<0.05) compared with healthy donors and patients with inactive sarcoidosis. BAFF serum levels were significantly higher in patients with active sarcoidosis (p<0.01 versus healthy donors and inactive sarcoidosis patients) and strongly correlated with serum hypergammaglobulinemia (r = 0.53, p<0.01) and angiotensin converting enzyme levels (r = 0.61, p = <0.01).

Conclusions/Significance

These data show that there is an altered B cell homeostasis in active sarcoidosis and suggest BAFF antagonist drugs as potential new treatments of this disease.     

Gender differences in traditional Chinese medicine use among adults in Taiwan

Objectives

The increasing use of complementary, alternative medicine (CAM) and traditional Chinese medicine (TCM) has attracted attention. We report on the gender difference in TCM use among the general population in Taiwan in a population-based, cross-sectional study.

Methods

We collected data on socio-demographic factors, lifestyle and health behavior from the 2001 Taiwan National Health Interview Survey. The medical records of interviewees aged 20–69 years were obtained from National Health Insurance claims data with informed consent. The prevalence of TCM use and the average frequency of TCM use were compared between women and men.

Results

Among 14,064 eligible participants, the one-year prevalence of TCM use for women and men was 31.8% and 22.4%, respectively. Compared with men, women had a higher average TCM use frequency (1.55 visits vs. 1.04 visits, p<0.001). This significant difference remained evident after excluding gender-specific diseases (1.43 visits vs. 1.03 visits, p<0.001). The average TCM use frequency was significantly higher in women than in men across all age groups. TCM use correlates differed for women and men. Marital status (odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.30–1.85), family income and unhealthy lifestyle (OR = 1.50, 95% CI = 1.30–1.74) were factors associated with TCM use in men but not in women.

Conclusions

In Taiwan, women used more TCM services than men and the gender differences in the TCM use profile persisted across age groups.     

Rising Diabetes Prevalence among Urban-Dwelling Black South Africans

Objective

To examine the prevalence of and the association of psychosocial risk factors with diabetes in 25–74-year-old black Africans in Cape Town in 2008/09 and to compare the prevalence with a 1990 study.

Research Design and Methods

A randomly selected cross-sectional sample had oral glucose tolerance tests. The prevalence of diabetes (1998 WHO criteria), other cardiovascular risk factors and psychosocial measures, including sense of coherence (SOC), locus of control and adverse life events, were determined. The comparison of diabetes prevalence between this and a 1990 study used the 1985 WHO diabetes criteria.

Results

There were 1099 participants, 392 men and 707 women (response rate 86%). The age-standardised (SEGI) prevalence of diabetes was 13.1% (95% confidence interval (CI) 11.0–15.1), impaired glucose tolerance (IGT) 11.2% (9.2–13.1) and impaired fasting glycaemia 1.2% (0.6–1.9). Diabetes prevalence peaked in 65–74-year-olds (38.6%). Among diabetic participants, 57.9% were known and 38.6% treated. Using 1985 WHO criteria, age-standardised diabetes prevalence was higher by 53% in 2008/09 (12.2% (10.2–14.2)) compared to 1990 (8.0% (5.8–10.3)) and IGT by 67% (2008/09: 11.7% (9.8–13.7); 1990: 7.0% (4.9–9.1)). In women, older age (OR: 1.05, 95%CI: 1.03–1.08, p<0.001), diabetes family history (OR: 3.13, 95%CI: 1.92–5.12, p<0.001), higher BMI (OR: 1.44, 95%CI: 1.20–1.82, p = 0.001), better quality housing (OR: 2.08, 95%CI: 1.01–3.04, p = 0.047) and a lower SOC score (≤40) was positively associated with diabetes (OR: 2.57, 95%CI: 1.37–4.80, p = 0.003). Diabetes was not associated with the other psychosocial measures in women or with any psychosocial measure in men. Only older age (OR: 1.05, 95%CI: 1.02–1.08, p = 0.002) and higher BMI (OR: 1.10, 95%CI: 1.04–1.18, p = 0.003) were significantly associated with diabetes in men.

Conclusions

The current high prevalence of diabetes in urban-dwelling South Africans, and the likelihood of further rises given the high rates of IGT and obesity, is concerning. Multi-facetted diabetes prevention strategies are essential to address this burden.     

Achieving secondary prevention low-density lipoprotein particle concentration goals using lipoprotein cholesterol-based data

Background

Epidemiologic studies suggest that LDL particle concentration (LDL-P) may remain elevated at guideline recommended LDL cholesterol goals, representing a source of residual risk. We examined the following seven separate lipid parameters in achieving the LDL-P goal of <1000 nmol/L goal for very high risk secondary prevention: total cholesterol to HDL cholesterol ratio, TC/HDL, <3; a composite of ATP-III very high risk targets, LDL-C<70 mg/dL, non-HDL-C<100 mg/dL and TG<150 mg/dL; a composite of standard secondary risk targets, LDL-C<100, non-HDL-C<130, TG<150; LDL phenotype; HDL-C≥40; TG<150; and TG/HDL-C<3.

Methods

We measured ApoB, ApoAI, ultracentrifugation lipoprotein cholesterol and NMR lipoprotein particle concentration in 148 unselected primary and secondary prevention patients.

Results

TC/HDL-C<3 effectively discriminated subjects by LDL-P goal (F = 84.1, p<10⁻⁶). The ATP-III very high risk composite target (LDL-C<70, nonHDL-C<100, TG<150) was also effective (F = 42.8, p<10⁻⁵). However, the standard secondary prevention composite (LDL-C<100, non-HDL-C<130, TG<150) was also effective but yielded higher LDL-P than the very high risk composite (F = 42.0, p<10⁻⁵) with upper 95% confidence interval of LDL-P less than 1000 nmol/L. TG<150 and TG/HDL-C<3 cutpoints both significantly discriminated subjects but the LDL-P upper 95% confidence intervals fell above goal of 1000 nmol/L (F = 15.8, p = 0.0001 and F = 9.7, p = 0.002 respectively). LDL density phenotype neared significance (F = 2.85, p = 0.094) and the HDL-C cutpoint of 40 mg/dL did not discriminate (F = 0.53, p = 0.47) alone or add discriminatory power to ATP-III targets.

Conclusions

A simple composite of ATP-III very high risk lipoprotein cholesterol based treatment targets or TC/HDL-C ratio <3 most effectively identified subjects meeting the secondary prevention target level of LDL-P<1000 nmol/L, providing a potential alternative to advanced lipid testing in many clinical circumstances.     

NT-proBNP and circulating inflammation markers in prediction of a normal myocardial scintigraphy in patients with symptoms of coronary artery disease

Background

Myocardial perfusion imaging (MPI) can detect myocardial perfusion abnormalities but many examinations are without pathological findings. This study examines whether circulating biomarkers can be used as screening modality prior to MPI.

Methodology/Principal Findings

243 patients with an intermediate risk of CAD or with known CAD with renewed suspicion of ischemia were referred to MPI. Blood samples were analyzed for N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP), YKL-40, IL-6, matrix metalloproteinase 9 (MMP-9) and high sensitive C-reactive protein (hsCRP). Patients with myocardial perfusion defects had elevated levels of NT-proBNP (p<0.0001), YKL-40 (p = 0.03) and IL-6 (p = 0.03) but not of hsCRP (p = 0.58) nor of MMP-9 (p = 0.14). The NT-proBNP increase was observed in both genders (p<0.0001), whereas YKL-40 (p = 0.005) and IL-6 (p = 0.02) were elevated only in men. A NT-proBNP cut off-concentration at 25 ng/l predicted a normal MPI with a negative predictive value >95% regardless of existing CAD.

Conclusions

20-25% of patients suspected of CAD could have been spared a MPI by using a NT-proBNP cut-off concentration at 25 ng/l with a negative predictive value >95%. NT-proBNP has the potential use of being a screening marker of CAD before referral of the patient to MPI.     

Skeletal muscle phosphodiester content relates to body mass and glycemic control

Background

Aging and insulin resistance have been related to reduced mitochondrial function and oxidative stress. Muscular phosphodiesters (PDE) are comprised of metabolites of phospholipid breakdown and may reflect membrane damage. We aimed to test the hypothesis that myocellular PDE are increased in patients with type 2 diabetes (T2D) and correlate inversely with mitochondrial ATP turnover.

Methods

A Cross-sectional study in the Clinical Research Facility of an University hospital was performed. 10 nonobese middle-aged patients with T2D, 10 healthy humans matched for sex, age and physical activity index (CONm) and 18 young healthy humans (CONy) were included. Myocellular PDE and unidirectional flux through ATP synthase (fATP) were measured with ³¹P magnetic resonance spectroscopy (MRS). Intramyocellular (IMCL) and hepatocellular lipid deposition (HCL) were quantified with ¹H MRS. Insulin sensitivity (Rd) was assessed from hyperinsulinemic-euglycemic clamp tests in 10 T2D, 10 CONm and 11 CONy.

Results

During fasting, T2D and CONm had 1.5 fold greater PDE than CONy (2.8±0.2, 2.5±0.2, 1.7±0.1 mmol/l, P = 0.004). Stimulation by insulin did not affect PDE in any group. PDE correlated negatively with Rd (r = −0.552, p<0.005) and fATP (r = −0.396, p<0.05) and positively with age (r = 0.656, p<0.001) and body mass (r = 0.597, p<0.001). PDE also related positively to HbA1c (r = 0.674, p<0.001) and fasting plasma glucose (r = 0.629, p<0.001) within T2D and across all participants.

Conclusions

Muscular PDE concentrations associate with age, lower resting mitochondrial activity and insulin resistance, which is determined mainly by body mass and glycemia.     

The NOD2 single nucleotide polymorphisms rs2066843 and rs2076756 are novel and common Crohn's disease susceptibility gene variants

Background

The aims were to analyze two novel NOD2 variants (rs2066843 and rs2076756) in a large cohort of patients with inflammatory bowel disease and to elucidate phenotypic consequences.

Methodology/Principal Findings

Genomic DNA from 2700 Caucasians including 812 patients with Crohn''s disease (CD), 442 patients with ulcerative colitis (UC), and 1446 healthy controls was analyzed for the NOD2 SNPs rs2066843 and rs2076756 and the three main CD-associated NOD2 variants p.Arg702Trp (rs2066844), p.Gly908Arg (rs2066847), and p.Leu1007fsX1008 (rs2066847). Haplotype and genotype-phenotype analyses were performed. The SNPs rs2066843 (p = 3.01×10⁻⁵, OR 1.48, [95% CI 1.23-1.78]) and rs2076756 (p = 4.01×10⁻⁶; OR 1.54, [95% CI 1.28-1.86]) were significantly associated with CD but not with UC susceptibility. Haplotype analysis revealed a number of significant associations with CD susceptibility with omnibus p values <10⁻¹⁰. The SNPs rs2066843 and rs2076756 were in linkage disequilibrium with each other and with the three main CD-associated NOD2 mutations (D''>0.9). However, in CD, SNPs rs2066843 and rs2076756 were more frequently observed than the other three common NOD2 mutations (minor allele frequencies for rs2066843 and rs2076756: 0.390 and 0.380, respectively). In CD patients homozygous for these novel NOD2 variants, genotype-phenotype analysis revealed higher rates of a penetrating phenotype (rs2076756: p = 0.015) and fistulas (rs2076756: p = 0.015) and significant associations with CD-related surgery (rs2076756: p = 0.003; rs2066843: p = 0.015). However, in multivariate analysis only disease localization (p<2×10⁻¹⁶) and behaviour (p = 0.02) were significantly associated with the need for surgery.

Conclusion/Significance

The NOD2 variants rs2066843 and rs2076756 are novel and common CD susceptibility gene variants.     

Diabetes is a risk factor for pulmonary tuberculosis: a case-control study from Mwanza, Tanzania

Background

Diabetes and TB are associated, and diabetes is increasingly common in low-income countries where tuberculosis (TB) is highly endemic. However, the role of diabetes for TB has not been assessed in populations where HIV is prevalent.

Methods

A case-control study was conducted in an urban population in Tanzania among culture-confirmed pulmonary TB patients and non-TB neighbourhood controls. Participants were tested for diabetes according to WHO guidelines and serum concentrations of acute phase reactants were measured. The association between diabetes and TB, and the role of HIV as an effect modifier, were examined using logistic regression. Since blood glucose levels increase during the acute phase response, we adjusted for elevated serum acute phase reactants.

Results

Among 803 cases and 350 controls the mean (SD) age was 34.8 (11.9) and 33.8 (12.0) years, and the prevalence of diabetes was 16.7% (95% CI: 14.2; 19.4) and 9.4% (6.6; 13.0), respectively. Diabetes was associated with TB (OR 2.2, 95% CI: 1.5; 3.4, p<0.001). However, the association depended on HIV status (interaction, p = 0.01) due to a stronger association among HIV uninfected (OR 4.2, 95% CI: 1.5; 11.6, p = 0.01) compared to HIV infected (OR 0.1, 95% CI: 0.01; 1.8, p = 0.13) after adjusting for age, sex, demographic factors and elevated serum acute phase reactants.

Conclusion

Diabetes is a risk factor for TB in HIV uninfected, whereas the association in HIV infected patients needs further study. The increasing diabetes prevalence may be a threat to TB control.     

Cognitive Dysfunction among HIV Positive and HIV Negative Patients with Psychosis in Uganda

Background

Cognitive impairment is an established phenomenon in HIV infected individuals and patients that have psychosis. However there is need to establish the severity of the impairment if patients are co morbid with both conditions.

Aim

To compare cognitive function among HIV positive individuals and HIV negative individuals with psychosis.

Methods

We recruited patients with psychosis at two national referral hospitals. A standardized demographics questionnaire and psychiatric, physical, and laboratory assessments were conducted. Types of psychosis were diagnosed using the Mini International Neuropsychiatric Inventory-PLUS while cognitive functioning was determined using the Mini mental state examination (MMSE) and a neuropsychological test battery. Follow-up assessments on cognitive function and severity of psychiatric illness were performed at 3 and 6 months. Pairwise comparison and multivariable logistic regression analysis were used to determine the differences between the HIV positive and HIV negative individuals.

Results

There were 156 HIV positive and 322 HIV negative participants. The mean age was 33 years for the HIV positive group and 29 years for the HIV negative group (p<0.001). The HIV positive individuals were almost three times (OR = 2.62 CI 95% 1.69–4.06) more likely to be cognitively impaired on the MMSE as well as the following cognitive tests:- WHO-UCLA Auditory Verbal Learning Test (OR 1.79, 95% CI 1.09–2.92), Verbal Fluency (OR 3.42, 95% CI 2.24–5.24), Color Trails 1 (OR 2.03, 95% CI 1.29–3.02) and Color Trails 2 (OR 3.50 95% 2.00–6.10) all p = 0.01. There was improvement in cognitive function at follow up; however the impairment remained higher for the HIV positive group (p<0.001).

Conclusion

Cognitive impairment in psychosis was worsened by HIV infection. Care plans to minimize the effect of this impairment should be structured for the management of individuals with HIV and psychosis.