Risk factors for penicillin-resistant Streptococcus pneumoniae acquisition in patients in Bangkok.

To identify risk factors for acquisition of penicillin-resistant Streptococcus pneumoniae (PRSP) in patients in Bangkok, using a case-control study, the study included patients with clinical specimens which grew S. pneumoniae during January to December 1997, treated at a teaching hospital in Bangkok. Penicillin susceptibility was determined by E-test and strains with MIC of > 0.1 microg/ml were considered resistant. Cases were the patients who had PRSP, and patients who had penicillin-susceptible S. pneumoniae (PSSP) were controls. The study variables included age 15 years or younger, immunocompromised status, ventilatory support, and antibiotic use or hospitalization within the previous 3 months. There were 73 cases and 51 controls. Their ages were 0 to 87 years, with median age of cases 4 and controls 49 years. Pneumonia was the most common type of infection, being 47% in cases and 45% in controls. Univariate analysis revealed significant association of PRSP acquisition with previous antibiotic use (p<0.0001), age < or = 15 years (p=0.001) and previous hospitalization (p=0.002). Logistic regression analysis in order to adjust for confounding effects showed that the only significant risk factor was previous antibiotic use (OR 18.4; 95% CI 6.2-54.6). The major risk factor for acquisition of PRSP in this study population is recent antibiotic use. Decreased antibiotic use would reduce risk of acquisition of PRSP.     

Inhaled corticosteroid for persistent cough following upper respiratory tract infection

OBJECTIVE: The aim of this study was to determine the clinical effect of inhaled corticosteroid treatment for persistent cough, post upper respiratory tract infection (URTI) in previously healthy individuals, and on bronchial hyperresponsiveness (BHR). METHODOLOGY: This was a prospective, randomized, double-blinded, placebo-controlled study conducted at a university hospital. A total of 30 non-asthmatic, non-smoking patients who were >15 years old and who had persistent post-URTI cough for >3 weeks were assessed by a physical examination, CXR and spirometry, and were allocated to receive inhaled budesonide (400 microg/puff, twice daily) or placebo for 4 weeks. If a patient suffered from sinusitis, it was a requirement that it had been well treated. A symptom score (frequency of cough, frequency of coughing bouts, symptoms associated with cough, night-time cough, frequency of taking medications to relieve cough, and number of medications) was recorded at entry, and after 2 and 4 weeks of treatment. A methacholine challenge test was performed at entry and after 4 weeks of treatment. RESULTS: The mean symptom scores for the treatment group (9.4) and the placebo group (9.8) at baseline were not significantly different (P=0.79), and no differences were found between the groups after week 2 and week 4 of treatment (3.93 and 4.27 vs 2.26 and 2.66, P=0.29). The mean change in symptom scores from baseline to week 2 and to week 4 of treatment were also not different between groups (5.93 and 5.6 vs 7.00 and 7.58, P=0.23). No difference between groups was found in the mean changes in FEV(1), FVC, and FEF(25--75%) after 4 weeks of treatment. A positive bronchial provocation test occurred in three patients (10%) but these were borderline. CONCLUSION: Inhaled corticosteroid is ineffective in treating persistent post-URTI cough in previously healthy individuals.     

Prevalence of Vitamin D insufficiency and low bone mineral density in elderly Thai nursing home residents

ABSTRACT: BACKGROUND: Numerous emerging data from research on osteoporosis among Asians found differences from Caucasians. Therefore, the aim of this study was to determine the prevalence of vitamin D insufficiency and osteoporosis in elderly participants from two nursing homes in Thailand, a country located near the equator. METHODS: The subjects of this cross-sectional study comprised 93 elderly Thai women who were living in institutional long-term nursing homes for the aged. Demographic data, daily food and calcium intake, physical activity, and sunlight exposure were measured. Lumbar spine and femoral neck bone mineral density (BMD) and biochemical levels including serum 25 hydroxyvitamin D [25(OH)D] and bone turnover markers were assessed. Vitamin D insufficiency was defined as 25(OH)D level < 70 nmol/l. RESULTS: The mean age of subjects was 75.2 +/- 6.0 (SD) years. Dietary calcium intake was low (322 +/- 158 mg/day) The mean 25(OH)D level was 64.3 +/- 14.9 nmol/L and the prevalence of vitamin D insufficiency was 38.7 % (95 % CI: 28.8 %, 49.4 %). There was no correlation between serum 25(OH)D concentrations and age (r = -.11, p = 0.3). The mean BMD of lumbar spine and femoral neck were 0.92 +/- 0.19 and 0.65 +/- 0.10 g/cm2, respectively. Nearly a half of the subjects had osteopenia (44.1 %, 95 % CI: 33.8 %, 54.8 %) and osteoporosis (47.3 %, 95 % CI: 36.9 %, 57.9 %). Circulating C-terminal telopeptide of type I collagen (CTx) level correlated significantly with both lumbar spine (r = -0.26, p = 0.01) and femoral neck BMD (r = -0.25, p = 0.02). CONCLUSIONS: More than one-third of Thai elderly women residing in nursing homes had vitamin D insufficiency. Almost all nursing home residents had osteoporosis and/or osteopenia.     

Causal association pathways between fetuin-A and kidney function: a mediation analysis

ObjectiveBody mass index (BMI), uric acid, diabetes mellitus, and hypertension are risk factors for reduced kidney function and are associated with fetuin-A levels, but their causal pathways remain unclear. The objective of this study was to investigate this knowledge gap.MethodsA repeated cross-sectional design was used to assess causal pathway effects of fetuin-A on the estimated glomerular filtration rate (eGFR), which is mediated through BMI, uric acid, diabetes mellitus, and hypertension.ResultsAmong 2305 participants, the mean eGFR at baseline decreased from 98.7 ± 23.6 mL/minute/1.73 m² in 2009 to 92.4 ± 22.9 mL/minute/1.73 m² in 2014. Fetuin-A was significantly associated with eGFR , suggesting that increasing fetuin-A levels predict a decrease in eGFR. Additionally, the indirect effect of fetuin-A on eGFR, as assessed through BMI, was also significant. The effects of fetuin-A on eGFR through other mediation pathways showed variable results.ConclusionsOur study revealed a possible role of fetuin-A in the etiology of declining renal function through mediating body mass index, uric acid, diabetes mellitus, and hypertension via complex causal pathways. Further studies to clarify these mediated effects are recommended.     

Developing and validating of Ramathibodi Appendicitis Score (RAMA-AS) for diagnosis of appendicitis in suspected appendicitis patients

Background

Diagnosis of appendicitis is still clinically challenging where resources are limited. The purpose of this study was to develop and externally validate Ramathibodi Appendicitis Score (RAMA-AS) in aiding diagnosis of appendicitis.

Methods

A two-phase cross-sectional study (i.e., derivation and validation) was conducted at Ramathibodi Hospital (for derivation) and at Thammasat University Hospital and Chaiyaphum Hospital (for validation). Patients with abdominal pain and suspected of having appendicitis were enrolled. Multiple logistic regression was applied to develop a parsimonious model. Calibration and discrimination performances were assessed. In addition, our RAMA-AS was compared with Alvarado’s score performances using ROC curve analysis.

Results

The RAMA-AS consisted of three domains with seven predictors including symptoms (i.e., progression of pain, aggravation of pain, and migration of pain), signs (i.e., fever and rebound tenderness), and laboratory tests (i.e., white blood cell count (WBC) and neutrophil). The model fitted well with data, and it performed better discrimination than the Alvarado score with C-statistics of 0.842 (95% CI 0.804, 0.881) versus 0.760 (0.710, 0.810). Internal validation by bootstrap yielded Sommer’s D of 0.686 (0.608, 0.763) and C-statistics of 0.848 (0.846, 0.849). The C-statistics of two external validations were 0.853 (0.791, 0.915) and 0.813 (0.736, 0.892) with fair calibrations.

Conclusion

RAMA-AS should be a useful tool for aiding diagnosis of appendicitis with good calibration and discrimination performances.

     

Different impacts of hepatitis B virus and hepatitis C virus on the outcome of kidney transplantation

Previous studies had shown that HBV and HCV infections lead to increased morbidity and mortality after kidney transplantation when compared with the nonhepatitis group. However, few studies have compared the impact among a population with a high prevalence of HBV and HCV infections. We studied the outcomes of 346 recipients including 23 HBsAg (+) patients (6.6%; group 1), 22 patients with anti-HCV+ (6.3%, group 2), and 301 nonhepatitis patients (group 3) in a single center during a 6-year period. No patient had evidence of precirrhosis or cirrhosis before transplant. The primary end point was graft and patient survival rates. Secondary end point was the rate of progression of chronic allograft, nephropathy. The median follow-up time was 3.7 (0.5-6.8) years. Five-year actuarial graft survival was 80% for group 1, 61% for group 2, and 88 % for group 3 (P = .005). Cox regression showed HCV (hazards ratio 2.96; 95% CI = 1.03-8.51) and acute rejection episode (HR 3.01; 95%CI = 1.86-4.87) to be significant predictors of graft survival. Actuarial 5-year patient survival of group 1 was significantly lower than group 2 or group 3 (79 % vs 89% and 96%; P = .003). Cox regression revealed that the hazards ratio of HBV for death was 7.63 (95%CI = 1.88-30.86; P = .004). In contrast, HCV infection had no significant effect on patient survival (HR 1.59; 95%CI = 0.28-9.02). The rate of chronic allograft nephropathy progression was significantly faster in group 1 (-6.74 mL/min per year) and group 2 (-6.14 mL/min per year) than the controls. We concluded that HBV infection decreased patient survival earlier than HCV and that HCV decreased graft survival more significantly than HBV. Both HBV and HCV were associated with rapid progression of chronic allograft nephropathy. HBV was the strongest risk factor for mortality compared with HCV, with acute rejection episode, with diabetes mellitus, or other hazardous factors.     

Relationship between hypercoagulable state and erythrocyte phosphatidylserine exposure in splenectomized haemoglobin E/beta-thalassaemic patients

Small pulmonary arterial thromboses can occur following splenectomy of patients with haemoglobin E/beta-thalassaemia (Hb E/beta-thal). We compared plasma markers of coagulation activation in vivo and red blood cell (RBC) markers of procoagulant activity in 15 Hb E/beta-thal patients who were not splenectomized (NS), 15 who had been splenectomized (S), and 15 normal controls (NC). Levels of plasma thrombin-antithrombin III complex (TAT) were significantly higher in the S group than in either the NS or the NC groups, and levels of prothrombin fragment 1.2 (F 1.2) were significantly higher in the S than in the NC group. Diluted Russell's viper venom clotting times were significantly shorter when RBCs from group S patients were added to the assay compared with RBCs from the NC group. Phosphatidylserine (PS) expression (% of annexin V-positive RBCs) on the outer leaflet of RBC membrane of both 'larger'- and 'smaller'-sized RBCs was significantly higher for the S than the NC group. The RBC PS expression of the S and the NS groups, respectively, accounted for 25 x 3% (P = 0 x 174) and 6.3% (P = 0 x 675) of the variation in plasma TAT levels. Our findings indicated that, when compared with NC, splenectomized patients with Hb E/beta-thal were in a chronic low-grade hypercoagulable state associated with increased numbers of circulating PS exposed RBCs. This condition may have a role in the risk of these patients for pulmonary arterial thromboses.     

Association between phosphodiesterase 4D gene and ischaemic stroke

Background

An association between the phosphodiesterase 4D (PDE4D) gene and risk of ischaemic stroke in an Icelandic population has been suggested by the deCODE group.

Methods

A case–control study of 151 hospitalised patients with first‐ever ischaemic stroke and 164 randomly selected age‐matched and sex‐matched community controls was conducted. PDE4D genotypes for the six single‐nucleotide polymorphisms (SNPs) previously reported to be independently associated with stroke were determined, common haplotypes were inferred using the expectation‐maximisation algorithm, and SNP and haplotype associations with stroke were examined. A meta‐analysis of published studies examining the association between PDE4D and stroke was also carried out.

Results

Our study of Australian patients with stroke showed an independent association between ischaemic stroke and PDE4D SNP 89 (CC: odds ratio (OR) 5.55, 95% confidence interval (CI) 1.02 to 30.19; CA: OR 1.68, 95% CI 0.96 to 2.96; AA: OR 1 (reference)), SNP 87 (CC: OR 2.13, 95% CI 1.08 to 4.20; TC: OR 1.64, 95% CI 0.89 to 3.00; TT: OR 1 (reference)) and SNP 83 (TT: OR 2.16, 95% CI 1.08 to 4.32; TC: OR 1.37, 95% CI 0.77 to 2.43; CC: OR 1 (reference)), and between ischaemic stroke and PDE4D haplotypes at SNP 89–87–83 (A–C–C: OR 2.13, 95% CI 1.15 to 3.96; C–C–T: OR 2.25, 95% CI 1.29 to 3.92), but no association between ischaemic stroke and PDE4D SNP 56, SNP 45 or SNP 41, or with PDE4D haplotypes at SNP 56–45–41. A meta‐analysis of nine case–control studies (including our current results) of 3808 stroke cases and 4377 controls confirmed a significant association between stroke and PDE SNP 87 (pooled p = 0.002), SNP 83 (0.003) and SNP 41 (0.003). However, there was statistical heterogeneity (p<0.1) among the studies in the direction of association for each of the individual SNPs tested.

Conclusions

Our results and the pooled analyses from all the studies indicate a strong association between PDE4D and ischaemic stroke. This strengthens the evidence that PDE4D plays a key part in the pathogenesis of ischaemic stroke. Heterogeneity among the studies in the direction of association between individual SNPs and stroke suggests that the SNPs tested are in linkage disequilibrium with the causal allele(s).Stroke is one of the leading causes of death and long‐term disability worldwide. About 80% of strokes are ischaemic in origin, most commonly caused by atherosclerosis.¹ By recognising and treating individuals and populations at risk, the burden of stroke can be reduced. As only about two thirds of ischaemic strokes seem to be attributable to known environmental risk factors,² there are likely to be other as yet unknown causal risk factors for ischaemic stroke.In recent years, there have been several reports of genetic polymorphisms that are associated with an increased (or decreased) risk of stroke.^3,4,5,6 In 2002, the deCODE group published the results of a genomewide screen for stroke susceptibility genes in Iceland.⁷ Among 260 phosphodiesterase 4D (PDE4D) single‐nucleotide polymorphisms (SNPs) examined, six were significantly associated with stroke after adjustment for multiple comparisons.To establish a causal association between the PDE4D gene and stroke, the results of the study by the deCODE group need to be validated externally in independent datasets. Recently published studies from different populations^{8,9,10,11,12,13,14,15} provide apparently conflicting evidence on the association between the PDE4D gene and stroke. We explored the relationship between PDE4D genotype and ischaemic stroke in a case–control study of consecutive Australian patients admitted to hospital with ischaemic stroke and a similar number of randomly selected community controls. We determined PDE4D genotypes among patients and controls for the six SNPs found by the deCODE group to be markedly associated with stroke (SNP 89, SNP 87, SNP 83, SNP 56, SNP 45 and SNP 41) and examined the association between these SNPs and PDE4D haplotypes and ischaemic stroke. We also carried out a meta‐analysis of published studies to explore the consistency of the association between PDE4D and stroke.