Grantham Hospital

OBJECTIVE: Our study examined the stress level and psychological distress of severe acute respiratory syndrome (SARS) survivors 1 year after the outbreak. METHOD: During the SARS outbreak in 2003, we used the 10-item Perceived Stress Scale (PSS-10) to assess SARS survivors treated in 2 major hospitals (non-health care workers, n = 49; health care workers, n = 30). We invited SARS survivors from the same hospitals (non-health care workers, n = 63; health care workers, n = 33) to complete the PSS-10 again in 2004. At that time, they were also asked to complete the General Health Questionnaire (GHQ-12) and measures of depression, anxiety, and posttraumatic symptoms. PSS-10 scores were also obtained from matched community control subjects during the outbreak (n = 145) and again in 2004 (n = 112). RESULTS: SARS survivors had higher stress levels during the outbreak, compared with control subjects (PSS-10 scores = 19.8 and 17.9, respectively; P < 0.01), and this persisted 1 year later (PSS-10 scores = 19.9 and 17.3, respectively; P < 0.01) without signs of decrease. In 2004, SARS survivors also showed worrying levels of depression, anxiety, and posttraumatic symptoms. An alarming proportion (64%) scored above the GHQ-12 cut-off that suggests psychiatric morbidity. During the outbreak, health care worker SARS survivors had stress levels similar to those of non-health care workers, but health care workers showed significantly higher stress levels in 2004 (PSS-10 score = 22.8, compared with PSS-10 score = 18.4; P < 0.05) and had higher depression, anxiety, posttraumatic symptoms, and GHQ-12 scores. CONCLUSIONS: One year after the outbreak, SARS survivors still had elevated stress levels and worrying levels of psychological distress. The situation of health care worker SARS survivors is particularly worrying. The long-term psychological implications of infectious diseases should not be ignored. Mental health services could play an important role in rehabilitation.

BACKGROUND: The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene resulting from the chromosome inversion inv(2)(p21;p23) recently was identified in nonsmall cell lung cancer (NSCLC). The authors of this study investigated the frequency, genetic and clinicopathologic profiles of EML4-ALK in Chinese patients with NSCLC. METHODS: EML4-ALK was investigated in 266 resected primary NSCLC, including adenocarcinomas (AD), lymphoepithelioma-like carcinomas, squamous cell carcinomas, mucoepidermoid carcinomas, and adenosquamous carcinomas, by reverse transcriptase-polymerase chain reaction and was verified by sequencing. EML4-ALK protein expression was studied by immunohistochemistry. RESULTS: Thirteen tumors (4.9%) had EML4-ALK comprising 4 fusion transcript variants with fusion of the variable segments from 5' EML4 to 3' ALK and with preservation of the ALK kinase domain. The most common variant consisted of 8 tumors with variant 3 that involved EML4 exon 6. The others included 2 tumors with variant 1 (exon 13), 2 tumors with variant 2 (exon 20), and 1 tumor with the novel variant 5 (exon 18). There were 11 ADs and 2 unusual carcinomas with mixed squamous and glandular components. Immunohistochemistry demonstrated diffuse ALK fusion proteins in the tumor cell cytoplasm. EML4-ALK was associated with nonsmokers (P = .009). Tumors with the fusion gene had the wild-type epidermal growth factor receptor (EGFR) (P = .001) and v-Ki-ras2/Kirsten rat sarcoma viral oncogene homolog (KRAS) genes. Patients who had EML4-ALK-positive AD had a younger median age (P = .018) compared with patients who did not have the fusion gene. CONCLUSIONS: The EML4-ALK fusion gene was present in various histologic types of NSCLC. It occurred in mutual exclusion to EGFR and KRAS mutations and was associated with nonsmokers. The authors concluded that EML4-ALK may be useful for predicting the potential response to ALK inhibitors as a therapeutic option for patients with lung cancer.

BACKGROUND: Patients with heart failure are frequently hospitalized for fluid overload. A reliable method for chronic monitoring of fluid status is therefore desirable. We evaluated an implantable system capable of measuring intrathoracic impedance to identify potential fluid overload before heart failure hospitalization and to determine the correlation between intrathoracic impedance and standard measures of fluid status during hospitalization. METHODS AND RESULTS: Thirty-three patients with NYHA class III and IV heart failure were implanted with a special pacemaker in the left pectoral region and a defibrillation lead in the right ventricle. Intrathoracic impedance was regularly measured and recorded between the lead and the pacemaker case. During hospitalizations, pulmonary capillary wedge pressure and fluid status were monitored. Ten patients were hospitalized for fluid overload 25 times over 20.7+/-8.4 months. Intrathoracic impedance decreased before each admission by an average of 12.3+/-5.3% (P<0.001) over an average of 18.3+/-10.1 days. Impedance reduction began 15.3+/-10.6 days (P<0.001) before the onset of worsening symptoms. There was an inverse correlation between intrathoracic impedance and pulmonary capillary wedge pressure (r=-0.61, P<0.001) and between intrathoracic impedance and net fluid loss (r=-0.70, P<0.001) during hospitalization. Automated detection of impedance decreases was 76.9% sensitive in detecting hospitalization for fluid overload, with 1.5 false-positive (threshold crossing without hospitalization) detections per patient-year of follow-up. CONCLUSIONS: Intrathoracic impedance is inversely correlated with pulmonary capillary wedge pressure and fluid balance and decreased before the onset of patient symptoms and before hospital admission for fluid overload. Regular monitoring of impedance may provide early warning of impending decompensation and diagnostic information for titration of medication.

BACKGROUND: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. METHODS AND FINDINGS: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]). CONCLUSIONS: In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment. Please see later in the article for the Editors' Summary.

BACKGROUND: Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10). Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10) from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells. METHODS: We used quantitative RT-PCR and ELISA to compare the profile of cytokine and chemokine gene expression induced by H5N1 viruses A/HK/483/97 (H5N1/97), A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04) with that of human H1N1 virus in human primary alveolar and bronchial epithelial cells in vitro. RESULTS: We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04) appeared to be even more potent at inducing IP-10 than H5N1/97 virus. CONCLUSION: The H5N1/97 and H5N1/04 subtype influenza A viruses are more potent inducers of proinflammatory cytokines and chemokines in primary human respiratory epithelial cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines may be relevant to the pathogenesis of human H5N1 disease.

CONTEXT: The antioxidant acetylcysteine prevents acute contrast nephrotoxicity in patients with impaired renal function who undergo computed tomography scanning. However, its role in coronary angiography is unclear. OBJECTIVE: To determine whether oral acetylcysteine prevents acute deterioration in renal function in patients with moderate renal insufficiency who undergo elective coronary angiography. DESIGN AND SETTING: Prospective, randomized, double-blind, placebo-controlled trial conducted from May 2000 to December 2001 at the Grantham Hospital at the University of Hong Kong. PARTICIPANTS: Two hundred Chinese patients aged mean (SD) 68 (6.5) years with stable moderate renal insufficiency (creatinine clearance <60 mL/min [1.00 mL/s]) who were undergoing elective coronary angiography with or without intervention. INTERVENTION: Participants were randomly assigned to receive oral acetylcysteine(600 mg twice per day; n = 102) or matching placebo tablets (n = 98) on the day before and the day of angiography. All patients received low-osmolality contrast agent. MAIN OUTCOME MEASURES: Occurrence of more than a 25% increase in serum creatinine level within 48 hours after contrast administration; change in creatinine clearance and serum creatinine level. RESULTS: Twelve control patients (12%) and 4 acetylcysteine patients (4%) developed a more than 25% increase in serum creatinine level within 48 hours after contrast administration (relative risk, 0.32; 95% confidence interval [CI], 0.10-0.96; P =.03). Serum creatinine was lower in the acetylcysteine group (1.22 mg/dL [107.8 micromol/L]; 95% CI, 1.11-1.33 mg/dL vs 1.38 mg/dL [122.9 micromol/L]; 95% CI, 1.27-1.49 mg/dL; P =.006) during the first 48 hours after angiography. Acetylcysteine treatment significantly increased creatinine clearance from 44.8 mL/min (0.75 mL/s) (95% CI, 42.7-47.6 mL/min) to 58.9 mL/min (0.98 mL/s) (95% CI, 55.6-62.3 mL/min) 2 days after the contrast administration (P<.001). The increase was not significant in the control group (from 42.1 to 44.1 mL/min [0.70 to 0.74 mL/s]; P =.15). The benefit of acetylcysteine was consistent among various patient subgroups and persistent for at least 7 days. There were no major treatment-related adverse events. CONCLUSION: Acetylcysteine protects patients with moderate chronic renal insufficiency from contrast-induced deterioration in renal function after coronary angiographic procedures, with minimal adverse effects and at a low cost.

PURPOSE: This study evaluated the mutational profile of epidermal growth factor receptor (EGFR) and KRAS in non-small cell lung cancers in Hong Kong and determined their relation with smoking history and other clinicopathologic features. EXPERIMENTAL DESIGN: Mutational profile of exons 18 to 21 of EGFR and codons 12, 13, and 61 of KRAS were determined in 215 adenocarcinomas, 15 squamous cell (SCC), and 11 EBV-associated lymphoepithelioma-like carcinomas (LELC). RESULTS: EGFR mutations were prevalent in adenocarcinomas (115 of 215), uncommon in LELC (1 of 11), and not found in SCC (P < 0.001). Among adenocarcinomas, mutations were associated with nonsmokers (83 of 111; P < 0.001), female gender (87 of 131; P < 0.001), and well-differentiated (55 of 86) compared with poorly differentiated (11 of 41) tumors (P < 0.001). Decreasing mutation rates with increasing direct tobacco exposure was observed, with 74.8% (83 of 111) in nonsmokers, 61.1% (11 of 18) in passive, 35.7% (10 of 28) in previous, and 19.0% (11 of 58) in current smokers. There were 53% amino acid substitutions, 43% in-frame deletions, and 4% insertions. Complex patterns with 13% double mutations, including five novel substitutions, were observed. For KRAS, mutations occurred in adenocarcinoma only (21 of 215) and were associated with smokers (11 of 58; P = 0.003), men (14 of 84; P = 0.009) and poorly differentiated (7 of 41) compared with well-differentiated (4 of 86) tumors (P = 0.037). EGFR and KRAS mutations occurred in mutually exclusive tumors. Regression analysis showed smoking history was the significant determinant for both mutations, whereas gender was a confounding factor. CONCLUSION: This study shows EGFR mutations are prevalent in lung adenocarcinoma and suggests that it plays an increasing oncogenic role with decreasing direct tobacco damage.

Tuberculosis (TB), smoking, HIV and chronic obstructive pulmonary disease (COPD) are burgeoning epidemics in developing countries. The link between TB and HIV is well established. Less well recognised is the strong relationship between tobacco smoking and the development and natural history of TB. These associations are of considerable relevance to public health and disease outcomes in individuals with TB. Moreover, tobacco smoking, a modifiable risk factor, is associated with poorer outcomes in HIV-associated opportunistic infections, of which TB is the commonest in developing countries. It is now also becoming clear that TB, like tobacco smoke, besides its known consequences of bronchiectasis and other pulmonary morbidity, is also a significant risk factor for the development of COPD. Thus, there is a deleterious and synergistic interaction between TB, HIV, tobacco smoking and COPD in a large proportion of the world's population. Further work, specifically mechanistic and epidemiological studies, is required to clarify the role of tobacco smoke on the progression of TB and HIV infection, and to assess the impact of smoking cessation interventions. These interactions deserve urgent attention and have major implications for coordinated public health planning and policy recommendations in the developing world.

Diabetes mellitus is associated with tuberculosis. A cohort of 42,116 clients aged 65 years or more, enrolled at 18 Elderly Health Service centers in Hong Kong in 2000, were followed up prospectively through the territory-wide tuberculosis registry for development of tuberculosis from 3 months after enrollment to December 31, 2005, by use of their identity card numbers as unique identifier. The effects of diabetes mellitus and diabetic control on tuberculosis risk were assessed with adjustment for sociodemographic and other background variables. Diabetes mellitus was associated with a modest increase in the risk of active, culture-confirmed, and pulmonary (with or without extrapulmonary involvement) but not extrapulmonary (with or without pulmonary involvement) tuberculosis, with adjusted hazard ratios of 1.77 (95% confidence interval: 1.41, 2.24), 1.91 (95% confidence interval: 1.45, 2.52), 1.89 (95% confidence interval: 1.48, 2.42), and 1.00 (95% confidence interval: 0.54, 1.86), respectively. Diabetic subjects with hemoglobin A1c <7% at enrollment were not at increased risk. Among diabetic subjects, higher risks of active, culture-confirmed, and pulmonary but not extrapulmonary tuberculosis were observed with baseline hemoglobin A1c > or =7% (vs. <7%), with adjusted hazard ratios of 3.11 (95% confidence interval: 1.63, 5.92), 3.08 (95% confidence interval: 1.44, 6.57), 3.63 (95% confidence interval: 1.79, 7.33), and 0.77 (95% confidence interval: 0.18, 3.35), respectively.

Isoniazid, pyrazinamide and rifampicin have hepatotoxic potential, and can lead to such reactions during antituberculosis chemotherapy. Most of the hepatotoxic reactions are dose-related; some are, however, caused by drug hypersensitivity. The immunogenetics of antituberculosis drug-induced hepatotoxicity, especially inclusive of acetylaor phenotype polymorphism, have been increasingly unravelled. Other principal clinical risk factors for hepatotoxicity are old age, malnutrition, alcoholism, HIV infection, as well as chronic hepatitis B and C infections. Drug-induced hepatic dysfunction usually occurs within the initial few weeks of the intensive phase of antituberculosis chemotherapy. Vigilant clinical (including patient education on symptoms of hepatitis) and biochemical monitoring are mandatory to improve the outcomes of patients with drug-induced hepatotoxicity during antituberculosis chemotherapy. Some fluoroquinolones like ofloxacin/levofloxacin may have a role in constituting non-hepatotoxic drug regimens for management of tuberculosis (TB) in the presence of hepatic dysfunction. Isoniazid administration is currently the standard therapy for latent TB infection. Rifamycins like rifampicin or rifapentine, alone or in combination with isoniazid, may also be considered as alternatives, pending accumulation of further clinical data. During treatment of latent TB infection, regular follow up is essential to ensure adherence to therapy and facilitate clinical monitoring for hepatic dysfunction. Monitoring of liver chemistry is also required for those patients at risk of drug-induced hepatotoxicity.

Liver toxicity is a common side effect of antituberculosis (anti-TB) drugs. We studied the differences in liver dysfunction observed during anti-TB treatment between hepatitis B virus carriers (HBV) and noncarriers. Three hundred twenty-four patients on anti-TB drugs were recruited and followed up for 1 year. Forty-three patients with HBV and 276 non-HBV patients were included for analysis. Liver function tests and viral markers were monitored monthly. Liver biopsy was requested whenever the alanine transaminase (ALT) was persistently abnormal. Eighty-six HBV carriers who were not given anti-TB drugs were chosen as a second control and evaluated prospectively. The incidence of liver dysfunction was significantly higher in HBV carriers given anti-TB drugs (34.9%) when compared to noncarriers (9.4%, P <.001) and with HBV carriers not given anti-TB drugs (8.1%, P <.001). For patients given anti-TB drugs, HBV carriers who developed liver dysfunction were younger (P =.011) and had more severe liver injury compared with noncarriers (P =.008). By multiple logistic regression analysis, age (P =.002) and hepatitis B infection (P <.001) were the only 2 significant risk factors for hepatotoxicity related to anti-TB therapy.

Nicotine and its derivatives, by binding to nicotinic acetylcholine receptors (nAChR) on bronchial epithelial cells, can regulate cellular proliferation and apoptosis via activating the Akt pathway. Delineation of nAChR subtypes in non-small-cell lung cancers (NSCLC) may provide information for prevention or therapeutic targeting. Expression of nAChR subunit genes in 66 resected primary NSCLCs, 7 histologically non-involved lung tissues, 13 NSCLC cell lines, and 6 human bronchial epithelial cell lines (HBEC) was analyzed with quantitative PCR and microarray analysis. Five nonmalignant HBECs were exposed to nicotine in vitro to study the variation of nAChR subunit gene expression with nicotine exposure and removal. NSCLCs from nonsmokers showed higher expression of nAChR alpha6 (P < 0.001) and beta3 (P = 0.007) subunit genes than those from smokers, adjusted for gender. In addition, nAChR alpha4 (P < 0.001) and beta4 (P = 0.029) subunit gene expression showed significant difference between NSCLCs and normal lung. Using Affymetrix GeneChip U133 Sets, 65 differentially expressed genes associated with NSCLC nonsmoking nAChR alpha6beta3 phenotype were identified, which gave high sensitivity and specificity of prediction. nAChR alpha1, alpha5, and alpha7 showed significant reversible changes in expression levels in HBECs upon nicotine exposure. We conclude that between NSCLCs from smokers and nonsmokers, different nAChR subunit gene expression patterns were found, and a 65-gene expression signature was associated with nonsmoking nAChR alpha6beta3 expression. Finally, nicotine exposure in HBECs resulted in reversible differences in nAChR subunit gene expression. These results further implicate nicotine in bronchial carcinogenesis and suggest targeting nAChRs for prevention and therapy in lung cancer.

OBJECTIVE: To examine the effects of home-based transitional palliative care for patients with end-stage heart failure (ESHF) after hospital discharge. METHODS: This was a randomised controlled trial conducted in three hospitals in Hong Kong. The recruited subjects were patients with ESHF who had been discharged home from hospitals and referred for palliative service, and who met the specified inclusion criteria. The interventions consisted of weekly home visits/telephone calls in the first 4 weeks then monthly follow-up, provided by a nurse case manager supported by a multidisciplinary team. The primary outcome measures were any readmission and count of readmissions within 4 and 12 weeks after index discharge, compared using χ(2) tests and Poisson regression, respectively. Secondarily, change in symptoms over time between control and intervention groups were evaluated using generalised estimating equation analyses of data collected using the Edmonton Symptom Assessment Scale (ESAS). RESULTS: The intervention group (n=43) had a significantly lower readmission rate than the control group (n=41) at 12 weeks (intervention 33.6% vs control 61.0% χ(2)=6.8, p=0.009). The mean number (SE) of readmissions for the intervention and control groups was, respectively, 0.42 (0.10) and 1.10 (0.16) and the difference was significant (p=0.001). The relative risk (CI) for 12-week readmissions for the intervention group was 0.55 (0.35 to 0.88). There was no significant difference in readmissions between groups at 4 weeks. However, when compared with the control group, the intervention group experienced significantly higher clinical improvement in depression (45.9% vs 16.1%, p<0.05), dyspnoea (62.2% vs 29.0%, p<0.05) and total ESAS score (73.0% vs 41.4%, p<0.05) at 4 weeks. There were significant differences between groups in changes over time in quality of life (QOL) measured by McGill QOL (p<0.05) and chronic HF (p<0.01) questionnaires. CONCLUSIONS: This study provides evidence of the effectiveness of a postdischarge transitional care palliative programme in reducing readmissions and improving symptom control among patients with ESHF. TRIAL REGISTRATION NUMBER: HKCTR-1562; Results.

BACKGROUND: Obesity is increasingly prevalent in both developed and developing areas. Although undernutrition is well associated with tuberculosis, few studies have systematically examined the association with obesity. Method A cohort of 42 116 individuals 65 years or older enrolled at 18 health centers for elderly patients in Hong Kong, China (which has a tuberculosis incidence of approximately 90 per 100,000 population), in 2000 were followed up prospectively through the territory-wide tuberculosis registry for the development of active tuberculosis from 3 months after enrollment until December 31, 2005, using the identity card number as the unique identifier. The association with body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters), as categorized by the Asian standards, was assessed with the control of other baseline characteristics. RESULTS: Obese (BMI>or=30) and overweight (BMI, 25 to <30) individuals were at significantly lower risks of developing active tuberculosis than normal-weight individuals (BMI, 18.5 to <25), with hazard ratios (95% confidence intervals) of 0.36 (0.20-0.66) and 0.55 (0.44-0.70), respectively, after adjustment for baseline demographic, social, and clinical variables. An inverse linear association was observed predominantly for pulmonary but not extrapulmonary tuberculosis. This association persisted after controlling for potential confounders or excluding individuals with known tuberculosis risk factors. CONCLUSIONS: Obesity is associated with a lower risk of active pulmonary tuberculosis in the older population of Hong Kong. The presence of such a strong but selective association across the whole spectrum of BMI could have major biological, clinical, and/or epidemiological implications. Further studies are indicated to explore the underlying mechanisms, potential clinical utilities, and possible epidemiological consequences.

BACKGROUND: Atrial fibrillation (AF) is common after coronary artery bypass surgery (CABG) and results in prolonged hospitalization. The purpose of this study was to evaluate the efficacy of biatrial pacing in preventing post-CABG AF compared with single-site atrial pacing. METHODS AND RESULTS: A total of 132 patients who had no history of AF and who underwent CABG were randomized to 1 of the following 4 groups: biatrial pacing (BiA), left atrial pacing (LA), right atrial pacing (RA), or no pacing (control) in postoperative period. Overdrive atrial pacing was performed for 5 days. The incidence of AF was significantly reduced in the BiA group (12.5%) compared with the other 3 groups (LA, 36.4%; RA, 33.3%; control, 41. 9%; P<0.05). The mean length of hospital stay was significantly reduced in the BiA group. At baseline, the mean P-wave duration (P(dur)) and dispersion (P(dis)) were not prolonged. BiA pacing resulted in the most significant percentage of reduction in P(dis) when compared with the LA or RA groups (BiA, 42+/-8%; LA, 13+/-6%; RA, 10+/-9%; P<0.05 for BiA versus LA or RA). No significant differences existed in mean P(dur) and P(dis) between patients who developed AF and those who remained in sinus rhythm at baseline. However, only those patients who remained in sinus rhythm had a significant reduction in mean P(dur) and P(dis) after pacing therapy. CONCLUSIONS: Biatrial overdrive pacing is more effective in preventing post-CABG AF than single-site atrial pacing; this therapy also results in a shortened hospital stay. The overall reduction in atrial activation time with BiA pacing was reflected in the reduction in P(dis).

BACKGROUND: The cardiovascular risk of individuals who are born small as a result of prematurity remains controversial. Given the previous findings of stiffer peripheral conduit arteries in growth restricted donor twins in twin-twin transfusion syndrome regardless of gestational age, we hypothesised that among children born preterm, only those with intrauterine growth retardation are predisposed to an increase in cardiovascular risks. AIM: To compare brachioradial arterial stiffness and systemic blood pressure (BP) among children born preterm and small for gestational age (group 1, n = 15), those born preterm but having birth weight appropriate for gestational age (group 2, n = 36), and those born at term with birth weight appropriate for gestational age (group 3, n = 35). METHODS: Systemic BP was measured by an automated device (Dinamap), while stiffness of the brachioradial arterial segment was assessed by measuring pulse wave velocity (PWV). The birth weight was adjusted for gestational age and expressed as a z score for analysis. RESULTS: The 86 children were studied at a mean (SD) age of 8.2 (1.7) years. Subjects from group 1, who were born at 32.3 (2.0) weeks' gestation had a significantly lower z score of birth weight (-2.29 (0.63), p<0.001), compared with those from groups 2 and 3. They had a significantly higher mean blood pressure (p<0.001) and their diastolic blood pressure also tended to be higher (p = 0.07). Likewise, their brachioradial PWV, and hence arterial stiffness, was the highest of the three groups (p<0.001). While subjects from group 2 were similarly born preterm, their PWV was not significantly different from that of group 3 subjects (p = 1.00) and likewise their z score of birth weight did not differ (-0.01 (0.71) v -0.04 (1.1), p = 1.00). Brachioradial PWV correlated significantly with systolic (r = 0.31, p = 0.004), diastolic (r = 0.38, p<0.001), and mean (0.47, p<0.001) BP, and with z score of birth weight (r = -0.43, p<0.001). Multiple linear regression identified mean BP and z score of birth weight as significant determinants of PWV. CONCLUSION: The findings of the present study support the hypothesis that among children born preterm, only those with intrauterine growth retardation are disadvantaged as a result of increase in systemic arterial stiffness and mean blood pressure.

A cohort of 42,655 clients that were first registered with the Elderly Health Service in 2000 were followed prospectively through the tuberculosis (TB) notification registry until the end of 2002. A total of 286 active TB cases (186 culture confirmed) were identified. The annual TB notification rates were 735, 427, and 174 per 100,000 among current smokers, ex-smokers, and never-smokers, respectively (p < 0.001). The trend in TB risk persisted after the control of background characteristics using Cox proportional hazards analysis (adjusted hazard ratios [HRs]: 2.63, 1.41, and 1, p < 0.001). In comparison with never-smokers, current smokers had an excess risk of pulmonary TB (adjusted HR, 2.87; 95% confidence interval [CI], 2.00-4.11; p < 0.001), but not extrapulmonary TB (adjusted HR, 1.04; 95% CI, 0.33-3.30; p = 0.95). Among the current smokers, those who developed TB smoked more cigarettes per day than those who did not (13.43, SD 8.76 vs. 10.96, SD 7.87, p = 0.01). A statistically significant dose-response relationship was observed with respect to active TB and culture-confirmed TB (both p < 0.05). Smoking accounted for 32.8% (95% CI, 14.9-48.0%), 8.6% (95% CI, 3.3-15.1%), and 18.7% (95% CI, 7.7-30.4%) of the TB risk among males, females, and the entire cohort, respectively. Approximately 44.9% (95% CI, 20.7-64.6%) of the sex difference was attributable to smoking.

BACKGROUND: Increased iron store has been linked to risk of cardiovascular disease. Structural alterations of arteries in beta-thalassemia major patients and in vitro functional disturbance of vascular endothelial cells by thalassemic serum have been described. We sought to determine whether arterial stiffness and endothelial function are altered in vivo. METHODS AND RESULTS: Thirty thalassemia patients (16 male) aged 22.2+/-7.4 years were recruited. Left ventricular (LV) mass and function were assessed echocardiographically. Carotid and brachioradial artery stiffness was assessed by stiffness index and pulse-wave velocity (PWV), respectively. Brachial artery endothelial function was assessed by vascular response to reactive hyperemia (flow-mediated dilation [FMD]) and sublingual glyceryl trinitrate. These indexes were compared with those of 30 age- and sex-matched controls. None of the patients had LV systolic or diastolic dysfunction. When compared with controls, patients had greater absolute (113.8+/-38.0 versus 109.0+/- 32.6 g, P=0.04) and indexed (82.4+/-17.5 versus 66.7+/-12.7 g/m(2), P<0.001) LV mass, carotid artery stiffness index (8.1+/-3.5 versus 5.5+/-1.6, P<0.001), and brachioradial PWV (8.9+/-2.4 versus 7.9+/-1.7 m/s, P= 0.03). Their FMD was impaired (3.5+/-3.3% versus 8.8+/-3.9%, P<0.001), whereas glyceryl trinitrate- mediated dilation was preserved (17.9+/-7.6% versus 16.3+/-6.1%, P=0.40). Both stiffness index and PWV correlated inversely with magnitude of FMD (r=-0.40, P=0.03; r=-0.41, P=0.03) and positively with indexed LV mass (r=0.50, P=0.005; r=0.40, P=0.027). Nonetheless, no significant correlation existed between ferritin level and carotid stiffness, PWV, or FMD. CONCLUSIONS: Increased arterial stiffness, endothelial dysfunction, and LV hypertrophy occur in patients with beta-thalassemia major, which may result in reduction of mechanical efficiency of the heart.

There is increasing evidence of a link between tuberculosis and smoking. This paper reviews the epidemiological evidence from the UK, China, India and the USA, summarizing some of the main papers which indicate an association. Where an association has been found there seems to be an increase in tuberculosis case rates of between two- and four-fold for those smoking in excess of 20 cigarettes a day, but it may be difficult to control for other factors, particularly alcohol consumption. The final part of the paper reviews possible mechanisms. A likely possibility is that nicotine turns off the production of TNF-alpha by the macrophages in the lungs, rendering the patient more susceptible to the development of progressive disease from latent Mycobacterium tuberculosis infection.

Acute renal failure (ARF) is one of the major complications after cardiopulmonary bypass for open heart operations. The present study was undertaken to identify the risk factors for the development of ARF following cardiopulmonary bypass (CPB). Four hundred and forty-seven consecutive patients who underwent open heart procedures from July 1994 to June 1995 were analyzed retrospectively. Their mean age was 55.6 ± 14.2 (SD) years (range, 18 to 80). Dialysis was instituted whenever a patient exhibited inadequate urine output ( &lt;0.5 mL/kg/hr) for 2 to 3 hours despite correction of hemodynamic status and diuretic therapy, especially if fluid overload, hyperkalemia, or metabolic acidosis were also present. Twenty variables were analyzed by univariate analysis; these included nine preoperative variables—age, sex, hypertension, atherosclerosis, diabetes mellitus, left ventricular end-diastolic dimension (LVEDD) &gt;5 cm, preoperative congestive heart failure, renal insufficiency (serum creatinine ≥130 μmol/L on two occasions), and sepsis—10 intraoperative variables—duration of CPB, redo procedures, emergency surgery, use of intraaortic balloon pump (IABP) in operating room, use of gentamicin, use of ceftriaxone, use of sulbactam/ampicillin, requirement of deep hypothermic circulatory arrest, duration of low mean perfusion pressure (mean pressure &lt; 50 mmHg for more than 30 minutes), operation on multiple valves—and one postoperative variable— significant hypotension (systolic blood pressure less than 90 mmHg for more than 1 hour). Significant variables or the variables having a trend (p &lt; 0.1 ) to be associated with ARF were included in stepwise multiple logistic regression analyses. Three regression analyses were performed separately. The incidence of ARF requiring dialysis in the study period was 15.0%. Significant risk factors for whole group of patients (regression I) were preoperative renal insufficiency (p &lt; 0.0001 ), postoperative hypotension (p &lt; 0.0001 ), cardiopulmonary bypass time more than 140 min (p&lt;0.005), preoperative congestive heart failure (p&lt;0.01),and history of diabetes mellitus (p&lt;0.01).The risk factors in the valve group of patients (regression II) were preoperative renal insufficiency (p&lt;0.0001) and postoperative hypotension (p&lt;0.05).Risk factors in the CABG patients (regression III) were postoperative hypotension (p=0.0001), CPB time more than 140 min (p&lt;0.05), preoperative renal insufficiency (p&lt;0.05),and age (p&lt;0.05).The authors conclude that preoperative renal insufficiency and postoperative hypotension are the most important independent risk factors for ARF in postcardiac surgical patients. In addition, CPB time greater than 140 minutes and old age are also independent risk factors for ARF in CABG patients. CPB time more than 140 minutes, history of diabetes mellitus, and preoperative congestive heart failure are independent risk factors for development of ARF in our total group of patients. These findings may have important clinical implications in the preven tion of ARF in postcardiac surgical patients.