Impact of delayed introduction of sulfadoxine–pyrimethamine and arthemeter–lumefantrine on malaria epidemiology in KwaZulu-Natal, South Africa

Objective  To investigate how delayed introduction of sulfadoxine–pyrimethamine (Fansidar^®) and arthemeter–lumefantrine (Coartem^®) as first-line drugs for malaria in KwaZulu-Natal contributed to the reported epidemics of 1985–1988 and 1997–2001.
Methods  Ecological study assessing the association between malaria incidence and the emergence and degree of resistance to chloroquine from 1982 to 1988 and to sulfadoxine–pyrimethamine from 1991 to 2001, when each was the first-line malaria treatment.
Results  The relative risk for malaria infection after the level of drug resistance reached 10% was 4.5 (95% CI: 4.0–5.2) in the chloroquine period and 5.9 (95% CI: 5.7–6.1) in the sulfadoxine–pyrimethamine period. In the chloroquine period, the relative risk of death from malaria was tenfold (95% CI: 1.3–78.1) and the case fatality doubled after drug resistance had reached 10%. The risk of death during the sulfadoxine–pyrimethamine period was 10.8 (95% CI: 5.9–19.2) and case fatality 1.8 times higher after drug resistance had reached 10%, than before.
Conclusion  Malaria epidemics in KwaZulu-Natal, South Africa have been exacerbated by failing drug regimens. The establishment of sentinel sites for monitoring drug failure and the prompt adoption of guidelines based on World Health Organization standards in drug resistance should improve malaria control.     

TRP64ARG polymorphism of the beta 3-adrenergic receptor gene and obesity risk: effect modification by a sedentary lifestyle

Aim: We performed a case–control study to assess the association between obesity risk and the Trp64Arg polymorphism of the β₃-adrenergic receptor gene.
Methods: Obese subjects [n = 159; body mass index (BMI) > 30 kg/m²] and controls (n = 154; BMI < 25 kg/m²) were compared using multivariable logistic regression to control for potential confounders.
Results: A higher obesity risk (adjusted OR: 2.98; 95% CI: 1.00–8.56; p = 0.05) was associated with the Trp64Arg polymorphism among sedentary, but not among more active people.
Conclusions: Our results suggest that the TRP64ARG polymorphism of the ADRB3 seems to be a risk factor for obesity that is dependent on a sedentary lifestyle.     

Non-invasive model predicting clinically-significant portal hypertension in patients with advanced fibrosis

Background and Aims:  Hepatic venous pressure gradient (HVPG) has been established as a predictor for the development of varices, clinical decompensation and death. In the present study, the primary objectives were to determine the diagnostic accuracy of the model developed by using readily-available data in predicting the presence of significant portal hypertension and esophageal varices.
Methods:  This study included a total of 61 consecutive treatment-naive patients with advanced fibrosis (METAVIR F3, F4), established by liver biopsy. All patients underwent subsequent HVPG measurement and upper gastrointestinal endoscopy within 1 week of liver biopsy.
Results:  Seventeen patients (F3, 2/26; F4, 15/35) had clinically-significant portal hypertension (HVPG ≥ 10 mmHg). The Risk Score for predicting significant portal hypertension was 14.2 − 7.1 × log₁₀ (platelet [10⁹/L]) + 4.2 × log₁₀ (bilirubin [mg/dL]). The area under the receiver–operator curve (AUC) curve was 0.91 (95% confidence interval [CI], 0.84–0.98). The optimized cut-off value (Risk Score = −1.0) offered a sensitivity of 88% (95% CI, 62–98%) and a specificity of 86% (95% CI, 72–94%). The AUC of the Risk Score in predicting varices was 0.82 (95% CI, 0.67–0.98). The cut-off had a sensitivity of 82% (95% CI, 48–97%) and a specificity of 76% (95% CI, 62–86%).
Conclusion:  A predictive model that uses readily-available laboratory results may reliably identify advanced fibrosis patients with clinically-significant portal hypertension as well as esophageal varices. However, before accepted, the results of the current study certainly should be validated in larger prospective cohorts.     

Turning points, reproduction number, and impact of climatological events for multi-wave dengue outbreaks

Objectives  To study climatological and public health events which might have affected the 2007 two-wave dengue outbreak in Taiwan, an island with both tropical and subtropical regions, where the 2007 dengue incidence exceeded the combined total of the previous four years.
Methods  A multi-phase Richards model was fitted to weekly cumulative dengue data to pinpoint the turning points of the outbreak. We obtained the 'initial' reproduction numbers for the two waves of the outbreak. By means of correlation analysis we explored the possible impact of climatological events on the occurrence of turning points.
Results  Three turning points occurred around early August, late August/early September, and late October/early November. The 'initial' reproduction number for the first wave was R _i  = 4.67 (95% CI: 0*–10.92), where 0* = max{0, lower bound}, and R _i  = 3.93 (95% CI: 1.74–6.13) for the second wave. The highest correlation was between dengue incidence and two climatological variables: maximum temperature at a lag of 5 weeks ( r  =   0.66 and 0.71) and total precipitation at a lag of seven weeks ( r  =   0.53).
Conclusions  The first two turning points were partially attributable to two typhoons around early to mid-August that brought a sharp drop in temperature and substantial rainfall. The drop in temperature first drove the dengue incidence down, then the rainfall drove it up at the beginning of fall. In recent years, Taiwan has witnessed increasingly frequent large summer dengue outbreaks that persisted into early winter, perhaps due to warmer autumns. This highlights the possible impact of global warming on the spread of infectious diseases.     

Minimal residual disease is a significant predictor of treatment failure in non T-lineage adult acute lymphoblastic leukaemia: final results of the international trial UKALL XII/ECOG2993

The predictive value of molecular minimal residual disease (MRD) monitoring using polymerase chain reaction amplification of clone-specific immunoglobulin or T-cell Receptor rearrangements was analysed in 161 patients with non T-lineage Philadelphia-negative acute lymphoblastic leukaemia (ALL) participating in the UK arm of the international ALL trial UKALL XII/Eastern Cooperative Oncology Group (ECOG) 2993. MRD positivity (≥10⁻⁴) in patients treated with chemotherapy alone was associated with significantly shorter relapse-free survival (RFS) at several time-points during the first year of therapy. MRD status best discriminated outcome after phase 2 induction, when the relative risk of relapse was 8·95 (2·85–28·09)-fold higher in MRD-positive (≥10⁻⁴) patients and the 5-year RFS 15% [95% confidence interval (CI) 0–40%] compared to 71% (56–85%) in MRD-negative (<10⁻⁴) patients ( P  = 0·0002) When MRD was detected prior to autologous stem cell transplantation (SCT), a significantly higher rate of treatment failure was observed [5-year RFS 25% (CI 0–55%) vs. 77% (95% CI 54–100%) in MRD-negative/<10⁻⁴, P  = 0·01] whereas in recipients of allogeneic-SCT in first complete remission, MRD positivity pre-transplant did not adversely affect outcome. These data provide a rationale for introducing MRD-based risk stratification in future studies for the delineation of those at significant risk of treatment failure in whom intensification of therapy should be evaluated.     

Cough-reflex sensitivity to inhaled capsaicin in COPD associated with increased exacerbation frequency

Background and objective:   The causes of exacerbations in COPD patients are poorly understood. This study examined the association between cough-reflex sensitivity in patients with stable COPD and the frequency of subsequent exacerbations.
Methods:   The sampling frame for cases and controls for this study was patients attending a hospital outpatient clinic. cough-reflex sensitivity was evaluated using the log concentration of capsaicin causing five or more coughs (log C₅). Subsequent COPD exacerbations were identified prospectively via symptom-based diaries over a 12-month period.
Results:   The study group comprised 45 COPD subjects and 10 controls. Mean log C₅ was lower in the COPD group than in the control group (0.97 (95% confidence interval (CI): 0.76–1.18) versus 1.26 (95% CI: 0.81–1.71), P  = 0.095). In the COPD group, log C₅ was negatively correlated with serum CRP level ( r  = −0.36, P  = 0.02) and significantly associated with the exacerbation frequency ( r  = −0.38, P  = 0.01). Stepwise multiple regression analysis showed that cough-reflex sensitivity was significantly associated with exacerbation frequency ( r ² = 0.15, P  = 0.01).
Conclusions:   Hypersensitivity of the cough reflex to inhaled capsaicin might reflect airway inflammation in stable COPD patients, which predisposes to frequent exacerbations.     

Cattle, other domestic animal ownership, and distance between dwelling structures are associated with reduced risk of recurrent Plasmodium falciparum infection in southern Zambia

Objectives  To examine the associations between household Plasmodium falciparum infection and a number of factors including domestic animal ownership, potential mosquito breeding sites, indoor darkness, density of people, distance between dwelling structures, and insecticide-treated bed net use.
Methods  Analyses were based on data collected from a household survey conducted in Macha, Zambia. Thirty-four households with recurrent malaria infection in 2005–2008 were selected as case households and compared with 37 control households with no malaria infection randomly selected from the same geographic area. Logistic regression models were used to identify factors associated with household P. falciparum infection.
Results  In multivariate analysis, cattle ownership was associated with reduced risk of P. falciparum infection (adjusted odds ratio = 0.19; 95% CI = 0.05–0.69), as was increased distance between dwelling structures (aOR = 0.26; 95% CI = 0.07–0.98). Ownership of the highest category of cattle, goats, dogs, or cats dramatically reduced the risk of P. falciparum infection (aOR = 0.13; 95% CI = 0.03–0.56).
Conclusion  Domestic animal, in particular cattle, ownership and greater distance between dwelling structures were associated with reduced risk of recurrent P. falciparum infection at the household level. These factors should be further investigated as supplemental measures for malaria control in rural African settings.     

Obesity: A Risk Factor for Severe Acute Biliary and Alcoholic Pancreatitis

Objective: In this study we evaluate the association between obesity and complication development in patients with a first-attack acute pancreatitis (AP), and investigate the influence of comorbid factors on this association.
Methods: Medical records of 150 patients with AP were reviewed. General data, AP etiology, admission AP prognostic criteria, and occurrence of complications were recorded. Patients were classified according to body mass index (BMI) as obese (  BMI > 25  kg/m²) and nonobese (  BMI ≤ 25  kg/m²).
Results: Prevalence of obesity was 57%. Thirty-eight percent of the obese patients developed complications as compared with 21% of the nonobese (  RR = 1.74  ; 95% CI, 1–2.9). The risk for severe AP increased according to the degree of obesity. Pancreatic and peripancreatic necrosis was more common in obese patients (17.6% vs 6%), as was the incidence of infectious complications. The risk for severe AP was highest in obese patients with either alcoholic (  RR = 5.3  ; 95% CI, 1.2–23) or biliary etiology (  RR = 5.2  , 95% CI, 1–26).
Conclusion: Obesity may predispose to a complicated course of AP, especially if it is secondary to alcohol or gallstones. Further studies are needed to establish the precise prognostic value of obesity in AP, as well as the pathogenic mechanisms involved in the process.     

Willingness to participate in preventive HIV vaccine trials in a community-based cohort in south western Uganda

Objectives  To assess willingness to participate in HIV vaccine trials and possible barriers to participation.
Methods  Questionnaire survey of participants completing a 2-year community-based HIV Vaccine Preparedness Study, followed by cross sectional analysis of data.
Results  95% of participants were willing to participate in a trial with similar attributes to the Vaccine Preparedness Study. Certain hypothetical trial attributes significantly reduced willingness to participate: The requirement to delay pregnancy (for females) had the largest effect, reducing willingness to participate from 97% to 23% ( P  < 0.0001). Larger blood draws had the second largest effect: 95–55% ( P  < 0.0001). The possibility of receiving either candidate vaccine or placebo had the third largest effect: 95–73% ( P  < 0.0001). Monthly study visits had the fourth largest effect: 95–92% ( P  < 0.0001). Trial duration longer than 2 years had the least effect: 95–93% ( P  = 0.0025). Combined attributes reduced willingness to participate from 95% to 43% (McNemar's χ² = 521.00; P  < 0.0001) overall and 97–11% (McNemar's χ² = 531.00; P  < 0.0001) for female participants. Physical harm concerns (adjusted OR = 34.9; 95% CI, 10.4–118) and a low risk behaviour index (adjusted OR = 0.09; 95% CI, 0.01–0.73) were associated with unwillingness to participate.
Conclusions  We found a high level of willingness to participate in HIV vaccine trials in this population. However, certain HIV vaccine trial requirements were associated with reduced willingness to participate. Community as well as individual concerns will have to be carefully addressed in planned HIV vaccine trials.     

Cross-border malaria control for internally displaced persons: observational results from a pilot programme in eastern Burma/Myanmar

Objectives  To document the feasibility of a cross-border community based integrated malaria control programme implemented by internally displaced persons in eastern Burma/Myanmar.
Methods  This pilot study was conducted from February 2003 through January 2005 in seven villages of displaced ethnic Karen. Interventions comprised early diagnosis of Plasmodium falciparum and treatment with mefloquine and artesunate, distribution of long-lasting insecticide treated nets (LLITNs), and educational messages. The primary outcome measure was P. falciparum prevalence during bi-annual universal screenings with the Paracheck-Pf^® (Orchid Biomedical Systems, Goa, India) device. Secondary outcomes were P. falciparum incidence and process indicators related to net use and malaria knowledge, attitudes and practices (KAP).
Results  P. falciparum prevalence in original programme areas declined from 8.4% [95% confidence interval (CI) 8.3–8.6] at baseline to 1.1% (95% CI 1.1–1.2) in the final screening. Annual incidence in original areas declined from 232 to 70 cases/1000/year [incidence rate ratio 0.30 (95% CI 0.24–0.39)]. The proportion of household members sleeping under a LLITN improved from 0% to 89% and malaria KAP improved in all areas.
Conclusions  Integrated malaria control organized and implemented by displaced persons is feasible in eastern Burma/Myanmar. The decline in P. falciparum prevalence and incidence suggest that it may be possible to reduce the burden of disease and the reservoir of malaria in eastern Burma/Myanmar, with implications for malaria control in the greater Mekong region.     

G-CSF alone mobilizes sufficient peripheral blood CD34+ cells for positive selection in newly diagnosed patients with myeloma and lymphoma

We have evaluated CD34⁺ cell positive selection from granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPC) in 26 patients with either multiple myeloma (MM, n  = 18) or follicular non-Hodgkin's lymphoma (NHL, n  = 8). 26 PBPC were collected with two leukaphereses: 16 contained sufficient numbers of CD34⁺ cells and were selected. The absolute number of CD34⁺ cells in the leukapheresis products was found to be significantly related to the duration of underlying disease and exposure to prior treatment. CD34⁺ cell positive selection allowed recovery of a median of 35% of CD34⁺ cells, the selected fraction containing a median number of 1.43 × 10⁶/kg CD34⁺ cells/kg (range 0.48–41.5). 10 patients were transplanted and received a median dose of 1.51 × 10⁶ CD34⁺ cells (range 0.48–4.2). The median time to granulocyte (>0.5 × 10⁹/l) and platelet (>20 × 10⁹/l) engraftment was 12 and 13 d respectively (ranges 10–13 and 0–95). Lymphoma cells were found by a sensitive polymerase chain reaction technique in four out of five CD34⁺ cell fractions tested.     

Neonatal thrombocytopenia: incidence and characterization of maternal antiplatelet antibodies by MAIPA assay

Neonatal thrombocytopenia (NNT) which is frequent in distressed newborns was uncommon in a non-selected population of neonates. The aim of this prospective study was to determine the frequency of NNT and, in confirmed NNT, to search for maternal antiplatelet antibodies with a monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay. Among the 8388 newborns studied, 40 (0.5%, 95% CI 0.3–0.6) had confirmed NNT, which was severe (platelet count < 50 × 10⁹/l) in 10 cases (0.12%, 95% CI 0.05–0.20). Antiplatelet antibodies were detected in 10/31 studied mothers of thrombocytopenic newborns (32.3%): they were alloantibodies in five cases and autoantibodies in five other cases. Among these 10 newborns, seven had severe thrombocytopenia and four had bleeding complications. As controls, antiplatelet antibodies were also searched for in mothers of non-thrombocytopenic newborns: antiplatelet antibodies were present in 8.5% (95% CI 5.9–11.7) of thrombocytopenic mothers ( n  = 400) and 3.2% (95% CI 0.7–9.0) of non-thrombocytopenic mothers ( n  = 95). The difference was significant between the control groups and the group of mothers of thrombocytopenic newborns. In conclusion, our data indicate that an immune origin is frequent in NNT and should be looked for, particularly when the platelet count is < 50 × 10⁹/l.     

Mental and motor development before and during growth hormone treatment in infants and toddlers with Prader-Willi syndrome

Background  Prader–Willi syndrome (PWS) is a neurogenetic disorder characterized by muscular hypotonia, psychomotor delay, feeding difficulties and failure to thrive in infancy. GH treatment improves growth velocity and body composition. Research on the effects of GH on psychomotor development in infants with PWS is limited.
Objective  To evaluate psychomotor development in PWS infants and toddlers during GH treatment compared to randomized controls.
Design/patients  Forty-three PWS infants were evaluated at baseline. Twenty-nine of them were randomized into a GH group ( n  = 15) receiving 1 mg/m²/day GH or a non-GH-treated control group ( n  = 14). At baseline and after 12 months of follow-up, analysis with Bayley Scales of Infant Development II (BSID-II) was performed. Data were converted to percentage of expected development for age (%ed), and changes during follow-up were calculated.
Results  Infants in the GH group had a median age of 2·3 years [interquartile range (IQR) 1·7–3·0] and in the control group of 1·5 years (IQR 1·2–2·7) ( P =  0·17). Both mental and motor development improved significantly during the first year of study in the GH group vs. the control group: median (IQR) change was +9·3% (–5·3 to 13·3) vs. –2·9% (–8·1 to 4·9) ( P  < 0·05) in mental development and +11·2% (–4·9 to 22·5) vs. –18·5% (–27·9 to 1·8) ( P  < 0·05) in motor development, respectively.
Conclusion  One year of GH treatment significantly improved mental and motor development in PWS infants compared to randomized controls.     

Impaired glucose metabolism and obesity in Swedish patients with borderline isolated systolic hypertension: Skaraborg Hypertension and Diabetes Project

Summary
Aim   To assess the prevalence of borderline isolated systolic hypertension (borderline ISH), and to examine its association with other cardiovascular risk factors.
Methods   A cross-sectional community-based study was carried out in 1993–1994 in Skara, Sweden, including 1109 randomly chosen subjects ≥ 40 years old. Normotension (NT) was defined as systolic blood pressure (SBP) < 140 and diastolic blood pressure (DBP) < 90 mmHg, borderline ISH as SBP 140–159 and DBP < 90 mmHg and hypertension (HT) as SBP ≥160 or DBP ≥ 90 mmHg or ongoing treatment.
Results   The prevalence of borderline ISH (n = 203) by age was 4% in ages 40–49 years, 15% in ages 50–59 years, 28% in ages 60–69 years and 25% in ages 70–79 years. With borderline ISH as reference, normotensive subjects less often had fasting blood glucose > 5.5 mmol/l (odds ratio (OR): 0.4, 95% CI: 0.26–0.75), BMI > 27 kg/m² (OR: 0.6, 95% confidence intervals (CI): 0.42–0.85) and known diabetes (OR: 0.4, 95% CI: 0.16–0.95). Hypertensive subjects more often had high density lipoprotein (HDL) cholesterol < 1.0 mmol/l (OR: 2.0, 95% CI: 1.35–2.99), a history of previous cardiovascular disease (CVD) (OR: 1.7, 95% CI: 1.01–2.72), known diabetes (OR: 2.4, 95% CI: 1.29–4.58) and microalbuminuria (men) (OR: 1.9, 95% CI: 1.15–3.11).
Conclusion   Borderline ISH is a common condition. It is associated with a more unfavourable risk factor profile than that of normotensive subjects concerning primarily glucose metabolism and obesity. The prevalence of known diabetes increased with the degree of hypertension.     

They just don't get enough! Variable intern experience in bedside procedural skills

Background: Medical school and resident training programmes offer different learning opportunities and outcomes. The aim of the study was to assess medical student and intern experience in common clinical procedures.
Methods: Interns employed in a metropolitan teaching hospital from 2000 to 2004 completed a survey of experience and confidence in clinical procedures at the beginning and end of their intern year. Attendance at and the contribution to procedural confidence of a voluntary procedural skill-training programme were examined.
Results: For the 314 interns, clinical experience before and during internship varied for each procedure and between year cohorts as did training programme attendance (44–84%). Student procedural confidence was predicted by pre-intern experience either on patients or by simulation ( β  = 0.17, 95% confidence interval (CI) 0.02–0.21, P  = 0.03) and age >30 years on commencing internship ( β  = 8.44, 95%CI 3.03–14.06, P  = 0.003. Adjusted R ² = 0.08, P  = 0.002). Intern procedural confidence by year's end was predicted by attendance at the training programme ( β  = 0.48, 95%CI 0.34–0.62, P  < 0.001), intern experience with patient procedures ( β  = 0.34, 95%CI 0.21–0.47, P  < 0.001) and a clear decision to enter a postgraduate training programme ( β  = 0.13, 95%CI 0.04–0.22, P  = 0.007, Adjusted R ² = 0.50, P  < 0.001).
Conclusion: Interns and students receive variable experience to carry out procedural skills on patients. This makes designing training programmes difficult as training needs vary each year. Both mandatory supervision of key skills and opportunities to supplement limited experience are needed during the intern year to ensure a uniform experience.     

Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group

Objectives:  Patients with primary refractory AML and with early relapses have unfavorable prognoses and require innovative therapeutic approaches. Purine analogs fludarabine (FA) and cladribine (2-CdA) increase cytotoxic effect of Ara-C in leukemic blasts and inhibit DNA repair mechanisms; therefore its association with Ara-C and mitoxantrone (MIT) results in a synergistic effect. In the current report, we present the final results of multi-center phase II study evaluating the efficacy and toxicity of CLAG-M salvage regimen in poor risk refractory/relapsed AML patients.
Methods:  The induction chemotherapy consisted of 2-CdA 5 mg/m², Ara-C 2 g/m², MIT 10 mg/m², and granulocyte-colony stimulating factor. In the case of PR, a second CLAG-M was administered. Patients in CR received consolidation courses based on high doses of Ara-C and MIT with or without 2-CdA.
Results:  One hundred and eighteen patients from 11 centers were registered; 78 primary resistant and 40 relapsed. Sixty-six patients (58%) achieved CR after one or two courses of CLAG-M, 49 (35%) were refractory, and 8 (7%) died early. WBC >10 g/L and age >34 yr were factors associated with increased risk of treatment failure. Hematological toxicity was the most prominent toxicity of this regimen. The probability of OS at 4 yr was 14% (95% CI 4–23%). OS was influenced by age, WBC >10 g/L and poor karyotype in both univariate and multivariate analyses. The probability of 4 yr DFS was 30% for all 66 patients in CR (95% CI 11–49%). Poor karyotype was the only factor associated with decreased probability of DFS.
Conclusions:  We conclude that CLAG-M is a well-tolerated and highly effective salvage regimen in poor risk refractory/relapsed AML.     

Association of TNFSF15 with Crohn's disease in Koreans

OBJECTIVES:  A recent genomewide association study from a Japanese population identified tumor necrosis factor superfamily member 15 ( TNFSF15 ) as an inflammatory bowel disease gene. Previous studies have shown that expression of TNFSF15 was upregulated in macrophages and lymphocytes of the intestinal lamina propria of Crohn's disease (CD) patients. Here, we have tested four single nucleotide polymorphisms (SNPs) of TNFSF15 in Korean patients to determine whether the gene is associated with susceptibility to CD in a closely related population.
METHODS:  Four SNPs across TNFSF15 were genotyped in 380 patients with CD and 380 healthy controls.
RESULTS:  Carriers of three polymorphisms, including rs3810936, rs6478108, and rs7848647, showed statistically significant association with CD (adjusted OR [aOR] 2.81, 95% confidence interval [CI] 1.94–4.07, P = 4.4 × 10⁻⁸; aOR 3.49, 95% CI 2.42–5.04, P = 2.7 × 10⁻¹¹; and aOR 3.49, 95% CI 2.42–5.03, P = 2.2 × 10⁻¹¹, respectively). Following haplotype analysis, homozygotes carrying two copies of the haplotype consisting of the risk alleles of those three SNPs showed statistically significant association with CD (aOR 5.39, 95% CI 3.19–9.10, P = 3.07 × 10⁻¹⁰).
CONCLUSIONS:  Our data support the hypothesis that the TNFSF15 genotypes play an important role in the pathogenesis of CD in Koreans.     

Non-invasive ventilation during arm exercise and ground walking in patients with chronic hypercapnic respiratory failure

Background and objective:   People with chronic hypercapnic respiratory failure (HRF) often have a ventilatory limitation to exercise with difficulty performing activities of daily living. Although non-invasive ventilation (NIV) appears to reduce the ventilatory limitation and improve exercise performance in people with severe COPD, the effect of NIV during functional activities such as unsupported arm exercise (UAE) and ground walking in people with chronic HRF is unclear.
Methods:   Seventeen patients with chronic HRF (PaCO₂ 52.1 ± 5.3 mm Hg) performed a series of UAE tests, and 15 patients (PaCO₂ 51.7 ± 3.8 mm Hg) performed a series of endurance shuttle walk tests, with and without NIV in a randomized cross-over design.
Results:   NIV during UAE increased endurance time by a mean of 91 s (95% confidence interval (CI): 10–172, P  = 0.031) and reduced dyspnoea by a mean of 2.3 on the Borg scale (95% CI: 1.0–3.7, P  = 0.002) compared with exercise without NIV. There was a non-significant increase in walking endurance time with NIV during exercise (119 s, 95% CI: −17 to 254, P  = 0.081); however, isotime dyspnoea was unchanged compared with walking without NIV (−1.0, 95% CI: −3.0 to 1.0, P  = 0.29).
Conclusion:   NIV during UAE increased endurance time and reduced dyspnoea compared with exercise without NIV in patients with chronic HRF. Investigation of the role of NIV as an adjunct to UAE training is warranted. In contrast, NIV during ground walking did not improve exercise capacity. However, the pressure support provided may have been inadequate as dyspnoea was not reduced.     

High mortality risk among individuals assumed to be TB-negative can be predicted using a simple test

Objectives  To determine mortality among assumed TB negative (aTBneg) individuals in Guinea-Bissau and to investigate whether plasma levels of soluble urokinase receptor (suPAR) can be used to determine post-consultation mortality risk.
Methods  This prospective West-African cohort study included 1007 aTBneg individuals who were enrolled from 2004 to 2006; 4983 age-matched controls were followed for comparison. Plasma suPAR levels were measured using the suPARnostic^® ELISA. Survival was analysed using Cox regression, ROC curves and Kaplan–Meier analysis.
Results  After 3 months of follow-up, mortality was 21 per 100 person-year-observation (PYO) among aTBneg individuals and three per 100 PYO among the control population [mortality rate ratio (MRR) = 6.92 (95% CI 4.48–10.7)]. SuPAR values ranged between 0.9 and 45 ng/ml in aTBneg individuals. A log-linear relationship was found between suPAR levels <15 ng/ml and mortality. In the log-linear range, a 1 ng/ml increase was associated with a 46% increase in the mortality rate: MRR = 1.46 (95% CI 1.34–1.59). The area under the ROC curves was 0.88 for HIV-positive individuals and 0.79 for HIV-negative individuals.
Conclusions  Our study showed a high mortality rate among aTBneg individuals and demonstrated that suPAR measurements can provide prognostic information on mortality among individuals without disease diagnosis. Measuring suPAR is a technically simple method for determining mortality risk in individuals that are assumed to be TB-negative.     

Increased number of peripheral blood CD34+ cells in lithium-treated patients

Eight adult patients with bipolar disorder were prospectively examined to find whether lithium carbonate increased their peripheral blood CD34⁺ haemopoietic stem cells. Following lithium therapy for 3–4 weeks their neutrophil counts increased by a mean of 88% (from 4625 ± 1350 × 10⁹/l, mean ± SD pretreatment, to a peak of 8300 ± 3910 × 10⁹/l). Concommitantly, there was a significant increment in their CD34⁺ cells (from 0.11 ± 0.01% to a peak of 0.18 ± 0.08%). There was a significant correlation between the rise in neutrophil count and that of the CD34⁺ cells ( r  = 0.795, P  = 0.019). Lithium therapy may be used to mobilize peripheral blood CD34⁺ cells for marrow transplantation.