Secondary attack rate of tuberculosis in urban households in Kampala, Uganda

Background

Tuberculosis is an ancient disease that continues to threaten individual and public health today, especially in sub-Saharan Africa. Current surveillance systems describe general risk of tuberculosis in a population but do not characterize the risk to an individual following exposure to an infectious case.

Methods

In a study of household contacts of infectious tuberculosis cases (n = 1918) and a community survey of tuberculosis infection (N = 1179) in Kampala, Uganda, we estimated the secondary attack rate for tuberculosis disease and tuberculosis infection. The ratio of these rates is the likelihood of progressive primary disease after recent household infection.

Results

The secondary attack rate for tuberculosis disease was 3.0% (95% confidence interval: 2.2, 3.8). The overall secondary attack rate for tuberculosis infection was 47.4 (95% confidence interval: 44.3, 50.6) and did not vary widely with age, HIV status or BCG vaccination. The risk for progressive primary disease was highest among the young or HIV infected and was reduced by BCG vaccination.

Conclusions

Early case detection and treatment may limit household transmission of M. tuberculosis. Household members at high risk for disease should be protected through vaccination or treatment of latent tuberculosis infection.     

Childhood Tuberculosis in Household Contacts of Newly Diagnosed TB Patients

Introduction

Childhood tuberculosis (TB), although estimated to account for a major proportion of the global TB disease burden, has a lower public health priority. Reliable research and surveillance data on childhood TB is limited in most regions of the world. This study was conducted to assess the burden of childhood TB among the household contacts of new TB patients in Karachi, Pakistan.

Methods

A retrospective analysis of children (<15 years) who were household contacts of new adult TB patients presenting to Marie Adelaide Leprosy Center (MALC) clinics in Karachi during the period of 2008 to 2010 was conducted.

Results

Of the household children contacts (n = 6613) screened, 317 were suspected and 121(1.8%) diagnosed with TB. These included 89 (73.6%) with pulmonary and 32 (26.4%) with extra-pulmonary disease. Smear positivity rate in pulmonary cases was 32.6%. Mean age of children diagnosed with TB was 11.7 (±2.8) years. Within the child-contacts screened, disease was found to be significantly higher among females (2.3%) in comparison to males (1.2%) (p-value <0.01). The commonest relationship of source cases to diagnosed children was the mother (n = 51, 42.1%). The source case was a female for 66.1% (n = 76) of the children.

Conclusion

A smear positivity rate of 32.6% amongst pulmonary cases suggests their potential to spread disease and emphasizes a need to review the contribution of children in transmission of TB within communities. Greater vulnerability of the female child and considerable role of mother in disease transmission highlights a need to increase focus on females in TB control programs in Pakistan.     

Influenza A (H1N1) in Victoria, Australia: a community case series and analysis of household transmission

Background

We characterise the clinical features and household transmission of pandemic influenza A (pH1N1) in community cases from Victoria, Australia in 2009.

Methods

Questionnaires were used to collect information on epidemiological characteristics, illness features and co-morbidities of cases identified in the 2009 Victorian Influenza Sentinel Surveillance program.

Results

The median age of 132 index cases was 21 years, of whom 54 (41%) were under 18 years old and 28 (21%) had medical co-morbidities. The median symptom duration was significantly shorter for children who received antivirals than in those who did not (p = 0.03). Assumed influenza transmission was observed in 63 (51%) households. Influenza-like illness (ILI) developed in 115 of 351 household contacts, a crude secondary attack rate of 33%. Increased ILI rates were seen in households with larger numbers of children but not larger numbers of adults. Multivariate analysis indicated contacts of cases with cough and diarrhoea, and contacts in quarantined households were significantly more likely to develop influenza-like symptoms.

Conclusion

Most cases of pH1N1 in our study were mild with similar clinical characteristics to seasonal influenza. Illness and case features relating to virus excretion, age and household quarantine may have influenced secondary ILI rates within households.     

Tuberculosis contact screening and isoniazid preventive therapy in a South Indian district: operational issues for programmatic consideration

Background

Under India''s Revised National Tuberculosis Control Programme (RNTCP), all household contacts of sputum smear positive Pulmonary Tuberculosis (PTB) patients are screened for TB. In the absence of active TB disease, household contacts aged <6 years are eligible for Isoniazid Preventive Therapy (IPT) (5 milligrams/kilogram body weight/day) for 6 months.

Objectives

To estimate the number of household contacts aged <6 years, of sputum smear positive PTB patients registered for treatment under RNTCP from April to June''2008 in Krishna District, to assess the extent to which they are screened for TB disease and in its absence initiated on IPT.

Methods

A cross sectional study was conducted. Households of all smear positive PTB cases (n = 848) registered for treatment from April to June''2008 were included. Data on the number of household contacts aged <6 years, the extent to which they were screened for TB disease, and the status of initiation of IPT, was collected.

Results

Households of 825 (97%) patients were visited, and 172 household contacts aged <6 years were identified. Of them, 116 (67%) were evaluated for TB disease; none were found to be TB diseased and 97 (84%) contacts were initiated on IPT and 19 (16%) contacts were not initiated on IPT due to shortage of INH tablets in peripheral health centers. The reasons for non-evaluation of the remaining eligible children (n = 56, 33%) include no home visit by the health staff in 25 contacts, home visit done but not evaluated in 31 contacts. House-hold contacts in rural areas were less likely to be evaluated and initiated on IPT [risk ratio 6.65 (95% CI; 3.06–14.42)].

Conclusion

Contact screening and IPT implementation under routine programmatic conditions is sub-optimal. There is an urgent need to sensitize all concerned programme staff on its importance and establishment of mechanisms for rigorous monitoring.     

Influenza transmission in a community during a seasonal influenza A(H3N2) outbreak (2010-2011) in Mongolia: a community-based prospective cohort study

Background

Knowledge of how influenza viruses spread in a community is important for planning and implementation of effective interventions, including social distancing measures. Households and schools are implicated as the major sites for influenza virus transmission. However, the overall picture of community transmission is not well defined during actual outbreaks. We conducted a community-based prospective cohort study to describe the transmission characteristics of influenza in Mongolia.

Methods and Findings

A total of 5,655 residents in 1,343 households were included in this cohort study. An active search for cases of influenza-like illness (ILI) was performed between October 2010 and April 2011. Data collected during a community outbreak of influenza A(H3N2) were analyzed. Total 282 ILI cases occurred during this period, and 73% of the subjects were aged <15 years. The highest attack rate (20.4%) was in those aged 1–4 years, whereas the attack rate in those aged 5–9 years was 10.8%. Fifty-one secondary cases occurred among 900 household contacts from 43 households (43 index cases), giving an overall crude household secondary attack rate (SAR) of 5.7%. SAR was significantly higher in younger household contacts (relative risk for those aged <1 year: 9.90, 1–4 years: 5.59, and 5–9 years: 6.43). We analyzed the transmission patterns among households and a community and repeated transmissions were detected between households, preschools, and schools. Children aged 1–4 years played an important role in influenza transmission in households and in the community at large. Working-age adults were also a source of influenza in households, whereas elderly cases (aged ≥65 years) had no link with household transmission.

Conclusions

Repeated transmissions between households, preschools, and schools were observed during an influenza A(H3N2) outbreak period in Mongolia, where subjects aged 1–4 years played an important role in influenza transmission.     

A preliminary evaluation of limb salvage surgery for osteosarcoma around knee joint

Objective

To evaluate the effectiveness and drawbacks of diversified procedures of limb salvage surgery (LSS), providing a reference of rational surgical criterion of LSS.

Methods

Fifty eight patients with stage IIB extremity osteosarcoma around knee joint area between 1992 and 2002 were studied retrospectively. Among them, 43 patients were treated by LSS followed by reconstruction. Reconstruction approaches included re-implantation of irradiation-devitalized tumor bone (n = 12), autoclaving-devitalized tumor bone (n = 8), prosthetic replacement (n = 11), allograft transplantation (n = 8) and vascularized fibula autograft implantation (n = 4). Amputations were performed in 15 patients. Patients were followed up for 6–16 years.

Results

There were no significant difference between LSS and amputation groups regarding disease free survival and local recurrence rates. The actuarial 5-year continuous disease free survival and local recurrence rate were 30.0% and 25.0% in patients of devitalized LSS group, whereas those were 56.5% and 8.7% in patients of non-devitalized reconstruction group. The complication rate was significantly higher in LSS group compared to amputation group (P = 0.003).

Conclusion

LSS with non-devitalized procedures is the optimal treatment for osteosarcoma around knee joint area. Prosthesis implantation is the preferred option for bone reconstruction following LSS. Prevention and treatment of post-operative complications should be paid more attention to get good long-term outcomes of surgery.     

The impact of asymptomatic helminth co-infection in patients with newly diagnosed tuberculosis in north-west ethiopia

Background

Areas endemic of helminth infection, tuberculosis (TB) and HIV are to a large extent overlapping. The aim of this study was to assess the impact of asymptomatic helminth infection on the immunological response among TB patients with and without HIV, their house hold contacts and community controls.

Methodology

Consecutive smear positive TB patients (n = 112), their household contacts (n = 71) and community controls (n = 112) were recruited in Gondar town, Ethiopia. Stool microscopy, HIV serology, serum IgE level, eosinophil and CD4 counts were performed and tuberculosis patients were followed up for 3 months after initiation of anti-TB treatment.

Results

Helminth co-infection rate was 29% in TB patients and 21% in both community control and household contacts (p = 0.3) where Ascaris lumbricoides was the most prevalent parasite. In TB patients the seroprevalence of HIV was 47% (53/112). Eosinophilia and elevated IgE level were significantly associated with asymptomatic helminth infection. During TB treatment, the worm infection rate of HIV+/TB patients declined from 31% (10/32) at week 0 to 9% (3/32) at week 2 of TB treatment, whereas HIV−/TB patients showed no change from baseline to week 2, 29% (13/45) vs. 22.2% (10/45). This trend was stable at week 8 and 12 as well.

Conclusion

One third of smear positive TB patients were infected with helminths. Eosinophilia and elevated IgE level correlated with asymptomatic worm infection, indicating an effect on host immunity. The rate of worm infection declined during TB treatment in HIV+/TB co-infected patients whereas no decline was seen in HIV−/TB group.     

Using Modelling to Disentangle the Relative Contributions of Zoonotic and Anthroponotic Transmission: The Case of Lassa Fever

Background

Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions.

Methodology/Principal Findings

Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals (‘super-spreaders’), as we found only of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) , with a maximum value up to .

Conclusions/Significance

This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.     

Clinical characteristics of 26 human cases of highly pathogenic avian influenza A (H5N1) virus infection in China

Background

While human cases of highly pathogenic avian influenza A (H5N1) virus infection continue to increase globally, available clinical data on H5N1 cases are limited. We conducted a retrospective study of 26 confirmed human H5N1 cases identified through surveillance in China from October 2005 through April 2008.

Methodology/Principal Findings

Data were collected from hospital medical records of H5N1 cases and analyzed. The median age was 29 years (range 6–62) and 58% were female. Many H5N1 cases reported fever (92%) and cough (58%) at illness onset, and had lower respiratory findings of tachypnea and dyspnea at admission. All cases progressed rapidly to bilateral pneumonia. Clinical complications included acute respiratory distress syndrome (ARDS, 81%), cardiac failure (50%), elevated aminotransaminases (43%), and renal dysfunction (17%). Fatal cases had a lower median nadir platelet count (64.5×10⁹ cells/L vs 93.0×10⁹ cells/L, p = 0.02), higher median peak lactic dehydrogenase (LDH) level (1982.5 U/L vs 1230.0 U/L, p = 0.001), higher percentage of ARDS (94% [n = 16] vs 56% [n = 5], p = 0.034) and more frequent cardiac failure (71% [n = 12] vs 11% [n = 1], p = 0.011) than nonfatal cases. A higher proportion of patients who received antiviral drugs survived compared to untreated (67% [8/12] vs 7% [1/14], p = 0.003).

Conclusions/Significance

The clinical course of Chinese H5N1 cases is characterized by fever and cough initially, with rapid progression to lower respiratory disease. Decreased platelet count, elevated LDH level, ARDS and cardiac failure were associated with fatal outcomes. Clinical management of H5N1 cases should be standardized in China to include early antiviral treatment for suspected H5N1 cases.     

Bone related health status in adolescent cyclists

Purpose

To describe bone status and analyse bone mass in adolescent cyclists.

Methods

Male road cyclists (n = 22) who had been training for a minimum of 2 years and a maximum of 7 years with a volume of 10 h/w, were compared to age-matched controls (n = 22) involved in recreational sports activities. Subjects were divided in 2 groups based on age: adolescents under 17 yrs (cyclists, n = 11; controls, n = 13) and over 17 yrs (cyclists, n = 11; controls, n = 9). Peak oxygen uptake (VO₂max) was measured on a cycloergometer. Whole body, lumbar spine, and hip bone mineral content (BMC), density (BMD) and bone area were assessed using dual x-ray absorptiometry (DXA). Volumetric BMD (vBMD) and bone mineral apparent density (BMAD) were also estimated.

Results

The BMC of cyclists was lower for the whole body, pelvis, femoral neck and legs; BMD for the pelvis, hip, legs and whole body and legs bone area was lower but higher in the hip area (all, P≤0.05) after adjusting by lean mass and height. The BMC of young cyclists was 10% lower in the leg and 8% higher in the hip area than young controls (P≤0.05). The BMC of cyclists over 17 yrs was 26.5%, 15.8% and 14.4% lower BMC at the pelvis, femoral neck and legs respectively while the BMD was 8.9% to 24.5% lower for the whole body, pelvis, total hip, trochanter, intertrochanter, femoral neck and legs and 17.1% lower the vBMD at the femoral neck (all P≤0.05). Grouped by age interaction was found in both pelvis and hip BMC and BMD and in femoral neck vBMD (all P≤0.05).

Conclusion

Cycling performed throughout adolescence may negatively affect bone health, then compromising the acquisition of peak bone mass.     

Beta defensin-2 is reduced in central but not in distal airways of smoker COPD patients

Background

Altered pulmonary defenses in chronic obstructive pulmonary disease (COPD) may promote distal airways bacterial colonization. The expression/activation of Toll Like receptors (TLR) and beta 2 defensin (HBD2) release by epithelial cells crucially affect pulmonary defence mechanisms.

Methods

The epithelial expression of TLR4 and of HBD2 was assessed in surgical specimens from current smokers COPD (s-COPD; n = 17), ex-smokers COPD (ex-s-COPD; n = 8), smokers without COPD (S; n = 12), and from non-smoker non-COPD subjects (C; n = 13).

Results

In distal airways, s-COPD highly expressed TLR4 and HBD2. In central airways, S and s-COPD showed increased TLR4 expression. Lower HBD2 expression was observed in central airways of s-COPD when compared to S and to ex-s-COPD. s-COPD had a reduced HBD2 gene expression as demonstrated by real-time PCR on micro-dissected bronchial epithelial cells. Furthermore, HBD2 expression positively correlated with FEV1/FVC ratio and inversely correlated with the cigarette smoke exposure. In a bronchial epithelial cell line (16 HBE) IL-1β significantly induced the HBD2 mRNA expression and cigarette smoke extracts significantly counteracted this IL-1 mediated effect reducing both the activation of NFkB pathway and the interaction between NFkB and HBD2 promoter.

Conclusions

This study provides new insights on the possible mechanisms involved in the alteration of innate immunity mechanisms in COPD.     

Poor cognitive flexibility in eating disorders: examining the evidence using the Wisconsin Card Sorting Task

Background

People with eating disorders (ED) frequently present with inflexible behaviours, including eating related issues which contribute to the maintenance of the illness. Small scale studies point to difficulties with cognitive set-shifting as a basis. Using larger scale studies will lend robustness to these data.

Methodology/Principal Findings

542 participants were included in the dataset as follows: Anorexia Nervosa (AN) n = 171; Bulimia Nervosa (BN) n = 82; Recovered AN n = 90; Healthy controls (HC): n = 199. All completed the Wisconsin Card Sorting Task (WCST), an assessment that integrates multiple measurement of several executive processes concerned with problem solving and cognitive flexibility. The AN and BN groups performed poorly in most domains of the WCST. Recovered AN participants showed a better performance than currently ill participants; however, the number of preservative errors was higher than for HC participants.

Conclusions/Significance

There is a growing interest in the diagnostic and treatment implications of cognitive flexibility in eating disorders. This large dataset supports previous smaller scale studies and a systematic review which indicate poor cognitive flexibility in people with ED.     

Erythropoietin levels are not independently associated with malaria-attributable severe disease in Mozambican children

Background

Severe malaria is difficult to differentiate from other forms of malaria or other infections with similar symptoms. Any parameter associated to malaria-attributable severe disease could help to improve severe malaria diagnosis.

Methodology

This study assessed the relation between erythropoietin (EPO) and malaria-attributable severe disease in an area of Mozambique with moderate malaria transmission. 211 children <5 years, recruited at Manhiça District Hospital or in the surrounding villages, were included in one of the following groups: severe malaria (SM, n = 44), hospital malaria without severity (HM, n = 49), uncomplicated malaria (UM, n = 47), invasive bacterial infection without malaria parasites (IBI, n = 39) and healthy community controls (C, n = 32). Malaria was diagnosed by microscopy and IBI by blood/cerebrospinal fluid culture.

Principal Findings

Mean EPO concentration in the control group was 20.95 U/l (SD = 2.96 U/l). Values in this group were lower when compared to each of the clinical groups (p = 0.026 C versus UM, p<0.001 C vs HM, p<0.001 C vs SM and p<0.001 C vs IBI). In the 3 malaria groups, values increased with severity [mean = 40.82 U/l (SD = 4.07 U/l), 125.91 U/l (SD = 4.99U/l) and 320.87 U/l (SD = 5.91U/l) for UM, HM and SM, respectively, p<0.001]. The IBI group [mean = 101.75 U/l (SD = 4.12 U/l)] presented lower values than the SM one (p = 0.002). In spite of the differences, values overlapped between study groups and EPO levels were only associated to hemoglobin. Hemoglobin means of the clinical groups were 93.98 g/dl (SD = 14.77 g/dl) for UM, 75.96 g/dl (SD = 16.48 g/dl) for HM, 64.34 g/dl (SD = 22.99 g/dl) for SM and 75.67 g/dl (SD = 16.58 g/dl) for IBI.

Conclusions

Although EPO levels increase according to malaria severity and are higher in severe malaria than in bacteremia, the utility of EPO to distinguish malaria-attributable severe disease is limited due to the overlap of values between the study groups and the main role of hemoglobin in the expression of EPO.     

Sarcoidosis and tuberculosis cytokine profiles: indistinguishable in bronchoalveolar lavage but different in blood

Background

The clinical, radiological and pathological similarities between sarcoidosis and tuberculosis can make disease differentiation challenging. A complicating factor is that some cases of sarcoidosis may be initiated by mycobacteria. We hypothesised that immunological profiling might provide insight into a possible relationship between the diseases or allow us to distinguish between them.

Methods

We analysed bronchoalveolar lavage (BAL) fluid in sarcoidosis (n = 18), tuberculosis (n = 12) and healthy volunteers (n = 16). We further investigated serum samples in the same groups; sarcoidosis (n = 40), tuberculosis (n = 15) and healthy volunteers (n = 40). A cross-sectional analysis of multiple cytokine profiles was performed and data used to discriminate between samples.

Results

We found that BAL profiles were indistinguishable between both diseases and significantly different from healthy volunteers. In sera, tuberculosis patients had significantly lower levels of the Th2 cytokine interleukin-4 (IL-4) than those with sarcoidosis (p = 0.004). Additional serum differences allowed us to create a linear regression model for disease differentiation (within-sample accuracy 91%, cross-validation accuracy 73%).

Conclusions

These data warrant replication in independent cohorts to further develop and validate a serum cytokine signature that may be able to distinguish sarcoidosis from tuberculosis. Systemic Th2 cytokine differences between sarcoidosis and tuberculosis may also underly different disease outcomes to similar respiratory stimuli.     

Myostatin is elevated in congenital heart disease and after mechanical unloading

Background

Myostatin is a negative regulator of skeletal muscle mass whose activity is upregulated in adult heart failure (HF); however, its role in congenital heart disease (CHD) is unknown.

Methods

We studied myostatin and IGF-1 expression via Western blot in cardiac tissue at varying degrees of myocardial dysfunction and after biventricular support in CHD by collecting myocardial biopsies from four patient cohorts: A) adult subjects with no known cardiopulmonary disease (left ventricle, LV), (Adult Normal), (n = 5); B) pediatric subjects undergoing congenital cardiac surgery with normal RV size and function (right ventricular outflow tract, RVOT), (n = 3); C) pediatric subjects with worsening but hemodynamically stable LV failure [LV and right ventricle (LV, RV,)] with biopsy collected at the time of orthotopic heart transplant (OHT), (n = 7); and D) pediatric subjects with decompensated bi-ventricular failure on BiVAD support with biopsy collected at OHT (LV, RV, BiVAD), (n = 3).

Results

The duration of HF was longest in OHT patients compared to BIVAD. The duration of BiVAD support was 4.3±1.9 days. Myostatin expression was significantly increased in LV-OHT compared to RV-OHT and RVOT, and was increased more than double in decompensated biventricular HF (BiVAD) compared to both OHT and RVOT. An increased myostatin/IGF-1 ratio was associated with ventricular dysfunction.

Conclusions

Myostatin expression in increased in CHD, and the myostatin/IGF-1 ratio increases as ventricular function deteriorates. Future investigation is necessary to determine if restoration of the physiologic myostatin/IGF-1 ratio has therapeutic potential in HF.     

Extravascular lung water correlates multiorgan dysfunction syndrome and mortality in sepsis

Background

This study was designated to investigate whether increased extravascular lung water index (EVLWI) may correlate multiple organ dysfunction syndrome (MODS) and mortality in sepsis.

Methods

We designed a prospective cohort study in an intensive care unit of a tertiary care hospital. Sixty-seven patients with severe sepsis were included. Data were used to determine an association between EVLWI and the development of MODS and mortality. These connections were determined by the multiple logistic regression, plotting the receiver operating characteristic (ROC) curve and by Spearman test.

Results

EVLWI levels were higher in MODS patients on day 1 (median (IQR), 18(12.8–23.9) ml/kg, n = 38, p<0.0001) than in those without (median (IQR), 12.4 (7.9–16.3) ml/kg, n = 29) and day 3 (median (IQR), 17.8 (11.2–22.8) ml/kg, n = 29, p = 0.004) than in those without (median (IQR), 12.4 (8.0–16.3) ml/kg, n = 29). EVLWI was used as an independent predictor of the development of MODS (odds ratio, 1.6; p = 0.005; 95% confidence interval, 1.2∼2.2) during ICU stay. The area under the ROC curve showed that EVLWI levels could predict MODS (0.866) and mortality (0.881) during ICU stay. Meanwhile, the higher of SOFA score, the more EVLWI was found on day 1 (r = 0.7041, p<0.0001) and day 3 (r = 0.7732, p<0.0001).

Conclusions

Increased EVLWI levels correlates development of MODS and mortality during the patients'' ICU stay. Further more, the potential of novel treatment in severe sepsis with lung injury may develop.     

Comprehensive Analysis of Inflammatory Immune Mediators of the Intraocular Fluid Aspirated from the Foldable Capsular Vitreous Body Filled-Eyes

Purpose

To analyze the level of human inflammatory immune mediators in the intraocular fluid aspirated from foldable capsular vitreous body (FCVB) filled-eyes during FCVB removal surgery, 3 months after implantation.

Methods

8 samples of intra-FCVB fluids (n = 8) were collected from 8 FCVB filled patients in our previous FCVB exploratory clinical trial. The intra-FCVB fluids were aspirated from the FCVB filled-eyes during the FCVB removal surgeries at the third month. For the control groups, the vitreous fluids were collected from patients with idiopathic macular hole (n = 9) or rhegmatogenous retinal detachment (n = 6) during pars plana vitrectomy. A multiplex immunoassay was used to determine levels of 9 cytokines (IL-1β, IL-2, IL-6, IL-8, IL-10, IL-17, TNF-α, IFN-γ and VEGF) in these samples. The VEGF level of some intra-FCVB fluids (n = 6) were re-tested using enzyme-linked immunosorbent assay (ELISA).

Results

In the intra-FCVB fluids, 9 cytokines concentrations of most samples (n = 5) measured by Multiplex immunoassay showed low values, except for Patient 02, 06, and 09. The VEGF concentrations of some intra-FCVB fluids (n = 6) tested by ELISA were in accordance with Multiplex immunoassay results. For all eight patients (n = 8), the concentrations of IL-1β, IL-2, IL-6, TNF-α, IFN-γ and VEGF were slightly higher as compared to the idiopathic macular hole control group. While, the concentrations of IL-8, IL-10, and IL-17 were not statistically significant different compared with the idiopathic macular hole control samples. Most cytokines concentrations (IL-2, IL-6, IL-8, IL-10, IL-17, TNF-α, IFN-γ, VEGF) were not statistically significant different compared to the rhegmatogenous retinal detachment control group except IL-1β.

Conclusions

The FCVB had sufficient porosity to allow cytokines to pass through. This study first discovered that the FCVB possesses favorable permeability of proteins in the human eye.     

Regression of moral reasoning during medical education: combined design study to evaluate the effect of clinical study years

Background

Moral reasoning is important for developing medical professionalism but current evidence for the relationship between education and moral reasoning does not clearly apply to medical students. We used a combined study design to test the effect of clinical teaching on moral reasoning.

Methods

We used the Defining Issues Test-2 as a measure of moral judgment, with 3 general moral schemas: Personal Interest, Maintaining Norms, and Postconventional Schema. The test was applied to 3 consecutive cohorts of second year students in 2002 (n = 207), 2003 (n = 192), and 2004 (n = 139), and to 707 students of all 6 study years in 2004 cross-sectional study. We also tested 298 age-matched controls without university education.

Results

In the cross-sectional study, there was significant main effect of the study year for Postconventional (F(5,679) = 3.67, P = 0.003) and Personal Interest scores (F(5,679) = 3.38, P = 0.005). There was no effect of the study year for Maintaining Norms scores. 3^rd year medical students scored higher on Postconventional schema score than all other study years (p<0.001). There were no statistically significant differences among 3 cohorts of 2^nd year medical students, demonstrating the absence of cohort or point-of-measurement effects. Longitudinal study of 3 cohorts demonstrated that students regressed from Postconventional to Maintaining Norms schema-based reasoning after entering the clinical part of the curriculum.

Interpretation

Our study demonstrated direct causative relationship between the regression in moral reasoning development and clinical teaching during medical curriculum. The reasons may include hierarchical organization of clinical practice, specific nature of moral dilemmas faced by medical students, and hidden medical curriculum.     

The spectrum of central nervous system infections in an adult referral hospital in hanoi, Vietnam

Objectives

To determine prospectively the causative pathogens of central nervous system (CNS) infections in patients admitted to a tertiary referral hospital in Hanoi, Vietnam.

Methods

From May 2007 to December 2008, cerebrospinal fluid (CSF) samples from 352 adults with suspected meningitis or encephalitis underwent routine testing, staining (Gram, Ziehl-Nielsen, India ink), bacterial culture and polymerase chain reaction targeting Neisseria meningitidis, Streptococcus pneumoniae, S. suis, Haemophilus influenzae type b, Herpes simplex virus (HSV), Varicella Zoster virus (VZV), enterovirus, and 16S ribosomal RNA. Blood cultures and clinically indicated radiology were also performed. Patients were classified as having confirmed or suspected bacterial (BM), tuberculous (TBM), cryptococcal (CRM), eosinophilic (EOM) meningitis, aseptic encephalitis/meningitis (AEM), neurocysticercosis and others.

Results

352 (male: 66%) patients were recruited: median age 34 years (range 13–85). 95/352 (27.3%) diagnoses were laboratory confirmed and one by cranial radiology: BM (n = 62), TBM (n = 9), AEM (n = 19), CRM (n = 5), and neurocysticercosis (n = 1, cranial radiology). S. suis predominated as the cause of BM [48/62 (77.4%)]; Listeria monocytogenese (n = 1), S. pasteurianus (n = 1) and N. meningitidis (n = 2) were infrequent. AEM viruses were: HSV (n = 12), VZV (n = 5) and enterovirus (n = 2). 5 patients had EOM. Of 262/352 (74.4%) patients with full clinical data, 209 (79.8%) were hospital referrals and 186 (71%) had been on antimicrobials. 21 (8%) patients died: TBM (15.2%), AEM (10%), and BM (2.8%).

Conclusions

Most infections lacked microbiological confirmation. S. suis was the most common cause of BM in this setting. Improved diagnostics are needed for meningoencephalitic syndromes to inform treatment and prevention strategies.