Varicella zoster virus reactivation following COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases: A cross-sectional Chinese study of 318 cases

Recently, varicella-zoster virus (VZV) reactivation has been observed after the administration of coronavirus disease 2019 (COVID-19) vaccines. Autoimmune inflammatory rheumatic diseases (AIIRDs) patients are at a higher risk for VZV reactivation for immunocompromised status. The study aimed to investigate the adverse events (AEs), especially VZV reactivation, following vaccination against  severe acute respiratory syndrome coronavirus-2 in a Chinese cohort of AIIRD patients. A cross-sectional survey using an online questionnaire was conducted among AIIRD patients and healthy controls (HCs). Multivariate logistic regression was used to identify potential factors associated with VZV reactivation. 318 AIIRD patients and 318 age and sex-matched HCs who got COVID-19 inactivated vaccines were recruited. The main AIIRDs are rheumatoid arthritis (31.8%) and systemic lupus erythematous (23.9%). Most of patients (85.5%) had stable disease and 13.2% of them had aggravation after vaccination. Compared to HCs, patients had higher rates of rash (p = 0.001), arthralgia (p < 0.001) and insomnia (p = 0.007). In addition, there were 6 (1.9%) AIIRD patients and 5 (1.6%) HCs reported VZV reactivation after the COVID-19 vaccination (p = 0.761). Multivariate logistic regression analysis illustrated that diabetes mellitus (odd ratio [OR], 20.69; 95% confidence interval [CI], 1.08−396.79; p = 0.044), chronic hepatitis B virus infection (OR, 24.34; 95% CI, 1.27−466.74; p = 0.034), and mycophenolate mofetil (OR, 40.61; 95% CI, 3.33−496.15; p = 0.004) independently identified patients with VZV reactivation. Our findings showed that the inactivated COVID-19 vaccination was safe for AIIRD patients though some patients could suffer from VZV reactivation.     

Effectiveness of a home-based pulmonary rehabilitation programme in pulmonary function and health related quality of life for patients with pulmonary tuberculosis: a pilot study

Background

Patients with Pulmonary Tuberculosis (PTB) often develop impairment in pulmonary function due to anatomical changes secondary to the illness. Physiotherapy in the form of pulmonary rehabilitation has been advocated.

Objective

The aim of the study was to determine whether adherence to a six-week home-based pulmonary rehabilitation programme (PRP) improved the baseline measurements of lung function, exercise tolerance and health-related quality of life (HRQoL) in patients receiving out-patient treatment for PTB.

Method

A single blinded randomized control study design was used to assess the effects of a six-week home- based PRP in patients receiving treatment for PTB at a local clinic in Khayelitsha, Western Cape. We evaluated lung function by spirometry (MINATO AUTOSPIRO-model no. AZ-505), exercise tolerance using the 6-min-walk test (6MWT), the Borg exercise exertion scale and HRQoL using the EQ-5 D questionnaire in an intervention group (n=34) and a control group (n=33). The trend of the effects of the PRP on lung function was towards increases, but there was no statistical difference between the intervention and control groups at the end of the sixth week in the values of FVC (p=0.2; 95% CI −0.9 to 0.51) as well as FEV1 (p=0.1; 95% CI −0.07 to 0.51). Similar trend was observed for exercise tolerance, and there was no significant difference in HRQoL (p=0.789).

Conclusion

The outcome of the study provides motivation for further consideration and implementation of a pulmonary rehabilitation programme for patients with PTB.     

Scoring system for risk stratification of viral reactivation during prophylactic antiviral treatment in Korean patients with hepatitis B undergoing anticancer chemotherapy: A multicenter study

Prophylactic antiviral therapy is recommended for hepatitis B virus (HBV)‐infected patients with malignancies who are undergoing systemic chemotherapy. In the current study, we aimed to develop a risk scoring system to guide the selection of prophylactic antiviral agents. In this retrospective analysis, we included consecutive chronic hepatitis B patients who received antiviral prophylaxis for chemotherapy of solid or hematologic malignancies at three large‐volume hospitals in Korea. The primary endpoint was HBV reactivation. The inverse probability treatment weighting method was used to minimize selection bias in terms of antiviral assignments. A total of 419 patients were enrolled: 129 patients received lamivudine (LAM), 216 received telbivudine (LdT), and 74 received entecavir (ETV), respectively. Of these, 36 patients developed on‐treatment HBV reactivation (LAM, 17; LdT, 18; ETV, 1). Multivariate analysis identified three independent predictors for reactivation: hepatitis B e‐antigen positivity, HBV DNA level, and type of malignancy. Accordingly, a risk scoring system was developed wherein one point was assigned for each of the risk factors. HBV reactivation occurred more frequently in the high‐risk group (score ≥ 2) than in the low‐risk group (hazards ratio, 14.17; P < 0.001). ETV exhibited superior prophylactic efficacy over LdT or LAM in the high‐risk group, whereas no significant difference was noted in the low‐risk group. The prognostic scoring system was useful for risk stratification of chemotherapy‐related HBV reactivation. High genetic barrier agents appear to be vital for high‐risk patients, whereas cost‐effectiveness may be more relevant for low‐risk patients.     

Evaluation of biphasic culture system for mycobacterial isolation from the sputum of patients with pulmonary tuberculosis

Mycobacterial diseases continue to cause high morbidity and mortality. Isolation, identification and sensitivity testing form the backbone of laboratory investigations. M. tuberculosis isolation needs 6-8 weeks on conventional egg containing media. For rapid isolation various methods have been evaluated. We evaluated biphasic system (Middlebrook 7H11 agar slant+Middlebrook 9H broth) in comparison with Lowenstein-Jensen (LJ) medium. In smear positive cases biphasic system showed the recovery rate of 97.05% as against 79.41% on LJ on incubation for 21+/-4.44 and 28+/-3.76 days respectively. In smear negative and culture positive cases biphasic system and LJ showed isolation rates of 91.66% and 66.6% after 36+/-3.44 and 41+/- 4.09 days respectively. Biphasic system showed lower contamination rate (1.33%). Biphasic medium is superior to LJ medium in isolation of M. tuberculosis.     

Vertebral body shape variation in the thoracic and lumbar spine: characterization of its asymmetry and wedging

This study was designed to characterize the vertebral body (VB) shape, focusing on vertebral wedging, along the thoracic and lumbar spine, and to look for shape variations with relation to gender, age, and ethnicity. All thoracic and lumbar (T1-L5) dissected vertebrae of 240 individuals were measured and analyzed by age, gender, and ethnicity. A 3D digitizer was used to measure all VB lengths, heights, and widths, and their ratios were calculated. This study showed that the VB size was independent of age or ethnicity. VB left lateral wedging was found in most vertebrae of most individuals, yet systematically was absent in six vertebrae (T4, T8-T9, T11, L3-L4) with a greater tendency in females than males ( approximately 92% vs. 86%). The VB was anteriorly wedged from T1 through L2 (peak at T7), nonwedged at L3, and posteriorly wedged at L4-L5 (peak at L5). VB width decreased from T1 to T4 and then increased toward L4-L5, so that the spinal configuration in the coronal plane resembled two pyramids of opposite directions, sharing an apex at T4. The inferior VB width was significantly greater than the superior width of both the same vertebra and the adjacent lower vertebra, indicating a trapezoidal shape of the VB and an inverted trapezoidal shape of the intervertebral space. In conclusion, these findings indicate that the human vertebra, in its normal condition, maintains its external dimensions with age, independent of gender or ethnic origin. Clinical and surgical implications of the unique thoracolumbar architecture are discussed.     

The Genetics of Obesity: What Have Genetic Studies Told Us About the Environment

Genetic studies have shown that both childhood and adult body mass index are substantially heritable. The evidence for shared family environmental influences is largely absent, even though there are clear indications that secular changes in energy expenditure have brought about a significant increase in the prevalence of obesity. This apparent inconsistency may be explained by the dual phenomena of the near-universality of access to environments that facilitate reductions in energy expenditure (e.g., TV as a recreational pastime), together with heritable individual differences in the response to or utilization of these environments. The impact of changes in nonshared environments on body weight can be estimated from biometrical genetical studies and is found to be both small and relatively short-lived. Genetic and environmental results from longitudinal studies are consistent with what is known about the changing distribution of adiposity during adulthood and clinical experience of the difficulty of maintaining behavioral-induced weight loss.     

Protection conferred by heterologous vaccination against tuberculosis is dependent on the ratio of CD4+/CD4+ Foxp3+ cells

CD4⁺ Foxp3⁺ regulatory T cells inhibit the production of interferon‐γ, which is the major mediator of protection against Mycobacterium tuberculosis infection. In this study, we evaluated whether the protection conferred by three different vaccines against tuberculosis was associated with the number of spleen and lung regulatory T cells. We observed that after homologous immunization with the 65 000 molecular weight heat‐shock protein (hsp 65) DNA vaccine, there was a significantly higher number of spleen CD4⁺ Foxp3⁺ cells compared with non‐immunized mice. Heterologous immunization using bacillus Calmette–Guérin (BCG) to prime and DNA‐hsp 65 to boost (BCG/DNA‐hsp 65) or BCG to prime and culture filtrate proteins (CFP)‐CpG to boost (BCG/CFP‐CpG) induced a significantly higher ratio of spleen CD4⁺/CD4⁺ Foxp3⁺ cells compared with non‐immunized mice. In addition, the protection conferred by either the BCG/DNA‐hsp 65 or the BCG/CFP‐CpG vaccines was significant compared with the DNA‐hsp 65 vaccine. Despite the higher ratio of spleen CD4⁺/CD4⁺ Foxp3⁺ cells found in BCG/DNA‐hsp 65‐immunized or BCG/CFP‐CpG‐immunized mice, the lungs of both groups of mice were better preserved than those of DNA‐hsp 65‐immunized mice. These results confirm the protective efficacy of BCG/DNA‐hsp 65 and BCG/CFP‐CpG heterologous prime‐boost vaccines and the DNA‐hsp 65 homologous vaccine. Additionally, the prime‐boost regimens assayed here represent a promising strategy for the development of new vaccines to protect against tuberculosis because they probably induce a proper ratio of CD4⁺ and regulatory (CD4⁺ Foxp3⁺) cells during the immunization regimen. In this study, this ratio was associated with a reduced number of regulatory cells and no injury to the lungs.     

Association of body mass index with respiratory symptoms and atopy: results from the European Community Respiratory Health Survey

BACKGROUND: There are several reports showing that obese adults report more respiratory symptoms suggestive of asthma than those who are not obese. OBJECTIVE: To determine the association of body mass index with respiratory symptoms and atopy in young adults METHOD: Information collected from 15,454 participants in the European Community Respiratory Health Survey, a multicentre cross-sectional survey of young adults, was analysed to determine the association of body mass index with respiratory symptoms and atopy. RESULTS: Men and women with a body mass index of greater than 30 were at an increased risk of wheeze with shortness of breath compared with those with a body mass of 20-24.99 (OR in men 1.85, 95% confidence interval 1.41-2.42; OR in women 2.03, 95% confidence interval 1.59-2.58). Similar associations were observed for other symptoms suggestive of asthma. Body mass index was not associated with 'hayfever or nasal allergies', specific IgE to house dust mite, grass or cat or with total IgE in men or women. CONCLUSION: Reported associations of body mass index with symptoms suggestive of asthma are unlikely to be explained by a higher risk of atopy in the obese. Alternative explanations must be sought.     

Analysis of three RFLPs of the COL1A2 (Type I Collagen) in the Amhara and the Oromo of Ethiopia

Background : The present composition of the Ethiopian population is the result of a complex and extensive intermixing of different peoples of North African, Near and Middle Eastern, and south-Saharan origin. The two main groups inhabiting the country are the Amhara, descended from Arabian conquerors, and the Oromo, the most important group among the Cushitic people. With the exception of some surveys on the general Ethiopian populations, little is known about the degree of genetic differentiation between the Amhara and the Oromo. Aim : The study seeks to investigate the genetic structure of these two heterogeneous Ethiopian populations and to characterize their relationships with other African and Mediterranean peoples. Subjects and methods : Amhara and Oromo individuals ( n = 171) were analysed for three RFLPs (restriction fragment length polymorphisms) of the COL1A2 gene. To better define the genetic relationship between the two Ethiopian groups, and also between African and non-African peoples, genetic distances among Amhara, Oromo and other populations were estimated using the COL1A2 allele and haplotype frequencies, and the allele frequencies of 16 additional classical markers. Results : &#104 2 analysis applied to the COL1A2 allele and haplotype frequencies showed a small but statistically significant degree of heterogeneity between the two Ethiopian populations. Combining the information obtained from the three RFLP markers, a significant level of differentiation (Fst = 0.0147, p = 0.036) was also detected between Amhara and Oromo. The genetic distance analysis showed the separation between African and non-African populations, with the Amhara and Oromo located in an intermediate position. This pattern is consistent with the location of the two Ethiopian groups in other genetic analysis and with cultural data. Conclusions : The present findings suggest the presence of a differential level of genetic relatedness with south-Saharan peoples in the two Ethiopian groups, which could reflect their different history and seems to indicate the existence of genetic sub-structure within the country.     

A Proposed Heuristic for Communicating Heritability Estimates to the General Public, with Obesity as an Example

It is well established that many continuously distributed traits have a heritable component. However, it is often difficult to communicate to the general public the meaning of quantitative estimates of heritability. To address this problem, the present paper introduces a heuristic for communicating heritability to nonscientific audiences. This heuristic involves adopting an extremely simplified model of inheritance and artificially (and somewhat arbitrarily) defining a cutoffs of low environmental risk and affectation status. Using body weight and obesity as an example, we present a table which gives estimates of the proportion of obese persons who are genetically obese assuming varying levels of environmental risk for obesity and relative body weight scores for defining obesity. The resulting statistic may prove useful for lay audiences in understanding a heritability estimate.     

Waist-to-Height Ratio as an Index for Cardiometabolic Risk in Adolescents: Results from the 1998-2008 KNHANES

PurposeTo describe the relationship between the waist-to-height ratio (WHtR) and cardiometabolic risk factors (CMRFs) and to evaluate the validity of WHtR in identifying adolescents with metabolic syndrome.ResultsWHtR was significantly related to systolic blood pressure, HDL-C, and triglycerides in both non-overweight and overweight adolescents (all p<0.01). Among overweight adolescents, the area under the curve (AUC) for WHtR in identifying multiple CMRFs was significantly greater than that for BMI (p=0.014). Metabolic syndrome was more common in overweight adolescents with a WHtR of ≥0.5 than in those with a WHtR of <0.5 (p<0.001). In non-overweight adolescents, the prevalences of multiple CMRFs (p=0.001) and metabolic syndrome (p<0.001) were higher in those with a WHtR of ≥0.5 than in those with a WHtR of <0.5. Among those without central obesity, the prevalence of multiple CMRFs was higher in those with a WHtR of ≥0.5 than in those with a WHtR of <0.5 (p=0.021).ConclusionWHtR is a simple and valid index for identifying adolescents with increased cardiometabolic risk and is related to CMRFs even in non-overweight adolescents. In adolescents already screened via BMI and waist circumference (WC), WHtR seems to be of additional help in discriminating those at higher cardiometabolic risk.     

Effects of fat on MR‐measured metabolite signal strengths: implications for in vivo MRS studies of the human brain

Recent MRS studies have indicated that a higher body mass index (BMI) is associated with lower brain metabolite levels. Generally, individuals with higher BMIs have more body fat deposits than individuals with normal BMIs. This single‐voxel spectroscopy (SVS) study investigated possible effects of fat on MR‐measured metabolite signal areas, which may at least partly explain the observed associations of BMI with MR‐measured brain metabolite levels in vivo. SVS data were acquired at 4 T from a phantom containing N‐acetylaspartate, glutamate and creatine, as well as from three healthy male adults. Back fat obtained from pig was used to assess the effects of fat on metabolite signals. With the same voxel size and placement, the phantom was first scanned without fat (baseline), and then with 0.7‐cm‐ and 1.4‐cm‐thick fat layers placed on it. Each participant was also scanned first without fat and then with two 0.7‐cm fat layers, one placed beneath the occiput and the other on the forehead. Two spectra were acquired per participant from the anterior cingulate and the parieto‐occipital cortices. The metabolite resonance and corresponding water peak areas were then fitted and metabolite to water signal ratios were used for analyses. In both phantom and in vivo experiments, the metabolite‐to‐water ratios decreased in the presence of fat relative to baseline metabolite‐to‐water ratios. The reduced metabolite signals in the presence of fat reported here are reminiscent of the negative correlations observed between BMI and MR‐measured metabolite levels. These apparent physical effects of fat have potentially far‐reaching consequences for the accuracy of MR measurements of brain metabolite levels and their interpretation, particularly when large fat stores exist around the skull, such as in individuals with higher BMI. Copyright © 2013 John Wiley & Sons, Ltd.     

Trends in the epidemiology of chronic obstructive pulmonary disease in England: a national study of 51 804 patients

Background

Patients with chronic obstructive pulmonary disease (COPD) constitute a substantial burden to healthcare services. Analysis of national healthcare datasets offers the possibility to advance understanding about the changing epidemiology of COPD.

Aim

To investigate the epidemiology of physician-diagnosed COPD in general practice.

Design of study

Cross-sectional study.

Settings

A total of 422 general practices in England contributing to the QRESEARCH database.

Method

Data were extracted on 2.8 million patients, including age, sex, socioeconomic status, and geographical area. Trends over time for recorded physician diagnosis of COPD were analysed (2001–2005).

Results

There was little change over time in the incidence rate of COPD (2005: 2.0 per 1000 patient-years, 95% confidence interval [CI] = 2.0 to 2.1), but a significant increase in lifetime prevalence rate (2001: 13.5 per 1000 patients [95% CI = 13.4 to 13.7]; 2005: 16.8 [95% CI = 16.7 to 17.0]; P<0.001). In 2005, 51 804 individuals or one in 59 people in England were recorded with physician-diagnosed COPD. The most deprived people (31.1 per 1000 patients; 95% CI = 30.6 to 31.7) and those living in the north east of England (29.2 per 1000 patients; 95% CI = 28.4 to 30.1) had the highest prevalence. The observed reduction in the rate of smoking by patients with COPD (overall decrease: 2.5%; P<0.001) varied according to socioeconomic group (most affluent: 6.5% decrease, most deprived: 1.3% decrease).

Conclusion

Given the peak in the incidence rate of COPD, we may be approaching the summit of COPD incidence and prevalence in England. However, the number of people affected remains high and poses a major challenge for health services, particularly those in the north east of the country and in the most deprived communities in England. The very limited decrease in smoking rates among the more deprived groups of patients with COPD is also a cause for concern.     

Considering the vascular hypothesis for the pathogenesis of small intestinal atresia: A case control study of genetic factors

Small intestinal atresia (SIA) is a rare congenital occlusion of the small intestine. SIA development, particularly in the jejunum and ileum, has been associated with in utero disruption of vascular supply. However, the number of studies of the vascular hypothesis is limited. This study considers the vascular hypothesis by exploring risks associated with 32 SNPs of genes involved in vascular processes of homocysteine metabolism, coagulation, cell–cell interactions, inflammatory response, and blood pressure regulation. A total of 206 SIA cases were ascertained by the California Birth Defects Monitoring Program, and 573 infants with no major congenital anomalies by their first birthday were selected as controls. Genomic DNA was genotyped for 32 SNPs involving the following genes: MTHFR, F2, F5, F7, SERPINE1, FGB, ITGA2, ITGB3, SELE, ICAM1, MMP3, TNF, LTA, NOS3, AGTR1, AGT, NPPA, ADD1, SCNN1A, GNB3, and ADRB2. Risks were estimated as odds ratios, adjusted for maternal age and race, with 95% confidence intervals. Cases were considered collectively and by subgroups based on atresia location (duodenal/jejunum/ileum). Three SNPs had reduced risk: SERPINE1 11053 T/G, MMP3 (‐1171) A6/A5, and ADRB2 gln27glu. Two had increased risk: ITGA2 873 G/A and NPPA 2238 T/C. No intestinal subphenotypes showed a unique pattern of SNP associations. The association of two SNPs with increased risk lends some, albeit limited, support to vascular impairment as a possible mechanism leading to SIA. These results also identify genes meriting further exploration in SIA studies. Hence, this study makes an important contribution by exploring the long‐held but not well‐investigated vascular hypothesis. © 2013 Wiley Periodicals, Inc.     

Evaluation of multiplex Polymerase chain reaction utilising multiple targets in Mycobacterium tuberculosis direct test negative but culture positive cases: A potential method for enhancing the diagnosis of tuberculosis

Purpose: To evaluate multiplex Polymerase Chain Reaction (MPCR) utilising multiple targets (IS6110, Protein b [Pab] and MPB64 genes) in Mycobacterium tuberculosis Direct Test (MTD) negative but culture positive cases and comparison of MPCR with Real-Time polymerase chain reaction (RT-PCR) for diagnosis of tuberculosis. Materials and Methods: MPCR was carried out on 28 culture positive sputum samples. Out of 28 culture positive samples, 17 were originally reported, as MTD test negative and 11 were MTD test positive, respectively. The results of MPCR were compared with RT-PCR. To check the specificity of the tests, MPCR and RT-PCR were also evaluated with 16 non-tuberculous mycobacterial (NTM) isolates. Results: Out of 28 culture positive sputum samples, MPCR was positive in all 28/28 samples, whereas RT-PCR was positive in 27/28 samples and MTD test was originally tested positive in six sputum samples and on repeating MTD testing, five more sputum samples were positive and thus total number of MTD positive were 11/28 sputum samples, respectively. All the tests were negative on evaluation with all the 16 NTMs, thus giving specificity of 100% to all the tests; sensitivity of MPCR, RT-PCR and MTD tests were 100%, 96.42% and 39.28%, respectively, in these specifically selected samples. Conclusions: MPCR may be an important tool in the rapid diagnosis of tuberculosis especially in disease endemic, resource limited countries.