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Vitamin-D deficiency predicts infections in young north Indian children: A secondary data analysis
No full textRecent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this paper, we examined the extent to which vitamin-D deficiency (<10 ng/ml) predicts ALRI, clinical pneumonia and diarrhea among 6 to 30 months old children.We used data from a randomized controlled trial (RCT) of daily folic acid and/or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Generalized estimating equations (GEE) were used to examine the associations between vitamin-D deficiency and episodes of ALRI, clinical pneumonia and diarrhea.Of the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status and season), that the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not associated with episodes of diarrhea or clinical pneumonia.Vitamin-D deficiency is common in young children in New Delhi and is associated with a higher risk of ALRI. The role of vitamin D in Indian children needs to be elucidated in further studies
Morphogene adsorption as a Turing instability regulator: Theoretical analysis and possible applications in multicellular embryonic systems
No full text-specific serology evaluated in a Brazilian cohort of leprosy patients (U-MDT/CT-BR)
No full text is suitable to evaluate its prognostic value for the development of reactions.IgM and IgG antibody responses to PGL-I, LID-1, ND-O-LID were evaluated by ELISA in 452 reaction-free leprosy patients at diagnosis, enrolled and monitored for the development of leprosy reactions during a total person-time of 780,930 person-days, i.e. 2139.5 person-years, with a maximum of 6.66 years follow-up time.Among these patients, 36% (160/452) developed reactions during follow-up: 26% (119/452) RR and 10% (41/452) had ENL. At baseline higher anti-PGL-I, anti-LID-1 and anti-ND-O-LID seropositivity rates were seen in patients who developed ENL and RR compared to reaction-free patients (p<0.0001). Seroreactivity in reactional and reaction-free patients was stratified by bacilloscopic index/BI categories. Among BI negative patients, higher anti-PGL-I levels were seen in RR compared to reaction-free patients (p = 0.014). In patients with 0<BI<3, (36 RR, 36 reaction-free), higher antibody levels to PGL-I (p = 0.014) and to LID-1 (p = 0.035) were seen in RR while difference in anti-ND-O-LID positivity was borderline (p = 0.052). Patients with BI≥3 that developed ENL had higher levels of anti-LID-1 antibodies (p = 0.028) compared to reaction-free patients. Anti-PGL-I serology had a limited predictive value for RR according to receiver operating curve/ROC analyses (area-under-the-curve/AUC = 0.7). Anti LID-1 serology at baseline showed the best performance to predict ENL (AUC 0.85).Overall, detection of anti-PGL-I, anti-LID-1 and anti-ND-O-LID antibodies at diagnosis, showed low sensitivity and specificity for RR prediction, indicating low applicability of serological tests for RR prognosis. On the other hand, anti-LID-1 serology at diagnosis has shown prognostic value for ENL development in BI positive patients
Cutaneous HPV8 and MmuPV1 E6 Proteins Target the NOTCH and TGF-β Tumor Suppressors to Inhibit Differentiation and Sustain Keratinocyte Proliferation
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Mutations Cause a Marinesco-Sjögren-Like Syndrome: Genetic and Biochemical Studies
No full textWith the advent new sequencing technologies, we now have the tools to understand the phenotypic diversity and the common occurrence of phenocopies. We used these techniques to investigate two Norwegian families with an autosomal recessive cerebellar ataxia with cataracts and mental retardation. in both families, c.1528_1529del [p.Met510Valfs*17]. Furthermore, we report the biochemical characterization of GBA2 in these patients. Our studies show that a reduced activity of GBA2 is sufficient to elevate the levels of glucosylceramide to similar levels as seen in Gaucher disease. Furthermore, leucocytes seem to be the proper enzyme source for in vitro analysis of GBA2 activity. mutations, and suggest that patients with Marinesco-Sjögren-like syndromes should be tested for mutations in this gene
Multi-arm Cost-Effectiveness Analysis (CEA) comparing different durations of adjuvant trastuzumab in early breast cancer, from the English NHS payer perspective
No full textTrastuzumab improves survival in HER2+ breast cancer patients, with some
evidence of adverse cardiac side effects. Current recommendations are to
give adjuvant trastuzumab for one year or until recurrence, although
trastuzumab treatment for only 9 or 10 weeks has shown similar survival
rates to 12-month treatment. We present here a multi-arm joint analysis
examining the relative cost-effectiveness of different durations of adjuvant
trastuzumab.Network meta-analysis (NMA) was used to examine which trials’ data to
include in the cost-effectiveness analysis (CEA). A network using FinHer (9
weeks vs. zero) and BCIRG006 (12 months vs. zero) trials offered the only
jointly randomisable network so these trials were used in the CEA. The 3-arm
CEA compared costs and quality-adjusted life-years (QALYs) associated with
zero, 9-week and 12-month adjuvant trastuzumab durations in early breast
cancer, using a decision tree followed by a Markov model that extrapolated
the results to a lifetime time horizon. Pairwise incremental
cost-effectiveness ratios (ICERs) were also calculated for each pair of
regimens and used in budget impact analysis, and the Bucher method was used
to check face validity of the findings. Addition of the PHARE trial (6
months vs. 12 months) to the network, in order to create a 4-arm CEA
including the 6-month regimen, was not possible as late randomisation in
this trial resulted in recruitment of a different patient population as
evidenced by the NMA findings. The CEA results suggest that 9 weeks’
trastuzumab is cost-saving and leads to more QALYs than 12 months’,
i.e. the former dominates the latter. The cost-effectiveness acceptability
frontier (CEAF) favours zero trastuzumab at willingness-to-pay levels below
£2,500/QALY and treatment for 9 weeks above this threshold. The
combination of the NMA and Bucher investigations suggests that the 9-week
duration is as efficacious as the 12-month duration for distant-disease-free
survival and overall survival, and safer in terms of fewer adverse cardiac
events.Our CEA results suggest that 9-week trastuzumab dominates 12-month
trastuzumab in cost-effectiveness terms at conventional thresholds of
willingness to pay for a QALY, and the 9-week regimen is also suggested to
be as clinically effective as the 12-month regimen according to the NMA and
Bucher analyses. This finding agrees with the results of the E2198
head-to-head study that compared 10 weeks’ with 14 months’
trastuzumab and found no significant difference. Appropriate trial design
and reporting is critical if results are to be synthesisable with existing
evidence, as selection bias can lead to recruitment of a different patient
population from existing trials. Our analysis was not based on head-to-head
trials’ data, so the results should be viewed with caution.
Short-duration trials would benefit from recruiting larger numbers of
participants to reduce uncertainty in the synthesised results
Prediction of diuretic response to tolvaptan by a simple, readily available spot urine Na/K ratio
No full textTolvaptan is vasopressin type 2 receptor antagonist that inhibits water reabsorption. It is used in combination with standard diuretics to treat ascites unresponsive to standard diuretic therapy or hyponatremia because of liver cirrhosis. This study evaluated the effectiveness and safety of tolvaptan in clinical practice and aimed to determine the factors related to its effectiveness.Tolvaptan was administered to 88 consecutive cirrhotic patients with ascites unresponsive to standard diuretic therapy. An effective treatment response was a ≥2% reduction in body weight on day 7. The association of patient pretreatment characteristics with therapeutic effects was analyzed.Mean weight reduction on day 7 of tolvaptan therapy was −2.9% ± 3.2%, and treatment was effective in 52% of patients. Multivariate analysis revealed that spot urine Na/K ratio ≥2.5 at baseline was the only factor independently related to therapeutic effect, with an odds ratio of 7.85 (95% confidence interval 2.64–23.40, p = 0.0002). Weight reduction percentage on day 7 was −4.0% ± 2.8% in patients with spot urine Na/K ≥2.5, which was significantly greater than the 0.7% ± 2.7% loss in those with urine Na/K < 2.5 (p < 0.05). A spot urine Na/K ratio ≥2.5 had a sensitivity of 85% and specificity of 60% for predicting effective treatment. No adverse events of treatment led to treatment discontinuation.Baseline spot urine Na/K was predictive of an effective response to tolvaptan therapy. It is simple to perform and readily available and might serve as an indicator of optimal timing of tolvaptan administration in patients with inadequate response to conventional Na diuretic therapy
