A Self-Observation Study of Headache Symptoms in Children

SYNOPSIS
The purpose of the present study was to examine symptom configurations experienced by children with problem headache and to determine whether headache symptoms in children can be analyzed along a continuum of severity. Forty-seven children between the ages of 8 and 17 years monitored their headache activity on a daily basis for a 3-week period. The self-observation data indicated that children did not show a tendency to experience their headache symptoms in terms of distinct muscle contraction and migraine symptom clusters. On the contrary, both categories of symptoms were observed to increase in frequency with increasingly problematic headaches. The presence of both muscle contraction and migraine symptoms increased in a linear fashion with the number of daily headache hours reported by the children during the self-observation period. The measure of headache hours also correlated significantly with the total number of head pain locations and symptoms reported by the children. A regression analysis revealed that the symptom of nausea with the addition of the symptoms of dull and aching pain, bilateral forehead pain, feelings of tightness and pressure, and light sensitivity accounted for 77% of the variance associated with the severity measure of headache hours. Further support for viewing headaches in children in terms of severity came from an analysis of the time of onset of headache activity characteristic of the different children in the sample. Children with more severe headache activity experienced their attacks at an earlier time of day than children with less severe headache activity. Overall, the self-observation data provided additional support for the severity model and supported the utility of extending the model to the study of headache disorders in children.     

Principal component analysis of dissolution data with missing elements

The use of principal component analysis (PCA) for incomplete dissolution data sets is examined. The PC space is constructed using a reference set and the test set is projected in that space. Several cases such as a reference set with missing data, an incomplete test set and both sets measured at different time points, are discussed using two examples: one simulation and one obtained from the pharmaceutical practice. From the many possibilities to deal with missing data, the expectation-maximization algorithm in combination with PCA was chosen. The influence on the similarity or f2 factor is examined too. The sampling with replacement or bootstrap technique, which can be used to obtain confidence limits, can also be used when missing data are present in one of the data sets.     

Comparison of hepatitis C virus testing recommendations in high-income countries

AIM To investigate hepatitis C virus(HCV) testing recommendations from the United States and other high-income countries.METHODS A comprehensive search for current HCV testing recommendations from the top quartile of United Nations Human Development Index(HDI) countries(very high HDI) was performed using Google and reviewed from May 1-October 30, 2014 and re-reviewed April 1-October 2, 2017. RESULTS Of the 51 countries identified, 16 had HCV testing recom-mendations from a government body or recommendations issued collaboratively between a government and a medical organization. Of these 16 countries, 15 had HCV testing recommendations that were primarily risk-based and highlight behaviors, exposures, and conditions that are associated with HCV transmission in that region. In addition to risk-based testing, the HCV Guidance Panel(United States) incorporates recommendations for aone-time test for individuals born during 1945-1965(the birth cohort) without prior ascertainment of risk into their guidance. In addition to the United States, six other countries either have an age-based testing recommendation or recommend one-time testing for all adults independent of risk factors typical of the region. CONCLUSION This review affirmed the similarities of the HCV Guidance Panel's guidance with those of recommendations from very high HDI countries.     

Use of mixed-treatment-comparison methods in estimating efficacy of treatments for heavy menstrual bleeding

Background

A variety of pharmacological and surgical treatments have been developed for heavy menstrual bleeding (HMB), which can have negative physical, social, psychological, and economic consequences. We conducted a systematic literature review and mixed-treatment-comparison (MTC) meta-analysis of available data from randomized controlled trials (RCTs) to derive estimates of efficacy for 8 classes of treatments for HMB, to inform health-economic analysis and future studies.

Methods

A systematic review identified RCTs that reported data on menstrual blood loss (MBL) at baseline and one or more follow-up times. Eight treatment classes were considered: COCs, danazol, endometrial ablation, LNG-IUS, placebo, progestogens given for less than 2 weeks out of 4 during the menstrual cycle, progestogens given for close to 3 weeks out of 4, and TXA. The primary measure of efficacy was the proportion of women who achieved MBL < 80 mL per cycle (month), as measured by the alkaline hematin method. A score less than 100 on an established pictorial blood-loss assessment chart (PBAC) was considered an acceptable substitute for MBL < 80 mL. Estimates of efficacy by treatment class and time were obtained from a Bayesian MTC model. The model also included effects for treatment class, study, and the combination of treatment class and study and an adjustment for baseline mean MBL. Several methodological challenges complicated the analysis. Some trials reported various summary statistics for MBL or PBAC, requiring estimation (with less precision) of % MBL < 80 mL or % PBAC < 100. Also, reported follow-up times varied substantially.

Results

The evidence network involved 34 RCTs, with follow-up times from 1 to 36 months. Efficacy at 3 months of follow-up (estimated as the posterior median) ranged from 87.5% for the levonorgestrel-releasing intrauterine system (LNG-IUS) to 14.2% for progestogens administered for less than 2 weeks out of 4 in the menstrual cycle. The 95% credible intervals for most estimates were quite wide, mainly because of the limited evidence for many combinations of treatment class and follow-up time and the uncertainty from estimating % MBL < 80 mL or % PBAC < 100 from summary statistics.

Conclusions

LNG-IUS and endometrial ablation are very efficacious in treating HMB. The study yielded useful insights on using MTC in sparse evidence networks. Diversity of outcome measures and follow-up times in the HMB literature presented considerable challenges. The Bayesian credible intervals reflected the various sources of uncertainty.     

The E23K variant in the Kir6.2 subunit of the ATP-sensitive K+ channel does not augment impaired glucose tolerance in Caribbean subjects with a family history of type 2 diabetes

The E23K variant of the Kir6.2 gene has been shown to be associated with type 2 diabetes mellitus in Caucasian subjects. Because offspring of type 2 diabetic patients have a genetically increased risk of developing diabetes, we sought to identify the E23K variant of the Kir6.2 gene in offspring of Caribbean patients with type 2 diabetes and assess the contribution of this variant to impaired glucose tolerance in these subjects. Forty-six offspring of patients with type 2 diabetes and 39 apparently healthy subjects whose immediate parents were not diabetic ('control') were studied after an overnight fast. Anthropometric indices were measured and blood samples were collected. Fasting and 2 h plasma glucose, insulin and lipids were subsequently determined. Insulin resistance was calculated using the homeostatic model assessment technique. The offspring and control subjects had similar frequencies of the E23K polymorphism (52.6 vs 45.5%, P>0.05) and the frequency of the E23K variant did not differ significantly between gender and ethnic distributions, irrespectively of a family history of diabetes (P>0.05). There were no significant differences in biochemical risk factors for developing diabetes in offspring carriers of the E23K variant compared with offspring non-carriers of the mutation. Offspring with the E23K mutation had even significantly higher 2 h insulin concentrations when compared with control subjects. It is concluded that the presence of the Kir6.2 E23K genotype in Caribbean subjects with an immediate positive family history of diabetes does not confer significantly higher levels of biochemical risk factors for the development of type 2 diabetes.