Development of A Minimum Dataset for the Monitoring of Recombinant Human Growth Hormone (rhGH) Therapy Use in Children with Growth Hormone Deficiency (GHD) - A GloBE-Reg Initiative.

Introduction Although there are some recommendations in the literature on the assessments that should be performed in children on recombinant human growth hormone (rhGH) therapy, the level of consensus on these measurements is not clear. The objective of the current study was to identify the minimum dataset (MDS) that could be measured in a routine clinical setting across the world, aiming to minimise burden on clinicians and improve quality of data collection. Methods This study was undertaken by the GH Scientific Study Group (SSG) in GloBE-Reg, a new project that has developed a common registry platform that can support long-term safety and effectiveness studies of drugs. Twelve clinical experts from 7 international endocrine organisations identified by the GloBE-Reg Steering Committee, 2 patient representatives and representatives from 2 pharmaceutical companies with previous GH registry expertise collaborated to develop this recommendation. A comprehensive list of data fields routinely collected by each of the clinical and industry experts for children with GHD was compiled. Each member was asked to determine the: (1) Importance of the data field and (2) Ease of data collection. Data fields that achieved 70% consensus in terms of importance qualified for the MDS, provided <50% deemed the item difficult to collect. Results A total of 246 items were compiled and 27 removed due to redundancies, with 219 items subjected to the grading system. Of the 219 items, 111 achieved at least 70% consensus as important data to collect when monitoring children with GH deficiency (GHD) on rhGH treatment. Sixty-nine of the 219 items were deemed easy to collect. Combining the criteria of importance and ease of data collection, 63 met the criteria for the MDS. Several anomalies to the MDS rule were identified and highlighted for discussion, including whether the patients were involved in current or previous clinical trials, need for HbA1c monitoring, other past medical history, and adherence, enabling formulation of the final MDS recommendation of 43 items; 20 to be completed once, 14 every 6 months and 9 every 12 months. Conclusion In summary, this exercise performed through the GloBE-Reg initiative provides a recommendation of the minimum dataset requirement, collected through real-world data, for the monitoring of safety and effectiveness of rhGH in children with GHD, both for the current daily preparations and the newer long-acting growth hormone.

The I-CAH Registry: A platform for international collaboration for improving knowledge and clinical care in congenital adrenal hyperplasia.

To provide an overview of the I-CAH Registry. Following the successful roll-out of the I-DSD Registry in the 2000s, it was felt that there was a need for a registry for congenital adrenal hyperplasia (CAH) and this was launched in 2014 as a dedicated module within the original registry. In addition to supporting and promoting research, the I-CAH Registry acts as an international tool for benchmarking of clinical care and it does this through the collection of standardised data for specific projects. Surveillance of novel therapies in the field of CAH can also be achieved via global collaborations. Its robust governance ensures adherence to the international standards for rare disease registries. Rare disease registries such as the I-CAH Registry are important tools for all stakeholders involved in the care of people with CAH.

Design, synthesis and preliminary biological studies of pyrrolidine derivatives as Mcl-1 inhibitors.

Anti-apoptotic proteins, such as B-cell lymphoma (Bcl-2) protein, myeloid cell leukemia sequence 1 (Mcl-1) protein, are potential targets for cancer treatment. In the studies, a series of pyrrolidine derivatives were developed as potent Mcl-1 inhibitors. The preliminary biological studies suggested that most of target compounds exhibit good abilities for targeting Mcl-1 protein. Among them, compound 21 (Ki=0.53µM) exhibited equal inhibitory activities towards Mcl-1 protein compared to positive control gossypol (Ki=0.39µM). This compound also possessed good antiproliferative activities against MDA-MB-231 and PC-3 cancer cells.

Association between PON1 L55M polymorphism and ischemic stroke: a systematic review and meta-analysis.

OBJECTIVE: The present study aims to evaluate the relation between PON1 L55M polymorphism and ischemic stroke by a meta-analysis method. METHODS: English and Chinese databases were retrieved to find qualified studies; a random or fixed effects model was used to merge the odds ratio (OR); Q test was used to assess the heterogeneity among studies, and Egger's test and funnel plot were used for the assessment of publication bias. RESULTS: 14 studies were included in the meta-analysis; in total populations, there was no association between PON1 gene L55M polymorphism and ischemic stroke in additive, dominant, and recessive model, respectively. Furthermore, we did not found associations between L55M and ischemic stroke in Asian or Caucasian population. CONCLUSION: Available evidences suggested that L55M polymorphism had no effect on the risk of ischemic stroke. However, this conclusion needs further validation by larger sample and well-designed studies.

Early enteral and parenteral nutritional support after hepatectomy in patients with hepatic carcinoma: a systematic review and meta-analysis.

BACKGROUND: This study sought to conduct a systematic review providing a comparative analysis of enteral nutrition (EN) and parenteral nutrition (PN) after hepatectomy. METHODS: PubMed, Embase, and the China National Knowledge Infrastructure databases were searched for publications describing randomized controlled trials that compared early EN and PN after hepatectomy. The time period for this search was from January 1990 to December 2013. In accordance with the inclusion criteria of this study, two researchers independently screened the retrieved literature, extracted data, and assessed methodological quality. A meta-analysis of the included publications was then performed using RevMan 5.2 software. RESULTS: The meta-analysis results indicated statistically significant differences between the group that received EN and the group that received PN during the early stages after hepatectomy with respect to average total bilirubin and alanine aminotransferase levels after nutrition, pre-albumin levels, incidence of diarrhea and abdominal bloating, time to flatus, and average cost of nutrition. To varying degrees, better results were observed in the EN group than in the PN group for these metrics. CONCLUSION: During the early stages after hepatectomy, EN has obvious advantages relative to PN; thus, EN merits more widespread promotion and application in this clinical context.

Preoperative lymphoscintigraphy predicts the successful identification but is not necessary in sentinel lymph nodes biopsy in breast cancer.

BACKGROUND: Although preoperative lymphoscintigraphy in sentinel lymph node biopsy (SLNB) for breast cancer patients is undergone commonly, its clinical significance remains controversial. METHODS: We retrospectively analyzed our database that contained 636 consecutive breast cancer patients who received preoperative lymphoscintigraphy before SLNB. RESULTS: The sentinel lymph nodes (SLNs) of 86.5% of patients were well imaged by lymphoscintigraphy, and SLN were located extra-axilla in 5.3% patients. The visualization of SLN in lymphoscintigraphy was not associated with histopathologic type, location, and stage of primary tumor, as well as the time interval from injection of radiocolloid to surgery. The negative lymphoscintigraphy results were associated with excision ;biopsy before injection of radiocolloid and positive axillary node statues. The SLN was successfully detected in 625 (98.3%) enrolled patients. Failure of surgical identification of axillary SLN was associated with whether hot spot was imaged by lymphoscintigraphy. However, we identified axillary SLN in 90 (90.9%) out of 99 patients with negative axillary findings in lymphoscintigram. The false negative rate of SLNB in our study was 16.0% (15 of 94) among patients of training group, and there was no significant difference in the false negative rate between patients who had axillary hot spot in lymphoscintigram and those who had not (P = .273). CONCLUSIONS: Visualization of SLN in preoperative lymphoscintigraphy predicted the successful SLN identification. However, it was less informative for the location of SLN during operation. Considering the complexity, time consumed, and cost, lymphoscintigraphy should at present be undergone for investigation purposes only.