ObjectivesThe prevalence of Huntington's disease (HD) recorded in the UK primary care records has increased twofold between 1990 and 2010. This investigation was undertaken to assess whether this might be due to an increased incidence. We have also undertaken a systematic review of published estimates of the incidence of HD.SettingIncident patients with a new diagnosis of HD were identified from the primary care records of the Clinical Practice Research Datalink (CPRD). The systematic review included all published estimates of the incidence of HD in defined populations.ParticipantsA total of 393 incident cases of HD were identified from the CPRD database between 1990 and 2010 from a total population of 9 282 126 persons.Primary and secondary outcome measuresThe incidence of HD per million person-years was estimated. From the systematic review, the extent of heterogeneity of published estimates of the incidence of HD was examined using the I2 statistic.ResultsThe data showed that the incidence of HD has remained constant between 1990 and 2010 with an overall rate of 7.2 (95% CI 6.5 to 7.9) per million person-years. The systematic review identified 14 independent estimates of incidence with substantial heterogeneity and consistently lower rates reported in studies from East Asia compared with those from Australia, North America and some—though not all—those from Europe. Differences in incidence estimates did not appear to be explained solely by differences in case ascertainment or diagnostic methods.ConclusionsThe rise in the prevalence of diagnosed HD in the UK, between 1990 and 2010, cannot be attributed to an increase in incidence. Globally, estimates of the incidence of HD show evidence of substantial heterogeneity with consistently lower rates in East Asia and parts of Europe. Modifiers may play an important role in determining the vulnerability of different populations to expansions of the HD allele.

BackgroundTreatment of chronic lymphocytic leukaemia (CLL) has seen a substantial improvement over the last few years. Combination immunochemotherapy, such as fludarabine, cyclophosphamide and rituximab (FCR), is now standard first-line therapy. However, the majority of patients relapse and require further therapy, and so new, effective, targeted therapies that improve remission rates, reduce relapses, and have fewer side effects, are required. The FLAIR trial will assess whether ibrutinib plus rituximab (IR) is superior to FCR in terms of progression-free survival (PFS).Methods/designFLAIR is a phase III, multicentre, randomised, controlled, open, parallel-group trial in patients with previously untreated CLL. A total of 754 participants will be randomised on a 1:1 basis to receive standard therapy with FCR or IR. Participants randomised to FCR will receive a maximum of six 28-day treatment cycles. Participants randomised to IR will receive six 28-day cycles of rituximab, and ibrutinib taken daily for 6 years until minimal residual disease (MRD) negativity has been recorded for the same amount of time as it took to become MRD negative, or until disease progression. The primary endpoint is PFS according to the International Workshop on CLL (IWCLL) criteria. Secondary endpoints include: overall survival; proportion of participants with undetectable MRD; response to therapy by IWCLL criteria; safety and toxicity; health-related quality of life (QoL); and cost-effectiveness.DiscussionThe trial aims to provide evidence for the future first-line treatment of CLL patients by assessing whether IR is superior to FCR in terms of PFS, and whether toxicity rates are favourable.Trial registration ISRCTN01844152. Registered on 8 August 2014, EudraCT number 2013-001944-76. Registered on 26 April 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2138-6) contains supplementary material, which is available to authorized users.

Background The use of cannabis for symptoms of endometriosis was investigated utilising retrospective archival data from Strainprint Technologies Ltd., a Canadian data technology company with a mobile phone application that tracks a range of data including dose, mode of administration, chemovar and their effects on various self-reported outcomes, including pelvic pain. Methods A retrospective, electronic record-based cohort study of StrainprintTM users with self-reported endometriosis was conducted. Self-rated cannabis efficacy, defined as a function of initial and final symptom ratings, was investigated across the included symptom clusters of cramps, pelvic pain, gastrointestinal pain, nausea, depression, and low libido. Cannabis dosage form, dose and cannabinoid ratio information was also recorded. Results A total number of 252 participants identifying as suffering endometriosis recorded 16193 sessions using cannabis between April 2017 and February 2020. The most common method of ingestion was inhalation (n = 10914, 67.4%), with pain as the most common reported symptom being treated by cannabis (n = 9281, 57.3%). Gastrointestinal symptoms, though a less common reason for cannabis usage (15.2%), had the greatest self-reported improvement after use. Inhaled forms had higher efficacy for pain, while oral forms were superior for mood and gastrointestinal symptoms. Dosage varied across ingestion methods, with a median dose of 9 inhalations (IQR 5 to 11) for inhaled dosage forms and 1 mg/mL (IQR 0.5 to 2) for other ingested dosage forms. The ratio of THC to CBD had a statistically significant, yet clinically small, differential effect on efficacy, depending on method of ingestion. Conclusions Cannabis appears to be effective for pelvic pain, gastrointestinal issues and mood, with effectiveness differing based on method of ingestion. The greater propensity for use of an inhaled dosage delivery may be due to the rapid onset of pain-relieving effects versus the slower onset of oral products. Oral forms appeared to be superior compared to inhaled forms in the less commonly reported mood or gastrointestinal categories. Clinical trials investigating the tolerability and effectiveness of cannabis for endometriosis pain and associated symptoms are urgently required.

In 2013, China launched the Belt and Road (B&R) Initiative in an effort to promote trade and economic collaboration. This study examined the change in life expectancy (LE) among countries along B&R and studied the impact of economic development on LE. Data from 65 B&R countries from 2000 to 2014 were compiled and analyzed. Trend of LE was examined by sex and country. Linear quantile mixed model was used to study the associations between LE and economic factors. In 2014, the average LE in all B&R countries was 69.7 years for men and 73.7 years for women. Across countries in 2014, LE for men ranged from 58.6 years in Afghanistan to 80.2 years in Israel. LE for women ranged from 61.3 years in Afghanistan to 85.9 in Singapore. GDP per capita was positively associated with longevity across B&R countries. The unemployment rate was positively associated with LE only for countries in the top LE quantiles. GDP growth rate and Inflation were negatively associated with LE for the countries in the bottom LE quantiles for men, not for women. LE increased substantially among B&R countries during 2000–2014. The influence of macroeconomic factors on LE was related to the distribution of LE.

Background To assess differences in platelet inhibition during ticagrelor monotherapy (TIC) or dual therapy with ticagrelor and aspirin (TIC+ASP) in patients after percutaneous coronary intervention using a comprehensive panel of functional tests. Methods and Results In a single‐center parallel group, open label, randomized controlled trial, 110 participants were randomized to receive either TIC (n=55) or TIC+ASP (n=55) for 4 weeks. The primary outcome was the platelet aggregation response with 10 μmol/L thrombin receptor activation peptide‐6 (TRAP‐6). The secondary outcomes were platelet aggregation responses and binding of surface activation markers with a panel of other activators. The mean percentage aggregation for 10 μmol/L TRAP‐6 was similar for the TIC and TIC+ASP groups (mean difference+4.29; 95% CI, −0.87 to +9.46). Aggregation was higher in the TIC group compared with the TIC+ASP group with 1 μg/mL (+6.47; +2.04 to +10.90) and 0.5 μg/mL (+14.00; +7.63 to +20.39) collagen related peptide. Aggregation responses with 5 μmol/L TRAP‐6, 5 μmol/L or 2.5 μmol/L thromboxane A 2 receptor agonist and surface activation marker binding with 5 μmol/L TRAP‐6 or 0.5 μg/mL collagen related peptide were the same between the treatment groups. Conclusions Patients with PCI show similar levels of inhibition of most platelet activation pathways with TIC compared with dual therapy with TIC + ASP. However, the greater aggregation response with collagen related peptide during TIC indicates incomplete inhibition of glycoprotein VI (collagen) receptor‐mediated platelet activation. This difference in pharmacodynamic response to anti‐platelet medication may contribute to the lower bleeding rates observed with TIC compared with dual antiplatelet therapy in recent clinical trials. Registration Information URL: https://www.isrctn.com ; Unique Identifier ISRCTN84335288.