Factors affecting the choice of first-line therapy in Parkinson’s disease patients in Wales: A population-based study

First line treatment for Parkinson’s disease (PD) is typically either L-dopa or a non-ergot dopamine agonist (DA). However, the options for the treatment of motor symptoms in PD patients have increased in the last thirty years, which have seen several new classes of PD medications introduced onto the market. The purpose of this study is to examine the changes in first line therapy of newly diagnosed Parkinson’s patients between 2000 and 2016 in Wales.A population-based study evaluated data from the Secure Anonymised Information Linkage (SAIL) Databank of residents in Wales, aged 40 years or older, newly treated with PD medications between 2000 and 2016. The data was compared across three intervals: 2000–2005, 2006–2011 and 2012–2016. Patients were classified by age at diagnosis into young: 40–60 years; mid, 61–80 years; and older >80 years. Logistic regression was undertaken to determine the predictors of PD medication prescribing.For the whole study period, the profiles of 9142 newly diagnosed PD patients were analysed. L-dopa was the most common first line therapy (80.6%), followed by non-ergot DAs (12.9%) and monoamine oxidase B (MAO-B) inhibitors (7.9%). Odds of L-dopa prescribing were greater in patients >80 years (OR = 20.46 95%CI: 16.25–25.76) and in the period 2012–2016 (OR = 1.98 95% CI: 1.70–2.29). Prescribing of non-ergot DAs significantly declined in 2012–2016 (OR = 0.42 95% CI: 0.35–0.49). Additional factors influencing first line therapy were deprivation, presence of diabetes and prior use of antidepressants. For example, PD patients residing in the least deprived area were less likely to be prescribed L-dopa compared to patients residing in the most deprived area (OR = 0.77 95% CI: 0.65–0.93).First line therapy in PD in Wales has undergone a significant switch towards L-dopa over the last 16 years. The data indicates reasonable compliance with guidelines on efficacy and safety issues related to Parkinson’s medications.     

Psychometric properties of a Chinese (Cantonese) version of the Tinnitus Questionnaire

The objective of this study was to determine the psychometric properties of a Chinese (Cantonese) version of the Tinnitus Questionnaire (TQ), which is a psychometric self-report measure of perceived tinnitus-related distress. The subjects were 114 adults who attended audiology clinics with a primary or secondary complaint of tinnitus. They completed the Chinese versions of the TQ (TQ-CH), Short-Form 36 Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HADS). The subjective severity of tinnitus and tinnitus-related problems were scored using rating scales. The TQ-CH and its subscales had good internal consistency reliability estimates (α=0.75–0.94), which were comparable to those of the original version. Significant correlations were observed between the TQ-CH and psychological distress, tinnitus-related problem ratings, and severity ratings. Factor analysis showed the high construct validity of the TQ-CH subscales. High test-retest reliablity (intraclass correlation coefficient=0.96) was observed. The results suggest that the TQ-CH is a reliable and valid measure of general tinnitus-related distress that can be used in clinical settings to quantify the impact of tinnitus on daily living.     

Single‐nucleotide polymorphisms in pigment genes and nonmelanoma skin cancer predisposition: a systematic review

Nonmelanoma skin cancer (NMSC) is the most common cancer in the U.S.A. The two most common NMSCs are basal cell carcinoma and squamous cell carcinoma. The associations of single‐nucleotide polymorphisms (SNPs) in pigmentation pathway genes with NMSC are not well characterized. There is a series of epidemiological studies that have tested these relationships, but there is no recent summary of these findings. To explain overarching trends, we undertook a systematic review of published studies. The summarized data support the concept that specific SNPs in the pigmentation pathway are of importance for the pathogenesis of NMSC. The SNPs with the most promising evidence include MC1R rs1805007(T) (Arg151Cys) and rs1805008(T) (Arg160Trp), and ASIP AH haplotype [rs4911414(T) and rs1015362(G)]. There are a few other SNPs found in TYR, OCA2 and SLC45A2 that may show additional correlation after future research. With additional research there is potential for the translation of future findings to the clinic in the form of SNP screenings, where patients at high risk for NMSC can be identified beyond their phenotype by genotypically screening for predisposing SNPs.     

MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals

While it is known that monosodium urate (MSU) crystals cause the disease gout, the mechanism by which these crystals stimulate this inflammatory condition has not been clear. Here we find that the Toll/IL-1R (TIR) signal transduction adaptor myeloid differentiation primary response protein 88 (MyD88) is required for acute gouty inflammation. In contrast, other TIR adaptor molecules, TIRAP/Mal, TRIF, and TRAM, are not required for this process. The MyD88-dependent TLR1, -2, -4, -6, -7, -9, and -11 and IL-18 receptor (IL-18R) are not essential for MSU-induced inflammation. Moreover, MSU does not stimulate HEK cells expressing TLR1-11 to activate NF-kappaB. In contrast, mice deficient in the MyD88-dependent IL-1R showed reduced inflammatory responses, similar to those observed in MyD88-deficient mice. Similarly, mice treated with IL-1 neutralizing antibodies also showed reduced MSU-induced inflammation, demonstrating that IL-1 production and IL-1R activation play essential roles in MSU-triggered inflammation. IL-1R deficiency in bone marrow-derived cells did not affect the inflammatory response; however, it was required in non-bone marrow-derived cells. These results indicate that IL-1 is essential for the MSU-induced inflammatory response and that the requirement of MyD88 in this process is primarily through its function as an adaptor molecule in the IL-1R signaling pathway.     

A tool for reliable self-home blood pressure monitoring designed according to the European Society of Hypertension recommendations: the Microlife WatchBP Home monitor

BACKGROUND: Self-blood pressure monitoring by patients at home (HBPM) is being increasingly used in clinical practice and has been endorsed by hypertension societies as an important adjunct to the conventional office blood pressure measurements. Several problems, however, exist regarding the application of HBPM in practice, such as device inaccuracy, observer bias and misreporting, variable monitoring schedule and variable method for summarizing measurements. The European Society of Hypertension Working Group (ESH-WG) on Blood Pressure Monitoring has published detailed recommendations on how to apply HBPM in clinical practice. OBJECTIVE: The Microlife WatchBP Home monitor is designed to provide reliable and unbiased self-blood pressure monitoring by patients at home, strictly according to the ESH-WG recommendations. DESIGN: Dual-function automated oscillometric monitor for HBPM in the arm, with memory, PC link capacity and embedded monitoring schedule. The device has a Usual mode for casual HBPM and a Diag (diagnostic) mode for HBPM strictly according to the ESH-WG proposed schedule (duplicate morning and evening measurements for 7 days). Readings are averaged by the device after exclusion of the initial day according to ESH-WG recommendations and can be transferred to PC for storing or printing. A pilot study in hypertensive patients with previous experience in HBPM suggested that the device is user-friendly and well accepted. CONCLUSION: The Microlife WatchBP Home monitor is a novel device that provides a reliable and unbiased assessment of home blood pressure strictly according to the ESH recommendations.     

The effects of early life adversity on growth,maturation, and steroid hormones in male and female rats

Early life adversity is a risk factor for psychiatric disorders, yet the mechanisms by which adversity increases this risk are still being delineated. Here, we used a limited bedding and nesting (LBN) manipulation in rats that models a low resource environment to examine effects on growth, developmental milestones, and endocrine endpoints. In LBN, dams and pups, from pups’ postnatal days 2–9, are exposed to an environment where dams lack proper materials to build a nest. This manipulation is compared to control housing conditions, where rat dams have access to ample nesting materials and enrichment throughout pups’ development. We found that the LBN condition altered maternal care, increasing pup‐directed behaviors while reducing self‐care. This, perhaps compensatory, increase in nursing and attention to pups did not mitigate against changes in metabolism, as LBN reduced weight gain in both sexes and this effect persisted into adulthood. Although adult stress hormone levels in both sexes and vaginal opening and estrous cycle length in females were not disrupted, there was other evidence of endocrine dysregulation. Compared to controls, LBN rats of both sexes had shortened anogenital distances, indicating reduced androgen exposure. LBN males also had higher plasma estradiol levels in adulthood. This combination of results suggests that LBN causes a demasculinizing effect in males that could contribute to lasting changes in the brain and behavior. Importantly, alterations in metabolic and endocrine systems due to early life adversity could be one mechanism by which stress early in life increases risk for later disease.