Traditional local medicines in the republic of Palau and non-communicable diseases (NCD), signs of effectiveness.

ETHNOPHARMACOLOGICAL RELEVANCE: The aim of this survey was to describe which traditional medicines (TM) are most commonly used for non-communicable diseases (NCD - diabetes, hypertension related to excess weight and obesity) in Pacific islands and with what perceived effectiveness. NCD, especially prevalent in the Pacific, have been subject to many public health interventions, often with rather disappointing results. Innovative interventions are required; one hypothesis is that some local, traditional approaches may have been overlooked. MATERIALS AND METHODS: The method used was a retrospective treatment-outcome study in a nation-wide representative sample of the adult population (about 15,000 individuals) of the Republic of Palau, an archipelago of Micronesia. RESULTS: From 188 respondents (61% female, age 16-87, median 48,), 30 different plants were used, mostly self-prepared (69%), or from a traditional healer (18%). For excess weight, when comparing the two most frequent plants, Morinda citrifolia L. was associated with more adequate outcome than Phaleria nishidae Kaneh. (P=0.05). In case of diabetes, when comparing Phaleria nishidae (=Phaleria nisidai) and Morinda citrifolia, the former was statistically more often associated with the reported outcome "lower blood sugar" (P=0.01). CONCLUSIONS: Statistical association between a plant used and reported outcome is not a proof of effectiveness or safety, but it can help select plants of interest for further studies, e.g. through a reverse pharmacology process, in search of local products which may have a positive impact on population health.

Variation in treatment strategies of Swiss general practitioners for subclinical hypothyroidism in older adults.

QUESTIONS UNDER STUDY: As the best management of subclinical hypothyroidism is controversial, we aimed to assess variations in treatment strategies depending on different Swiss regions, physician and patient characteristics. METHODS: We performed a case-based survey among general practitioners (GPs) in different Swiss regions, which consisted of eight hypothetical cases presenting a female patient with subclinical hypothyroidism and nonspecific complaints differing by age, vitality status and thyroid-stimulating hormone (TSH) concentration. RESULTS: A total of 262 GPs participated in the survey. There was considerable variation in the levothyroxine starting dose chosen by GPs, ranging from 25 µg to 100 µg. Across the Swiss regions, GPs in the Bern region were significantly more inclined to treat, with a higher probability of initiating treatment (60%, p = 0.01) and higher mean starting doses (45 µg, p <0.01) compared with the French-speaking region (44%, 36 µg); the Zurich region had intermediate values (52%, 39 µg). We found no association between treatment rate and other physician characteristics. GPs were more reluctant to initiate treatment in 85-year-old than in 70-year-old women (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.63-0.94), and more likely to treat women with a TSH of 15 mU/l than those with a TSH of 6mU/l (OR 8.71, 95% CI 6.21-12.20). CONCLUSIONS: There are strong variations in treatment strategies for elderly patients with subclinical hypothyroidism across different Swiss regions, including use of higher starting doses than the recommended 25 µg in the Swiss guidelines, which recommend a starting dose of 25 µg. These variations likely reflect the current uncertainty about the benefits of treatment, which arise from the current lack of evidence from adequately powered clinical trials.

Relevance of cohort studies for the study of transplant infectious diseases.

The debate on the merits of observational studies as compared with randomized trials is ongoing. We will briefly touch on this subject, and demonstrate the role of cohort studies for the description of infectious disease patterns after transplantation. The potential benefits of cohort studies for the clinical management of patients outside of the expected gain in epidemiological knowledge are reviewed. The newly established Swiss Transplantation Cohort Study and in particular the part focusing on infectious diseases will serve as an illustration. A neglected area of research is the indirect value of large, multicenter cohort studies. These benefits can range from a deepened collaboration to the development of common definitions and guidelines. Unfortunately, very few data exist on the role of such indirect effects on improving quality of patient management. This review postulates an important role for cohort studies, which should not be viewed as inferior but complementary to established research tools, in particular randomized trials. Randomized trials remain the least bias-prone method to establish knowledge regarding the significance of diagnostic or therapeutic measures. Cohort studies have the power to reflect a real-world situation and to pinpoint areas of knowledge as well as of uncertainty. Prerequisite is a prospective design requiring a set of inclusive data coupled with the meticulous insistence on data retrieval and quality.

Genetics of calcium homeostasis in humans: continuum between monogenic diseases and continuous phenotypes

Extracellular calcium participates in several key physiological functions, such as control of blood coagulation, bone calcification or muscle contraction. Calcium homeostasis in humans is regulated in part by genetic factors, as illustrated by rare monogenic diseases characterized by hypo or hypercalcaemia. Both serum calcium and urinary calcium excretion are heritable continuous traits in humans. Serum calcium levels are tightly regulated by two main hormonal systems, i.e. parathyroid hormone and vitamin D, which are themselves also influenced by genetic factors. Recent technological advances in molecular biology allow for the screening of the human genome at an unprecedented level of detail and using hypothesis-free approaches, such as genome-wide association studies (GWAS). GWAS identified novel loci for calcium-related phenotypes (i.e. serum calcium and 25-OH vitamin D) that shed new light on the biology of calcium in humans. The substantial overlap (i.e. CYP24A1, CASR, GATA3; CYP2R1) between genes involved in rare monogenic diseases and genes located within loci identified in GWAS suggests a genetic and phenotypic continuum between monogenic diseases of calcium homeostasis and slight disturbances of calcium homeostasis in the general population. Future studies using whole-exome and whole-genome sequencing will further advance our understanding of the genetic architecture of calcium homeostasis in humans. These findings will likely provide new insight into the complex mechanisms involved in calcium homeostasis and hopefully lead to novel preventive and therapeutic approaches. Keyword: calcium, monogenic, genome-wide association studies, genetics.