International variation in GP treatment strategies for subclinical hypothyroidism in older adults: a case-based survey

Background

There is limited evidence about the impact of treatment for subclinical hypothyroidism, especially among older people.

Aim

To investigate the variation in GP treatment strategies for older patients with subclinical hypothyroidism depending on country and patient characteristics.

Design and setting

Case-based survey of GPs in the Netherlands, Germany, England, Ireland, Switzerland, and New Zealand.

Method

The treatment strategy of GPs (treatment yes/no, starting-dose thyroxine) was assessed for eight cases presenting a woman with subclinical hypothyroidism. The cases differed in the patient characteristics of age (70 versus 85 years), vitality status (vital versus vulnerable), and thyroid-stimulating hormone (TSH) concentration (6 versus 15 mU/L).

Results

A total of 526 GPs participated (the Netherlands n = 129, Germany n = 61, England n = 22, Ireland n = 21, Switzerland n = 262, New Zealand n = 31; overall response 19%). Across countries, differences in treatment strategy were observed. GPs from the Netherlands (mean treatment percentage 34%), England (40%), and New Zealand (39%) were less inclined to start treatment than GPs in Germany (73%), Ireland (62%), and Switzerland (52%) (P = 0.05). Overall, GPs were less inclined to start treatment in 85-year-old than in 70-year-old females (pooled odds ratio [OR] 0.74 [95% confidence interval [CI] = 0.63 to 0.87]). Females with a TSH of 15 mU/L were more likely to get treated than those with a TSH of 6 mU/L (pooled OR 9.49 [95% CI = 5.81 to 15.5]).

Conclusion

GP treatment strategies of older people with subclinical hypothyroidism vary largely by country and patient characteristics. This variation underlines the need for a new generation of international guidelines based on the outcomes of randomised clinical trials set within primary care.     

The role of glutathione reductase in maintaining human granulocyte function and sensitivity to exogenous H2O2

Human granulocytes (polymorphonuclear leukocytes, PMN) produce H2O2 and other reactive oxygen species while undergoing phagocytosis. To examine the role of the glutathione cycle in metabolizing H2O2, we incubated PMN with 1,3-bis (2-chloroethyl) nitrosourea (BCNU). Incubation of PMN with BCNU results in a dose-dependent inhibition of PMN glutathione reductase (GRED), with 50% inhibition occurring at approximately 2 micrograms/mL BCNU. PMN hexose monophosphate shunt activity stimulated with an exogenous H2O2-generating system was inhibited only when the GRED activity was reduced to less than 30% of control. BCNU-treated cells contained lower levels of reduced sulfhydryls and reduced glutathione, which decreased even more in the presence of an exogenous H2O2-generating system. The effect of BCNU and exogenous H2O2 on various aspects of phagocytosis were examined. Exposure of BCNU-treated PMN to an H2O2-generating system resulted in an inhibition of chemotactic peptide-induced shape changes and degranulation. The ability of BCNU-treated cells to produce O2- was diminished only when the PMN were incubated with an H2O2-generating system in the presence of cyanide. Ingestion of opsonized bacteria by BCNU-treated PMN was unaffected by incubation in an H2O2-generating system even in the presence of cyanide. We conclude that PMN GRED is inhibited by BCNU, the ability of PMN to metabolize H2O2 is affected only when GRED is reduced more than 70%, this inhibition affects the glutathione content of these cells, and some, but not all of the phagocytic functions of GRED-inhibited PMN are inhibited after exposure to an H2O2-generating system.     

New perspectives on dry needling following a medical model: are we screening our patients sufficiently?

ABSTRACT

Myofascial trigger points are not an isolated neuromusculoskeletal phenomenon and have been implicated in systemic, visceral, and metabolic pathology, as a side effect of some medications and in the presence of psychological risk factors. This complexity can complicate adequate screening of patients prior to choosing dry needling as a treatment intervention. Regardless of whether clinicians practice in a direct access setting, they should be cognizant of medical conditions, comorbidities, and risk factors that will influence clinical decisions for dry-needling appropriateness, technique chosen, and potential adverse responses to treatment. Of primary concern are conditions that can either manifest with myalgia and/or myopathy or masquerade as a more common musculoskeletal condition. This clinical commentary reviews system-specific considerations and other common disorders that should be screened for and discusses not only whether dry needling is appropriate but comments on technique and dosage considerations when initiating dry needling.     

Laboratory integration and utilization of tandem mass spectrometry in neonatal screening: a model for clinical mass spectrometry in the next millennium

Clinical and neonatal screening methods using a tandem mass spectrometer are clearly a model for modern laboratory testing in the new Millennium. By the year 2000, more than 1 million blood and plasma samples will have been tested in laboratories throughout the world for a battery of metabolic disorders using a tandem mass spectrometer as the primary analytical device. A tandem mass spectrometer is considered the ultimate analytical detector in a variety of biochemical and clinical methods because of its very high accuracy, selectivity, precision, versatility and robust nature. The ability to achieve very high and reproducible sample throughput (∼600 samples/ instrument/24 h) has made this technology cost-effective for newborn screening. In order to reliably measure markers of inborn errors of metabolism while maintaining low costs and high efficiency, accuracy and quality, much attention needs to be placed on monitoring and maintenance of all components of the entire testing system. These components include specimen collection and sample preparation methods, analysis by LC tandem mass spectrometry, conversion of raw mass spectra (data) into clinically meaningful results (concentration), expert interpretation of these results so that the clinician can be provided with information to facilitate a diagnose, and follow-up and education so that the maximum benefits of newborn screening translate into prevention of disease symptoms or more effective treatments. Addressing each part of the whole system will produce a quality screening program that will detect a battery of disorders using tandem mass spectrometry with a disease frequency of nearly 1 in 4000 infants.     

A comparative assessment of the acute inhalation toxicity of vanadium compounds

Vanadium compounds have become important in industrial processes, resulting in workplace exposure potential and are present in ambient air as a result of fossil fuel combustion. A series of acute nose-only inhalation toxicity studies was conducted in both rats and mice in order to obtain comparative data on the acute toxicity potential of compounds used commercially. V₂O₃, V₂O₄, and V₂O₅, which have different oxidation states (+3,?+4,?+5, respectively), were delivered as micronized powders; the highly water-soluble and hygroscopic VOSO₄ (+4) could not be micronized and was instead delivered as a liquid aerosol from an aqueous solution. V₂O₅ was the most acutely toxic micronized powder in both species. Despite its lower overall percentage vanadium content, a liquid aerosol of VOSO₄ was more toxic than the V₂O₅ particles in mice, but not in rats. These data suggest that an interaction of characteristics, i.e., bioavailability, solubility and oxidation state, as well as species sensitivity, likely affect the toxicity potential of vanadium compounds. Based on clinical observations and gross necropsy findings, the lung appeared to be the target organ for all compounds. The level of hazard posed will depend on the specific chemical form of the vanadium. Future work to define the inhalation toxicity potential of vanadium compounds of various oxidation states after repeated exposures will be important in understanding how the physico-chemical and biological characteristics of specific vanadium compounds interact to affect toxicity potential and the potential risks posed to human health.     

mdx muscle pathology is independent of nNOS perturbation

In skeletal muscle, neuronal nitric oxide synthase (nNOS) is anchored to the sarcolemma via the dystrophin-glycoprotein complex. When dystrophin is absent, as in Duchenne muscular dystrophy patients and in mdx mice, nNOS is mislocalized to the interior of the muscle fiber where it continues to produce nitric oxide. This has led to the hypothesis that free radical toxicity from mislocalized nNOS may contribute to mdx muscle pathology. To test this hypothesis directly, we generated mice devoid of both nNOS and dystrophin. Overall, the nNOS- dystrophin null mice maintained the dystrophic characteristics of mdx mice. We evaluated the mice for several features of the dystrophic phenotype, including membrane damage and muscle morphology. Removal of nNOS did not alter the extent of sarcolemma damage, which is a hallmark of the dystrophic phenotype. Furthermore, muscle from nNOS-dystrophin null mice maintain the histological features of mdx pathology. Our results demonstrate that relocalization of nNOS to the cytosol does not contribute significantly to mdx pathogenesis.      

Treatment-independent pregnancy rate in patients with severe reproductive disorders

A long waiting list for in-vitro fertilization (IVF) offers the possibility to study treatment-independent pregnancy rates in patients with severe reproductive disorders. We performed a retrospective cohort study with a nested case-control design in which the cases achieved a spontaneous pregnancy while on the waiting list for IVF, or for IVF with intracytoplasmic sperm injection (ICSI), and the controls did not become pregnant while on the waiting list. Spontaneous pregnancies occurred in 76 of 1391 patients on the waiting list. Significant differences between pregnant and non-pregnant patients were found for duration of subfertility (couples on the IVF waiting list), and for progressive sperm motility and basal 17beta-oestradiol (couples on the ICSI waiting list). The 12 months cumulative pregnancy rate for patients on the waiting list was 2.4% (95% CI 1.2-3.9%) for tubal subfertility patients, 5.9 % (3.7-8.7%) for longstanding unexplained subfertility patients, and 6.6% (4.5-9.3%) for male subfertility patients. Of the 76 control patients, 21% of tubal subfertility patients, 18% of unexplained subfertility patients, and 17% of male subfertility patients achieved a pregnancy in their first IVF or ICSI treatment cycle. We confirm that the treatment-independent pregnancy rate in patients with severe reproductive disorders is low. More than 75% of the spontaneous pregnancies in the tubal subfertility and unexplained subfertility couples occurred during their first three months on the waiting list, whereas spontaneous pregnancy rate in male subfertility couples showed a more gradual but persisting increase. We conclude that one cycle of IVF or ICSI is superior to 12 months of expectant management in patients with severely impaired fertility due to tubal, unexplained or male factors.