Quantity not sufficient rates and delays in sweat testing in US infants with cystic fibrosis.

BACKGROUND: Diagnostic sweat testing is required for infants with positive newborn-screening (NBS) tests for cystic fibrosis (CF). Infants have "quantity not sufficient" (QNS) sweat volumes more often than older children. A comprehensive study of QNS sweat volumes in infants has not previously been reported. METHODS: We surveyed US CF Centers to obtain QNS rates in all infants who had sweat testing at under 14 days and under 3 months of age. We then calculated QNS rates reported to the Cystic Fibrosis Foundation Patient Registry (CFFPR) 2010-2018 in 10-day increments from 1 to 60 days of life. We compared QNS sweat test rates in preterm (<37-weeks gestational age) vs term infants. We assessed age at sweat test and proportion of infants who did not have a sweat test reported by 60 days of age. RESULTS: Thirty-nine of 144 (27%) of CF Centers reported a mean QNS rate of 10.5% (range, 0-100) in infants 14-days-old or younger. CFFPR data showed the highest QNS rates in the youngest infants and in those born before 37 weeks of gestation. The median age at sweat testing decreased over time, but more than 22% of infants did not have a sweat test reported by 60 days. CONCLUSION: Higher QNS rates are seen in the youngest infants with CF, but more than 80% of infants younger than 2 weeks of age have adequate sweat volumes. Sweat testing should not be delayed in infants with a positive CF NBS test.

Subclinical hypothyroidism and risk for incident ischemic stroke among postmenopausal women.

BACKGROUND: Subclinical hypothyroidism (SCH) is postulated to increase stroke risk via atherogenic changes associated with abnormal thyroid function. However, the direct relationship of SCH with subsequent stroke is poorly studied. METHODS: In this nested case-cohort study, we prospectively evaluated the association between any SCH and severity of SCH in relation to incident ischemic stroke risk among postmenopausal women in the Women's Health Initiative Observational Study. Trained Women's Health Initiative staff, masked to thyroid status, adjudicated stroke cases. We assessed thyroid function using baseline blood specimens. Women with normal free thyroxine levels and thyrotropin (TSH) levels ≥4.69 mU/L were considered to have SCH. Primary analysis included 639 ischemic stroke cases and 2927 randomly selected subcohort members with an average of seven years of follow-up. RESULTS: The multivariable adjusted hazard ratios (HR) from weighted Cox models were 1.06 (95% confidence interval [CI]: 0.77, 1.46) and 0.99 (95% CI: 0.67, 1.47) for women with any SCH and with mild SCH (TSH 4.69 to 6.99 mU/L), when compared with women with normal thyroid function. The HR for moderate/severe SCH (TSH ≥7.00 mU/L) was modestly elevated (HR: 1.22; 95% CI: 0.73, 2.05). CONCLUSIONS: We found no evidence to suggest an association between SCH and ischemic stroke among healthy postmenopausal women.

Sixty-five years since the New York heat wave: advances in sweat testing for cystic fibrosis.

The sweat test remains important as a diagnostic test for cystic fibrosis (CF) and has contributed greatly to our understanding of CF as a disease of epithelial electrolyte transport. The standardization of the sweat test, by Gibson and Cooke [Gibson and Cooke (1959) Pediatrics 1959;23:5], followed observations of excessive dehydration amongst patients with CF and confirmed the utility as a diagnostic test. Quantitative pilocarpine iontophoresis remains the gold standard for sweat induction, but there are a number of collection and analytical methods. The pathophysiology of electrolyte transport in sweat was described by Quinton [Quinton (1983) Nature 1983;301:421-422], and this complemented the developments in genetics that discovered the cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial-based electrolyte transport protein. Knowledge of CF has since increased rapidly and further developments in sweat testing include: new collection methods, further standardization of the technique with international recommendations and age related reference intervals. More recently, sweat chloride values have been used as proof of effect for the new drugs that activate CFTR. However, there remain issues with adherence to sweat test guidelines in many countries and there are gaps in our knowledge, including reference intervals for some age groups and stability of sweat samples in transport. Furthermore, modern methods of elemental quantification need to be explored as alternatives to the original analytical methods for sweat electrolyte measurement. The purpose of this review is therefore to describe the development of the sweat test and consider future directions.

Subclinical hypothyroidism and risk for incident myocardial infarction among postmenopausal women.

CONTEXT: Subclinical hypothyroidism (SCH) has been associated with an increased risk for cardiovascular disease. However, few studies have specifically examined the association between SCH and myocardial infarction (MI), and the relationship is poorly understood. OBJECTIVES: The purpose of this study was to evaluate incident MI risk in relation to SCH and severities of SCH among postmenopausal women. METHODS: We used a population-based nested case-cohort design within the Women's Health Initiative observational study to examine the association between SCH and incident first-time MI risk among postmenopausal women in the United States. SCH was assessed using blood specimens collected at baseline. Participants presenting with normal free T4 levels and with thyrotropin levels of greater than 4.68-6.99 mU/L or 7.00 mU/L or greater were defined as having mild SCH or moderate/severe SCH, respectively. MI cases were centrally adjudicated by trained Women's Health Initiative staff. The primary analysis included 736 incident MI cases and 2927 randomly selected subcohort members. Multivariable adjusted Cox-proportional hazard models were used to assess MI risk in relation to SCH. RESULTS: Compared with euthyroid participants, the multivariable adjusted hazard ratio (HR) for participants with any SCH was 1.05 [95% confidence interval (CI) 0.77-1.44]. HRs for participants with mild SCH, moderate/severe SCH, and moderate/severe SCH and the presence of antithyroid peroxidase antibodies (TPOAb) were 0.99 (95% CI 0.67-1.46), 1.19 (95% CI 0.72-1.96), and 0.90 (95% CI 0.47-1.74), respectively. CONCLUSION: We did not find evidence to suggest that SCH is associated with increased MI risk among a population of predominantly older postmenopausal women with no prior history of MI.

The need for quality improvement in sweat testing infants after newborn screening for cystic fibrosis.

The proportion of insufficient sweat tests after positive newborn screening for cystic fibrosis was determined. Infants ≤ 3 months old had a mean (± standard deviation) rate of 7.2% (± 7.6) (range, 0% to 40%). Collection methods did not affect the rates. The high and variable rates indicate a need for quality improvement.

Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report.

Newborn screening (NBS) for cystic fibrosis (CF) is increasingly being implemented and is soon likely to be in use throughout the United States, because early detection permits access to specialized medical care and improves outcomes. The diagnosis of CF is not always straightforward, however. The sweat chloride test remains the gold standard for CF diagnosis but does not always give a clear answer. Genotype analysis also does not always provide clarity; more than 1500 mutations have been identified in the CF transmembrane conductance regulator (CFTR) gene, not all of which result in CF. Harmful mutations in the gene can present as a spectrum of pathology ranging from sinusitis in adulthood to severe lung, pancreatic, or liver disease in infancy. Thus, CF identified postnatally must remain a clinical diagnosis. To provide guidance for the diagnosis of both infants with positive NBS results and older patients presenting with an indistinct clinical picture, the Cystic Fibrosis Foundation convened a meeting of experts in the field of CF diagnosis. Their recommendations, presented herein, involve a combination of clinical presentation, laboratory testing, and genetics to confirm a diagnosis of CF.

Teaching method validation in the clinical laboratory science curriculum.

With the Clinical Laboratory Improvement Amendment's (CLIA) final rule, the ability of the Clinical Laboratory Scientist (CLS) to perform method validation has become increasingly important. Knowledge of the statistical methods and procedures used in method validation is imperative for clinical laboratory scientists. However, incorporating these concepts in a CLS curriculum can be challenging, especially at a time of limited resources. This paper provides an outline of one approach to addressing these topics in lecture courses and integrating them in the student laboratory and the clinical practicum for direct application.

Association of leukocyte count with progression of aortic atheroma in stroke/transient ischemic attack patients.

BACKGROUND AND PURPOSE: Leukocyte count is an independent predictor of stroke. We investigated the association between leukocyte count and progression of aortic atheroma over 12 months in stroke/transient ischemic attack (TIA) patients. METHODS: Consecutive ischemic stroke and transient ischemic attack patients underwent 12-month sequential transesophageal echocardiography and were assessed for total and differential leukocyte counts on admission. Paired aortic plaque images were assessed for several parameters, including changes in grade, intimal-medial thickness (IMT), and cross-sectional area. Multivariate linear and logistic regressions were used to calculate the effect of leukocyte count on the change in aortic atheromas over 12 months. RESULTS: Of the 115 participants (mean+/-SD age, 64.6+/-11.9 years; 53.1% men; 73.4% white, 24.2% black, and 2.3% Asian), 45 (35%) showed clinically significant progression of aortic atheromas (maximal change in IMT >0.70 mm over 12 months). The mean admission leukocyte count was higher in the progression group compared with the no-progression group (8.6+/-2.2 vs 7.3+/-2.2 x 10(9)/L respectively, P=0.002). Each unit increase in leukocyte count was associated with a 0.26-mm increase in aortic arch IMT over 12 months (P=0.006). After adjustment for other atherosclerosis risk factors, the relation persisted (mean increase in aortic arch IMT per unit increase in leukocyte count=0.27 mm, P=0.007). Each unit increase in leukocyte count was associated with an increased risk of significant progression of aortic atheromas (adjusted odds ratio=1.33; 95% CI, 1.09 to 1.61). CONCLUSIONS: In stroke/transient ischemic attack patients, leukocyte count is independently associated with the progression of aortic atheroma over 12 months (>0.70 mm), which is associated with cardiovascular risk.

La prueba del sudor para el diagnostico de fibrosis quistica / The test of the sweat for the diagnosis of quística fibrosis

La fibrosis quística es un trastorno autosómico recesivo que se caracteriza por presentar enfermedad pulmonar obstructiva crónica, insuficiencia pancreática y electrolitos elevados en el sudor. El análisis cuantitativo del cloruro en el sudor, realizado en el laboratorio clínico, es considerada la prueba de elección para el diagnóstico de fibrosis quística.Palabras clave: prueba del sudor, cloruro, diagnóstico, genética, nitrato de pilocarpina, iontoforesis, tamizaje, sensibilidad, especificidad.

Sweat-testing in preterm and full-term infants less than 6 weeks of age.

Our objective was to examine the characteristics of preterm and full-term infants < or = 6 weeks old that influence the success of obtaining sufficient sweat for diagnosis of CF, and corresponding sweat chloride concentrations. A retrospective chart review of 119 sweat tests was performed on 103 preterm and full-term infants < or = 6 weeks of age. Bivariate and multivariate regression analyses were used to determine the predictors of successful sweat testing and characteristics influencing sweat chloride concentrations. Adequate amounts of sweat (> or = 75 mg) were obtained for analysis in 73.8% of initial attempts in the infant group. The following characteristics were associated with increased odds of obtaining a quantity not sufficient (QNS) for sweat chloride concentration measurement: African-American race, infant weight < 2,000 g, preterm birth, and postmenstrual age (PMA) < 36 weeks. With a multivariable logistic model, the only significant predictors were African-American race (7.3, 2.4-21.7) and PMA < 36 weeks (17.9, 4.2-75.9). Sweat chloride concentration in non-CF individuals is inversely related to both gestational age and age at testing, and this effect is additive in a linear regression model. In conclusion, sweat collection can be reliably performed in infants > or = 36 weeks postmenstrual age, > 2,000 g, and > 3 days postnatal age. Maturational factors have a mild impact on sweat chloride concentration.

The clinical consequences and diagnosis of hypothyroidism.

Hypothyroidism represents a common disorder especially in older women. Left untreated, it can lead to abnormalities in lipid metabolism and subsequent progression to overt hypothyroidism, with significant clinical consequences of myocardial infarction and stroke. More research needs to be performed to investigate the link between subclinical hypothyroidism and cardiovascular disease risk and to evaluate the health and economic outcomes of randomized trials of TSH screening.