Prenatal diagnosis of X-linked ichthyosis

Prenatal diagnosis of X-linked ichthyosis in a case of steroid sulfatase deficiency was made at 16 weeks by the demonstration of (1) high levels of dehydroepiandrosterone sulfate in amniotic fluid; (2) gross deficiency of steroid sulfatase activity in cultured amniotic fluid cells; (3) very low estriol concentrations in maternal blood and urine; (4) increased maternal plasma dehydroepiandrosterone sulfate; and (5) a characteristic maternal urinary steroid profile with greatly increased levels of 16 alpha-hydroxydehydroepiandrosterone. The latter method is particularly useful since it requires no invasive procedures for the patient and is very specific.     

Observational Study of the Clinical Efficacy of Voriconazole and Its Relationship to Plasma Concentrations in Patients

Voriconazole is approved for treating invasive fungal infections. We examined voriconazole exposure-response relationships for patients from nine published clinical trials. The relationship between the mean voriconazole plasma concentration (C_avg) and clinical response and between the free C_avg/MIC ratio versus the clinical response were explored using logistic regression. The impact of covariates on response was also assessed. Monte Carlo simulation was used to estimate the relationship between the trough concentration/MIC ratio and the probability of response. The covariates individually related to response were as follows: study (P < 0.001), therapy (primary/salvage, P < 0.001), primary diagnosis (P < 0.001), race (P = 0.004), baseline bilirubin (P < 0.001), baseline alkaline phosphatase (P = 0.014), and pathogen (yeast/mold, P < 0.001). The C_avg for 72% of the patients was 0.5 to 5.0 μg/ml, with the maximum response rate (74%) at 3.0 to 4.0 μg/ml. The C_avg showed a nonlinear relationship to response (P < 0.003), with a lower probability at the extremes. For patients with C_avg < 0.5 μg/ml, the response rate was 57%. The lowest response rate (56%) was seen with a C_avg ≥ 5.0 μg/ml (18% of patients) and was associated with significantly lower mold infection responses compared to yeasts (P < 0.001) but not with voriconazole toxicity. Higher free C_avg/MIC ratios were associated with a progressively higher probability of response. Monte Carlo simulation suggested that a trough/MIC ratio of 2 to 5 is associated with a near-maximal probability of response. The probability of response is lower at the extremes of C_avg. Patients with higher free C_avg/MIC ratios have a higher probability of clinical response. A trough/MIC ratio of 2 to 5 can be used as a target for therapeutic drug monitoring.     

Review of the benefits of treating hypertension.

The main points covered in this review are as follows: 1. Hypertension is a major determinant of cardiovascular disease (CVD). As such it is a major cause of mortality, potential years of life lost, morbidity and long-term disability. 2. The incidence of CVD is directly related to BP. It is likely that this extends over the full range of BP although some writers believe that a J-curve of risk exists for CHD. 3. The relationship between long-term disability from CVD and BP requires further study. 4. Because of regression dilution bias, the gradient in risk of stroke and CHD with BP has been underestimated in the past. Recent research suggests that the risk of stroke increases at least tenfold and CHD sixfold over a range of usual DBP of 30 mmHg (equivalent to approximately 50 mmHg baseline DBP). 5. The population attributable risk (PAR) of CVD related to general elevation of BP in the population from a mean daily excess of sodium intake of 100 mmol/day is at least 30%. In typical industrialised countries the PAR for stroke and CHD from clinical hypertension is 36% and 22%, respectively. These estimates of PAR provide a guide to the maximum benefit that could result from either restriction of sodium intake in the whole population or ideal management of all persons with hypertension. In practice such targets are unlikely to be realised. 6. Recent analyses of clinical trials of treatment of hypertension suggest that the risk of stroke is reduced at all levels of initial BP to the extent predicted from observational studies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-Term Air Humidification Therapy Is Cost-Effective for Patients with Moderate or Severe Chronic Obstructive Pulmonary Disease or Bronchiectasis

ObjectiveTo establish the cost-effectiveness of long-term humidification therapy (LTHT) added to usual care for patients with moderate or severe chronic obstructive pulmonary disease or bronchiectasis.MethodsResource usage in a 12-month clinical trial of LTHT was estimated from hospital records, patient diaries, and the equipment supplier. Health state utility values were derived from the St. Georges Respiratory Questionnaire (SGRQ) total score. All patients who remained in the trial for 12 months and who had at least 90 days of diary records were included (87 of 108).ResultsClinical costs were NZ $3973 (95% confidence interval [CI] $1614–$6332) for the control group and NZ $3331 (95% CI $948–$6920) for the intervention group. The mean health benefit per patient was ?6.9 SGRQ units (95% CI ?13.0 to ?7.2; P < 0.05) or +0.0678 quality-adjusted life-years (95% CI 0.001–0.135). With the intervention costing NZ $2059 annually, the mean cost per quality-adjusted life-year was NZ $20,902 (US $18,907) and the bootstrap median was NZ $19,749 (2.5th percentile ?$40,923, 97.5th percentile $221,275). At a willingness-to-pay (WTP) threshold of NZ $30,000, the probability of cost-effectiveness was 61%, ranging from 49% to 72% as the cost of LTHT was varied by ±30%. At a WTP of NZ $20,000, the probability was 49% (range 34%–61%).ConclusionsLTHT is moderately cost-effective for patients with moderate to severe chronic obstructive pulmonary disease or bronchiectasis at a WTP threshold that is acceptable for public funding of medicines in New Zealand. These findings must be interpreted with caution because of the modest size of the clinical study, necessary lack of blinding in the clinical trial, and uncertainty in estimating health state utility from the SQRQ.