This study is a double-blind, placebo-controlled, randomised clinical trial to evaluate the clinical and microbiological efficacy and safety of single dose ofloxacin for acute diarrhoea. Eligible patients were 16 years of age or older with a history of acute diarrhoea lasting no more than 48 h; 117 patients were randomised and 97.4% (114/117) were evaluable for efficacy. Of these, 58% were suspected to have ingested contaminated foods. Enteric pathogens were isolated in 61.5% of the patients, Salmonella enteritidis being reported in 87.5%. The patients received either a single 400 mg dose of ofloxacin, or placebo. The average duration of diarrhoea was 2.56 +/- 2.21 days in the ofloxacin group and 3.41 +/- 2.5 in the placebo group (P = 0.117). The average duration of fever was 0.63 +/- 0.95 days in the ofloxacin group and 1.05 +/- 0.96 in the placebo group (P = 0.02). Symptoms remained unchanged for more than 48 h in only 7% of the patients who received ofloxacin, compared with 12% in the placebo group (P = 0.485). Only 32% of patients in the ofloxacin group remained culture positive after 48 h compared with 59% in the placebo group (P = 0.0018). These represent a relative risk reduction (RRR) for stool clearance of 45.5% and absolute risk reduction (ARR) of 27% (95% Cl, 8-44.7), with a number of patients needed to treat (NNT) of 3.7 (95%, 2.7-11.3). After 15 days, 23.3% of patients in the ofloxacin group had a positive culture compared with 28.9% in the placebo (P = 0.63). This represents an RRR of 19%, an ARR of 5.6% and a NNT of 17.8. Adverse events in the ofloxacin group were observed in only one patient who reported headache and in one patient in the placebo group who developed a rash. In summary, empirical treatment with a single dose of ofloxacin in acute diarrhoea did not reduce the intensity or duration of symptoms (except possibly length of fever). It was notable however that stool cultures became negative for S. enteritidis by 48 h, with no relapse after 2 weeks of follow-up.

Familial hypercholesterolemia is an autosomal dominant disease of lipid metabolism caused by defects in the genes LDLR, APOB, and PCSK9. The prevalence of heterozygous familial hypercholesterolemia (HeFH) is estimated between 1/200 and 1/250. Early detection of patients with FH allows initiation of treatment, thus reducing the risk of coronary heart disease. In this study, we performed in vitro characterization of new LDLR variants found in our patients. Genetic analysis was performed by Next Generation Sequencing using a customized panel of 198 genes in DNA samples of 516 subjects with a clinical diagnosis of probable or definitive FH. All new LDLR variants found in our patients were functionally validated in CHO‐ldlA7 cells. The LDLR activity was measured by flow cytometry and LDLR expression was detected by immunofluorescence. Seven new variants at LDLR were tested: c.518 G>C;p.(Cys173Ser), c.[684 G>T;694 G>T];p.[Glu228Asp;Ala232Ser], c.926C>A;p.(Pro309His), c.1261A>G;p.(Ser421Gly), c.1594T>A;p.(Tyr532Asn), and c.2138delC;p.(Thr713Lysfs*17). We classified all variants as pathogenic except p.(Ser421Gly) and p.(Ala232Ser). The functional in vitro characterization of rare variants at the LDLR is a useful tool to classify the new variants. This approach allows us to confirm the genetic diagnosis of FH, avoiding the classification as “uncertain significant variants”, and therefore, carry out cascade family screening.

We report a patient with inappropriate secretion of thyrotropin (TSH) and a pituitary mass. Although she had been treated for biochemical hyperthyroidism with thyroid surgery and radioiodine ablation, she had never complained of specific symptoms or demonstrated signs of overt thyroid dysfunction. On evaluation, she had increased free thyroxine and TSH levels, normal serum glycoprotein alpha-subunit levels, and a significant TSH over-response to exogenous thyrotropin-releasing hormone stimulation. Magnetic resonance imaging with gadolinium enhancement showed a pituitary enlargement with suprasellar extension. An indium In 111 pentetreotide scan showed an abnormal focus of radionuclide accumulation in the pituitary area. Sequencing of the TRbeta gene showed that the patient was heterozygous for a new single nucleotide substitution resulting in the replacement of the normal arginine with a serine at amino acid 320 (R320S). We review the difficulties encountered in establishing a correct diagnosis in patients with inappropriate secretion of TSH in combination with pituitary enlargement. Due to its possible false-negative results, we do not recommend the use of indium In 111 pentetreotide as a tool in the differential diagnosis of inappropriate secretion of TSH.

Daytime and 24 h average blood pressure may indeed carry similar information for diagnosing hypertension and assessing the effects of antihypertensive treatment in clinical practice. Ambulatory blood pressure monitoring used only during the daytime period could be better tolerated and agreed to by patients than 24 h monitoring.

Multiple BP measurements had no impact on the final ABI or on the subsequent diagnosis of PAD.