The effect of patients’ preference on outcome in the EVerT cryotherapy versus salicylic acid for the treatment of plantar warts (verruca) trial

Background Randomised controlled trials are widely accepted as the gold standard method to evaluate medical interventions, but they are still open to bias. One such bias is the effect of patient’s preference on outcome measures. The aims of this study were to examine whether patients’ treatment preference affected clearance of plantar warts and explore whether there were any associations between patients’ treatment preference and baseline variables in the EverT trial. Methods Two hundred and forty patients were recruited from University podiatry schools, NHS podiatry clinics and primary care. Patients were aged 12 years and over and had at least one plantar wart which was suitable for treatment with salicylic acid and cryotherapy. Patients were asked their treatment preference prior to randomisation. The Kruskal-Wallis test was performed to test the association between preference group and continuous baseline variables. The Fisher’s exact test was performed to test the association between preference group and categorical baseline variables. A logistic regression analysis was undertaken with verruca clearance (yes or no) as the dependent variable and treatment, age, type of verruca, previous treatment, treatment preference as independent variables. Two analyses were undertaken, one using the health professional reported outcome and one using the patient’s self reported outcomes. Data on whether the patient found it necessary to stop the treatment to which they had been allocated and whether they started another treatment were summarised by treatment group. Results Pre-randomisation preferences were: 10% for salicylic acid; 42% for cryotherapy and 48% no treatment preference. There was no evidence of an association between treatment preference group and either patient (p=0.95) or healthcare professional (p=0.46) reported verruca clearance rates. There was no evidence of an association between preference group and any of the baseline variables except gender, with more females expressing a preference for salicylic acid (p=0.004). There was no evidence that the number of times salicylic acid was applied was different between the preference groups at one week (p=0.89) or at three weeks (p=0.24). Similarly, for the number of clinic visits for cryotherapy (p=0.71) Conclusions This secondary analysis showed no evidence to suggest that patients’ baseline preferences affected verruca clearance rates or adherence with the treatment

Changing Patterns in Residential Services for the Mentally Retarded

https://digitalcommons.unmc.edu/wolf_books/1007/thumbnail.jp

Truncating Homozygous Mutation of Carboxypeptidase E (CPE) in a Morbidly Obese Female with Type 2 Diabetes Mellitus, Intellectual Disability and Hypogonadotrophic Hypogonadism

Carboxypeptidase E is a peptide processing enzyme, involved in cleaving numerous peptide precursors, including neuropeptides and hormones involved in appetite control and glucose metabolism. Exome sequencing of a morbidly obese female from a consanguineous family revealed homozygosity for a truncating mutation of the CPE gene (c.76_98del; p.E26RfsX68). Analysis detected no CPE expression in whole blood-derived RNA from the proband, consistent with nonsense-mediated decay. The morbid obesity, intellectual disability, abnormal glucose homeostasis and hypogonadotrophic hypogonadism seen in this individual recapitulates phenotypes in the previously described fat/fat and Cpe knockout mouse models, evidencing the importance of this peptide/hormone-processing enzyme in regulating body weight, metabolism, and brain and reproductive function in humans

Location of c.76_98del; p. E26RfsX68 <i>CPE</i> mutation.

<p>A: Schematic overview of the exons of <i>CPE</i> (Refseq: NM_001873). Dark shaded areas are UTRs and light grey areas are coding regions. B: Human CPE protein (UniprotKB: P16870). Location of the E26RfsX68 mutation is shown by the red diagonally striped region. Arrow shows the location of Arg283Trp. SP, signalling peptide; PP, pro-peptide. C: Indicative chromatogram of the deletion in the proband and the normal wild-type sequence. The deletion is indicated in red. Amino acid changes caused by the frameshift are shown above the chromatogram.</p

Clinical features of proband with homozygous truncating <i>CPE</i> mutation.

<p>Photograph of proband carrying a homozygous truncating deletion of <i>CPE</i>. Specific written consent for the photograph and case details was obtained from proband and mother. At the time of examination, the proband had a weight of 130.2 kg and height of 1.59 m with body mass index (BMI) 51.5 kg/m². There was some intellectual disability, for example despite adequate schooling she was unable to read or write words. She had newly diagnosed type 2 diabetes mellitus with fasting glucose 383 mg/dL, 21.1 mmol/L; HbA1c 114 mmol/mol, 12.6%) and hypogonadotrophic hypogonadism with primary amenorrhea (serum oestradiol 78 pmol/L [post-menopausal range <100 pmol/L], 21.2 pg/mL; LH 2.7 IU/L, FSH 2.0 IU/L). Serum hormone analysis excluded other causes of amenorrhoea including polycystic ovary syndrome and hyperprolactinaemia (testosterone 1.2 nmol/L (normal <2.7), 0.35 ng/mL (normal <0.78); normal androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone sulphate (DHEAS), prolactin). There was no history of depression or anxiety.</p

CPE mRNA expression levels.

<p>Real time PCR analysis of <i>CPE</i> mRNA expression in blood samples from the proband (II.6), heterozygous sibling (II.5) and six controls. For controls mean ± SEM (standard error of the mean) is depicted. All analyses were conducted in triplicate.</p