Response to growth hormone treatment in Prader-Willi syndrome: auxological criteria versus genetic diagnosis.

AIM: The Australian Prader-Willi Syndrome (PWS) database was established to monitor the efficacy and safety of growth hormone (GH) treatment in PWS. This study aims to compare response to GH based on eligibility criteria. METHODS: Comparative study: 72 children received GH on the basis of short stature or evidence of GH deficiency (pre-2009: PWS-SS) and 94 on a genetic diagnosis (post-2009: PWS-Dx). We report on mandatory patient data for GH prescription: median and standard deviation score (SDS) for height and body mass index (BMI), waist/height ratio, bone age/chronological age ratio and adverse events. Comparisons were made using non-parametric tests. RESULTS: At baseline, the PWS-SS cohort was shorter (height SDS: -2.6 vs. -1.1, P < 0.001), had a lower BMI (0.6 vs. 1.5 SDS, P < 0.05) and greater bone age delay (bone age/chronological age: 0.7 vs. 0.9, P < 0.05) than the PWS-Dx cohort. PWS-SS parents were shorter (mid-parental height SDS: -0.13 vs. 0.28, P < 0.005). Mean change in height over 2 years was 0.9 SDS and in BMI using PWS reference standards -0.3 SDSPWS (n = 106) (year 2, height SDS: PWS-SS = -1.7, PWS-Dx = 0.1; BMI SDSPWS : PWS-SS = -1.0, PWS-Dx = -0.6). The waist/height ratio reduced (PWS-Dx: 0.60 vs. 0.56, P < 0.05) and bone age delay was unchanged over this period. No serious adverse events were reported. CONCLUSIONS: The PWS-SS cohort represents a subgroup of the wider PWS-Dx population; however both cohorts improved height SDS with normalisation of height in the PWS-Dx cohort and lowering of BMI relative to PWS standards supporting the efficacy of treatment under the current Australian GH programme.

Prader-Willi syndrome - care of adults in general practice.

BACKGROUND: Prader-Willi syndrome is a severely disabling genetic condition. Treatments are available, but there is no cure. Children aged up to 18 years may benefit from growth hormone treatment, which normalises height and assists in preventing obesity by decreasing fat mass and increasing muscle mass and physical ability. Adults, however, are treated predominantly for the many disabling secondary complications of the morbid obesity characteristic of this syndrome, and therefore require frequent care from their general practitioner. OBJECTIVE: Despite improvements in the genetic diagnosis of infants with Prader-Willi syndrome, diagnosis in adults appears to be lacking or is based on uncertain clinical characteristics. This article provides information and advice that may assist in the diagnosis and management of Prader-Willi syndrome in adults. DISCUSSION: The GP can play an important role in identifying Prader-Willi syndrome among adult patients who may have remained undiagnosed. Specific care and treatments can then be provided in the general practice setting.

Intellectual disability, sexuality and sexual abuse prevention - a study of family members and support workers.

BACKGROUND: People with intellectual disability experience difficulty forming intimate relationships and are prone to sexual exploitation and abuse. This study sought information from people involved in the care of adults with intellectual disability regarding how they supported them in the areas of sexuality, relationships and abuse prevention. METHODS: Semistructured interviews and focus groups were held with 28 family members and paid support workers caring for adults with intellectual disabilities. Interviews and focus groups were audio recorded, transcribed, coded and analysed qualitatively. RESULTS: Major themes emerging included views on sexuality and intellectual disability, consent and legal issues, relationships, sexual knowledge and education, disempowerment, exploitation and abuse, sexual health and parenting. DISCUSSION: People with intellectual disability were described as lonely, disempowered and vulnerable to abuse. The sex industry, internet and mobile telephones were identified as new forms of risk. While this study looked at the views of both family members and support workers, the sample was too small to identify any meaningful differences between the two groups.

Surgical repair of spontaneous perineal tears that occur during childbirth versus no intervention.

BACKGROUND: Perineal tears commonly occur during childbirth. They are sutured most of the time. Surgical repair can be associated with adverse outcomes, such as pain, discomfort and interference with normal activities during puerperium and possibly breastfeeding. Surgical repair also has an impact on clinical workload and human and financial resources. OBJECTIVES: To assess the evidence for surgical versus non-surgical management of first- and second-degree perineal tears sustained during childbirth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 May 2011), CENTRAL (The Cochrane Library 2011, Issue 2 of 4) and MEDLINE (Jan 1966 to 2 May 2011). We also searched the reference lists of reviews, guidelines and other publications and contacted authors of identified eligible trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) investigating the effect on clinical outcomes of suturing versus non-suturing techniques to repair first- and second-degree perineal tears sustained during childbirth. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and assessed trial quality. Three review authors independently extracted data. MAIN RESULTS: We included two RCTs (involving 154 women) with a low risk of bias. It was not possible to pool the available studies. The two studies do not consistently report outcomes defined in the review. However, no significant differences were observed between the two groups (surgical versus non-surgical repair) in incidence of pain and wound complications, self-evaluated measures of pain at hospital discharge and postpartum and re-initiation of sexual activity. Differences in the use of analgesia varied between the studies, being high in the sutured group in one study. The other trial showed differences in wound closure and poor wound approximation in the non-suturing group, but noted incidentally also that more women were breastfeeding in this group. AUTHORS' CONCLUSIONS: There is limited evidence available from RCTs to guide the choice between surgical or non-surgical repair of first- or second-degree perineal tears sustained during childbirth. Two studies find no difference between the two types of management with regard to clinical outcomes up to eight weeks postpartum. Therefore, at present there is insufficient evidence to suggest that one method is superior to the other with regard to healing and recovery in the early or late postnatal periods. Until further evidence becomes available, clinicians' decisions whether to suture or not can be based on their clinical judgement and the women's preference after informing them about the lack of long-term outcomes and the possible chance of a slower wound healing process, but possible better overall feeling of well being if left un-sutured.

Women with intellectual disabilities--a study of sexuality, sexual abuse and protection skills.

BACKGROUND: Sexual abuse and abusive relationships are known to be especially common in people with intellectual disability. This study explored how women with intellectual disability understand sex, relationships and sexual abuse, the effects of sexual abuse on their lives, and how successfully they protect themselves from abuse. METHODS: Semistructured narrative interviews with nine women with mild intellectual disability in Queensland, Australia. Interviews were audio recorded, transcribed, coded and analysed qualitatively. RESULTS: Major themes that emerged were: sexual knowledge and sources of knowledge; negotiating sexual relationships; declining unwanted sexual contact; self protection strategies; sexual abuse experiences; and sequelae of sexual abuse. DISCUSSION: Most participants reported unwanted or abusive sexual experiences. They described sequelae such as difficulties with sex and relationships, and anxiety and depression. They described themselves as having inadequate self protection skills and difficulty reporting abuse and obtaining appropriate support. Their understanding of sex was limited and they lacked the literacy and other skills to seek information independently. It is important for general practitioners to be aware of the possibility of sexual abuse against women with intellectual disability, and to offer appropriate interventions.

Low dose growth hormone treatment in infants and toddlers with Prader-Willi syndrome is comparable to higher dosage regimens.

OBJECTIVE: Evaluate benefit and risk of low dose growth hormone treatment (GHT, 4.5mg/m2/week) in very young children with Prader-Willi Syndrome (PWS). DESIGN: Prospective longitudinal clinical intervention. METHODS: We evaluated 31 infants (aged 2-12months) and 42 toddlers (13-24months) from the PWS-OZGROW database for height, weight and BMI using the World Health Organization standard deviation scores (SDSWHO) and PWS specific BMI (SDSPWS), bone age, insulin-like growth factor 1 (IGF-I) levels and adverse events over 3years of GHT. RESULTS: At commencement of GHT infants had a lower BMI SDSWHO (-0.88 vs 0.40) than toddlers, while toddlers had a lower height SDSWHO (-1.44 vs -2.09) (both P<0.05). All increased height SDSWHO (2year delta height infants +1.26 SDS, toddlers+1.21 SDS), but infants normalised height sooner, achieving a height SDS of -0.56 within 1year, while toddlers achieved a height SDS of -0.88 in two years. BMI SDSWHO increased, while BMI SDSPWS decreased (both P<0.0001) and remained negative. The GHT response did not differ with gestation (preterm 23%) or genetic subtype (deletion vs maternal uniparental disomy). Bone age advancement paralleled chronological age. All children had low serum IGF-I at baseline which increased, but remained within the age-based reference range during GHT (for 81% in first year). Four children had spinal curvature at baseline; two improved, two progressed to a brace and two developed an abnormal curve over the observation period. Mild to severe central and/or obstructive sleep apnoea were observed in 40% of children prior to GHT initiation; 11% commenced GHT on positive airway pressure (PAP), oxygen or both. Eight children ceased GHT due to onset or worsening of sleep apnoea: 2 infants in the first few months and 6 children after 6-24months. Seven resumed GHT usually after adjusting PAP but five had adenotonsillectomy. One child ceased GHT temporarily due to respiratory illness. No other adverse events were reported. Two children substantially improved their breathing shortly after GHT initiation. CONCLUSION: Initiation of GHT in infants with 4.5mg/m2/week was beneficial and comparable in terms of auxological response to a dose of 7mg/m2/week. Regular monitoring pre and post GH initiation assisted in early detection of adverse events. IGF-I levels increased with the lower dose but not excessively, which may lower potential long-term risks.