The interplay of sun damage and genetic risk in Australian multiple and single primary melanoma cases and controls.

BACKGROUND: Skin phenotype, host genotype and ultraviolet (UV) damage play a role in the development of melanoma. OBJECTIVES: To ascertain whether the level of UV damage at the site of melanomas was associated with genetic polymorphisms. METHODS: Deep phenotyping was performed on 1244 individuals; 281 with multiple primary melanomas (MPMs), 304 with single primary melanoma (SPM) and 659 convenience controls. Genotype data was generated using the Illumina CoreExome microarray platform, assaying over 500 000 single-nucleotide polymorphisms. A subset of variants were combined to assess a polygenic risk score (PRS) for melanoma. RESULTS: Most MPM cases were diagnosed in patients aged > 40 years, in sites with visible chronic UV damage. Women and those diagnosed at age ≤ 40 years were less likely to have perilesional UV damage. Patients with MPM had higher frequencies of MITF E318K, MC1R R-alleles and the ASIP risk haplotype. Individuals who had melanoma in a visibly UV-damaged site were more likely to carry MC1R rs75570604 [odds ratio (OR) 2·5], 9q31.2 rs10816595 (OR 1·4) and MTAP rs869329 (OR 1·4). These same alleles were more common in patients with MPM who were diagnosed at age ≤ 40 years. The mean PRS was significantly higher in MPM than in SPM and controls. Naevus count was comparable in early-onset MPM cases and those diagnosed at age > 40 years. CONCLUSIONS: Our cohort demonstrated higher frequencies of previously reported alleles associated with melanoma. MPM melanomas more commonly occur in UV-damaged areas, and these individuals are more likely to carry MC1R red hair colour alleles. Awareness of the interplay of genetic vulnerability with UV damage can stratify risk and guide recommendations for melanoma screening. What's already known about this topic? Skin phenotype, host genotype and ultraviolet (UV) damage all play a role in melanoma development. One of the main risk factors is a personal history of melanoma; second and subsequent primary melanomas account for over 20% of all melanomas registered in Queensland. Multiple loci are associated with melanoma risk, including many low-penetrance loci, which may have a cumulatively significant risk. Population-wide screening programmes for melanoma are not yet economically viable. What does this study add? Patients diagnosed with melanoma at age ≤ 40 years were more likely than older patients to have melanomas in non-UV-damaged sites. Patients with multiple melanomas had higher frequencies of MITF E318K, MC1R R-alleles, and the ASIP extended risk haplotype than patients with single melanoma. CDKN2A, MC1R and MTAP variants were more frequent in patients who developed melanomas at a younger age, but also in those whose melanomas were all on visibly UV-damaged sites. What is the translational message? Incorporating these genetic findings into the known risk factors of skin phenotype and visible UV damage may allow for a more customized and economically feasible approach to early detection of melanoma, particularly in younger patients. Plain language summary available online.

Safeguarding maternal and child health in South Africa by starting the Child Support Grant before birth: Design lessons from pregnancy support programmes in 27 countries.

BACKGROUND: Deprivation during pregnancy and the neonatal period increases maternal morbidity, reduces birth weight and impairs child development, with lifelong consequences. Many poor countries provide grants to mitigate the impact of poverty during pregnancy. South Africa (SA) offers a post-delivery Child Support Grant (CSG), which could encompass support during pregnancy, informed by lessons learnt from similar grants. OBJECTIVES: To review design and operational features of pregnancy support programmes, highlighting features that promote their effectiveness and efficiency, and implications thereof for SA. METHODS: Systematic review of programmes providing cash or other support during pregnancy in low- and middle-income countries. RESULTS: Thirty-two programmes were identified, across 27 countries. Programmes aimed to influence health service utilisation, but also longer-term health and social outcomes. Half included conditionalities around service utilisation. Multifaceted support, such as cash and vouchers, necessitated complex parallel administrative procedures. Five included design features to diminish perverse incentives. These and other complex features were often abandoned over time. Operational barriers and administrative costs were lowest in programmes with simplified procedures and that were integrated within child support. CONCLUSIONS: Pregnancy support in SA would be feasible and effective if integrated within existing social support programmes and operationally simple. This requires uncomplicated enrolment procedures (e.g. an antenatal card), cash-only support, and few or no conditionalities. To overcome political barriers to implementation, the design might initially need to include features that discourage pregnancy incentives. Support could incentivise service utilisation, without difficult-to-measure conditionalities. Beginning the CSG in pregnancy would be operationally simple and could substantially transform maternal and child health.

Systematic review: psychological morbidity in young people with inflammatory bowel disease - risk factors and impacts.

BACKGROUND: Psychological morbidity in young people aged 10-24 years, with inflammatory bowel disease (IBD) is increased, but risk factors for and impacts of this are unclear. AIM: To undertake a systematic literature review of the risk factors for and impact of psychological morbidity in young people with IBD. METHODS: Electronic searches for English-language articles were performed with keywords relating to psychological morbidity according to DSM-IV and subsequent criteria; young people; and IBD in the MEDLINE, PsychInfo, Web of Science and CINAHL databases for studies published from 1994 to September 2014. RESULTS: One thousand four hundred and forty-four studies were identified, of which 30 met the inclusion criteria. The majority measured depression and anxiety symptoms, with a small proportion examining externalising behaviours. Identifiable risk factors for psychological morbidity included: increased disease severity (r(2) = 0.152, P < 0.001), lower socioeconomic status (r(2) = 0.046, P < 0.001), corticosteroids (P ≤ 0.001), parental stress (r = 0.35, P < 0.001) and older age at diagnosis (r = 0.28, P = 0.0006). Impacts of psychological morbidity in young people with IBD were wide-ranging and included abdominal pain (r = 0.33; P < 0.001), sleep dysfunction (P < 0.05), psychotropic drug use (HR 4.16, 95% CI 2.76-6.27), non-adherence to medication (12.6% reduction) and negative illness perceptions (r = -0.43). CONCLUSIONS: Psychological morbidity affects young people with IBD in a range of ways, highlighting the need for psychological interventions to improve outcomes. Identified risk factors provide an opportunity to develop targeted therapies for a vulnerable group. Further research is required to examine groups under-represented in this review, such as those with severe IBD and those from ethnic minorities.

Counseling sexually active very young adolescent girls.

PIP: The sexually active young adolescent female presents herself to the adolescent health program at the Community Health Clinics, Inc., in Nampa, Idaho in several ways: the pregnancy scare; agency referrals; routine physical examinations; the homeless adolescent; and repeated infections. The approach to the adolescent is dependent upon the situation. An important consideration in seeking information regarding sexuality is to be knowledgeable about the individual state laws concerning the right of minors to seek and receive treatment for venereal disease and fertility control without parental consent. The age in Idaho is 14 years. Another important factor in talking to early adolescents about their sexual activity is to be certain that the terminology used means the same thing to the adolescent as it does to the counselor and the parents. The most successful interviewing style, generally, is warm honest, concerned and presented with a gentle sense of humor. When an early adolescent comes in for routine health maintenance activities, her psychosocial development and her level of knowledge about human sexuality are evaluated. Interviewing the adolescent female about her sexual behavior is not always easy. A few potential problems are that clients sometimes lie, mothers may remain in the room for the entire interview and physical examination, and the youth may refuse to communicate. Possibly, the most important help a clinician can give a young client is to aid her in sorting out her feelings about her own sexuality and the use of contraception.^ieng