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Context  Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer.

Objective  To estimate risk and mortality reduction stratified by mutation and prior cancer status.

Design, Setting, and Participants  Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009.

Main Outcomes Measures  Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality.

Results  No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer–specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer–specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]).

Conclusions  Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer–specific mortality, and ovarian cancer–specific mortality.

Context  Although preterm delivery is a well-established risk factor for cerebral palsy (CP), preterm deliveries contribute only a minority of affected infants. There is little information on the relation of CP risk to gestational age in the term range, where most CP occurs.

Objective  To determine whether timing of birth in the term and postterm period is associated with risk of CP.

Design, Setting, and Participants  Population-based follow-up study using the Medical Birth Registry of Norway to identify 1 682 441 singleton children born in the years 1967-2001 with a gestational age of 37 through 44 weeks and no congenital anomalies. The cohort was followed up through 2005 by linkage to other national registries.

Main Outcome Measures  Absolute and relative risk of CP for children surviving to at least 4 years of age.

Results  Of the cohort of term and postterm children, 1938 were registered with CP in the National Insurance Scheme. Infants born at 40 weeks had the lowest risk of CP, with a prevalence of 0.99/1000 (95% confidence interval [CI], 0.90-1.08). Risk for CP was higher with earlier or later delivery, with a prevalence at 37 weeks of 1.91/1000 (95% CI, 1.58-2.25) and a relative risk (RR) of 1.9 (95% CI, 1.6-2.4), a prevalence at 38 weeks of 1.25/1000 (95% CI, 1.07-1.42) and an RR of 1.3 (95% CI, 1.1-1.6), a prevalence at 42 weeks of 1.36/1000 (95% CI, 1.19-1.53) and an RR of 1.4 (95% CI, 1.2-1.6), and a prevalence after 42 weeks of 1.44 (95% CI, 1.15-1.72) and an RR of 1.4 (95% CI, 1.1-1.8). These associations were even stronger in a subset with gestational age based on ultrasound measurements: at 37 weeks the prevalence was 1.17/1000 (95% CI, 0.30-2.04) and the relative risk was 3.7 (95% CI, 1.5-9.1). At 42 weeks the prevalence was 0.85/1000 (95% CI, 0.33-1.38) and the relative risk was 2.4 (95% CI, 1.1-5.3). Adjustment for infant sex, maternal age, and various socioeconomic measures had little effect.

Conclusion  Compared with delivery at 40 weeks' gestation, delivery at 37 or 38 weeks or at 42 weeks or later was associated with an increased risk of CP.

Context  Optimal treatment to postpone functional decline in patients with dementia is not established.

Objective  To test a nonpharmacologic intervention realigning environmental demands with patient capabilities.

Design, Setting, and Participants  Prospective 2-group randomized trial (Care of Persons with Dementia in their Environments [COPE]) involving patients with dementia and family caregivers (community-living dyads) recruited from March 2006 through June 2008 in Pennsylvania.

Interventions  Up to 12 home or telephone contacts over 4 months by health professionals who assessed patient capabilities and deficits; obtained blood and urine samples; and trained families in home safety, simplifying tasks, and stress reduction. Control group caregivers received 3 telephone calls and educational materials.

Main Outcome Measures  Functional dependence, quality of life, frequency of agitated behaviors, and engagement for patients and well-being, confidence using activities, and perceived benefits for caregivers at 4 months.

Results  Of 284 dyads screened, 270 (95%) were eligible and 237 (88%) randomized. Data were collected from 209 dyads (88%) at 4 months and 173 (73%) at 9 months. At 4 months, compared with controls, COPE patients had less functional dependence (adjusted mean difference, 0.24; 95% CI, 0.03-0.44; P = .02; Cohen d = 0.21) and less dependence in instrumental activities of daily living (adjusted mean difference, 0.32; 95% CI, 0.09-0.55; P = .007; Cohen d = 0.43), measured by a 15-item scale modeled after the Functional Independence Measure; COPE patients also had improved engagement (adjusted mean difference, 0.12; 95% CI, 0.07-0.22; P = .03; Cohen d = 0.26), measured by a 5-item scale. COPE caregivers improved in their well-being (adjusted mean difference in Perceived Change Index, 0.22; 95% CI, 0.08-0.36; P = .002; Cohen d = 0.30) and confidence using activities (adjusted mean difference, 0.81; 95% CI, 0.30-1.32; P = .002; Cohen d = 0.54), measured by a 5-item scale. By 4 months, 64 COPE dyads (62.7%) vs 48 control group dyads (44.9%) eliminated 1 or more caregiver-identified problems (21 = 6.72, P = . 01).

Conclusion  Among community-living dyads, a nonpharmacologic biobehavioral environmental intervention compared with control resulted in better outcomes for COPE dyads at 4 months. Although no group differences were observed at 9 months for patients, COPE caregivers perceived greater benefits.

Trial Registration  clinicaltrials.gov Identifier: NCT00259454

Context  For more than 30 years, guidelines for perinatal regionalization have recommended that very low-birth-weight (VLBW) infants be born at highly specialized hospitals, most commonly designated as level III hospitals. Despite these recommendations, some regions continue to have large percentages of VLBW infants born in lower-level hospitals.

Objective  To evaluate published data on associations between hospital level at birth and neonatal or predischarge mortality for VLBW and very preterm (VPT) infants.

Data Sources  Systematic search of published literature (1976–May 2010) in MEDLINE, CINAHL, EMBASE, and PubMed databases and manual searches of reference lists.

Study Selection and Data Extraction  Forty-one publications met a priori inclusion criteria (randomized controlled trial, cohort, and case-control studies measuring neonatal or predischarge mortality among live-born infants ≤1500 g or ≤32 weeks' gestation delivered at a level III vs lower-level facility). Paired reviewers independently assessed publications for inclusion and extracted data using standardized forms. Discrepancies were decided by a third reviewer. Publications were reviewed for quality by 3 authors based on 2 content areas: adjustment for confounding and description of hospital levels. We calculated weighted, combined odds ratios (ORs) using a random-effects model and comparative unadjusted pooled mortality rates.

Data Synthesis  We observed increased odds of death for VLBW infants (38% vs 23%; adjusted OR, 1.62; 95% confidence interval [CI], 1.44-1.83) and VPT infants (15% vs 17%; adjusted OR, 1.55; 95% CI, 1.21-1.98) born outside of level III hospitals. Consistent results were obtained when restricted to higher-quality evidence (mortality in VLBW infants, 36% vs 21%; adjusted OR, 1.60; 95% CI, 1.33-1.92 and in VPT infants, 7% vs 12%; adjusted OR, 1.42; 95% CI, 1.06-1.88) and infants weighing less than 1000 g (59% vs 32%; adjusted OR, 1.80; 95% CI, 1.31-2.46). No significant differences were found through subgroup analysis of study characteristics. Meta-regression by year of publication did not reveal a change over time (slope, 0.00; P = .87).

Conclusion  For VLBW and VPT infants, birth outside of a level III hospital is significantly associated with increased likelihood of neonatal or predischarge death.