Patient Knowledge and Qualities of Treatment Decisions for Localized Prostate Cancer.

BACKGROUND: Controversy surrounds treatment for localized prostate cancer (LPC). OBJECTIVES: To assess men's localized prostate cancer (LPC) knowledge and its association with decision-making difficulty, satisfaction and regret. METHODS: Population-based sample of 201 men (104 white, 97 black), ≤ 75 years with newly diagnosed LPC completed a self-administered survey. RESULTS: Mean age was 61(±7.6) years; two-thirds had less than a Bachelor's degree. Mean LPC knowledge was low, 5.87 (±2.53, maximum score 11). More than a third of men who received surgery or radiation did not know about serious long-term treatment side effects. Fewer than half of the men correctly answered comparative side effect and survival benefit questions between surgery and radiation. Knowledge gaps were greatest among black men, men with lower education, single men. Tumor aggressiveness (i.e. PSA level, Gleason score) and treatment choice were not associated with knowledge. Knowledge was not associated with decisional satisfaction or regret. However, greater knowledge was associated with greater decision-making difficulty (P = .018). CONCLUSIONS: Significant LPC knowledge gaps existed across groups, with greater knowledge gaps among black men. The association of decision-making difficulty with knowledge was independent of race. Better patient education is needed, but may not alleviate men's decision-making difficulty due to inherent scientific uncertainty.

Primary care appointment availability and nonphysician providers one year after Medicaid expansion.

OBJECTIVES: With insurance enrollment greater than expected under the Affordable Care Act, uncertainty about the availability and timeliness of healthcare services for newly insured individuals has increased. We examined primary care appointment availability and wait times for new Medicaid and privately insured patients before and after Medicaid expansion in Michigan. STUDY DESIGN: Simulated patient ("secret shopper") study. METHODS: Extended follow-up of a previously reported simulated patient ("secret shopper") study assessing accessibility of routine new patient appointments in a stratified proportionate random sample of Michigan primary care practices before versus 4, 8, and 12 months after Medicaid expansion. RESULTS: During the study period, approximately 600,000 adults enrolled in Michigan's Medicaid expansion program, representing 57% of the previously uninsured nonelderly adult population. One year after expansion, we found that appointment availability remained increased by 6 percentage points for new Medicaid patients (95% CI, 1.6-11.1) and decreased by 2 percentage points for new privately insured patients (95% CI, -0.5 to -3.8). Over the same period, the proportion of appointments scheduled with nonphysician providers (nurse practitioners or physician assistants) increased from 8% to 21% of Medicaid appointments (95% CI, 5.6-20.2) and from 11% to 19% of private-insurance appointments (95% CI, 1.3-14.1). Median wait times remained stable for new Medicaid patients and increased slightly for new privately insured patients, both remaining within 2 weeks. CONCLUSIONS: During the first year following Medicaid expansion in Michigan, appointment availability for new Medicaid patients increased, a greater proportion of appointments could be obtained with nonphysician providers, and wait times remained within 2 weeks.

Primary care appointment availability for new Medicaid patients increased after Medicaid expansion in Michigan.

The Affordable Care Act expands health insurance coverage to millions of Americans, but the availability of health care services for the newly insured population remains uncertain. We conducted a simulated patient (or "secret shopper") study to assess primary care appointment availability and wait times for new patients with Medicaid or private insurance before and after implementation of Michigan's Medicaid expansion in 2014. The expansion, which was made possible through a section 1115 waiver, has a unique requirement that new beneficiaries must be seen by a primary care provider within 60-90 days of enrollment. During a period of rapid coverage expansion in Michigan, we found that appointment availability increased 6 percentage points for new Medicaid patients and decreased 2 percentage points for new privately insured patients, compared to availability before the expansion. Wait times remained stable, at 1-2 weeks for both groups. Further research is needed to determine whether access to primary care for newly insured patients will endure over time.

Does Patient Sex Affect the Rate of Mortality and Complications After Spine Surgery? A Systematic Review.

BACKGROUND: Available studies disagree regarding the influence of patient sex on mortality and complications after spine surgery. We sought to conduct a systematic review and pool the results of existing research to better understand this issue. QUESTIONS/PURPOSES: We performed a systematic review to address two questions: (1) Does sex (male versus female) influence mortality after spine surgery? (2) Does sex impact the development of postoperative complications after spine surgery? METHODS: This systematic review was performed through a query of PubMed using a structured search algorithm. Additional queries of Embase, SCOPUS, Web of Science, and the tables of contents of orthopaedic and neurosurgical journals were also conducted using search terms such as "sex factors", "male or female", "risk factors", and "spine surgery". Selected papers were independently abstracted by three of the authors (AJS, ENR, EIW) and pooling was performed. Our literature search returned 720 studies, of which 99 underwent full review. Of these, 50 were selected for final abstraction. The Cochrane Q test was used to assess study heterogeneity; significant study heterogeneity was present and so a random-effects model was used. A Harbord test was used to evaluate for the presence of publication bias; this analysis found no statistically significant evidence of publication bias. RESULTS: Males were at increased odds of mortality after spine surgery (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.35-1.97; p<0.001). No differences between the sexes were identified for the odds of complications (OR, 1.04; 95% CI, 0.95-1.13; p=0.42). CONCLUSIONS: Our results determined that males were at elevated odds of mortality but not of complications after spine surgery. These results should be used to inform preoperative discussion and decision-making at the time of surgical consent. Future work should be directed at determining the underlying factors responsible for increased mortality among males and prospective studies specifically designed to evaluate sex-based differences in outcomes after spine surgery. LEVEL OF EVIDENCE: Level III, therapeutic study.

Atypical frontal-striatal-thalamic circuit white matter development in pediatric obsessive-compulsive disorder.

OBJECTIVE: Atypical development of frontal-striatal-thalamic circuitry (FSTC) has been hypothesized to underlie the early course of obsessive-compulsive disorder (OCD); however, the development of FSTC white matter tracts remains to be studied in young patients. METHOD: To address this gap, we scanned 36 patients with pediatric OCD compared to 27 healthy controls, aged 8 to 19 years, with diffusion tensor imaging (DTI) to measure fractional anisotropy (FA), an index of white matter coherence. Tract-based spatial statistics (TBSS) were used to test differential effects of age on FA, across the whole brain, in those with OCD compared to healthy youth, followed by analyses in a priori regions of interest (anterior corpus callosum, anterior cingulum bundle, and anterior limb of the internal capsule [ALIC]) to further characterize developmental differences between groups. RESULTS: Patients with OCD showed more pronounced age-related increases in FA than controls in regions of interest, as well as several other white matter tracts. In patients, greater FA in anterior cingulum bundle correlated with more severe symptoms after controlling for age. CONCLUSIONS: Our findings support theories of atypical FSTC maturation in pediatric OCD by providing the first evidence for altered trajectories of white matter development in anterior corpus callosum, anterior cingulum bundle, and ALIC in young patients. Steeper age-related increases of FA in these and other select white matter tracts in OCD, compared to those in healthy controls, may derive from an early delay in white matter development and/or prolonged white matter growth; however, confirmation of these possibilities awaits longitudinal work.

The chromatin remodeling protein CHD7, mutated in CHARGE syndrome, is necessary for proper craniofacial and tracheal development.

BACKGROUND: Heterozygous mutations in the chromatin remodeling gene CHD7 cause CHARGE syndrome, a developmental disorder with variable craniofacial dysmorphisms and respiratory difficulties. The molecular etiologies of these malformations are not well understood. Homozygous Chd7 null mice die by E11, whereas Chd7(Gt/+) heterozygous null mice are a viable and excellent model of CHARGE. We explored skeletal phenotypes in Chd7(Gt/+) and Chd7 conditional knockout mice, using Foxg1-Cre to delete Chd7 (Foxg1-CKO) in the developing eye, ear, nose, pharyngeal pouch, forebrain, and gut and Wnt1-Cre (Wnt1-CKO) to delete Chd7 in migrating neural crest cells. RESULTS: Foxg1-CKO mice exhibited postnatal respiratory distress and death, dysplasia of the eye, concha, and frontal bone, hypoplastic maxillary shelves and nasal epithelia, and reduced tracheal rings. Wnt1-CKO mice exhibited frontal and occipital bone dysplasia, hypoplasia of the maxillary shelves and mandible, and cleft palate. In contrast, heterozygous Chd7(Gt/+) mice had apparently normal skeletal development. CONCLUSIONS: Conditional deletion of Chd7 in ectodermal and endodermal derivatives (Foxg1-Cre) or migrating neural crest cells (Wnt1-Cre) results in varied and more severe craniofacial defects than in Chd7(Gt/+) mice. These studies indicate that CHD7 has an important, dosage-dependent role in development of several different craniofacial tissues.

Delayed fusion and altered gene expression contribute to semicircular canal defects in Chd7 deficient mice.

Proper morphogenesis of inner ear semicircular canals requires precise regulation of cellular proliferation, epithelial-to-mesenchymal transition, and fusion of epithelial plates. Epigenetic regulation of these processes is not well understood, but is likely to involve chromatin remodeling enzymes. CHD7 is a chromodomain-containing, ATP dependent helicase protein that is highly expressed in the developing ear and is required for semicircular canal development in both humans and mice. Here we report that mice with heterozygous loss of Chd7 function exhibit delayed semicircular canal genesis, delayed Netrin1 expression and disrupted expression of genes that are critical for semicircular canal formation (Bmp2, Bmp4, Msx1 and Fgf10). Complete loss of Chd7 results in aplasia of the semicircular canals and sensory vestibular organs, with reduced or absent expression of Otx1, Hmx3, Jagged1, Lmo4, Msx1 and Sox2. Our results suggest that Chd7 may have critical selector gene functions during inner ear morphogenesis. Detailed analysis of the epigenetic modifications underlying these gene expression changes should provide insights into semicircular canal development and help in the design of therapies for individuals with inner ear malformations.

Interleukin 18 induces angiogenesis in vitro and in vivo via Src and Jnk kinases.

BACKGROUND: Interleukin 18 (IL-18) is a novel mediator of angiogenesis in rheumatoid arthritis (RA). OBJECTIVE: To examine the role of IL-18 in RA angiogenesis and the signalling mechanisms involved. METHODS: Human dermal microvascular endothelial cell (HMVEC) chemotaxis, capillary morphogenesis assays and Matrigel plug angiogenesis assays were performed in vivo using IL-18 with or without signalling inhibitors. A novel model of angiogenesis was devised using dye-tagged HMVECs to study their homing into RA and normal (NL) synovial tissues (STs) engrafted in severe combined immunodeficient (SCID) mice. RESULTS: IL-18-mediated angiogenesis depended on Src and Jnk, as the inhibitors of Src and Jnk blocked IL-18-induced HMVEC chemotaxis, tube formation and angiogenesis in Matrigel plugs. However, inhibitors of Janus kinase 2, p38, MEK, phosphatidylinositol-3-kinase and neutralising antibodies to vascular endothelial growth factor or stromal derived factor-1α did not alter IL-18-induced HMVEC migration. These results were confirmed with Jnk or Src sense or antisense oligodeoxynucleotides. Moreover, IL-18 induced phosphorylation of Src and Jnk in HMVECs. As proof of principle, IL-18 null mice had a significantly decreased angiogenesis compared with wild-type mice in Matrigel plug angiogenesis assays in vivo. IL-18 markedly enhanced mature HMVEC homing to human RA ST compared with NL ST in SCID mice, confirming the role of IL-18-induced angiogenesis in RA ST in vivo. CONCLUSION: Targeting IL-18 or its signalling intermediates may prove to be a potentially novel therapeutic strategy for angiogenesis-dependent diseases, such as RA.