Sensory deprivation and motor restriction associated with extensive oxygen therapy may lead to poor oromotor control in preterm infants. Non-nutritive suck is one of the first complex oromotor behaviors infants perform. This study determined the spatiotemporal variability of non-nutritive suck (NNS) pressure trajectories in three preterm groups with differing oxygen histories—one control group with minimal or no O2 therapy, and two Respiratory Distress Syndrome (RDS) groups with either a mild/moderate (RDS1) or moderate/severe (RDS2) O2 history. The Non-nutritive Suck Spatiotemporal Index (NNS STI) quantifies spatial and temporal variability across kinematic trajectories, and was calculated from digital representations of infants’ suck pressure signals. An ANCOVA revealed a significant effect for group (p < .001) on the NNS STI measure, with RDS2 infants showing highly variable NNS patterning, and thus relatively underdeveloped suck. Extensive oxygen therapy, which alters the oral sensory environment and reduces motor experiences, disrupts the development of coordinated NNS in preterm infants.
Premature infant; Respiratory Distress Syndrome; Non-nutritive suck; Oromotor control; Spatiotemporal index; Suck variability; Suck central pattern generator; Oxygen therapy; Motor function
Background & Aims
Zebrafish mutants generated by ethylnitrosourea (ENU)-mutagenesis provide a powerful tool for dissecting the genetic regulation of developmental processes, including organogenesis. One zebrafish mutant, “flotte lotte” (flo), displays striking defects in intestinal, liver, pancreas and eye formation at 78hpf. In this study we sought to identify the underlying mutated gene in flo and link the genetic lesion to its phenotype.
Positional cloning was employed to map the flo mutation. Sub-cellular characterization of flo embryos was achieved using histology, immunocytochemistry, bromodeoxyuridine incorporation analysis, confocal and electron microscopy.
The molecular lesion in flo is a nonsense mutation in the elys (embryonic large molecule derived from yolk sac) gene which encodes a severely truncated protein lacking the Elys C-terminal AT-hook DNA binding domain. Recently, ELYS has been shown to play a critical, and hitherto unsuspected, role in nuclear pore assembly. Though elys mRNA is expressed broadly during early zebrafish development, widespread early defects in flo are circumvented by the persistence of maternally-expressed elys mRNA until 24hpf. From 72hpf, elys mRNA expression is restricted to proliferating tissues, including the intestinal epithelium, pancreas, liver and eye. Cells in these tissues display disrupted nuclear pore formation; ultimately intestinal epithelial cells undergo apoptosis.
Our results demonstrate that Elys regulates digestive organ formation.
BACKGROUND & AIMS
Hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic syndromes, including central nervous system (CNS) abnormalities. However, it is unclear whether such cognitive abnormalities are a function of systemic disease, impaired hepatic function, or virus infection of the CNS.
We measured levels of HCV RNA and expression of the viral entry receptor in brain tissue samples from 10 infected individuals (and 3 uninfected individuals, as controls) and human brain microvascular endothelial cells by using quantitative polymerase chain reaction and immunochemical and confocal imaging analyses. HCV pseudoparticles and cell culture–derived HCV were used to study the ability of endothelial cells to support viral entry and replication.
Using quantitative polymerase chain reaction, we detected HCV RNA in brain tissue of infected individuals at significantly lower levels than in liver samples. Brain microvascular endothelia and brain endothelial cells expressed all of the recognized HCV entry receptors. Two independently derived brain endothelial cell lines, hC-MEC/D3 and HBMEC, supported HCV entry and replication. These processes were inhibited by antibodies against the entry factors CD81, scavenger receptor BI, and claudin-1; by interferon; and by reagents that inhibit NS3 protease and NS5B polymerase. HCV infection promotes endothelial permeability and cellular apoptosis.
Human brain endothelial cells express functional receptors that support HCV entry and replication. Virus infection of the CNS might lead to HCV-associated neuropathologies.
Virus Tropism; HCVpp; HCVcc; Neurologic Defect
The risk of anal cancer is substantially increased in HIV-infected individuals. Thus, the HIV epidemic may have influenced the increasing anal cancer trends in the United States. We estimated the impact of the HIV epidemic on trends in anal cancer incidence in the United States during 1980–2005.
Data on anal cancer cases with and without AIDS were obtained from the HIV/AIDS Cancer Match Study. The number of HIV-infected anal cancer cases without AIDS was estimated from the number of anal cancers occurring before diagnosis of AIDS. The proportion of anal cancer cases with HIV infection in the general population was calculated. We estimated temporal trends in the incidence rates of anal cancer in the general population overall and after exclusion of HIV-infected cancer cases by calculating annual percent changes and 95% confidence intervals (CIs) using a Joinpoint log-linear model. All incidence rates were standardized to the 2000 US population by age, sex, and race.
During 1980–2005, of the 20 533 estimated anal cancer cases, 1665 (8.1%) were HIV-infected. During 2001–2005, the proportion of anal cancer cases with HIV infection was the highest—1.2% (95% CI = 0.93 to 1.4%) among females and 28.4% (95% CI = 26.6 to 29.4%) among males. During 1980–2005, HIV infection did not have an impact on the trends in anal cancer among females (incidence rates increased by 3.3% [95% CI = 3.0 to 3.7%] annually overall, and by 3.3% [95% CI = 2.9 to 3.6%] annually without HIV-infected anal cancer cases) but had a strong impact on the trends in anal cancer among males (incidence rates increased by 3.4% [95% CI = 2.9 to 3.9%] annually overall, and by 1.7% [95% CI = 1.2 to 2.3%] annually without HIV infection).
During 1980–2005, the increasing anal cancer incidence rates in the United States were strongly influenced by the HIV epidemic in males but were independent of HIV infection in females.
Metastatic melanoma is a malignant cancer with generally poor prognosis, with no targeted chemotherapy. To identify epigenetic changes related to melanoma, we have determined genome-wide methylated CpG island distributions by next-generation sequencing. Melanoma chromosomes tend to be differentially methylated over short CpG island tracts. CpG islands in the upstream regulatory regions of many coding and noncoding RNA genes, including, for example, TERC, which encodes the telomerase RNA, exhibit extensive hypermethylation, whereas several repeated elements, such as LINE 2, and several LTR elements, are hypomethylated in advanced stage melanoma cell lines. By using CpG island demethylation profiles, and by integrating these data with RNA-seq data obtained from melanoma cells, we have identified a co-expression network of differentially methylated genes with significance for cancer related functions. Focused assays of melanoma patient tissue samples for CpG island methylation near the noncoding RNA gene SNORD-10 demonstrated high specificity.
School visits to farms are a positive educational experience but pose risks due to the spread of zoonotic infections. A lesson plan to raise awareness about microbes on the farm and preventative behaviours was developed in response to the Griffin Investigation into the E. coli outbreak associated with Godstone Farm in 2009. This study evaluated the effectiveness of the delivery of the lesson plan in increasing knowledge about the spread of infection on the farm, amongst school students.
Two hundred and twenty-five 9–11 year old students from seven junior schools in England participated. Two hundred and ten students filled in identical questionnaires covering microbes, hand hygiene, and farm hygiene before and after the lesson. Statistical analysis assessed knowledge change using difference in percentage correct answers.
Significant knowledge improvement was observed for all sections. In the ‘Farm Hygiene’ section, girls and boys demonstrated 18% (p<0.001) and 11% (p<0.001) improvement, respectively (girls vs. boys p<0.004). As girls had lower baseline knowledge the greater percentage improvement resulted in similar post intervention knowledge scores between genders (girls 80%, boys 83%).
The lesson plan was successful at increasing awareness of microbes on the farm and infection prevention measures and should be used by teachers in preparation for a farm visit.
The Wnt signaling pathway is implicated in major physiologic cellular functions, such as proliferation, migration, cell fate specification, maintenance of pluripotency and induction of tumorigenicity. Proliferation and migration are important responses of T-cells, which are major cellular targets of HIV infection. Using an informatics screen, we identified a previously unsuspected interaction between HIV’s Nef protein and β-catenin, a key component of the Wnt pathway. A segment in Nef contains identical amino acids at key positions and structurally mimics the β-catenin binding sites on endogenous β-catenin ligands. The interaction between Nef and β-catenin was confirmed in vitro and in a co-immunoprecipitation from HEK293 cells. Moreover, the introduction of Nef into HEK293 cells specifically inhibited a Wnt pathway reporter.
Cerebral spinal fluid (CSF) Aβ42, tau and p181tau are widely accepted biomarkers of Alzheimer’s disease (AD). Numerous studies show that CSF tau and p181tau levels are elevated in mild-to-moderate AD compared to age-matched controls. In addition, these increases might predict preclinical AD in cognitively normal elderly. Despite their importance as biomarkers, the molecular nature of CSF tau and ptau is not known. In the current study, reverse-phase high performance liquid chromatography was used to enrich and concentrate tau prior to western-blot analysis. Multiple N-terminal and mid-domain fragments of tau were detected in pooled CSF with apparent sizes ranging from <20 kDa to ~40 kDa. The pattern of tau fragments in AD and control samples were similar. In contrast, full-length tau and C-terminal-containing fragments were not detected. To quantify levels, five tau ELISAs and three ptau ELISAs were developed to detect different overlapping regions of the protein. The discriminatory potential of each assay was determined using 20 AD and 20 age-matched control CSF samples. Of the tau ELISAs, the two assays specific for tau containing N-terminal sequences, amino acids 9-198 (numbering based on tau 441) and 9-163, exhibited the most significant differences between AD and control samples. In contrast, CSF tau was not detected with an ELISA specific for a more C-terminal region (amino acids 159-335). Significant discrimination was also observed with ptau assays measuring amino acids 159-p181 and 159-p231. Interestingly, the discriminatory potential of p181 was reduced when measured in the context of tau species containing amino acids 9-p181. Taken together, these results demonstrate that tau in CSF occurs as a series of fragments and that discrimination of AD from control is dependent on the subset of tau species measured. These assays provide novel tools to investigate CSF tau and ptau as biomarkers for other neurodegenerative diseases.
Acute exercise at the time of vaccination can enhance subsequent immune responses. However, the potential benefit of this effect will be its efficacy in boosting poor responses, and thus protection in at-risk populations. The current study tested the effect of exercise on the response to either a full- or half-dose Pneumococcal (Pn) vaccination to elicit stronger and weaker responses. Subjects were 133 young healthy adults, randomized to one of four groups: Exercise or control task, receiving a full- or half-dose Pn vaccination. Prior to vaccination, exercise groups completed a 15min arm and shoulder exercise task, control groups rested quietly. Antibody levels to 11 Pn strains were evaluated at baseline and 1- month. Across all participants, exercise groups showed significantly greater increase in antibody levels than control groups. When doses were compared, it emerged that those who exercised had significantly larger responses than those who rested in the half-dose group, but in the full-dose groups responses were similar. This data indicates the effectiveness of exercise as a vaccine adjuvant, particularly in weaker responses. Thus, given the potential public health benefits of no-cost behavioural intervention to enhance response to vaccination, testing in at-risk populations should be pursued.
pneumococcal vaccination; acute exercise; antibody; behavioural adjuvant
Differentiation of pulmonary arterial hypertension (PAH) and pulmonary venous hypertension (PVH) often requires right heart catheterization (RHC). We sought to determine whether a combination of clinical and echocardiographic variables could predict the pulmonary diastolic to wedge (PAd-PWP) gradient and thus differentiate patients with PAH and PVH.
We prospectively enrolled 108 patients presenting for PH evaluation. We developed a multivariate model to predict PAd-PWP gradient and validated this model using bootstrapping technique.
PAH patients had worse hemodynamics and were more likely to have evidence of right ventricular dilation and dysfunction whereas patients with PVH were older and more likely to have features of the metabolic syndrome. PAd-PWP gradient of ≥ 6mmHg accurately discriminated patients with PAH compared to PVH. Our model including clinical and echocardiographic variables was highly accurate for the prediction of PAd-PWP gradient with a slope 0.89 (slope of 1 represents perfect prediction).
In this prospective study of patients referred for PH evaluation, a model of readily available clinical parameters and simple echocardiographic measurements accurately predicted the PAd-PWP gradient, allowing discrimination of patients with PAH and PVH. This model requires validation in a larger cohort, but may afford clinicians more parsimony with referral for invasive testing in the evaluation of PH.
Malignancies that occur in excess among HIV-infected individuals may be caused by immunosuppression or infections. Because histologically-defined cancer subtypes have not been systematically evaluated, we assessed their risk among people with AIDS.
Analyses included 569,268 people with AIDS from the HIV/AIDS Cancer Match Study, a linkage of 15 U.S. population-based HIV/AIDS and cancer registries during 1980–2007. Standardized incidence ratios (SIRs) were estimated to compare cancer risk in people with AIDS to the general population overall, and stratified by age, calendar period (a proxy of changing HIV therapies) and time since AIDS (a proxy of immunosuppression).
Sixteen individual cancer histologies or histology groupings manifested significantly elevated SIRs. Risks were most elevated for adult T-cell leukemia/lymphoma (SIR=11.3), neoplasms of histiocytes and accessory lymphoid cells (SIR=10.7), giant cell carcinoma (SIR=7.51) and leukemia not otherwise specified (NOS) (SIR=6.69). SIRs ranged from 1.4 to 4.6 for spindle cell carcinoma, bronchioloalveolar adenocarcinoma, adnexal and skin appendage neoplasms, sarcoma NOS, spindle cell sarcoma, leiomyosarcoma, mesothelioma, germ cell tumors, plasma cell tumors, immunoproliferative diseases, acute lymphocytic leukemia and myeloid leukemias. For several of these cancer subtypes, we observed significant declines in SIRs across calendar periods (consistent with decreasing risk with improved HIV therapies) or increase in SIRs with time since AIDS (i.e., prolonged immunosuppression).
The elevated risk of certain cancer subtypes in people with AIDS may point to an etiologic role of immunosuppression or infection. Future studies are needed to further investigate these associations and evaluate candidate infectious agents.
HIV; immunosuppression; infection; cancer
Despite intensive scientific investigation and public health imperatives, drug addiction treatment outcomes have not significantly improved in more than 50 years. Non-invasive brain imaging has, over the past several decades, contributed important new insights into the neuroplastic adaptations that result from chronic drug intake, but additional experimental approaches and neurobiological hypotheses are needed to better capture the totality of the motivational, affective, cognitive, genetic and pharmacological complexities of the disease. Recent advances in assessing network dynamics through resting-state functional connectivity (rsFC) may allow for such systems-level assessments. In this review, we first summarize the nascent addiction-related rsFC literature and suggest that in using this tool, circuit connectivity may inform specific neurobiological substrates underlying psychological dysfunctions associated with reward, affective and cognitive processing often observed in drug addicts. Using nicotine addiction as an exemplar, we subsequently provide a heuristic framework to guide future research by linking recent findings from intrinsic network connectivity studies with those interrogating nicotine’s neuropharmacological actions. Emerging evidence supports a critical role for the insula in nicotine addiction. Likewise, the anterior insula, potentially together with the anterior cingulate cortex, appears to pivotally influence the dynamics between large-scale brain networks subserving internal (default-mode network) and external (executive control network) information processing. We suggest that a better understanding of how the insula modulates the interaction between these networks is critical for elucidating both the cognitive impairments often associated with withdrawal and the performance-enhancing effects of nicotine administration. Such an understanding may be usefully applied in the design and development of novel smoking cessation treatments.
fMRI; connectivity; drug abuse; nicotine; insula; default mode; attention
Insight/delusionality of beliefs is an important dimension of psychopathology across psychiatric disorders. This construct is of increasing interest in obsessive-compulsive and related disorders, including obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD). Even though OCD and BDD are considered closely related, no prior study has compared these disorders across a range of categories of global insight (excellent, good, fair, poor, absent/delusional), and only one study has compared these disorders on individual components of insight. Using the reliable and valid Brown Assessment of Beliefs Scale (BABS), this study examined insight/delusionality of OCD- or BDD-related beliefs in 211 individuals with primary OCD versus 68 individuals with primary BDD. In both disorders, levels of insight spanned the full range, from excellent to absent (i.e., delusional beliefs). However, the distribution of BABS scores across insight categories differed significantly by disorder, with the majority of OCD subjects showing excellent or good insight, and the majority of BDD subjects showing poor or absent insight. Compared to OCD subjects, BDD subjects had significantly poorer insight both overall (total BABS score) and on all individual BABS items. BABS score was significantly correlated with BDD and OCD severity, but in regressions it accounted for only 21% of the variance in OCD and 28% in BDD. In summary, both global insight and its individual components are poorer in BDD than in OCD, which has implications for research and clinical care, as well as understanding of the relationship between these disorders. Disorder severity is associated with but not equivalent to insight/delusionality.
obsessive-compulsive disorder; body dysmorphic disorder; delusional disorder; insight; delusions
To compare the immunogenicity of one vs. two doses of meningococcal conjugate vaccine (MCV4) in youth infected with HIV.
P1065 was a Phase I/II immunogenicity and safety trial of MCV4 in 324 youth infected with HIV performed at 27 sites of the IMPAACT network in the U.S. At entry subjects received one dose of MCV4. At 24 weeks, those with screening CD4% ≥15 were randomized to receive a second dose or not, and all with screening CD4% <15 received a second dose. Immunogenicity was evaluated as the proportion of subjects with a ≥4-fold rise from entry in serum bactericidal antibody against each meningococcal serogroup at weeks 28 and 72. Logistic regression models adjusting for HIV disease severity were used to evaluate the effect of one vs. two MCV4 doses among those with screening CD4% ≥15.
Subjects randomized to receive two vs. one MCV4 dose had significantly higher response rates to all serogroups at week 28 and to all except N meningitidis serogroupY at week 72, with adjusted ORs of 2.5–5.6. In 31 subjects with screening CD4% <15 who received two MCV4 doses, response rates ranged from 22–55% at week 28 and 6–28% at week 72.
In youth infected with HIV with a CD4% ≥15, a second dose of MCV4 given six months after the initial dose significantly improves response rates at 28 and 72 weeks. Subjects with CD4% <15 at entry had lower response rates despite 2 doses of MCV4.
The Forkhead box transcription factors Foxc1 and Foxc2 are crucial for development of the eye, cardiovascular network, and other physiological systems, but their cell type–specific and post-developmental functions are unknown, in part because conventional (i.e., whole-organism) homozygous-null mutations of either factor result in perinatal death. Here, we describe the generation of mice with conditional-null Foxc1flox and Foxc2flox mutations that are induced via Cre-mediated recombination. Mice homozygous for the unrecombined alleles are viable and fertile, indicating that the conditional alleles retain their wild-type function. The embryos of Foxc1flox or Foxc2flox mice crossed with Cre-deleter mice that are homozygous for the recombined allele (i.e., Foxc1Δ/Δ or Foxc2Δ/Δ embryos) lack expression of the corresponding gene and show the same developmental defects observed in conventional homozygous mutant embryos. We expect these conditional mutations to enable characterization of the cell-type specific functions of Foxc1 and Foxc2 in development, disease, and adult animals.
conditional knockout; gene targeting; Cre recombination; Foxc1; Foxc2
Isocyanate chemicals essential for polyurethane production are widely used industrially, and are increasingly found in consumer products. Asthma and other adverse health effects of isocyanates are well-documented and exposure surveillance is crucial to disease prevention. Hexamethylene diisocyanate (HDI)-specific serum immunoglobulin G (IgG) was evaluated as an exposure biomarker among workers at a US Air Force Air Logistics Center, which includes a large aircraft maintenance facility.
HDI-specific IgG (HDI-IgG) titers in serum samples (n = 74) were measured using an enzyme-linked immunosorbent assay based upon the biuret form of HDI conjugated to human albumin. Information on personal protective equipment (PPE), work location/tasks, smoking, asthma history, basic demographics, and HDI skin exposure was obtained through questionnaire.
HDI-specific serum IgG levels were elevated in n = 17 (23%) of the workers studied. The prevalence and/or end-titer of the HDI-IgG was significantly (P < 0.05) associated with specific job titles, self-reported skin exposure, night-shift work, and respirator use, but not atopy, asthma, or other demographic information. The highest titers were localized to specific worksites (C-130 painting), while other worksites (generator painting) had no or few workers with detectable HDI-IgG.
HDI-specific immune responses (IgG) provide a practical biomarker to aid in exposure surveillance and ongoing industrial hygiene efforts. The strategy may supplement current air sampling approaches, which do not assess exposures via skin, or variability in PPE use or effectiveness. The approach may also be applicable to evaluating isocyanate exposures in other settings, and may extend to other chemical allergens.
biomarker; exposure; HDI; hygiene; occupational
We conducted a genome-wide association study of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 single nucleotide polymorphisms (SNPs). We report a combined analysis of 2,240 GC cases, 2,115 ESCC cases, and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex, and study, multiple variants at 10q23 had genome-wide significance for GC and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for GC (P=8.40×1010; per allele odds ratio (OR) = 1.31) and ESCC (P=3.85×10−9; OR = 1.34). The association with GC differed by anatomic subsite. For tumors located in the cardia the association was stronger (P=4.19 × 10−15; OR= 1.57) and for those located in the noncardia stomach it was absent (P=0.44; OR=1.05). Our findings at 10q23 could provide insight into the high incidence rates of both cancers in China.
To develop a Risk Score (RS) to predict distant recurrence among premenopausal women with node-negative endocrine-responsive early breast cancer.
The Cox model was used to develop the RS using clinical and histopathological features from 378 women participating in the IBCSG Trial VIII who received endocrine therapy alone or following chemotherapy. The performance of the resulting model was validated on a cohort of 1005 patients from a single institution who received endocrine therapy alone.
In a multivariable analysis, the risk of distant recurrence was associated with tumor size, ER, Ki-67 and peritumoral vascular invasion. In the validation cohort, patients with high RS were at greater risk of distant recurrence compared to patients with low RS (HR, 17.41 ; 95% CI, 5.72 to 52.95).
In premenopausal women with node-negative endocrine-responsive early breast cancer, the RS identifies patients at higher risk of distant recurrence.
breast cancer; histopathological features; risk score; endocrine therapy; chemotherapy
SCFSlimb-mediated down-regulation of the condensin II subunit Cap-H2 is required to maintain proper organization and morphology of the interphase nucleus.
Condensin complexes play vital roles in chromosome condensation during mitosis and meiosis. Condensin II uniquely localizes to chromatin throughout the cell cycle and, in addition to its mitotic duties, modulates chromosome organization and gene expression during interphase. Mitotic condensin activity is regulated by phosphorylation, but mechanisms that regulate condensin II during interphase are unclear. Here, we report that condensin II is inactivated when its subunit Cap-H2 is targeted for degradation by the SCFSlimb ubiquitin ligase complex and that disruption of this process dramatically changed interphase chromatin organization. Inhibition of SCFSlimb function reorganized interphase chromosomes into dense, compact domains and disrupted homologue pairing in both cultured Drosophila cells and in vivo, but these effects were rescued by condensin II inactivation. Furthermore, Cap-H2 stabilization distorted nuclear envelopes and dispersed Cid/CENP-A on interphase chromosomes. Therefore, SCFSlimb-mediated down-regulation of condensin II is required to maintain proper organization and morphology of the interphase nucleus.
The course of lung function in community members exposed to World Trade Center (WTC) dust and fumes remains undefined. We studied longitudinal spirometry among patients in the WTC Environmental Health Center (WTCEHC) treatment program.
Observational study of 946 WTCEHC patients with repeated spirometry measures analyzed on the population as a whole and stratified by smoking status, initial spirometry pattern and WTC-related exposure category.
Improvement in forced expiratory volume (FVC; 54.4 ml/year; 95% CI: 45.0-63.8) and forced expiratory volume in one second (FEV1; 36.8 ml/year; 95% CI: 29.3-44.3) was noted for the population as a whole. Heavy smokers did not improve. Spirometry changes differed depending on initial spirometry pattern and exposure category.
These data demonstrate spirometry improvement in select populations suggesting reversibility in airway injury and reinforcing the importance of continued treatment.
The metrics used to assess quality of care and pay for performance are increasingly important. Medicare established the Physician Quality Reporting System (PQRS) that allowed physicians to report performance measures for many conditions including osteoporosis and rheumatoid arthritis (RA). We described the frequency and nature of physician-reported reasons why recommended care for individual osteoporosis and RA patients was not provided.
Using national data on Medicare fee-for-service beneficiaries (2007-2009), we identified healthcare providers reporting on quality of care for any of 3 osteoporosis or 3 RA measures. PQRS reason codes allowed physicians to submit explanations why recommended care was not given.
In 2009, 1775 physicians reported on >= 1 osteoporosis PQRS measure, and 630 physicians reported on >= 1 RA measure. For patients for whom their physician reported via PQRS on lifetime DXA screening since age 60, 76% of older women had received such screening. Among patients with physician-diagnosed osteoporosis reported via PQRS, 82% received prescription osteoporosis medication in the preceding year. For RA medication use reported via PQRS, 89% of patients received a DMARD or a biologic. For the remaining 11-24% of osteoporosis and RA patients, their physicians reported medical, patient, system, or other reasons why care was considered but not provided.
A substantial fraction of Medicare enrollees who did not receive recommended osteoporosis or RA care had physician-documented reasons for why care was not provided. For Medicare and other health plans that implement penalties for apparent nonperformance (or delivery of suboptimal care), it will be important for allow physicians to provide reasons that care was considered medically inappropriate, refused, or otherwise not feasible.
osteoporosis; rheumatoid arthritis; quality; Medicare; DMARD
This study examined attachment styles in patients with lung cancer and their spouses and associations between attachment styles and patient and spouse adjustment.
One hundred twenty-seven patients with early stage lung cancer completed measures of attachment style, marital quality, self-efficacy, pain, depression, anxiety, and quality of life. Their spouses completed measures of attachment style, marital quality, self-efficacy, caregiver strain, and mood.
Analyses indicated that, among patients, those high in either attachment anxiety or avoidance had significantly higher levels of anxiety and poorer social well-being. Attachment avoidance was also significantly associated with higher levels of depression and poorer marital quality and functional well-being. Spouse avoidant attachment was significantly associated with patient reports of increased pain and poorer functional well-being, and spouse anxious attachment was associated with poorer patient marital quality. Among spouses, those high in attachment avoidance reported significantly higher levels of caregiver strain, anger, depressed mood, and poorer marital quality; those high in attachment anxiety reported higher anxious mood. Dyads in which both partners were insecurely attached had significantly poorer adjustment compared to dyads in which both partners reported secure attachment.
These preliminary findings raise the possibility that attachment styles of cancer patients and their spouses as individuals and as a dyad may be important factors affecting adjustment in multiple domains.
Attachment; Lung cancer; Adjustment; Quality of life; Couples; Caregiving
Treatment options for schizophrenia that address all symptom categories (positive, negative, and cognitive) are lacking. Novel compounds that regulate signaling by the major excitatory neurotransmitter in the brain, glutamate, are emerging as a novel approach for the treatment of this disorder. Currently available medications ameliorate positive symptoms but do not have efficacy in reducing negative symptoms or cognitive disturbances. It is possible that agents that target glutamatergic signaling in the CNS could have efficacy in reducing all major symptom clusters, providing a more comprehensive treatment strategy, and also avoiding some of the adverse effects that are seen with currently available treatments. Three major approaches for targeting glutamate signaling are now advancing in preclinical and clinical development. First are inhibitors for a transporter for glycine termed GlyT1. Glycine is a co-agonist with glutamate for a specific subtype of glutamate receptor, termed the NMDA receptor, which is thought to be critically involved in brain circuits that are disrupted in schizophrenia patients. Inhibiting GlyT1 increases glycine levels and can selectively increase NMDA receptor signaling. Another promising approach is to increase activity of another family of glutamate receptors, termed metabotropic glutamate receptors (mGlus), which play important modulatory roles in brain circuits that are thought to be disrupted in schizophrenia patients. Activation of the group I (mGlu5) and the group II (mGlu2 and mGlu3) mGlus is hypothesized to normalize the disruption of aberrant signaling in these circuits. Novel drug-like molecules that increase activity of these receptors have robust efficacy in animal models that predict efficacy in treatment of schizophrenia. Early clinical studies provide some support for potential utility of these targets in reducing symptoms in schizophrenia patients. Clinical studies that are underway will provide further insights into the potential utility of these compounds in the treatment of multiple symptom domains in schizophrenia patients.