Cell-specific inhibitory modulation of sound processing in the auditory thalamus.

Inhibition along the auditory pathway is crucial for processing of acoustic information. Within the auditory thalamus, a key region in the central auditory pathway, inhibition is provided by the thalamic reticular nucleus (TRN), comprised of two large classes of inhibitory neurons, parvalbumin (PV TRN ) and somatostatin (SST TRN ) positive. In the auditory cortex, PV and SST neurons differentially shape auditory processing. We found that the ventral MGB, the thalamic region in the direct ascending auditory pathway, receives inputs predominantly from PV TRN neurons, whereas SST TRN neurons project to the dorso-medial regions of MGB. Consistently, inactivating PV TRN neurons increased sound-evoked activity in over a third of neurons in the vMGB, with another large fraction of neurons being suppressed. By contrast, inactivating SST TRN neuronal activity largely reduced tone-evoked activity in vMGB neurons. Cell type-specific computational models revealed candidate circuit mechanisms for generating the bi-directional effects of TRN inactivation on MGB sound responses. These differential inhibitory pathways within the auditory thalamus suggest a cell-specific role for thalamic inhibition in auditory computation and behavior.

Proactive text messaging (GetReady2Quit) and nicotine replacement therapy to promote smoking cessation among smokers in primary care: A pilot randomized trial protocol.

INTRODUCTION: Most smokers see a physician each year, but few use any assistance when they try to quit. Text messaging programs improve smoking cessation in community and school settings; however, their efficacy in a primary care setting is unclear. The current trial assesses the feasibility and preliminary clinical outcomes of text messaging and mailed nicotine replacement therapy (NRT) among smokers in primary care. METHODS: In this single-center pilot randomized trial, eligible smokers in primary care are offered brief advice by phone and randomly assigned to one of four interventions: (1) Brief advice only, (2) text messages targeted to primary care patients and tailored to quit readiness, (3) a 2-week supply of nicotine patches and/or lozenges (NRT), and (4) both text messaging and NRT. Randomization is stratified by practice and intention to quit. The text messages (up to 5/day) encourage those not ready to quit to practice a quit attempt, assist those with a quit date through a quit attempt, and promote NRT use. The 2-week supply of NRT is mailed to patients' homes. RESULTS: Feasibility outcomes include recruitment rates, study retention, and treatment adherence. Clinical outcomes are assessed at 1, 2, 6, and 12-weeks post-enrollment. The primary outcome is ≥1self-reported quit attempt(s). Secondary clinical outcomes include self-reported past 7- and 30-day abstinence, days not smoked, NRT adherence, and exhaled carbon monoxide. CONCLUSIONS: This pilot assesses text messaging plus NRT, as a proactively offered intervention for smoking cessation support in smokers receiving primary care and will inform full-scale randomized trial planning. TRIAL REGISTRATION: ClinicalTrials.govNCT03174158.

Inhibitory synaptic plasticity: spike timing-dependence and putative network function.

While the plasticity of excitatory synaptic connections in the brain has been widely studied, the plasticity of inhibitory connections is much less understood. Here, we present recent experimental and theoretical findings concerning the rules of spike timing-dependent inhibitory plasticity and their putative network function. This is a summary of a workshop at the COSYNE conference 2012.

Shedding light on an extremophile lifestyle through transcriptomics.

The tropical intertidal ecosystem is defined by trees - mangroves - which are adapted to an extreme and extremely variable environment. The genetic basis underlying these adaptations is, however, virtually unknown. Based on advances in pyrosequencing, we present here the first transcriptome analysis for plants for which no prior genomic information was available. We selected the mangroves Rhizophora mangle (Rhizophoraceae) and Heritiera littoralis (Malvaceae) as ecologically important extremophiles employing markedly different physiological and life-history strategies for survival and dominance in this extreme environment. For maximal representation of conditional transcripts, mRNA was obtained from a variety of developmental stages, tissues types, and habitats. For each species, a normalized cDNA library of pooled mRNAs was analysed using GSFLX pyrosequencing. A total of 537,635 sequences were assembled de novo and annotated as > 13,000 distinct gene models for each species. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology annotations highlighted remarkable similarities in the mangrove transcriptome profiles, which differed substantially from the model plants Arabidopsis and Populus. Similarities in the two species suggest a unique mangrove lifestyle overarching the effects of transcriptome size, habitat, tissue type, developmental stage, and biogeographic and phylogenetic differences between them.

Pre-pregnancy and pregnancy-related factors and the risk of excessive or inadequate gestational weight gain.

OBJECTIVE: Gestational weight gain consistent with the Institute of Medicine's recommendations is associated with better maternal and infant outcomes. The objective was to quantify the effect of pre-pregnancy factors, pregnancy-related health conditions, and modifiable pregnancy factors on the risks of inadequate and excessive gestational weight gain. METHOD: A longitudinal cohort of pregnant women (N=1100) who completed questions about diet and weight gain during pregnancy and delivered a singleton, full-term infant. RESULTS: Gestational weight gain was inadequate for 14% and excessive for 53%. Pre-pregnancy factors contributed 74% to excessive gain, substantially more than pregnancy-related health conditions (15%) and modifiable pregnancy factors (11%). Pre-pregnancy factors, pregnancy-related health conditions, and modifiable pregnancy factors contributed fairly equally to the risk of inadequate gain. CONCLUSION: Interventions to prevent excessive gestational gain may need to start before pregnancy. Women at risk for inadequate gain would also benefit from interventions directed toward modifiable factors during pregnancy.

Bupropion in breast milk: an exposure assessment for potential treatment to prevent post-partum tobacco use.

OBJECTIVES: To assess potential infant exposure to bupropion and its active metabolites in breast milk such as would occur during treatment to prevent post-partum relapse to tobacco use, and to compare the concentrations of bupropion in urine and saliva with plasma and breast milk. DESIGN AND SETTING: Cohort study, outpatient clinical research centre. SUBJECTS: Ten healthy post-partum volunteers who agreed to take bupropion for seven days, pump and discard their breast milk, and have samples of breast milk, plasma, saliva, and urine analysed. INTERVENTION: Bupropion 150 mg a day for three days and then 300 mg a day for four days. MAIN OUTCOME MEASURES: Concentrations of bupropion and its active metabolites (hydroxybupropion, erythrohydrobupropion, threohydrobupropion) in breast milk, plasma, saliva, and urine. Determination of average infant exposure. RESULTS: The calculated average dosage of bupropion in breast milk was 6.75 microg/kg/day. Therefore, the average infant exposure is 0.14% of the standard adult dose of bupropion, corrected for the difference in body weight. Considering the sum of bupropion and its active metabolites, the average infant exposure is expected to be 2% of the standard maternal dose on a molar basis. The concentration of bupropion and its active metabolites in breast milk was not associated with age, body mass index, use of oral contraceptive pills, age of infant, or the frequency of breast feeding at the time the study was initiated. The coefficient of determination (r2) between the concentration of bupropion in breast milk and in urine was 0.77 (p < 0.01). CONCLUSIONS: Bupropion and its active metabolites are present in the breast milk of lactating women. The concentrations of bupropion in breast milk and urine were highly correlated. These results indicate that the daily dose of bupropion and metabolites that would be delivered to an infant of a woman taking a therapeutic dose of bupropion is small. These results suggest that the effectiveness of bupropion to prevent post-partum relapse to tobacco use should be evaluated without excluding women who plan to breast feed.

Intention to discontinue care among primary care patients: influence of physician behavior and process of care.

BACKGROUND: Specific elements of health care process and physician behavior have been shown to influence disenrollment decisions in HMOs, but not in outpatient settings caring for patients with diverse types of insurance coverage. OBJECTIVE: To examine whether physician behavior and process of care affect patients' intention to return to their usual health care practice. DESIGN: Cross-sectional patient survey and medical record review. SETTING: Eleven academically affiliated primary care medicine practices in the Boston area. PATIENTS: 2,782 patients with at least one visit in the preceding year. MEASUREMENT: Unwillingness to return to the usual health care practice. RESULTS: Of the 2,782 patients interviewed, 160 (5.8%) indicated they would not be willing to return. Two variables correlated significantly with unwillingness to return after adjustment for demographics, health status, health care utilization, satisfaction with physician's technical skill, site of care, and clustering of patients by provider: dissatisfaction with visit duration (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4 to 7.4) and patient reports that the physician did not listen to what the patient had to say (OR, 8.8; 95% CI, 2.5 to 30.7). In subgroup analysis, patients who were prescribed medications at their last visit but who did not receive an explanation of the purpose of the medication were more likely to be unwilling to return (OR, 4.9; 95% CI, 1.8 to 13.3). CONCLUSION: Failure of physicians to acknowledge patient concerns, provide explanations of care, and spend sufficient time with patients may contribute to patients' decisions to discontinue care at their usual site of care.

Influence of financial productivity incentives on the use of preventive care.

PURPOSE: We examined whether physician factors, particularly financial productivity incentives, affect the provision of preventive care. SUBJECTS AND METHODS: We surveyed and reviewed the charts of 4,473 patients who saw 1 of 169 internists from 11 academically affiliated primary care practices in Boston. We abstracted cancer risk factors, comorbid conditions, and the dates of the last Papanicolaou (Pap) smear, mammogram, cholesterol screening, and influenza vaccination. We obtained physician information including the method of financial compensation through a mailed physician survey. We used multivariable logistic regression to examine the association between physician factors and four outcomes based on Health Plan Employer Data and Information Set (HEDIS) measures: (1) Pap smear within the prior 3 years among women 20 to 75 years old; (2) mammogram in the prior 2 years among women 52 to 69 years old; (3) cholesterol screening within the prior 5 years among patients 40 to 64 years old; and (4) influenza vaccination among patients 65 years old and older. All analyses accounted for clus-tering by provider and site and were converted into adjusted rates. RESULTS: After adjustment for practice site, clinical, and physician factors, patients cared for by physicians with financial productivity incentives were significantly less likely than those cared for by physicians without this incentive to receive Pap smears (rate difference, 12%; 95% confidence interval [CI]: 5% to 18%) and cholesterol screening (rate difference, 4%; 95% CI: 0% to 8%). Financial incentives were not significantly associated with rates of mammography (rate difference, -3%; 95% CI: -15% to 10%) or influenza vaccination (rate difference, -13%; 95% CI: -28% to 2%). CONCLUSIONS: Our findings suggest that some financial productivity incentives may discourage the performance of certain forms of preventive care, specifically Pap smears and cholesterol screening. More studies are needed to examine the effects of financial incentives on the quality of care, and to examine whether quality improvement interventions or incentives based on quality improve the performance of preventive care.

Factors associated with the health care utilization of homeless persons.

CONTEXT: Homeless persons face numerous barriers to receiving health care and have high rates of illness and disability. Factors associated with health care utilization by homeless persons have not been explored from a national perspective. OBJECTIVE: To describe factors associated with use of and perceived barriers to receipt of health care among homeless persons. DESIGN AND SETTING: Secondary data analysis of the National Survey of Homeless Assistance Providers and Clients. SUBJECTS: A total of 2974 currently homeless persons interviewed through homeless assistance programs throughout the United States in October and November 1996. MAIN OUTCOME MEASURES: Self-reported use of ambulatory care services, emergency departments, and inpatient hospital services; inability to receive necessary care; and inability to comply with prescription medication in the prior year. RESULTS: Overall, 62.8% of subjects had 1 or more ambulatory care visits during the preceding year, 32.2% visited an emergency department, and 23.3% had been hospitalized. However, 24.6% reported having been unable to receive necessary medical care. Of the 1201 respondents who reported having been prescribed medication, 32.1% reported being unable to comply. After adjustment for age, sex, race/ethnicity, medical illness, mental health problems, substance abuse, and other covariates, having health insurance was associated with greater use of ambulatory care (odds ratio [OR], 2.54; 95% confidence interval [CI], 1.19-5.42), inpatient hospitalization (OR, 2.60; 95% CI, 1.16-5.81), and lower reporting of barriers to needed care (OR, 0.37; 95% CI, 0.15-0.90) and prescription medication compliance (OR, 0.35; 95% CI, 0.14-0.85). Insurance was not associated with emergency department visits (OR, 0.90; 95% CI, 0.47-1.75). CONCLUSIONS: In this nationally representative survey, homeless persons reported high levels of barriers to needed care and used acute hospital-based care at high rates. Insurance was associated with a greater use of ambulatory care and fewer reported barriers. Provision of insurance may improve the substantial morbidity experienced by homeless persons and decrease their reliance on acute hospital-based care.

Obstacles to collaborative quality improvement: the case of ambulatory general medical care.

OBJECTIVE: To assess the effectiveness of inter-site collaboration and report-card style feedback of quality measures on quality improvement in the outpatient setting and to identify major barriers to improvement. DESIGN: A collaborative quality improvement effort consisting of a large cross-sectional data collection effort (chart reviews and patient surveys), feedback of comparative quality of care data to improvement teams, and collaboration between sites. SETTING: Eleven primary care sites in the Boston area. STUDY PARTICIPANTS: Quality improvement teams at each site with physician leaders. INTERVENTION: Education about techniques of rapid-cycle quality improvement, coaching of on-site teams, and report-card style feedback of comparative site-specific quality of care data. RESULTS: Multiple quality improvement projects were undertaken through this collaboration. However, though we were careful to educate teams on methods of continuous quality improvement and to name specific clinical leaders, the degree of collaboration and quality improvement fell short of expectations. Major impediments to improvement included lack of team members' time and resources, lack of incentives, and unempowered team leadership. The primary obstacle to collaboration was the diversity of sites and inability of teams to create interventions that were relevant to other sites. CONCLUSION: Despite ample quality of care data, quality improvement education, and a structured collaborative process, achieving quality improvement in the ambulatory setting is still a difficult challenge. Organizations need to find ways of overcoming the obstacles faced by improvement teams in order to maximize quality improvement.

Differences in the quality of care for women with an abnormal mammogram or breast complaint.

OBJECTIVE: To examine factors associated with variation in the quality of care for women with 2 common breast problems: an abnormal mammogram or a clinical breast complaint. DESIGN: Cross-sectional patient survey and medical record review. SETTING: Ten general internal medicine practices in the Greater Boston area. PARTICIPANTS: Women who had an abnormal radiographic result from a screening mammogram or underwent mammography for a clinical breast complaint (N = 579). MEASUREMENTS AND MAIN RESULTS: Three measures of the quality of care were used: (1) whether or not a woman received an evaluation in compliance with a clinical guideline; (2) the number of days until the appropriate resolution of this episode of breast care if any; and (3) a woman's overall satisfaction with her care. Sixty-nine percent of women received care consistent with the guideline. After adjustment, women over 50 years (odds ratio [OR], 1.58; 95% [CI], 1.06 to 2.36) and those with an abnormal mammogram (compared with a clinical breast complaint: OR, 1.75; 95% CI, 1.16 to 2.64) were more likely to receive recommended care and had a shorter time to resolution of their breast problem. Women with a managed care plan were also more likely to receive care in compliance with the guideline (OR, 1.72; 95% CI, 1.12 to 2.64) and have a more timely resolution. There were no differences in satisfaction by age or type of breast problem, but women with a managed care plan were less likely to rate their care as excellent (43% vs 53%, P <.05). CONCLUSIONS: We found that a substantial proportion of women with a breast problem managed by generalists did not receive care consistent with a clinical guideline, particularly younger women with a clinical breast complaint and a normal or benign-appearing mammogram.

Drug complications in outpatients.

OBJECTIVE: Outpatient drug complications have not been well studied. We sought to assess the incidence and characteristics of outpatient drug complications, identify their clinical and nonclinical correlates, and evaluate their impact on patient satisfaction. DESIGN: Retrospective chart reviews and patient surveys. SETTING: Eleven Boston-area ambulatory clinics. PATIENTS: We randomly selected 2,248 outpatients, 20 to 75 years old. MEASUREMENTS AND MAIN RESULTS: Among 2,248 patients reporting prescription drug use, 394 (18%) reported a drug complication. In contrast, chart review revealed an adverse drug event in only 64 patients (3%). In univariate analyses, significant correlates of patient-reported drug complications were number of medical problems, number of medications, renal disease, failure to explain side effects before treatment, lower medication compliance, and primary language other than English or Spanish. In multivariate analysis, independent correlates were number of medical problems (odds ratio [OR] 1.17; 95% confidence interval [95% CI] 1.05 to 1.30), failure to explain side effects (OR 1.65; 95% CI, 1.16 to 2.35), and primary language other than English or Spanish (OR 1.40; 95% CI, 1.01 to 1.95). Patient satisfaction was lower among patients who reported drug complications (P <.0001). In addition, 48% of those reporting drug complications sought medical attention and 49% experienced worry or discomfort. On chart review, 3 (5%) of the patients with an adverse drug event required hospitalization and 8 (13%) had a documented previous reaction to the causative drug. CONCLUSIONS: Drug complications in the ambulatory setting were common, although most were not documented in the medical record. These complications increased use of the medical system and correlated with dissatisfaction with care. Our results indicate a need for better communication about potential side effects of medications, especially for patients with multiple medical problems.

Is the professional satisfaction of general internists associated with patient satisfaction?

BACKGROUND: The growth of managed care has raised a number of concerns about patient and physician satisfaction. An association between physicians' professional satisfaction and the satisfaction of their patients could suggest new types of organizational interventions to improve the satisfaction of both. OBJECTIVE: To examine the relation between the satisfaction of general internists and their patients. DESIGN: Cross-sectional surveys of patients and physicians. SETTING: Eleven academically affiliated general internal medicine practices in the greater-Boston area. PARTICIPANTS: A random sample of English-speaking and Spanish-speaking patients (n = 2,620) with at least one visit to their physician (n = 166) during the preceding year. MEASUREMENTS: Patients' overall satisfaction with their health care, and their satisfaction with their most recent physician visit. MAIN RESULTS: After adjustment, the patients of physicians who rated themselves to be very or extremely satisfied with their work had higher scores for overall satisfaction with their health care (regression coefficient 2.10; 95% confidence interval 0.73-3.48), and for satisfaction with their most recent physician visit (regression coefficient 1.23; 95% confidence interval 0.26-2.21). In addition, younger patients, those with better overall health status, and those cared for by a physician who worked part-time were significantly more likely to report better satisfaction with both measures. Minority patients and those with managed care insurance also reported lower overall satisfaction. CONCLUSIONS: The patients of physicians who have higher professional satisfaction may themselves be more satisfied with their care. Further research will need to consider factors that may mediate the relation between patient and physician satisfaction.

The stability of preferences for life-sustaining care among persons with AIDS in the Boston Health Study.

BACKGROUND: Clinicians recognize the importance of eliciting patient preferences for life-sustaining care, yet little is known about the stability of those preferences for patients with serious disease. OBJECTIVES: To examine the stability of preferences for life-sustaining care among persons with AIDS and to assess factors associated with changes in preferences. DESIGN: Two patient surveys and medical record reviews, administered four months apart in 1990-1991. SETTING: Three health care settings in Boston. PATIENTS: 252 of 505 eligible persons with AIDS who participated in both baseline and follow-up surveys. MAIN OUTCOME MEASURES: A single question assessing desire for cardiac resuscitation and a scale of preferences for life-extending treatment conditional on hypothetical health states. RESULTS: Approximately one-fourth of the respondents changed their minds about life-sustaining care during a four-month period. Of patients who initially desired cardiac resuscitation, 23% decided to forego it four months later, and of those who initially said they would decline care, 34% later said they would accept it. Of those who initially desired any of the life-extending treatments, 25% decided to forego them four months later, and of those who initially said they would decline life-extending care, 24% later said they would accept some treatment. Patients reporting changes in physical function, pain, or suicide ideation were more likely to modify their desires to be resuscitated (all p< or =0.05). Patients lacking an advance directive, not completing high school, or becoming more severely ill were more likely to change their preferences on the Life Extension scale (p< or =0.05). Patients who discussed their preferences with at least one physician were just as likely as others to change desires for cardiac resuscitation. Age, gender, race, emotional health, clinical severity, social support, and site of care were not significant correlates of change for either measure. CONCLUSIONS: Health care providers should periodically reassess preferences for life-sustaining care, particularly for patients with progressive disease, given the instability in patient preferences. However, predictors of instability may vary with how preferences are measured. In particular, changes in health status may be related to instability of preferences for certain types of treatments.

Outcomes and health status of socially disadvantaged women during pregnancy.

We sought to examine the health status of disadvantaged pregnant women more broadly and to consider if poor maternal health predisposes a woman to an adverse birth outcome. We surveyed 250 women recruited from six health centers in the greater Boston area during their third trimester. The main predictor variables were maternal physical functioning (PF), emotional health (EH), and overall health status in the month prior to pregnancy. The main outcome variables were the decline of maternal PF and EH during pregnancy and adverse birth outcomes. Mean PF scores fell from 91.9 prior to pregnancy to 63.7 during the third trimester (mean scores transformed 0 to 100, where a higher score represents better health). EH remained unchanged during pregnancy. After adjustment, women with a preexisting medical condition reported a lower PF score prior to pregnancy (87.8 versus 94.5, p < 0.05). Poor PF prior to pregnancy or during the third trimester was associated with an increased risk of preterm labor (odds ratio 2.02, 95% confidence interval 1.03-3.97). This study is the first to employ general health status measures to examine changes in health during pregnancy. Our findings support the use of preconception care to improve the health status of disadvantaged women with pre-existing conditions. This study suggests that poor maternal health may predispose a woman to an increased risk of preterm labor.

Differences in the professional satisfaction of general internists in academically affiliated practices in the greater-Boston area. Ambulatory Medicine Quality Improvement Project Investigators.

Managed care has created more professional constraints for general internists. We surveyed 198 general internists at 12 academically affiliated practices in the greater-Boston area to examine professional satisfaction. Overall, these physicians were moderately satisfied (mean of 59.1 on a 100-point scale). Before adjustment, women had lower overall satisfaction than men, as well as poorer satisfaction with the domains of career concerns and patient access. Gender had no independent effect on satisfaction after adjustment for age, income, percentage of time providing direct patient care, work status, and site. Younger physicians also had lower overall satisfaction, and these differences remained after adjustment. Improvements in professional satisfaction may be required to ensure the continued recruitment of young physicians, particularly women, into general internal medicine.