A phase 2 trial of induction nab-paclitaxel and cetuximab given with cisplatin and 5-fluorouracil followed by concurrent cisplatin and radiation for locally advanced squamous cell carcinoma of the head and neck.

Background: Complete response (CR) at the primary tumor site as assessed by clinical examination following induction chemotherapy with PF (cisplatin and 5-fluorouracil [5-FU]) is a favorable predictive factor for overall survival and disease control in patients with locally advanced squamous cell carcinoma of the head and neck. In most series, the rate of CR at the primary site after induction PF was 20% to 30%. This study evaluated the efficacy and feasibility of induction nab-paclitaxel and cetuximab given with PF (ACPF) followed by definitive chemoradiation (CRT) in a phase 2 trial.

Race-ethnicity and health trajectories: tests of three hypotheses across multiple groups and health outcomes.

Racial-ethnic disparities in static levels of health are well documented. Less is known about racial-ethnic differences in age trajectories of health. The few studies on this topic have examined only single health outcomes and focused on black-white disparities.

Radiotherapeutic management of cervical lymph node metastases from an unknown primary site.

Objective: To determine whether ipsilateral radiotherapy affects overall survival, cause-specific survival, or local control in patients with a cancer from an unknown primary of the head and neck compared with comprehensive radiotherapy.

Design: Retrospective medical record review.

Setting: Academic tertiary care hospital.

Pharmacy students' attitudes toward geriatric nursing home patients.

Objective: To determine the attitudes of second-year pharmacy students toward older people in general and geriatric patients in particular after attending an Early Pharmacy Practice Experiences 2 course.

Methods: One hundred forty-four second-year pharmacy students completed the Geriatrics Knowledge Test and Attitudes Survey between 2008 and 2010.

Results: On 11 of 14 items, most students had a favorable opinion of older people and providing geriatric care (mean > 3.

Genome-wide pharmacogenomic study of citalopram-induced side effects in STAR*D.

Affecting about 1 in 12 Americans annually, depression is a leading cause of the global disease burden. While a range of effective antidepressants are now available, failure and relapse rates remain substantial, with intolerable side effect burden the most commonly cited reason for discontinuation. Thus, understanding individual differences in susceptibility to antidepressant therapy side effects will be essential to optimize depression treatment.

Head and neck carcinoma in the United States: first comprehensive report of the Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN).

Background: Detailed information about how patients with head and neck carcinoma (HNC) are treated across practice settings does not exist. The authors conducted a prospective, observational study to examine the patterns of care for a series of patients with newly diagnosed HNC in the United States and to test 2 hypotheses: 1) There is no difference in the pattern of care between community and academic settings; and 2) the results of major randomized clinical trials will change the pattern of care in both practice settings within 1 year of publication in peer-reviewed journals.

Methods: Patients aged ≥ 18 years were enrolled in the Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN) after providing written informed consent if they had a confirmed diagnosis of new HNC and were scheduled to receive treatment other than surgery alone.

Delivering free healthcare to rural Central Appalachia population: the case of the Health Wagon.

Central Appalachia residents present unique healthcare challenges. This vulnerable population faces poor health status and low access to health care. 'The Health Wagon' was established to innovatively enhance access to health care for the poor and marginalized rural population of Central Appalachia.

The glial cell modulators, ibudilast and its amino analog, AV1013, attenuate methamphetamine locomotor activity and its sensitization in mice.

Over 800,000 Americans abuse the psychomotor stimulant, methamphetamine, yet its abuse is without an approved medication. Methamphetamine induces hypermotor activity, and sensitization to this effect is suggested to represent aspects of the addiction process. Methamphetamine's regulation of 3'-5'-cyclic adenosine monophosphate (cAMP) levels may be partially responsible for its behavioral effects, and compounds that inhibit phosphodiesterase (PDE), the enzyme that degrades cAMP, can alter methamphetamine-induced behaviors.

The influence of five monoamine genes on trajectories of depressive symptoms across adolescence and young adulthood.

The influence of five monoamine candidate genes on depressive symptom trajectories in adolescence and young adulthood were examined in the Add Health genetic sample. Results indicated that, for all respondents, carriers of the dopamine receptor D4 5-repeat allele were characterized by distinct depressive symptom trajectories across adolescence and early adulthood. Similarly, for males, individuals with the monoamine oxidase A 3.

Genome-wide association mapping of loci for antipsychotic-induced extrapyramidal symptoms in mice.

Tardive dyskinesia (TD) is a debilitating, unpredictable, and often irreversible side effect resulting from chronic treatment with typical antipsychotic agents such as haloperidol. TD is characterized by repetitive, involuntary, purposeless movements primarily of the orofacial region. In order to investigate genetic susceptibility to TD, we used a validated mouse model for a systems genetics analysis geared toward detecting genetic predictors of TD in human patients.

Pharmacogenomic study of side-effects for antidepressant treatment options in STAR*D.

Background: Understanding individual differences in susceptibility to antidepressant therapy side-effects is essential to optimize the treatment of depression.

Method: We performed genome-wide association studies (GWAS) to search for genetic variation affecting the susceptibility to side-effects. The analysis sample consisted of 1439 depression patients, successfully genotyped for 421K single nucleotide polymorphisms (SNPs), from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study.

Racial differences in depression trajectories among older women: socioeconomic, family, and health influences.

Despite recent increases in life course research on mental illness, important questions remain about the social patterning of, and explanations for, depression trajectories among women in later life. The authors investigate competing theoretical frameworks for the age patterning of depressive symptoms and the physical health, socioeconomic, and family mechanisms differentiating black and white women. Using data from the National Longitudinal Survey of Mature Women, the authors use linear mixed (growth curve) models to estimate trajectories of distress for women aged 52 to 81 years (N = 3,182).

Analysis of efficacy and side effects in CATIE demonstrates drug response subgroups and potential for personalized medicine.

Objective: This study aims to improve understanding of antipsychotic non/response and assess the potential for personalized schizophrenia treatment.

Methods: We used data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) and neurocognitive functioning.

A phase I study of the safety and pharmacokinetics of the hypoxia-activated prodrug TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma.

Purpose: The purpose of this study was to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), safety, pharmacokinetics and preliminary activity of TH-302, a hypoxia-activated prodrug, in combination with doxorubicin in patients with advanced soft tissue sarcoma.

Patients And Methods: TH-302 was administered intravenously on days 1 and 8 and doxorubicin 75 mg/m² on day 1 (2 h after TH-302) of every 3-week cycle. TH-302 starting dose was 240 mg/m² with a classic 3 + 3 dose escalation.

A phase 2 study of temsirolimus (CCI-779) in patients with soft tissue sarcomas: a study of the Mayo phase 2 consortium (P2C).

Background: The primary goal of this trial was to evaluate the confirmed response rate of temsirolimus (CCI-779), a mammalian target of rapamycin in patients with advanced soft tissue sarcomas (STS).

Methods: Patients ≥18 years with measurable advanced STS, no prior chemotherapy for metastatic disease (adjuvant and neoadjuvant chemotherapy allowed), adequate organ function, and performance status of ≤2 were eligible. After premedication with an antihistamine, CCI-779 was given intravenously at 25 mg over 30 minutes on Days 1, 8, 15, and 22, repeated every 4 weeks.

Genome-wide pharmacogenomic study of neurocognition as an indicator of antipsychotic treatment response in schizophrenia.

Neurocognitive deficits are a core feature of schizophrenia and, therefore, represent potentially critical outcome variables for assessing antipsychotic treatment response. We performed genome-wide association studies (GWAS) with 492K single nucleotide polymorphisms (SNPs) in a sample of 738 patients with schizophrenia from the Clinical Antipsychotic Trials of Intervention Effectiveness study. Outcome variables consisted of a neurocognitive battery administered at multiple time points over an 18-month period, measuring processing speed, verbal memory, vigilance, reasoning, and working memory domains.

Antipsychotic-induced vacuous chewing movements and extrapyramidal side effects are highly heritable in mice.

Pharmacogenomics is yet to fulfill its promise of manifestly altering clinical medicine. As one example, a predictive test for tardive dyskinesia (TD) (an adverse drug reaction consequent to antipsychotic exposure) could greatly improve the clinical treatment of schizophrenia but human studies are equivocal. A complementary approach is the mouse-then-human design in which a valid mouse model is used to identify susceptibility loci, which are subsequently tested in human samples.

Distributed versus focal cortical stimulation to enhance motor function and motor map plasticity in a rodent model of ischemia.

Background: Motor rehabilitation after cerebral ischemia can enhance motor performance and induce motor map reorganization. Electrical stimulation of the cortex (CS) during rehabilitative training (CS/RT) augments motor map plasticity and confers gains in motor function beyond those observed with motor rehabilitation alone. However, it is unclear how the distribution of electrical stimulation across the cortex accomplishes these changes.

Genome-wide association study of antipsychotic-induced QTc interval prolongation.

QT prolongation is associated with increased risk of cardiac arrhythmias. Identifying the genetic variants that mediate antipsychotic-induced prolongation may help to minimize this risk, which might prevent the removal of efficacious drugs from the market. We performed candidate gene analysis and five drug-specific genome-wide association studies (GWASs) with 492K single-nucleotide polymorphisms to search for genetic variation mediating antipsychotic-induced QT prolongation in 738 schizophrenia patients from the Clinical Antipsychotic Trial of Intervention Effectiveness study.

Squamous cell cancer of the head and neck with distant metastasis at presentation.

Background: Current literature reports widely different rates of distant metastasis at presentation for squamous cell carcinoma of the head and neck (SCCHN). We used the Surveillance Epidemiology and End Results (SEER) database to determine the rate of and risk factors for distant metastasis.

Methods: We identified patients with SCCHN diagnosed between 1988 and 2003.

The organization of the forelimb representation of the C57BL/6 mouse motor cortex as defined by intracortical microstimulation and cytoarchitecture.

The organization of forelimb representation areas of the monkey, cat, and rat motor cortices has been studied in depth, but its characterization in the mouse lags far behind. We used intracortical microstimulation (ICMS) and cytoarchitectonics to characterize the general organization of the C57BL/6 mouse motor cortex, and the forelimb representation in more detail. We found that the forelimb region spans a large area of frontal cortex, bordered primarily by vibrissa, neck, shoulder, and hindlimb representations.

A Phase 1 study of UCN-01 in combination with irinotecan in patients with resistant solid tumor malignancies.

Purpose: UCN-01 (7-hydroxystaurosporine) is a multi-targeted protein kinase inhibitor that exhibits synergistic activity with DNA-damaging agents in preclinical studies. We conducted a Phase I study to determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetic, and pharmacodynamic effects of UCN-01 and irinotecan in patients with resistant solid tumors.

Experimental Design: Patients received irinotecan (75-125 mg/m(2) IV on days 1, 8, 15, 22) and UCN-01 (50-90 mg/m(2) IV on day 2 and 25-45 mg/m(2) on day 23 and subsequent doses) every 42 days.