Neonatal medication surveillance by the pharmacist

Data on prenatal, labor and delivery, and postnatal medication exposure to neonates were collected. During an 11-week period, 100 neonates consecutively admitted to a hospital were studied. The pharmacist obtained a social and medication history from the mothers and reviewed maternal anesthesia records and the charts of the neonates. Fifteen definite and possible adverse medication reactions were detected in 13 neonates. The median number of different medications ingested prenatally was 4.7. The four most commonly ingested prenatal medications were vitamins (97%), iron preparations (90%), headache/pain/arthritis medications (68%) and antinausea/vomiting medications (40%). The most commonly used medications during labor and delivery were oxytocin (73%), meperidine (33%) and promazine (25%). The use of strong narcotics during this period produced neonatal respiratory depression in some cases. The four most commonly prescribed postnatal medications were vitamin K1 (100%), gentamicin (10%), ampicillin (8%) and Poly-Vi-Sol (6%). The maternal interview indicated that most mothers were unaware of the influence that many medications can play upon the fetus. It is recommended that the pharmacist conduct a maternal medication interview prior to labor and delivery.     

The Evolution of Behavioral Primary Care.

The financing, organization, and delivery of behavioral health care services has undergone dramatic change in the past 25 to 30 years. The authors trace the evolution of behavioral health care delivery in the United States over the past several decades and find (a) that the value of mental health "carve-outs" has diminished greatly and that they are being replaced by "carve-ins," (b) that primary care physicians (PCPs) are becoming a primary source of mental health care secondary to the introduction of new medications, and (c) that PCP treatment of mental health disorders is suboptimal. The authors conclude that the behavioral health care system is entering an era of flux as it experiments with ways of integrating behavioral and primary care. Opportunities for psychologists are explored. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prediction of fetal lung maturity from near-infrared spectra of amniotic fluid

A total of 189 infants of 24-29 weeks' gestation were born in a regional perinatal centre during a 2-year period. They were divided into groups according to the primary cause of preterm delivery: antepartum haemorrhage (n = 37, 20%), preeclampsia (n = 27), 14%), preterm premature rupture of membranes (n = 64, 34%), preterm labour (n = 27, 14%), chorioamnionitis (n = 16, 8%), other complications (n = 18, 10%). The perinatal mortality rate (PMR) was 286/1,000 of whom 44% were stillbirths. The 'other complication' group had the highest PMR due to a large number of intrauterine deaths, with no differences in neonatal mortality between the groups. Preeclampsia was associated with an increased risk of necrotizing enterocolitis and chorioamnionitis was associated with an increased risk of periventricular haemorrhage. Follow-up to at least 2 years was performed in 122 (97%) of survivors. Cerebral palsy occurred in 7%, while 18% had neurodevelopmental disability. No relationship was found between primary cause of preterm delivery and outcome. This information should be of value in counselling parents when preterm delivery is imminent.     

The haemodynamic effects of dopexamine infusion in the critically ill

Superficial dorsal penile vein thrombosis was diagnosed 8 times in 7 patients between 19 and 40 years old (mean age 27 years). All patients related the onset of the thrombosis to vigorous sexual intercourse. No other etiological medications, drugs or constricting devices were implicated. Three patients were treated acutely with anti-inflammatory medications, while 4 were managed expectantly. The mean interval to resolution of symptoms was 7 weeks. Followup ranged from 3 to 30 months (mean 11) at which time all patients noticed normal erectile function. Only 1 patient had recurrent thrombosis 3 months after the initial episode, again related to intercourse. We conclude that this is a benign self-limited condition. Anti-inflammatory agents are useful for acute discomfort but they do not affect the rate of resolution.     

Safety and efficacy of sildenafil citrate in the treatment of male erectile dysfunction

Sildenafil citrate, an oral therapy for erectile dysfunction, is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), the predominant isozyme metabolizing cGMP in the corpus cavernosum. Chemically, it is a compound of the pyrazolo-pyrimidinyl-methylpiperazine class. Sildenafil has no direct relaxant effect on human corpus cavernosum but enhances the relaxant effect of nitric oxide (NO) on the corpus cavernosum by inhibiting PDE5, which is responsible for degradation of cGMP in this tissue. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil increases concentrations of cGMP in the corpus cavernosum, causing smooth muscle relaxation and blood flow into the penis, resulting in an erection. Sildenafil at recommended doses has no effect in the absence of sexual stimulation. The drug is rapidly absorbed after oral administration, with absolute bioavailability of 40%. Its pharmacokinetics are dose proportional over the recommended dosage range. Maximum plasma concentrations are reached within 30 to 120 minutes after oral dosing in the fasting state. Sildenafil is cleared predominantly by the hepatic microsomal isoenzymes CYP3A4 (major route) and CYP2C9 (minor route). Clinical studies assessed the effect of sildenafil on the ability of men with erectile dysfunction to engage in sexual activity and, specifically, to achieve and maintain an erection sufficient for satisfactory sexual intercourse. Sildenafil was evaluated at doses of 25, 50, and 100 mg in randomized, double-masked, placebo-controlled clinical trials of up to 6 months' duration. The drug was administered to hundreds of patients aged 19 to 87 years having erectile dysfunction of various etiologies for a mean duration of 5 years. Sildenafil was associated with statistically significant improvement in erectile function compared with placebo. Adverse effects reported at a rate of >2% were headache, flushing, dyspepsia, nasal congestion, urinary tract infection, abnormal vision, diarrhea, dizziness, and rash. No cases of priapism were reported. The use of sildenafil is contraindicated in men who are taking organic nitrates, because of the potential for a precipitous decrease in blood pressure. Postmarketing reports and surveillance have revealed at least 39 deaths with sildenafil use in men having a history of heart disease, men taking nitrate medications, and men in poor physical health due to lack of exercise. Many of the men who experienced serious adverse effects or death had a variety of concomitant diseases and were taking multiple medications.     

A review and economic evaluation of bronchodilator delivery methods in hospitalized patients

BACKGROUND: Bronchodilator delivery by metered dose inhaler (MDI) to treat airflow obstruction is considered to be less expensive and as effective as nebulized therapy. OBJECTIVES: To document the utilization of bronchodilator delivery methods in a tertiary care Canadian university teaching hospital and to perform an economic evaluation. METHODS: A prospective 6-week audit of 4 preselected hospital wards (respiratory, thoracic surgery, general surgery, and a general internal medicine clinical teaching unit) and a cost-minimization economic evaluation were performed. Bronchodilator (salbutamol and ipratropium bromide) doses, frequency, and delivery methods, either MDI or wet nebulizer (WN), were recorded for 95 patients treated with aerosolized bronchodilators. Direct costs for medications and hourly wages including benefits and equipment were obtained. Time and motion studies identified time allocated to MDI and WN delivery. We used sensitivity analyses to test assumptions that could significantly affect treatment costs, especially assumptions about medications, labor, and spacer devices. Costs are expressed in Canadian dollars (Can$1 = US$0.75). RESULTS: Sixty-seven patients (70.5%) were treated with WN, 6 (6.3%) with MDI, and 22 (23.2%) with both WN and MDI. Self-administration of salbutamol by MDI was the least expensive: $1.27 for 200-microgram doses and $1.73 for 400-microgram doses compared with $2.62 for a 2.5-mg dose delivered by WN. The difference in cost between equivalent treatments (400-microgram MDI vs 2.5-mg WN) is only $0.89. Sensitivity analyses showed that MDI was the least expensive therapy when self-administration was possible and for all levels of supervision if more than 4 minutes was needed to administer a WN treatment. CONCLUSIONS: Bronchodilator delivery by WN is commonly prescribed for hospitalized patients despite evidence for equivalency of effect using MDI and in the absence of substitution protocols. Previous studies have estimated a far greater cost differential based on unrealistic labor estimates. We found that supervision of patients using MDIs minimized the differential cost between WN and MDI therapy and that cost savings are maximal in patients who can self-administer MDI therapy. Methodologically sound economic evaluations can better identify true cost savings and variables that need further study.     

Malaria chemotherapy trial at a minimal effective dose of mefloquine/sulfadoxine/pyrimethamine compared with equivalent doses of sulfadoxine/pyrimethamine or mefloquine alone

We studied the effects of levodopa (L-dopa), which is reported to increase the dopamine level in the brain, on male erectile function. Of the 21 subjects studied, 12 subjects who were 50 years old or older showed significant increases of two nocturnal penile tumescence (NPT) parameters, NPT frequency and total tumescence time, with L-dopa. On the other hand, in nine subjects who were younger than 50 years, maximum penile circumference increase showed a significant increment with L-dopa. This significant increment of NPT with L-dopa was not observed in the subjects who had low androgen levels. The results of this preliminary study show a positive relationship between administration of L-dopa and erectile function. L-Dopa administration may improve erectile function in subjects aged 50 years and older who have normal androgen levels.     

Homozygous deletion of the PTEN tumor suppressor gene in a subset of prostate adenocarcinomas

PURPOSE: Intracavernosal injection therapy is one of the most popular therapies for erectile dysfunction today. Yet, most clinicians consider intracavernosal injection a palliative treatment for erectile dysfunction because of the high patient initiated dropout rate. In contrast, penile prostheses appear to offer a more permanent cure for erectile dysfunction. We compare the long-term outcomes of both therapies in contemporaneously treated patients and determine the reasons for failure of each. MATERIALS AND METHODS: Telephone survey and chart review was conducted on the first 115 patients treated with intracavernosal injection and 65 patients undergoing insertion of a penile prosthesis during the same period at our institution. Mean patient age was 57 and 60 years, respectively, and mean followup of all patients was 5.4 years (range of 3.3 to 16). RESULTS: An equal percentage of patients were lost to followup in both groups, including 19% of the intracavernosal injection group and 18% of the penile prosthesis group. Of the intracavernosal injection patients 6 (6%) died during followup and 10 (19%) of the prosthetic patients died (p < 0.05). At the time of contact only 41% of the patients were still using intracavernosal injection. In contrast, 70% of the patients were still sexually active with the prosthesis (p < 0.01). Mean duration of use of the penile prosthetics was 63 months compared to 37 months for intracavernosal injection (p < 0.001). The most common reasons for discontinuing intracavernosal injection were inadequate erections (16 cases), lack of spontaneity (14), side effects (12), lack of partner (10), loss of sexual interest (6) and spontaneous return of normal erections (4). More than half of the patients (61%) who discontinued intracavernosal injection remain sexually active with other therapies, including penile prosthesis in 11, vacuum devices in 4, vascular surgery in 1 and oral medication in 1, and 14 without any therapy. We could not identify any significant clinical parameters that would accurately predict which patients most benefited by the long-term use of intracavernosal injection therapy. In contrast, only 6 patients discontinued use of the implant because of complications (infection, erosion and malfunction) and 7 for reasons independent of the implant (that is lack of partner, loss of sexual interest and co-morbidity). CONCLUSIONS: Intracavernosal injection serves as only a palliative therapy for the majority of patients with erectile dysfunction but there exists a core group who derives long-term satisfaction with its use. The majority of patients who discontinue intracavernosal injection remain sexually active yet do not progress to more invasive or effective therapies. The reason for discontinuing therapies for erectile dysfunction is often unrelated to the actual therapeutic modality. Our findings suggest that further improvements in intracavernosal injection therapy and the development of alternative methods of delivery of vasoactive agents will have only a limited impact on the overall outcome of therapy for erectile dysfunction and that increased attention to issues separate from the erection is warranted.     

Inhaled medications and bronchodilator usage in the horse

The advantages of aerosol medications include the direct, topical application to the target organ (airways); rapid effect; and low systemic availability. There are now more efficient methods for aerosol delivery that facilitate the use of increasingly sophisticated aerosol drugs. This article reviews the principles of aerosol deposition and the pharmacology of current medications.     

Maternal anthropometric factors and risk of primary cesarean delivery

OBJECTIVES: This study examined absolute and proportional gestational weight gain and prepregnancy body mass index as predictors of primary cesarean delivery. METHODS: Data were derived from a prospective study of pregnancy outcome risk factors in 2301 women in greater New Haven, Conn, who had singleton deliveries by primary cesarean (n = 312) or vaginal delivery (n = 1989) and for whom height, prepregnancy weight, and weight gain were available. Women were divided into 4 body mass index groups (underweight, low average, high average, and obese) and further subdivided into 8 groups according to median proportional or absolute weight gain. RESULTS: Risk of cesarean delivery increased with increasing body mass index and gestational weight gain greater than the median for one's body mass index. Proportional weight gain was more predictive of cesarean delivery than absolute weight gain. Underweight women gaining more than 27.8% of their prepregnancy weight had a 2-fold adjusted relative risk of cesarean delivery. CONCLUSIONS: Proportional weight gain is an important predictor of cesarean delivery for underweight women; high body mass index is also predictive of increased risk.     

Craniofacial and TMJ effects after glutamate and TRH microsphere implantation in proximity to trigeminal motoneurons of growing rats

The sequelae of sustained, in vivo delivery of two important neurotransmitter substances, glutamate and thyrotropin-releasing hormone (TRH), upon craniofacial growth and development have previously not been investigated. Our purpose was to document and compare the relative effects of glutamate and TRH microspheres stereotactically placed in proximity to trigeminal motoneurons within the trigeminal motor nucleus. The following null hypotheses were tested: (1) TRH microspheres in proximity to trigeminal motoneurons have no significant effect upon the craniofacial skeleton, and (2) there are no significant differences between the relative effects of chronic, long-term delivery of glutamate and TRH upon the neuromusculoskeletal system of growing rats. Forty male Sprague-Dawley rats were divided into 4 experimental groups (glutamate microspheres, TRH microspheres, blank microspheres, sham surgeries) and underwent stereotactic neurosurgery at 35 days; 5 rats of each group were killed at 14 and 21 days for data collection. Histology revealed that implants were clustered in the pontine reticular formation, close to the ventrolateral tegmental nucleus. Both glutamate and TRH rats had implant-side deviation of their facial skeleton and snout regions; 4 x 2 ANOVA and post hoc t-tests revealed significant (P < or = 0.05, 0.01) differences between groups and sides for motoneuron count, muscle weight, and osteometric data. TRH rats also demonstrated larger implant-side TMJ discs and mandibular fossae in comparison with the other groups. The stated null hypotheses were therefore rejected.     

The emerging role of glutamate as a new pharmacologic target.

Neurotransmitters serve as functional substrates for receptor signaling, as well as dynamic mediators of psychotropic drug activity. Identifying dysregulations in specific neurotransmitter systems has greatly contributed to increased understanding of the pathophysiology of various disorders. Several primary neurotransmitters have received the greatest attention as they relate to neuropsychiatric disorders--namely, acetylcholine, and the biogenic monoamines (norepinephrine, dopamine, and serotonin). In addition to these 'classic' neurotransmitters, various amino acids, such as gamma-aminobutyric acid (GABA), glutamate, aspartate, and glycine, have also been identified as having neurotransmitter properties within the central nervous system (CNS). The excitatory amino acid glutamate, the most prevalent neurotransmitter in the CNS and a primary mediator of excitatory synaptic transmission, has begun receiving attention. Clinicians will benefit from this overview of glutamate's neurobiology, pharmacological activity, and suspected involvement in the pathophysiology of various disease states. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Self-efficacy change as a mediator of associations between therapeutic bond and one-year outcomes in treatments for alcohol dependence.

Empirically-supported treatments for alcohol dependence exist, yet understanding of influences contributing to the intended behavior change is limited. The current study, a secondary analysis of the recent multisite COMBINE trial (The COMBINE Study Research Group, 2003), tested a mediational model wherein change in client self-efficacy for abstinence was examined as a potential mediator of associations between client report of the therapeutic bond and one-year outcomes of drinking frequency, drinking consequences, and psychiatric functioning. For analyses, the 1383 COMBINE trial participants were grouped as follows: 1) those receiving study medications (naltrexone, acamprosate, naltrexone + acamprosate, placebo) and enrolled in medication management (MM) only (n = 607), 2) those receiving study medications/MM and also enrolled in a combination behavioral intervention (CBI) as well (n = 619), and 3) those enrolled in CBI only (n = 157). Mediation analyses using the product-of-coefficients approach indicated self-efficacy change during treatment significantly mediated associations between the therapeutic bond with the CBI therapist and each of the three one-year outcomes among those exclusively receiving CBI, but failed to do so among those receiving pills/MM (with or without CBI). Effect sizes were small, but indicated that variance in bond-outcome associations was partially mediated by self-efficacy change for trial participants. Findings advance understanding of proximal client change processes during delivery of treatments for alcohol dependence. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

A controlled trial of desmopressin and behavioral therapy for nocturnal enuresis

Erectile dysfunction may have psychological as well as a variety of organic causes. This necessitates in each case a careful medical evaluation. Various commonly used drugs, as well as alcohol and narcotics, may interfere with erection and should, whenever possible, be discontinued before starting treatment. Organic diseases should be identified and, if feasible, specially treated. In the remaining majority of afflicted men, psychological treatment and partner counseling may produce an improvement, but ultimately what is necessary remains an effective and safe medication. The drug, Sildenafil, introduces a new therapeutic principle. During sexual nerve stimulation, nitric oxide (NO) is released from nerves into the cells of the penile erectile bodies. NO activates in turn its "second messenger", the substance cyclic GMP, and the latter induces the vasorelaxation and blood filling of the erectile bodies. Orally administered Sildenafil competitively inhibits phosphodiesterase type 5, which physiologically inactivates cyclic GMP in the erectile bodies. Thus, Sildenafil increases in men with erectile dysfunction the NO-stimulated cyclic GMP concentration and, thereby, improves erection. This new therapy is attractive because 1. Sildenafil is the first pill (for oral use) with established efficacy that benefits most men with insufficient erection; 2. compared with previous therapeutic approaches (such as drug injections in the penis, instillations into the urinary duct, vacuum pumps or even prostheses), Sildenafil is at least as effective, is easy to take and appears well tolerated with no risk of a prolonged erection; 3. remarkably, this medication stimulates erection only during sexual arousal and, thus, has a rather "natural" effect, and 4. side effects (including headache, facial flushing and dyspepsia or epigastric discomfort) were mostly of mild degree and transient, so that only 4% of men interrupted treatment for this reason. Sildenafil does not need to be taken daily, but may be taken, when needed, 1 hour before a planned sexual activity. The new pill has the potential to enliven the boys "wunder horn" with fresh sound.     

Psychology can be indispensable to health care reform and the patient-centered medical home.

The Patient Protection and Affordable Care Act (PPACA) was passed into legislation in March 2010, making health care reform a reality. Perhaps the most well-developed model of primary care that aligns with the PPACA's agenda is the patient-centered medical home (PCMH). Integrated care, as defined by collaborative care between mental health and primary care providers and systems, will undoubtedly play a critical role in the success of the PCMH. The role of psychology and integrated care in the PCMH as well as training implications for psychologists are discussed. This article is intended to challenge our discipline to embrace psychology as a health care profession that must prepare for and solidify its added value in the health care delivery models of the future. Requisite skill sets for primary care psychologists and existing training opportunities are presented. Finally, possible mechanisms for training psychologists in integrated care and the professional roles primary care psychologists can expect to fill are proposed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Silent glutamatergic synapses and nociception in mammalian spinal cord

Neurons in the superficial dorsal horn of the spinal cord are important for conveying sensory information from the periphery to the central nervous system. Some synapses between primary afferent fibres and spinal dorsal horn neurons may be inefficient or silent. Ineffective sensory transmission could result from a small postsynaptic current that fails to depolarize the cell to threshold for an action potential or from a cell with a normal postsynaptic current but an increased threshold for action potentials. Here we show that some cells in the superficial dorsal horn of the lumbar spinal cord have silent synapses: they do not respond unless the holding potential is moved from -70 mV to +40 mV. Serotonin (5-hydroxytryptamine, 5-HT), an important neurotransmitter of the raphe-spinal projecting pathway, transforms silent glutamatergic synapses into functional ones. Therefore, transformation of silent glutamatergic synapses may serve as a cellular mechanism for central plasticity in the spinal cord.     

Assessment of dynamic neurotransmitter changes with bolus or infusion delivery of neuroreceptor ligands

To describe the effect of endogenous dopamine on [11C]raclopride binding, we previously extended the conventional receptor ligand model to include dynamic changes in neurotransmitter concentration. Here, we apply the extended model in simulations of neurotransmitter competition studies using either bolus or bolus-plus-infusion (B/I) tracer delivery. The purpose of this study was (1) to develop an interpretation of the measured change in tracer binding in terms of underlying neurotransmitter changes, and (2) to determine tracer characteristics that maximize sensitivity to neurotransmitter release. A wide range of kinetic parameters was tested based on existing reversible positron emission tomography tracers. In simulations of bolus studies, the percent reduction in distribution volume (deltaV) caused by a neurotransmitter pulse was calculated. For B/I simulations, equilibrium was assumed, and the maximum percent reduction in tissue concentration (deltaC) after neurotransmitter release was calculated. Both deltaV and deltaC were strongly correlated with the integral of the neurotransmitter pulse. The values of deltaV and deltaC were highly dependent on the kinetic properties of the tracer in tissue, and deltaV could be characterized in terms of the tissue free tracer concentration. The value of deltaV was typically maximized for binding potentials of approximately 3 to 10, with deltaC being maximized at binding potentials of approximately 1 to 2. Both measures increased with faster tissue-to-blood clearance of tracer and lower nonspecific binding. These simulations provide a guideline for interpreting the results of neurotransmitter release studies and for selecting radiotracers and experimental design.