bluuebunny/crossref_metadata_2025 huggingface dataset:
Computer Simulation of the Inflation Process in Blow Molding
Authors: Liu Shih-Jung
Published: July 2017

A finite element numerical analysis of parison inflation associated with the extrusion blow molding process has been developed using a novel overlay viscoelastic model. The model uses 2-D six noded overlay isoparametric elements. The analysis is capable of predicting final wall thickness distribution for axisymmetric mold geometries. Experimental studies were carried out on an extrusion blowing molding machine with two axisymmetric molds. High density polyethylene was used in the experiment. The predicted wall thickness distribution is in reasonable agreement with the experimental data. Non-uniformity in the initial thickness and the non-isothermal temperature profile of the parison was found to have the most significant impact on the inflation behavior and the resulting wall thickness. Numerical simulation of a blow molding process can be used to optimize the molds and the molding parameters to achieve a product with ideal thickness distribution.
Cytotoxicity of xenobiotics and expression of glutathione-S-transferases in immortalised rat hepatocyte cell lines
Authors: Anderson K , Andrews R , Yin L , McLeod R , MacDonald C , Hayes J D , Grant M H
Published: July 2017

1 Immortalised rat hepatocyte cell lines are more sensitive to the cytotoxicity of 1-chloro-2,4-dinitroben-zene and ethacrynic acid than primary cultures of hepatocytes.

2 Class alpha glutathione S-transferases are not expressed in immortalised hepatocyte cell lines. Class pi glutathione S-transferase expression is elevated in the immortalised cell lines compared with freshly isolated hepatocytes, but it is not as high as in the HTC rat hepatoma cell line.

3 Immortalised hepatocyte cell lines may provide a sensitive model system for detecting cytotoxicity associated with xenobiotics which are detoxified by glutathione S-transferases.
Fatal multi-organ failure after suicidal overdose with MDMA, `Ecstasy': case report and review of the literature
Authors: Walubo A , Seger D
Published: July 2017

A 53-year-old prisoner died of multiorgan failure after a suicidal overdose with 3,4-methylenedeoxymethamphe-tamine (MDMA, `Ecstasy'). Twelve hours after ingestion of MDMA, the patient became severely hyperthermic (107.2°F) with evidence of rhabdomyolysis. He subsequently developed acute respiratory distress syndrome (ARDS), disseminated intravascular coagulopathy (DIC) and acute renal failure. At autopsy, plasma concentration of MDMA was 3.05 mg/L. This case shows that MDMA is still abused in our community and clinicians should know the symptoms of MDMA intoxication. In particular, MDMA should be considered when patients have symptoms or signs of increased sympathetic activity. The pathophysiology and treatment of MDMA-induced hyperthermia are discussed.
Clinical and subclinical neurological involvement in children of conjugal multiple sclerosis patients
Authors: Constantinescu CS , Grossman RI , Finelli PF , Kamoun M , Zmijewski C , Cohen JA
Published: July 2017

We report the occurrence of clinically definite multiple sclerosis in an offspring of a couple with conjugal multiple sclerosis. Extensive investigation of all members of this family, which includes two additional asymptomatic children, eliminated the possibility of alternative neurological diagnoses. All family members were studied with magnetic resonance imaging (MRI), evoked potentials, and human leukocyte antigen (HLA) typing. An asymptomatic child had subtle white matter abnormalities on MRI, suggesting subclinical neurological involvement This study documents the third case of multiple sclerosis in the child of conjugal multiple sclerosis patients and provides the first report of MRI lesions in an asymptomatic offspring of the same parents. Neurodiagnostic and immunogenetic investigations of such rare family clusters may contribute to the elucidation of the pathogenesis of multiple sclerosis.
Expression of IFN-γ, IL-4, and TGF-β in multiple sclerosis in relation to HLA-Dw2 phenotype and stage of disease
Authors: Söderström M , Hillert J , Link J , Navikas V , Fredrikson S , Link H
Published: July 2017

Multiple sclerosis (MS) is associated with upregulation of both proinflammatory (interferonγ, IFNγ) and immunosuppressive (transforming growth factorβ, TGFβ) cytokines. To examine a possible relation between the MS-related HLA haplotype Dw2 and cytokine prof iles, we used in situ hybridization with labeled cDNA oligonucleotide probes to detect transcripts of the T helper type I (ThI) cell related IFNγ, the Th2 cell related interleukin-4 (IL-4) and of TGFβ in blood and cerebrospinal fluid (CSF) mononuclear cells from 62 patients with MS. Compared to patients with other neurological diseases and healthy controls, MS patients had elevated numbers of IFNγ, IL-4 and TGFβ mRNA expressing cells in blood and further augmented in CSF. Although several HLA-Dw2-positive individuals showed very high numbers of cells expressing these cytokines, no significant difference was found in comparison with Dw2-negative patients. However, expression of IL-4 and TGFβ mRNA was significantly increased in patients with shorter duration and minor disability and, for IL-4, in patients still in the relapsing-remitting phase compared to patients with secondary chronic progressive MS. Surprisingly, these changes which favour a beneficial, disease-downregulating effect of IL-4 and TGFβ in MS, were found to be confined to HLA-Dw2-positive patients. Our findings suggest that the HLA phenotype does not influence the overall level of immune reactivity in MS, but may distinguish subgroups characterized by particular cytokine expression patterns.
Medicine and the Behavioral Sciences
Authors: Lindén Victor
Published: July 2017

Medicine and the behavioral sciences are both concerned with the understanding and treatment of man. Consequently communication and co-operation between them are essential, so far as both the clients and the sciences are concerned. There are, however, various factors—ideological, practical, educational and semantic—which at present make such approaches difficult, sometimes even impossible. Is the present flight from general practice connected with this situation? Can the problems be solved without a medical education providing thorough instruction in the behavioral sciences and vice versa.
Injury Diagnoses within Morbidity Statistics
Authors: Thorson Jan
Published: July 2017

The present investigation set out to determine the sensitivity of injury classification according to body area and to study the specificity of “commotio cerebri”. It was preceded by several related essays on injury statistics. The sensitivity was at least 0.94 for all body areas except neck and back, for which areas the values were 2/3 (adults) and 4/5 (all age groups). The specificity analysis showed that about half of the “commotio cerebri” diagnoses were not based on incontestable facts; one-seventh of them had no clinical basis at all according to the records.
Mortality and Causes of Death in Men Found to be Mentally Abnormal by Forensic Psychiatrists
Authors: Reiter K.
Published: July 2017

Four-hundred subjects, found to be mentally abnormal when examined at the ages of 15–29 by forensic psychiatrists, were followed over approximately 20 years. Forty-three of them died during the observation period. The deaths were analysed in comparison with the expected mortality in the general population. A marked excess mortality was demonstrated, especially for two groups categorized as “insane” and “equivalent to insane”. A moderate excess mortality was found for a more heterogeneous group “mentally disturbed”. For the group “mentally retarded”, the excess mortality was only slightly in excess of normal. The excess mortality obviously results from the high suicide rate and from other forms of violence.
Minimum Variability in the Need for Care in Geriatric Institutions
Authors: Mackeprang Bent , Bentzon Michael Weis
Published: July 2017

Based on an account of the need for nursing care in the entire patient population in De Gamles By, Copenhagen, on January IS, 1967, and again on January 15, 1969, it is shown that the need for care varies considerably, despite a policy of admitting only independent persons. The consequences of this variability for the size of the nursing staff required are discussed, together with some aspects of admittance policy.
Mortality among Bricklayers and Carpenters/cabinet makers
Authors: Olsen Jørn , Sabroe Svend
Published: July 2017

Mortality among members of two medium-sized trade unions, the union of carpenters/cabinet makers and the union of bricklayers, has been studied during the period 1.1.71–31.12.75, primarily to investigate if the greater exposure to dust and organic solvents of the carpenters/ cabinet makers caused any increase in the mortaility from lung diseases. The study did not reveal any significant differences in mortality regarding any category of diagnoses except suicide, when the analysis was based on the main diagnosis recorded on the death certificate. However, when including underlying causes of death too, statistically significant increased death rates from larynx cancer, asthma, bronchitis and emphysema were found among the bricklayers, as compared with the carpenters/ cabinet makers. No explanation can be given for these observations. They may be a result of an unequal distribution of confounding variables in the two groups, or they may reflect various grades and forms of “Healthy Worker” selection. This study is a cross-section study and such studies and longitudinal studies over a period of a few years of occupational mortality are very sensitive to the selection of the occupational groupings. The analysis is based on deaths among life-insured members under the age of 67 years, in the two trade unions. Copies of the death certificates were obtained from the National Health Service and then coded by us along the lines indicated by the NHS.
Inverse Association Between Risk Factors for Benign and Malignant Breast Lesions
Authors: Soini Irma , Hakama Matti
Published: July 2017

The purpose of the present study was to compare the risk of breast cancer and the risk of benign breast disease using known risk factors for breast cancer. The series was taken during breast cancer screening of women aged 41–60 in an industrial city in Finland. 158 breast lesions were diagnosed, 27 of which were malignant. Women with breast disease and 534 controls were interviewed to obtain epidemiological data. The prevalence of benign lesions decreased after menopause but the prevalence of carcinomas was essentially the same over the age span 41–60. Several risk factors for breast cancer, such as selected reproductive and hormonal characteristics, were not associated with the risk of benign breast disease. Thus it was concluded that benign and malignant breast lesions are not associated in general, and the decrease in the prevalence of benign breast lesions after menopause is more likely to be due to regression than to transition to carcinoma.
Physical Work Capacity of Young Men in Sweden
Authors: Jonsson Björn G. , Berggren Gunnar
Published: July 2017

Each year between 1961 and 1975 all male students in a secondary school were submaximally tested on several occasions on bicycle ergometers with regard to estimated maximal aerobic power. The school is situated in central Sweden (Falun). The students were between 16 and 20 years of age. Data from the tests in Falun and data compiled from other sources cannot confirm the hypothesis that young men of today have a lower maximal aerobic power than young men of the 1960s. The results indicate that Swedish boys aged 16 to 20 have, on average, a maximal aerobic power of about 45 ml O2 x (kg x min)-1. The standard deviation is about 8 ml O2.
Total Consumption of Health Services by Schoolchildren in a Primary Health Care District in Southern Sweden: A Contemporary Registration of Consumption at the School Health Clinic, the Community Care Centre and the Hospital
Authors: Kornfält Ragnhild , Ejlertsson Göran
Published: July 2017

During one year all consumption of health services by 1147 schóolchildren aged 7–16 years was recorded. The average frequency of visits per child and year was 5.3 to the School Health Clinic, 1.1 to the Community Care Centre and 0.9 to the ambulatories at the hospital. The rate of hospitalization was 0.05. The consultations at the School Health Clinic show a peak in frequency at 13 years of age and girls predominated. In 40% of the visits to the school nurse no somatic disease corresponding to the complaint could be found and the nurse was clearly being used as a resort by the children in any sort of trouble. Injuries and accidents were the predominant diagnoses in both in-and outpatient care. The high consumption of and need for health services of schoolchildren must be taken into consideration in the overall planning. The School Health Clinic plays an important role for the children and its contributions are underestimated. Apart from health surveillance, it provides medical care for many children, but above all support. The key person is the school nurse and she is best placed in the school even if school health services are in future to be integrated in the Health Services of the County Council at the Community Care Centre (15).
Screening for Neuropsychiatrie Dysfunction: A Latent Structure Analysis of Two Questionnaires
Authors: Olsen Jørn , Sabroe Svend
Published: July 2017

Summing up information from interview or questionnaire data into a single number, an index, is not uncommon in social medical research, but the conceptual and mathematical background for this is too often neglected. The so-called “Rasch models” specify circumstances where a single index can be used. The necessary computer programs for doing this are now generally available (10, II). Two often used questionnaires concerning neurotoxicity due to solvent exposure are tested using a Rasch model. None of the questionnaires were found to be in agreement with the necessary requirements for the model and no single number describes the respondent's degree of neuropsychiatrie dysfunction. Much more work is needed before a suitable screening questionnaire is available.
Childhood Psychologic Environmental Exposure in Women with Diagnosed Somatoform Disorders
Authors: Hartvig Pål , Sterner Grethe
Published: July 2017

Fifty-three female patients with diagnosed somatoform disorders (having pronounced somatic symptoms without objective somatic signs) were studied regarding childhood exposure to death, divorce, serious somatic illness and prolonged pain in members of their core family. Similar registrations were made in a control group of 53 healthy women. The two groups were compared using the case-control method. The results revealed a more frequent exposure in the somatoform disorder patients regarding all four items, and for serious somatic illness and prolonged pains the difference was statistically significant. Further elaboration of the data suggested that exposure to pain in the family was the most important of the studied factors.

The findings are thought to demonstrate the environmental etiologic impact on somatoform disorders occasioned by such psychologic exposure as those registered. The possibility of a genetic etiologic implication of the findings is also discussed.
Socio-Economic Factors and Feto-Infant Mortality
Authors: Cnattingius Sven , Haglund Bengt
Published: July 2017

During this century, improvements in fetal and infant mortality have been dramatic in the western world, mainly as a result of improved socio-economic conditions. Relative to many other developed countries, the decrease has been more dramatic in the Nordic countries. Population-based health registries exist in all Nordic countries. By record-linkage between birth registries and census data, it is possible to perform population-based studies on the association between social factors and feto-infant mortality. Such studies have recently been carried out in Denmark, Finland, Norway and Sweden and socio-economic differences in late fetal and postneonatal death rates were seen. Death rates as well as the relative importance of socio-economic factors differed between these countries. In Norway, infants delivered by women with 9 years or less of schooling faced an almost three-fold increased risk of dying postneonatally as compared to infants delivered by women with at least 12 years of education. In order to successfully decrease the socio-economic differences in feto-infant mortality between and within the Nordic countries, it is necessary to analyse possible preventable risk factors that are distributed unevenly not only in different socio-economic groups but also between the Nordic countries.
Life Satisfaction and Activity Preferences in Parents of Down's Syndrome Children
Authors: Bränholm Inga-Britt , Degerman Else-Ann
Published: July 2017

The impact of parenting a child with Down's syndrome on life satisfaction and non-work activities was investigated in 37 couples using mailed checklists. The results were compared with those found in all 89 parents from a randomly selected population. Only for 7 of the 41 non-work activities were there differences between the two groups of parents. The vast majority of both groups were satisfied or very satisfied with life as a whole and with partnership relations, sexual life and family life. The 8 domains of life satisfaction formed 3 factors. In congruence with previous findings in a non-selected sample these factors were significant classifiers for satifaction with life as a whole, an expressive (emotion related) factor being the major classifier. The close similarities in non-work activities and life satisfaction are interpreted as a result of adequate adaptive resources within the majority of families of children with Down's syndrome.
Stability of therapeutic alliance and its relationship to outcome in short-term inpatient psychiatric care
Authors: Hansson Lars , Berglund Mats
Published: July 2017

The relationship of therapeutic alliance to patient and treatment characteristics and to outcome, was studied in a sample of 106 patients consecutively admitted to a short-term psychiatric ward. The main finding was that a better therapeutic alliance at discharge was related to a greater improvement in symptoms during treatment. A multivariate model for prediction of outcome revealed a significant contribution from therapeutic alliance at discharge but not from alliance at admission or from changes in alliance during treatment. Improvement in alliance was seen in 41.5% of the patients, no change in 28.3% and a deterioration in 30.2%. Patients who improved their alliance did not differ from the others in background characteristics, but were more often subject to psychopharmocological treatment and were more often treated in a basic activation group. Patients with a stable poor alliance more often stated physically oriented target complaints at admission while patients with a stable satisfactory alliance more often presented interpersonally related complaints. It is concluded that further research in the field would benefit from a closer description of the change in the alliance and its relationship to treatment characteristics and outcome.
Tear/Plasma Urea Ratio as a Correction Coefficient for Drug Monitoring in Tears
Authors: Gavrilov Vladimir , Lifshitz Tova , Shany Shraga , Weinstein Orly , Lifshitz Matitiahu
Published: July 2017

Objective:

To formulate the tear/plasma urea ratio as a coefficient for correcting drug concentrations in tears.

Subjects and Methods:

Urea concentrations were measured in 14 paired tear and plasma samples from seven healthy adult volunteers (3 women, 4 men). A second sample was obtained one hour after the first. The samples were simultaneously assayed for urea concentrations by a urease method (Boehringer Mannheim).

Results:

Our data show a highly significant correlation between tear and plasma urea concentrations in all the samples (r = 0.985, p < 0.001; r = 0.928, p < 0.003; and r = 0.944, p < 0.001 in the first, second, and total collection of samples, respectively). In all paired tear and plasma samples, urea content in tears was higher than in plasma (p < 0.001, p < 0.015, and p < 0.001 in the first, second, and total samples, respectively). The tear/plasma urea ratio in all samples ranged from 1.016 to 1.225 (mean ± SD 1.126 ± 0.068) and had a significant negative correlation (r = −0.538; p < 0.05) with tear volume (range 25–155 μL, mean ± SD 83.9 ± 42.6).

Conclusions:

Higher urea concentrations in tears than in plasma and a negative correlation between tear volume and the tear/plasma urea ratio indicate that tear evaporation and, consequently, tear concentration occur during sample collection. These data and the highly significant correlation between tear and plasma urea concentrations justify the use of the tear/plasma urea ratio as a correction coefficient for monitoring drug concentrations in tears.
Clinical Effectiveness of Sertraline Three Times a Week Compared with Once-Daily Regimen
Authors: Karki Shyam D , Bellnier Terrance J , Masood Gule-Rana , Patterson William R
Published: July 2017

Objective:

To evaluate the clinical effectiveness of sertraline three-times-a-week regimen in community nursing home residents who were stabilized on sertraline once-daily regimen for ≥12 weeks for management of depression.

Methods:

All residents with diagnosis of depression stabilized on sertraline once-daily for ≥12 weeks for management of depression were entered into the study. After assessing depression at baseline by the 30-item Geriatric Depression Scale (GDS), 17-item Hamilton Depression Scale (HAM-D), and a five-item Clinical Global Impression Scale (CGI), the treatment regimen of all residents was changed to equivalent doses of sertraline three times a week. Depression was reassessed at 12 weeks by the GDS, HAM-D, and CGI scales.

Results:

Forty-four residents of a community nursing home participated in the study. Their mean ± SD age was 83 ± 12 years; there were 13 men and 31 women. Depression scores at baseline and after the three-times-weekly regimen was initiated were GDS (7.7 ± 0.9 vs. 7.4 ± 0.6), HAM (4.3 ± 0.5 vs. 4.2 ± 0.4), and CGI (3.0 ± 0.5 vs. 3.0 ± 0.4). Mean daily sertraline cost was $1.88 ± 0.4 before and $0.76 after the change in regimen.

Conclusions:

Our results indicate that sertraline three times weekly is as clinically effective as the once-daily regimen in the management of depression in our population of nursing home residents and achieves significant cost savings.
Interferon Therapy in Liver Cirrhosis Type C
Authors: Ben-Noun Liubov L
Published: July 2017

Objective:

To review current information on the role of interferon (IFN) therapy in patients with liver cirrhosis type C.

Data Sources:

All relevant articles from 1989 to December 1998 were identified by a MEDLINE search using the terms interferon treatment and liver cirrhosis. Some studies were identified from bibliographies of selected articles.

Study Selection:

More than 97 articles were identified. Reports were included if they contained new or relevant information on the hepatitis C virus (HCV), IFN therapy in liver fibrosis and cirrhosis, outcome of cirrhosis, hepatocellular carcinoma (HCC), or adverse effects related to IFN. Abstracts were included only when they added information not otherwise available in the literature.

Data Synthesis:

Response to IFN is unfavorably influenced by the presence of cirrhosis; there are several other predictors of response. IFN therapy can decrease the risk of development of HCC in some patients. In patients with compensated cirrhosis type C, a higher dosage of IFN-alfa and longer duration of therapy are associated with a better response. Combined therapy with IFN-alfa 2b and ribavirin is more effective than therapy with IFN-alfa alone. Therapy with human lymphoblastoid IFN (L-IFN) produces sustained response rates equivalent to those of recombinant IFN-alfa. Consensus IFN (CIFN) is more effective than IFN-alfa 2b. Larger dosages of CIFN are associated with better results. Normal alanine transaminase concentration and the absence of serum HCV RNA after treatment and again after 24 weeks of observation indicate a successful end point of IFN therapy. Adverse effects related to IFN treatment are usually minor.

Conclusions:

Although the presence of cirrhosis predicts a poor response to IFN treatment, some patients benefit from this therapy. Reasonable treatment regimens for patients with compensated HCV cirrhosis include IFN-alfa therapy, 6 MU subcutaneously three times weekly for 12 months, L-IFN 3 MU intramuscularly three times weekly for six months, or CIFN 9 or 12 μg subcutaneously three times weekly for six months. Patients receiving IFN should be seen every two to four weeks, with frequent monitoring of complete blood count and serum transaminase concentrations.
Ziprasidone: A New Atypical Antipsychotic Agent
Authors: Yu Bong G , Merrick Jacqueline P
Published: July 2017

Objective:

To evaluate ziprasidone for the treatment of schizophrenia with respect to its pharmacology, pharmacokinetics, adverse effect profiles, and drug interaction potential.

Data Source:

A MEDLINE search (1966-May 2001) was conducted for primary and secondary sources focusing on atypical antipsychotics and ziprasidone.

Study Selection:

All of the articles identified from the data source were evaluated and all information deemed relevant was included.

Data Synthesis:

Like other atypical antipsychotics, ziprasidone works by blocking serotonin and dopamine receptors in the mesolimbic and mesocortical regions of the brain. Ziprasidone is equally effective as haloperidol in treating schizophrenia or schizoaffective disorders. A proposed advantage of ziprasidone over other atypical antipsychotics is lower incidence of weight gain. As with a number of other psychotropic agents such as thioridazine, prolongation of the QTc interval should be monitored for patients receiving ziprasidone.

Conclusions:

Based on adverse effect profiles and relatively fewer drug interactions, ziprasidone is recommended for patients who are elderly and taking multiple medications.
A Pharmacist Consultation Service in Community-Based Family Practices: A Randomized, Controlled Trial in Seniors
Authors: Sellors Connie , Dalby Dawn M , Howard Michelle , Kaczorowski Janusz , Sellors John
Published: July 2017

Objective:

To conduct a pilot study for a larger randomized trial investigating the efficacy and cost-effectiveness of a pharmacist consultation (PC) program for elderly patients in family practice.

Design:

Randomized, observer-blinded, controlled trial with two patient groups: PC and control. The study pharmacist interviewed each PC program participant in their physician's office, prepared a letter, and reviewed the drug regimen recommendations in the letter with the physician. The number and types of recommendations made, the proportion of the pharmacist's recommendations implemented by physicians, and daily medication use and costs at the end of six months are reported.

Setting:

One hundred thirty-two patients aged 65 years and older from four family practices in Stoney Creek, Ontario, Canada, who regularly were taking four or more medications.

Results:

Patient participation rates demonstrated feasibility: 191 patients were eligible, with 132 (69.1%) of these consenting to be enrolled. A mean ± SD of 3.0 ± 1.7 recommendations per patient were made for 62 (93.9%) of 66 patients in the PC group, and 77.8% (119/153) of these recommendations were implemented or partially implemented by the physicians. After six months, the mean numbers of medication units were 14.7 ± 10.8 and 13.9 ± 8.2, p = 0.66. The mean daily medication costs were $2.73 ± 1.78 and $2.47 ± 1.78, p = 0.43 in the control and PC groups, respectively.

Conclusions:

This pilot study demonstrated the need, the feasibility, and the potential effects of the PC program. The results were used to design a larger trial in which physicians rather than patients were randomized to further evaluate the program.
A Primer of Drug Safety Surveillance: An Industry Perspective
Authors: Allan Marjorie C.
Published: July 2017

Objective:

To place the fundamentals of clinical drug safety surveillance in a conceptual framework that will facilitate understanding and application of adverse drug event data to protect the health of the public and support a market for pharmaceutical manufacturers' products. Part II of this series discusses specific issues regarding product labeling, such as developing the labeling, changing the labeling, and the legal as well as commercial ramifications of the contents of the labeling. An adverse event report scenario is further analyzed and suggestions are offered for maintaining the product labeling as an accurate reflection of the drug safety surveillance data. This article also emphasizes the necessity of product knowledge in adverse event database management. Both scientific and proprietary knowledge are required. Acquiring product knowledge is a part of the day-to-day activities of drug safety surveillance. A knowledge of the history of the product may forestall adverse publicity, as shown in the illustration.

Data Sources:

This review uses primary sources from the federal laws (regulations), commentaries, and summaries. Very complex topics are briefly summarized in the text. Secondary sources, ranging from newspaper articles to judicial summaries, illustrate the interpretation of adverse drug events and opportunities for drug safety surveillance intervention.

Study Selection:

The reference materials used were articles theoretically or practically applicable in the day-to-day practice of drug safety surveillance.

Data Synthesis:

The role of clinical drug safety surveillance in product monitoring and drug development is described. The process of drug safety surveillance is defined by the Food and Drug Administration regulations, product labeling, product knowledge, and database management. Database management is subdivided into the functions of receipt, retention, retrieval, and review of adverse event reports. Emphasis is placed on the dynamic interaction of the components of the process. Suggestions are offered to facilitate communication of a review of adverse event data for various audiences.

Conclusions:

Careful drug safety surveillance is beneficial to the health of the public and the commercial well-being of the manufacturer. Attention to the basic principles is essential and, as illustrated, may be sufficient to resolve some problems.
Issues in Contemporary Drug Delivery
Authors: Hilleman Daniel E. , Banakar Umesh V.
Published: July 2017

Objective:

To identify and discuss the clinical utility of new delivery systems and formulations of cardiac drugs.

Data Sources:

Studies describing or evaluating new drug delivery systems for cardiac drugs were identified through a MEDLINE literature search.

Study Selection:

All studies describing or evaluating new delivery systems for cardiac drugs were reviewed.

Data Extraction:

Data were abstracted and evaluated by each author independently.

Data Synthesis:

The most common oral sustained-release formulations include the wax-matrix system, the gastrointestinal therapeutic system (GITS), and the spheroidal oral drug absorption system (SODAS). The wax-matrix delivery system is limited by the occurrence of “dose-dumping.” In a low-pH setting, the wax-matrix formulation may dissolve too rapidly, liberating the entire dose in a short period of time. The clinical relevance of this phenomenon is unknown. The GITS and SODAS formulations are less likely to be affected by pH and food. Nitroglycerin is available by many routes of administration. The topical patch forms are convenient to use, but are associated with the development of tolerance. A buccal formulation incorporates a relatively short onset of effect with a three- or four-times-daily dosing regimen. Although tolerance is less of a problem with buccal nitroglycerin than with topical nitrates, this formulation is less convenient to use because of buccal irritation and interference with eating and talking. A new spray formulation of nitroglycerin offers longer shelf-life storage stability and an easier mode of administration. The spray canister is stable for three years compared with 12 weeks for an opened bottle of sublingual nitroglycerin tablets. Sublingual administration of oral cardiac drugs offers the potential for a more rapid onset of effects. Although nifedipine is often given sublingually, objective data indicate that it is not absorbed buccally but rather in the stomach. It appears that the chew-and-swallow route is most appropriate for nifedipine. Captopril is absorbed sublingually but its efficacy has not been demonstrated. Transdermal clonidine improves compliance and is associated with fewer adverse effects than oral clonidine. Transdermal formulations of beta-blockers are currently being evaluated.

Conclusions:

Further advancements in the development of novel delivery systems for cardiac drugs are expected in the future.
Myocardial Infarction and Dynamic Left Ventricular Outflow Obstruction Induced by Bronchodilator Therapy
Authors: Raggi Paolo , Rodney Evens , El-Jandali Amer , Vasavada Balendu C. , Sacchi Terrence J.
Published: July 2017

Objective:

To report a case of myocardial infarction with patent coronary arteries and left ventricular outflow obstruction induced by a combination of aminophylline and beta2-agonists treatment.

Case Summary:

A 61-year-old woman, without risk factors for coronary artery disease, was admitted with an exacerbation of bronchial asthma. She received intravenous aminophylline and aerosolized beta2-agonists. She developed hemodynamic and echocardiographic features of obstructive hypertrophic cardiomyopathy and had a myocardial infarction. Her serum theophylline concentration was normal. At cardiac catheterization the coronary arteries were patent and the obstructive features disappeared when the asthma drug treatment was discontinued.

Discussion:

This case describes the occurrence of a very unusual combination of cardiovascular adverse effects induced by drugs widely used for treatment of bronchial asthma. Aminophylline and beta2-agonists can cause myocardial ischemia by inducing tachycardia, hypercontractility, and coronary artery spasm.

Conclusions:

Aminophylline and beta2-agonists can induce severe and life-threatening myocardial ischemia, even when used at therapeutic drug concentrations.
Value of Pharmacy-Related Bulletin Board Services as a Drug Information Resource
Authors: Gora-Harper Mary Lea
Published: July 2017

Objective:

To orient pharmacists to bulletin board services (BBSs) as a source of drug information, and to provide information concerning equipment, services, and resources, as well as examples of systems that are used frequently.

Discussion:

Pharmacy-related BBSs allow pharmacists who have no experience with a new formulation or therapeutic use for a medication to obtain information from those who have such experience.

Conclusions:

As computers become increasingly common in both hospital and community pharmacies and because many BBSs provide free access to newsletters and databases for drug information, pharmacy-related BBSs represent an easy, inexpensive method to share ideas and obtain information on medication use.
Reevaluation of Gentamicin Dosing in the Neonatal Population
Authors: Gray Thomas M
Published: July 2017

Objective:

To determine whether current recommendations for gentamicin dosing in full-term newborns yield a serum peak concentration of 6–7 μg/mL and a trough concentration less than 2 μg/mL in treating suspected neonatal sepsis.

Design:

Two-year retrospective chart review.

Setting:

Community hospital.

Results:

Sample consisted of 175 newborns with a gestational age ranging from 36 to 43 weeks and 188 sets of concentrations. Pharmacokinetic parameters were calculated using a one-compartment, first-order elimination model and were reported as follows: volume of distribution 0.59 kg/L, elimination rate constant (ke) 0.11 h−1 (half-life [t1/2] 6.8 h) at 36–37 weeks of age, with a significant change (p < 0.05) in rate constant occurring at 38–43 weeks of life, and ke 0.12 h−1 (t1/2 6.0 h) when using a two-tailed, two-sample t-test. Extrapolated mean peak concentrations were 5.8 ± 1.2 μg/mL and trough concentrations were 1.5 ± 0.5 μg/mL. Furthermore, 14% of newborns had an extrapolated trough concentration of 2.0 μg/mL or more.

Conclusions:

The current 2.5-mg/kg dosage is appropriate for the neonatal population studied. However, to decrease the number of potentially toxic trough concentrations, the initial dosing interval should be extended to every 18 hours for full-term neonates (>37 weeks gestation) with normal kidney function and for neonates with a gestational age of 36–37 weeks.
Linearity in Dose—Response from Zinc Lozenges in Treatment of Common Colds
Authors: Eby George A
Published: July 2017

Objective:

To test the hypothesis that major variations in daily zinc ion availability (ZIA) between lozenge formulations caused greatly differing results and to describe the biologically closed electric circuit between the mouth and nose.

Data Sources:

Data sources included clinical and in vitro reports, zinc speciation computations, and unpublished data from the original researchers and manufacturers.

Data Extraction:

Data were extracted to determine the composition and usage of lozenges and resultant changes in common cold duration. Lozenge ZIA values were determined from Zn2+ ion concentrations and oral contact time.

Data Synthesis:

Data synthesis disclosed that lozenges releasing Zn2+ ions at physiologic pH (positive ZIA values) shortened the duration of colds. Conversely, lozenges that released negatively charged zinc complexes (ZnLN−) at physiologic pH (negative ZIA values) lengthened the duration of colds. ZIA 100 lozenges reduced the duration of colds by 7 days. ZIA 0 lozenges had no effect. ZIA −55 lozenges lengthened the duration of colds by 4.4 days.

Conclusions:

The hypothesis is valid that major variations in ZIA from different zinc lozenge formulations used in clinical trials caused greatly differing results. A linear dose-response relationship exists between ZIA values of zinc lozenges and changes in duration of common colds. In agreement with in vitro activity, Zn2+ ions from lozenges inhibit replication of rhinoviruses, induce interferon release, and stabilize cell membranes in common cold treatment. Linearity in dose-response shows efficacy against common cold duration from clinically untested lozenges to be predictable on the basis of readily determined ZIA values of experimental lozenges.
Zidovudine Compliance as Measured by Different Methods in an HIV Ambulatory Clinic
Authors: Geletko Sandra M , Segarra Marisel , Ravin Donna S , Babich Mark P
Published: July 2017

Objective:

To measure and compare medication compliance by patient reports, pill counts, physician assessments, and electronic monitoring with the Medication Event Monitoring System (MEMS) in patients infected with HIV.

Methods:

Five patients monitored in a Veterans Affairs Medical Center HIV clinic were dispensed zidovudine for 3 months in MEMS vials. Zidovudine was refilled every month, at which time MEMS data were retrieved and pill counts were performed. Medication compliance surveys requesting the number of missed doses were also administered to patients and their physicians every month for 3 months.

Results:

Compliance assessments were as follows: patient report 80–100%, physician assessment less than 30–100%, pill counts 50–100%, and MEMS 9–100%. MEMS identified one patient's misunderstanding of zidovudine dosing. Three patients removed zidovudine from MEMS vials and placed the medication in a smaller vial for easy transport, thereby decreasing the usefulness of MEMS data.

Conclusions:

A combination of compliance assessment tools produces a more accurate representation of zidovudine dosing and facilitates identification of patient dosing errors. Use of multiple compliance tools, including MEMS data, during patient counseling may be an effective strategy for enhancing medication compliance.
Diuretic Drug Utilization Study
Authors: Torelló Jaime , Durán José A , Serrano María I
Published: July 2017

Objective:

To evaluate the present use of diuretics in our institution, and determine the appropriateness of that use and the incidence of adverse reactions and interactions.

Design:

This retrospective study describes the indications for use of an identified drug or combination of drugs. By the time the data were collected, some patients had been discharged or had died.

Setting:

The study was carried out in a referral center, the University Hospital “Virgen Macarena,” Seville, Spain.

Patients:

All patients receiving diuretic therapy. Those undergoing hemodialysis or receiving home care were excluded from the study.

Intervention:

A therapeutic audit was performed using specific standards of reference. Two models were used — one for each of the most frequent indications, ascites and congestive heart failure (CHF).

Main Outcome Measures:

A structured protocol gathered data on (1) demographic characteristics, (2) causes of admission and pathologic antecedents, (3) diuretic treatment, (4) basic controls (24-h diuresis and daily basal weight), (5) clinical evolution, and (6) concurrent complementary studies. The protocol included a checklist of the most frequent adverse drug reactions and interactions whose degree of causality was determined by applying the modified algorithm of Karch-Lasagna, used in the World Health Organization voluntary reporting system of adverse drug reactions.

Results:

One hundred twenty-six patients (16% of total admissions) received diuretic therapy. Of these, 71% were analyzed; information in the medical records was incomplete for the rest (29%). Fifty-one percent of the patients were more than 60 years old. The most frequent admission diagnoses were cardiovascular (51.5%), followed by digestive (16.7%) diseases. A total of 134 cardiac symptoms was seen in 50 patients. The most notable were acute pulmonary edema (26%), ischemic cardiopathy (12%), and cardiogenic shock (8%). Most patients receiving diuretic therapy (47.3%) were admitted to the internal medicine service. The most-prescribed diuretic was furosemide (59%), followed by spironolactone (27%). The combined use of furosemide and spironolactone occurred in all but 1 of the patients with hepatic ascites (92%), whereas in those with CHF the figure for the combined use of furosemide and spironolactone fell to 38% (p = 0.001). In 63% of the patients with ascites, the spironolactone dosage was changed in the first 48 hours of treatment. There was a high percentage of deaths (21%) in the study patients.

Conclusions:

Therapeutic strategy often does not follow the guidelines laid down in the standards of reference on diuretic use in serious CHF and/or ascites in this institution.
Impact of Pharmacy Efforts to Promote the Optimal Use of Ranitidine in a University Teaching Hospital
Authors: Sterné Sharette C , Hayward Shelly L , Ferrill Mary J , Iteen Scott A
Published: July 2017

Objective:

To determine whether the development, implementation, and outcome of a hospital-wide, pharmacy-initiated, educational and intervention program impacted ranitidine prescribing patterns specific to institution guidelines.

Methods:

The development of a standardized ranitidine medication utilization guideline (R-MUG) form was established by the departments of pharmacy and gastroenterology in conjunction with the pharmacy and therapeutics committee at the University of California, Irvine. Using this standardized R-MUG form, all hospitalized patients (excluding pediatric, mental health, and labor and delivery) receiving ranitidine during their hospitalization were identified and evaluated for appropriate ranitidine use patterns. A baseline evaluation phase that included 240 patients was conducted, and diagnosis, dosage, and dosage form were recorded. This was followed by an educational program and subsequently a posteducational pharmacist intervention phase involving 210 patients, in which data were collected over a 3-week period. From these data, projected ranitidine cost savings were calculated. Results were used to determine the impact the educational process had on modifying ranitidine prescribing patterns.

Results:

Initially, ranitidine was prescribed according to the guidelines in 74% of the patients. After educational inservice sessions this number rose to 96% (p < 0.001). The 3-week intervention phase saved approximately $930 compared with the baseline period by limiting the amount of ranitidine used. The optimal choice of ranitidine dosage form increased significantly from baseline (87%) to the posteducational data collection period (94%) (p < 0.01). Targeted intervention of high-need areas of the hospital (surgical and burn intensive care units) resulted in a significant decrease (p < 0.001) in the percentage of inappropriate dosing with continuous ranitidine infusion, but not with intravenous piggyback or syrup.

Conclusions:

This program was an effective method of educating healthcare professionals regarding ranitidine prescribing, improving the pattern of use of ranitidine, and decreasing costs to the institution. It may serve as a model for addressing other medication usage concerns.
Dalteparin, a Low-Molecular-Weight Heparin: Review of Pharmacology and Pharmacotherapy
Authors: Kandrotas Robert J
Published: July 2017

Objective:

To review the current literature concerning the use of dalteparin in thromboembolic disease. The chemistry, pharmacokinetics, pharmacodynamics and clinical efficacy for approved and nonapproved uses, and adverse effects are presented.

Data Sources:

A MEDLINE search of the English-language literature between 1980 and 1996.

Data Extraction:

The data presented are primarily from controlled studies of dalteparin in humans. Some of the pharmacokinetic/pharmacodynamic and basic pharmacologic data are from animal studies. The majority of the clinical investigations were blind.

Data Synthesis:

Dalteparin sodium is approved for use in the prophylaxis of thromboembolic disease after major abdominal surgery. Dalteparin is a low-molecular-weight heparin (LMWH) with a mean molecular weight of 5,000 Da. It produces its antithrombotic effect through the inhibition of activated factor X and, to a lesser extent, activated factor II.

Conclusions:

Thromboembolic disease may occur in patients such as those over 40 years of age undergoing major surgical procedures lasting longer than 30 minutes. In addition, prolonged bed rest may result in development of thromboembolism due to immobilization and venous stasis. Anticoagulant prophylaxis for deep-vein thrombosis is warranted in these patients. As with other LMWHs, laboratory monitoring of coagulation parameters (e.g., activated partial thromboplastin time and activated coagulation time) is unnecessary. Dalteparin sodium has been demonstrated to be efficacious and safe for the prophylaxis of thromboembolic disease after major abdominal surgery and is a reasonable alternative to unfractionated heparin in these patients. The use of dalteparin for other indications, such as treatment of thromboembolic disease, hemodialysis, and unstable coronary artery disease, also appears to be promising.