bluuebunny/crossref_metadata_2025 huggingface dataset:
Acceptance of Screening for Colorectal Cancer by Flexible Sigmoidoscopy
Authors: Cockburn J , Thomas R J S , McLaughlin S J , Reading D
Published: January 2017

Objective —

To determine the acceptance rate of screening by flexible sigmoidoscopy in a sample of general practice patients aged 50 to 60, and the acceptability of the procedure among those undergoing the test.

Setting —

Recruitment took place in selected general practices in Melbourne, Australia. Flexible sigmoidoscopies were performed at the local public hospital.

Patients and methods —

187 patients aged between SO and 60, and without bowel symptoms, were seen by one of 12 non-randomly selected general practitioners during the study period. At the conclusion of routine consultation general practitioners discussed colorectal screening with eligible patients and recommended that they attend a free screening clinic at the local hospital. The patients who attended the clinic underwent flexible sigmoidoscopy performed by experienced endoscopists. Clinic attenders completed a questionnaire which measured perceptions of the screening visit.

Results —

The attendance rate was 49%. All clinic attenders were satisfied with the care received at clinic. Sixty five per cent of people experienced either no discomfort or mild discomfort, while 15% of people experienced moderate or severe pain. A bloated feeling was common (80%), with around 36% of people experiencing moderate or extreme bloating. Most people said that they were not at all embarrassed (64%), though 9% reported moderate or extreme embarrassment. Seventeen people (19%) were found to have polyps.

Conclusions —

Although the procedure was acceptable to those who underwent the screening test, further research on effective recruitment strategies is required if a full scale flexible sigmoidoscopy screening programme is to be considered feasible.
What are Women Told about Pap Smears That Lack Endocervical Cells?
Authors: Schofield Margot J , Byles Julie E , Sanson-Fisher Rob
Published: January 2017

Background —

Debate exists about the definition of what constitutes an adequate Pap smear and about the recommended rescreening interval for Pap smears lacking an endocervical component. This study aimed at determining whether women are currently informed about the endocervical status of their Pap smears and what rescreening recommendations are made to women whose smears lack endocervical cells.

Method —

Consecutive Pap smears lacking an endocervical component were identified from pathology records. After obtaining consent from the referring doctor, 165 women were interviewed by telephone.

Results —

Only 110 (67%) of 165 women received active notification of their Pap test result and only six (4%) were aware that their smear lacked endocervical cells. Thirteen (8%) had been advised to have a repeat smear within three months. Nearly half the women reported that they would like more information about their result.

Conclusions —

It seems that current Pap smear notification patterns for women in New South Wales could be improved. One third are not actively informed at all about their results, and few are given detailed information about their Pap test results. Methods of enhancing the level of information women are given about their medical and screening tests need to be improved.
Characteristics of Subgroups of Attenders and Non-Attenders in an Organised Screening Programme for Cervical Cancer
Authors: Larsen Lars Peter Skovgaard , Olesen Frede
Published: January 2017

Objective

–Several studies have compared attenders and non-attenders in organised cervical screening programmes but few have analysed subgroups of at-tenders and non-attenders. This study presents social and other characteristics of such subgroups. Setting—Aarhus County, Denmark.

Methods

–A case-control study in a cohort of 133 500 women, aged 23–60, included in the programme from 1 October 1990 to 1 April 1994. The participation rate was 75%, and those taking part comprised women with opportunistic screening or who had had a smear owing to symptoms in the previous three years (“active” attenders), and women who were invited for screening because they had not been otherwise tested (“passive” attenders). “Passive” (n = 708) and “active” attenders (n = 692) were compared. Women who had never had a smear test (“never” attenders, n = 287) were then compared with “ever” attenders (n = 1215)—that is, women who had not had a smear test during the previous 42 months, but had had at least one previous test. Data were collected by mailed questionnaires.

Results

–The response rate was 81% and 53% for attenders and non-attenders, respectively. After correction for age, there was no difference between the “active” and “passive” attenders for cancer risk factors (smoking, age of first intercourse, number of sexual partners, and social group), or in the degree of responsibility for close relatives, but “active” attenders seemed to have more frequent contact with their general practitioner. “Never” attenders had less frequent contact with their general practitioner than “ever” attenders. They were more often living alone and nullipara, but had no overrepresentation of cancer risk factors.

Conclusions

–Increased effect cannot be obtained by focusing on the described groups, but by increasing the participation rate. “Never” attenders do not belong to a special risk group.
Relation between the Incidence of Invasive Cervical Cancer and the Screening Interval: Is a Five Year Interval Too Long?
Authors: Herbert Amanda , Stein K , Bryant T N , Breen Catherine , Old P
Published: January 2017

Objective

–To examine the incidence of invasive cervical cancer per 100 000 women years at risk and relative risk according to screening history among eligible women aged 25–69 in Southampton and South West Hampshire during the three years after completion of the first round of comprehensive screening.

Results

–There was a significantly higher incidence of invasive cervical cancer in women who had not been screened during the preceding 0.5–5.5 years than in those who had been screened (relative risk (RR) 2.6; 95% confidence interval (CI) 1.6 to 4.3). Among the latter group of women (with interval cancers) there was a significantly higher incidence in those with a long interval of 3.5–5.5 years since their most recent smear than in those with a short interval of 0.5–3.5 years (RR 2.2; 95% CI 1.3 to 3.8). Among women with non-interval cancers, there was a significantly higher incidence among those who had no cytology record than among those who had been screened but were overdue for a smear (RR 3.0; 95% CI 1.2 to 7.3). When screen detected cancers were excluded from the figures the relative risks for all the comparative groups described above were greater, though the 95% confidence limits were wider because the numbers were smaller. The most pronounced difference in incidence was between symptomatic cancers in women with a short screening interval (5.8 per 100 000 women years at risk) and in women with no cytology record (71.3 per 100 000 years at risk). Most cancers were interval cancers (76%) because of the high screening coverage: 89.2% of eligible women aged 25–69 had been screened during the preceding 0.5–5.5 years. The overall incidence per 100 000 women years at risk approached that of interval cancers, and was nearer to that observed in the short than the long interval because 74.7% of women had been screened within 3.5 years.

Conclusion

–The results confirm the effectiveness of screening but suggest that a five year screening interval may be too long, at least during the early rounds of screening.
A Collaborative Approach to Cervical Cancer Screening
Authors: Brown Wendy J , Byles Julie E
Published: January 2017

Objectives

–The main objective of this project was to evaluate a collaborative nurse and general practitioner approach to improve screening for cervical cancer. Design—Multiple group time series design.

Setting

–Six postal areas in the Hunter Valley of New South Wales, Australia, chosen as intervention sites because of very low Pap test rates compared with the rest of NSW (fewer than 50% of women screened). Six regions of similar size and with similar baseline screening levels were selected as comparison sites. Subjects—All women selected in the resident postal areas.

Interventions

–Women's health nurses worked in collaboration with general practitioners within the communities selected from within the Hunter area to prond provide screening for cervical cancer.

Main Outcome Measures

–Qualitative information on initial expectations and impressions of the collaborative processes were collected at the start of the project period. Process data on client characteristics and Pap test results were obtained from minimum data collections; client satisfaction was assessed from client surveys. Outcome data on the increase in the number of women in each community who were screened for cervical cancer were obtained from Health Insurance Commission claims for screening Pap tests (and from nurses' records where Pap tests were examined under block funding arrangements).

Results

–This project showed that nurses and general practitioners can collaborate to provide appropriate and highly acceptable cervical cancer screening services for women. Many of the women screened by the nurses were in the high risk age range for cervical cancer (40 years and older) and had only basic education levels, thus representing women who are most likely to have poor screening rates. Further, 33.1% of the women screened had not had a Pap test in the past four years or had never been screened. The number of women having a Pap test during the first six months of the project, compared with the number expected from preintervention patterns, was significantly greater in four intervention areas (P < 0.01). No corresponding increase was seen in comparison areas with similar screening rates at baseline.

Conclusions

–There is great potential for nurses to work in collaboration with general practitioners to improve the availability and coverage of community cervical cancer screening programmes.
Regional Economic Integration in Africa
Authors: Tuluy Hasan
Published: January 2017

Regional economic cooperation and integration can be an effective means for countries to overcome constraints of size and fragmentation, and to allow small landlocked countries to more efficiently connect to larger, deeper regional and global markets. The need for scale and market consolidation is particularly relevant for the 54 African countries, many of which are small, landlocked economies with small populations. Notwithstanding frequent and strong reaffirmation of political commitment to integration by African leaders, progress on the ground has been slow and challenging. While there is great diversity among sub-regions, three sets of constraints (“hard” infrastructure, “soft” infrastructure, and political cooperation and institutions) typically impede progress toward greater regional integration in Africa. The Asian experience of economic cooperation suggests another approach, focused on flexible, bottom-up platforms, improved hard and soft infrastructure, strong coalitions, deepened trade, and strengthened institutions, which could advance the regional integration agenda in parallel to the traditional political stream/process. A number of encouraging initiatives that incorporate some of these features are underway in Africa today, and hold the promise of becoming building blocks of an increasingly integrated African economic space.
Semiquantitative immunohistochemical detection of progesterone receptors in male accessory sex glands as a screening assay for anabolic steroid use in bulls
Authors: Zanardello Claudia , Capello Katia , Stella Roberto , Biancotto Giancarlo , Vascellari Marta
Published: January 2017

We investigated the immunohistochemical expression of progesterone receptors (PRs) in the prostate and bulbourethral glands of thirty-two 10–14-mo-old Charolais bulls following treatment with a low dosage of estrogens. Animals were divided into 2 groups: 16 animals (group T) were treated for 71 d with a therapeutic dose of trenbolone acetate and estradiol by subcutaneous implant, 16 animals (group C) received no treatment. Urine samples were collected both at the beginning of the trial and 9 times during the study. A semiquantitative analysis of immunohistochemistry (IHC) was performed by counting the number of positive cells in 10 randomly selected high-power fields (hpf). Both groups showed no significant histologic lesions. IHC examination showed positive cells in the epithelium of both glands, with different patterns of distribution between groups. In group C, IHC-positive cells per hpf varied from 0 to 40 in the prostate and from 0 to 32 in the bulbourethral gland. In group T, positive cells varied from 0 to 85 per hpf in the prostate and from 0 to 75 in the bulbourethral gland. The treated group showed significantly higher median numbers of positively stained cells in both organs than the controls (  p < 0.001). Chemical analysis of the urine samples confirmed that the experimental treatment mimics continuous, low-dose administration of anabolic steroids. IHC quantification showed good sensitivity with a high predictive power to correctly classify treated animals and could be used as a preliminary screening test in bulls.
Family Management Style Framework: A New Tool With Potential to Assess Families Who Have Children With Brain Tumors
Authors: Deatrick Janet A. , Thibodeaux Annaka G. , Mooney Kim , Schmus Cynthia , Pollack Rosanna , Davey Barbara Hieb
Published: January 2017

Qualitative studies of families with children who have cancer or other serious illnesses have found that families often come to view their child and their lives as normal. They manage illness-related demands using family management styles that sustain usual patterns of family and child functioning. Few studies have addressed the family management styles of families who express less satisfaction with family and child functioning or who are identified by health care professionals as having difficulty with family functioning. Such families are likely to be overrepresented among those whose children are being treated for brain tumors that entail extremely burdensome treatments as well as a range of unfavorable prognoses and long-term sequelae. In fact, little is known about how these families manage on a day-to-day basis and how the interdisciplinary team can best provide supportive care to optimize their functioning. The purpose of this article is to present the Family Management Styles Framework as a tool that is useful in both clinical practice and research for assessing families who have children with cancer, including those with brain tumors.
Family Management Style and the Challenge of Moving From Conceptualization to Measurement
Authors: Knafl Kathleen A. , Deatrick Janet A.
Published: January 2017

This article describes the process of translating the Family Management Style (FMS) Framework into a measure of FMS Survey. The conceptual underpinnings of the FMS Survey are briefly described as are the steps for translating the FMS major components and dimensions into a questionnaire to assess the family response to a childhood chronic illness. Content validity testing has been completed on the FMS Survey. Future plans include full-scale field testing of remaining psychometric properties.
Clinical Application of Family Management Styles to Families of Children With Cancer
Authors: Ogle Susan K.
Published: January 2017

The potential clinical application of family management styles for working with families who have children with cancer is discussed. Case studies are used to illustrate the usefulness and clinical application of the model.
Favorite Children’s Books for Vocal Exploration and Pitch-Matching Activities
Authors: Cardany Audrey Berger
Published: January 2017

In this article, the author shares favorite children’s books and stories for integrating language and music during shared-book experiences. The music activities described are aimed to contribute to the overall singing development for children in preschool and primary grades. Music and reading teachers will enjoy sharing these books with early readers in ways that foster expressive speaking and singing through vocal exploration and singing repeated melodic patterns.
Making Sense in Pitch Darkness: An Exploration of the Sociomateriality of Sensemaking in Crises
Authors: Berthod Olivier , Müller-Seitz Gordon
Published: January 2017

A brief failure of one item on the display of the information system (IS) on Flight AF 447 wrought havoc in the coordination between the pilots and the aircraft, leading to the loss of all 228 lives on board. In this essay, we ask the following question: How can the very instruments supposed to ensure our safety and make organizations more reliable lead a team to destruction? We propose that the imbrication of material and human agencies in such highly automated systems drives an attitude of “mindful indifference” (i.e., the capacity for experienced operators to distinguish problems that could turn into critical ones from problems that can be tolerated on account of the overall system reliability). An abrupt change in this imbrication provoked emotional distress and focused the pilots’ attention toward the machine, instead of triggering an organizational process of sensemaking. We highlight the role of leadership in such situations.
Organizational Responses to Proto-Institutions: How the Semi-edited and Unedited Accounts Clash
Authors: Hensel Przemysław G.
Published: January 2017

While adoption of institutionalized structures has received immense attention from organizational scholars, the processes associated with adoption of proto-institutions are infrequently studied. Drawing on an ethnographic longitudinal study of Producer Choice adoption by a public broadcasting organization, I contribute to the extant literature by offering three findings. First, I show how the semi-edited account of an initial implementation of proto-institution clashes with multiple unedited accounts of subsequent adoptions and results in increased ambiguity regarding the structure. Second, I shed light on how actors involved in the focal adoption struggled to follow incompatible accounts and gauge the proto-institution’s value. Last, I show how actors produce their own adoption by borrowing the justification for reform from the semi-edited account but founding its design on a previous adoption that was perceived as failed.
Aerosolized Pentamidine and Pneumocystis Carinii Pneumonia: Patient Compliance and Outcomes
Authors: Bjornson Darrel C. , Oster Charles N. , Cortese Linda M. , Nelson Bruce A.
Published: January 2017

OBJECTIVE:

The study objectives were to compare compliance between every-two-week and every-four-week aerosolized pentamidine regimens, and to determine if patients who were more compliant with the use of aerosolized pentamidine were at decreased risk for developing Pneumocystis carinii pneumonia (PCP).

DESIGN:

Nonrandomized observational study of patients receiving aerosolized pentamidine for PCP prophylaxis using the hospital pharmacy computer system to document aerosolized pentamidine use and compliance, and the Patient Administration Division's computer to document cases of PCP.

SETTING:

Tertiary care, US Army medical center.

PATIENTS:

All patients who were prescribed aerosolized pentamidine (60 mg every two weeks, 300 mg every four weeks, or both) over a 3.5-year period.

MAIN OUTCOME MEASURES:

Mean percent compliance was determined and compared between every-two-week and every-four-week regimens. The relationship between compliance and cases of PCP was determined using nonparametric statistics.

RESULTS:

Patients (n=146) who were prescribed aerosolized pentamidine 60 mg every two weeks were more compliant (p=0.006) than those prescribed 300 mg every four weeks. In addition, those patients who initially received the 60-mg regimen and were switched to the 300-mg regimen were more compliant when taking the 60-mg dose (p=0.027). There was no association between compliance with either regimen and cases of PCP. Compliance generally was poor with both regimens.

CONCLUSIONS:

Patients on every-two-week regimens of aerosolized pentamidine were more compliant than those on every-four-week regimens. However, regardless of compliance, some patients failed aerosolized pentamidine over the 3.5-year period. Other agents that lend themselves to compliance may be more appropriate for PCP prophylaxis than aerosolized pentamidine.
Clarithromycin: Review of a New Macrolide Antibiotic with Improved Microbiologic Spectrum and Favorable Pharmacokinetic and Adverse Effect Profiles
Authors: Sturgill Marc G. , Rapp Robert P.
Published: January 2017

OBJECTIVE:

To compare the new macrolide antibiotic clarithromycin with erythromycin in terms of in vitro activity, pharmacokinetics, pharmacodynamics, clinical efficacy, and toxicity.

DATA IDENTIFICATION:

An English-language literature search employing MEDLINE (1987–91), Index Medicus (1987–91), Program and Abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy (1990), Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy (1991), and bibliographic reviews of related textbooks and review articles.

STUDY SELECTION:

Eighty-five articles were selected. Clinical trials with clarithromycin have been limited, and emphasis was placed on trials reported in the Program and Abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy and Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy.

DATA EXTRACTION:

Articles were assessed for study quality and specific information addressing the stated purpose. In articles reporting the results of clinical trials, emphasis was placed on comparative efficacy and toxicity.

RESULTS OF DATA ANALYSIS:

A review of 24 human trials suggests that clarithromycin is equally effective as erythromycin, penicillin VK, ampicillin, or amoxicillin for treatment of a variety of upper and lower respiratory tract or skin infections. Clarithromycin also appears to be better tolerated than these agents, with a lower incidence of gastrointestinal adverse effects. Limited clinical studies in patients with Mycobacterium leprae or Mycobacterium aviumintracellulare complex (MAI) suggest that clarithromycin may prove to be efficacious and well tolerated in the treatment of these infections.

CONCLUSIONS:

Clarithromycin is as effective in vivo as erythromycin, with less gastrointestinal irritation. Additionally, clarithromycin appears to expand the traditional spectrum of macrolide antibiotics, with promising activity against M. leprae and MAI.
Implications of the Study Population in the Early Evaluation of Anticholinesterase Inhibitors for Alzheimer's Disease
Authors: Cutler Neal R. , Sramek John J. , Murphy Michael F. , Nash Ralph J.
Published: January 2017

OBJECTIVE:

Velnacrine testing for tolerance and safety in both normal elderly subjects and patients with Alzheimer's disease (AD) is reviewed to illustrate the importance of Phase I trials in the target group as more predictive of safety and tolerance for subsequent multicenter trials than those conducted in healthy elderly subjects.

DESIGN:

Both a single-dose and a randomized, double-blind, placebo-controlled, ascending, multiple-dose study were performed with healthy, elderly men. In the multiple-dose study, the subjects were randomized to four groups of 14, with 10 subjects receiving velnacrine and 4 receiving placebo. The doses were velnacrine 25 (group 1), 50 (group 2), and 100 mg (group 3), respectively, administered twice daily; group 4 received 100 mg three times daily for 28 days. Blood and urine were collected serially for the pharmacokinetic assessment. With AD patients, 24 subjects were randomly assigned to receive either placebo or velnacrine for 10 days in a double-blind, sequential escalation study in a hospital setting. There were three groups of 8 subjects. Six patients in each group received velnacrine and 2 placebo. The three groups received respective dosages of 450, 300, and 225 mg/d three times daily. Adverse events were closely monitored and recorded.

PATIENTS/PARTICIPANTS:

The multiple-dose test in healthy elderly men included 56 men, aged 60–74 years. Rigorous screening for any potential complications that could affect absorption, distribution, metabolism, or excretion preceded patient entry in the AD patient study. Patients with a history of major psychiatric, neurologic, and cardiovascular disorders were excluded. The patients ranged in age from 56 to 89 years, and were equally distributed between gender.

INTERVENTION:

Velnacrine was administered in various doses.

MAIN OUTCOME MEASURES:

We emphasize the extreme adverse effects encountered in the AD patient group compared with the healthy group. Plasma concentrations of velnacrine over time in both groups are given, as well as the drug's half-life and excretion rates.

RESULTS:

The tolerable dosage predicted by studies performed in healthy elderly subjects was 300 mg/d. This dosage was not tolerable among the AD patients. A dosage as high as 450 mg/d resulted in a tonic seizure in one patient. The predicted dosage of 300 mg/d produced an adverse effect profile in AD patients that included dizziness, nausea and/or vomiting, headaches, and severe diarrhea. AD patients tolerated a dosage of 225 mg/d.

CONCLUSIONS:

A velnacrine dosage of 300 mg/d that was tolerated in healthy elderly subjects was not tolerated by AD patients.
Serum Albumin Concentrations: Who Needs Them?
Authors: Erstad Brian L.
Published: January 2017

OBJECTIVE:

To examine the multiple factors that influence serum albumin concentrations and to discuss settings in which the monitoring of such concentrations provides clinically useful information.

DATA SOURCES:

Original investigations, review articles, books, and abstracts published in English.

STUDY SELECTION:

Studies pertaining to factors affecting serum albumin concentration were chosen based on general applicability. Recommendations related to the appropriate monitoring of albumin concentrations were based on studies performed in the clinical setting with direct applicability to patient care.

DATA EXTRACTION:

Data on factors affecting serum albumin concentration were extracted from studies that resulted in similar conclusions regardless of assay technique. Appropriate indications for albumin monitoring were derived from studies demonstrating direct clinical relevance.

DATA SYNTHESIS:

A number of factors may influence serum albumin concentration and ultimately affect interpretation of the concentration. Serum albumin concentrations generally are useful in the institutional setting shortly after admission or preoperatively to determine patient prognosis. Albumin concentrations have limited merit for predicting the free fractions of various hormones, electrolytes, and drugs. When used as an indicator of nutritional support, albumin concentrations are most helpful when measured over longer periods in relatively stable patients.

CONCLUSIONS:

Serum albumin determinations should be limited to those situations in which the concentrations are likely to provide clinically useful information. Such situations are limited.
Using Memory for Pain in Analgesic Research
Authors: Babul Najib , Darke Andrew C. , Johnson Donald H. , Charron-Vincent Karen
Published: January 2017

OBJECTIVE:

To determine the validity of pain intensity recall at 24 and 48 hours as a substitute for hourly pain assessments in repeated-dose analgesic studies.

SETTING:

Orthopedic unit of an acute care teaching hospital.

PARTICIPANTS:

Eighty-four patients undergoing arthroscopic reconstruction of the anterior cruciate ligament, using the patellar tendon, who were participating in a randomized, double-blind, parallel-group analgesic study.

INTERVENTIONS:

Patients rated their pain intensity every hour (while awake) for 48 hours and their recall of worst, least, and usual pain intensity at 24 and 48 hours using a visual analog scale (VAS).

MAIN OUTCOME MEASURES:

This study examined the relationship between recall of worst, least, and usual pain intensity at 24 and 48 hours and the experienced maximum, minimum, and mean pain intensity VAS scores obtained from hourly assessments over the 0–24- and 0–48-hour periods, respectively. The significance of differences between recalled and experienced pain intensity variables was assessed.

RESULTS:

Worst, least, and usual pain recall at 24 and 48 hours were highly correlated with experienced maximum, minimum, and mean pain from hourly reports, respectively, over the 0–24- and 0–48-hour periods (Pearson correlation coefficients, r=0.80–0.89, p<0.0001). Among the three pain recall variables, usual pain showed the highest correlation with hourly measurements. There were no significant differences between recalled pain and the corresponding measures of pain from the hourly VAS scores, except in the case of 48-hour recall of worst pain (Student's t-test, p=0.001).

CONCLUSIONS:

The close agreement between actual pain experience and recall of pain provides support for the use of pain recall in assessing analgesic efficacy in clinical trials.
Apparent Valproic Acid Neurotoxicity in a Hypoalbuminemic Patient
Authors: Gidal Barry E. , Collins D. Michael , Beinlich Brad R.
Published: January 2017

OBJECTIVE:

To report a case of possible neurotoxicity caused by markedly elevated free valproic acid (VPA) plasma concentrations.

CASE SUMMARY:

A patient with a history of a mixed-type seizure disorder that had been treated with oral VPA 1000 mg four times daily for the previous two years was admitted to the neurology service with the chief complaint of increasing difficulty in walking and involuntary muscle jerks that were new in onset. The patient was hypersomnolent and dysarthric. The total plasma VPA concentration was 103 μg/mL, which was only slightly above the recommended therapeutic range (50–100 μg/mL). VPA free fraction and free plasma concentrations, however, were unexpectedly elevated (26 percent, 26.8 μg/mL, respectively). Further laboratory evaluation revealed a serum albumin concentration of 33 g/L. The neurologic symptoms resolved upon VPA dosage reduction.

DISCUSSION:

VPA displays concentration-dependent protein binding, resulting in disproportionate increases in drug free fraction with increasing drug concentration. This effect may be magnified in patients with decreased plasma protein-binding capacity. The plasma protein-binding kinetics of VPA are reviewed and the implications for therapeutic drug monitoring are discussed.

CONCLUSIONS:

It is likely that the markedly elevated free VPA plasma concentrations contributed to the neurologic symptoms displayed in this patient. In patients with decreased albumin concentrations, failure to recognize concentration-dependent protein binding, as well as exclusive reliance upon total drug concentrations, may lead to erroneous pharmacokinetic and therapeutic interpretations.
Maternal Noncompliance with Antibiotics during Breastfeeding
Authors: Ito Shinya , Koren Gideon , Einarson Thomas R.
Published: January 2017

OBJECTIVE:

To determine the incidence of antibiotic prescription failure in breastfeeding women, and to characterize breastfeeding patterns during antibiotic therapy.

DESIGN:

Prospective cohort study by telephone follow-up of 203 breastfeeding women who were prescribed antibiotics as monotherapy.

SETTING:

A teratogen/drug information service (the Motherisk Program) in a tertiary care, pediatric hospital in Toronto, Canada.

MAIN OUTCOME MEASURES:

Number of breastfeeding women who did not initiate the antimicrobial therapy, and breastfeeding patterns during therapy in women who started it.

RESULTS:

Of 203 breastfeeding women who consulted the Motherisk Program for information about the safety of antimicrobials during breastfeeding, 125 (62 percent) were followed within 32 weeks (median 11). Nineteen of the 125 (15 percent) did not initiate the antimicrobial therapy. Of the remaining 106 women, 7 (7 percent) stopped breastfeeding during therapy. Despite reassuring advice, 1 in 5 women either did not initiate therapy or did not continue breastfeeding.

CONCLUSIONS:

Physicians should be aware of the substantial rate of noncompliance with drug regimens among nursing women and the potential negative impact of drug therapy on breastfeeding.
Antifungal Prophylaxis in Immunocompromised Hosts
Authors: Reents Stan , Goodwin S. Diane , Singh Vipul
Published: January 2017

OBJECTIVE:

To review the literature on the efficacy and safety of antifungal agents for prophylaxis of fungal infections in populations of immunocompromised hosts (key words: hematology-oncology, surgical, solid organ transplant, HIV infection), and to develop guidelines and recommendations regarding safe and effective drug regimens for antifungal prophylaxis in this patient population.

DATA EXTRACTION:

Comprehensive review of clinical trials of antifungal prophylaxis published in the English literature, with an emphasis on controlled trials, and discussion of key clinical trials illustrating efficacy and safety of agents for antifungal prophylaxis in immunocompromised patients.

RESULTS:

Much of the clinical data evaluating the efficacy and safety of antifungal prophylaxis has been generated in cancer patients. The choice of antifungal agent for prophylaxis in this population remains controversial. However, azole compounds such as clotrimazole, ketoconazole and fluconazole appear to be more effective and better tolerated than nystatin suspension. Although ketoconazole has been shown to reduce fungal colonization in surgical patients, current data do not support the routine use of antifungal prophylaxis in this population. In renal transplant recipients, clotrimazole troches have been shown to be more effective than placebo or nystatin suspension. Selective bowel decontamination with nonabsorbable antibiotics and nystatin may be useful in reducing Candida colonization in liver transplant patients but no definitive recommendations may be made at this time regarding optimal antifungal prophylaxis in these patients. In patients with advanced HIV disease or history of prior fungal disease prophylaxis for oropharyngeal candidiasis is indicated, although the agent of choice remains controversial. Fluconazole is the drug of choice for prevention of relapse of cryptococcal meningitis in patients with AIDS. Finally, only limited data exist assessing the relationship between local colonization and systemic fungal infection. Adverse effects associated with antifungal prophylaxis, generally limited to nausea and vomiting and transient elevations in hepatic transaminases, occur with similar frequency among available oral or topical agents. However, the incidence of nausea and vomiting with resultant poor patient tolerance and compliance is usually higher with nystatin.

CONCLUSIONS:

Based on available data from controlled clinical trials, azole agents are currently the most effective and best-tolerated drugs for antifungal prophylaxis in immunocompromised hosts. Choice of one agent in this group over another may be dictated by cost. As new antifungal treatments are released onto the market, these drugs should be compared with existing agents in controlled clinical trials. Future studies should be designed to evaluate the relationship between local colonization and disseminated infection.
Beta-Agonists in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Authors: Dasta Joseph F. , Kuhl David A. , Agiri Olakunbi A. , Mauro Laurie S.
Published: January 2017

OBJECTIVE:

To critically evaluate the following issues regarding the use of beta-agonists in the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD): (1) optimal dose, (2) use of nebulizer (NEB) versus metered-dose inhaler-spacer devices (MDISs), (3) comparison with anticholinergic agents, and (4) use in mechanically ventilated patients. The patient populations addressed are limited primarily to emergency department (ED) and intensive care/acute care settings.

DATA SOURCES:

English-language journal articles published between 1977 and 1993.

STUDY SELECTION:

Nine studies were evaluated that included beta-agonists alone or in combination with other bronchodilators in the treatment of acute exacerbation of COPD. Many of the studies contained design flaws or were limited in size, making interpretation difficult. In studies containing both asthma and COPD patients, focus was restricted to analysis of COPD patients when possible.

DATA EXTRACTION:

Performed subjectively by the authors. Studies were evaluated for methodologic strengths and weaknesses.

DATA SYNTHESIS:

Dosing studies in patients with stable disease show a relationship between dose and the various pulmonary function tests (PFTs). Dose also correlates with duration of action and incidence of adverse effects. Four studies compared NEBs versus MDISs. Studies revealed significant improvement in PFTs for both treatments, with no significant difference between groups noted. Five studies compared various combinations of beta-agonists and ipratropium. Both ipratropium and beta-agonists caused statistically significant increases in PFTs from baseline. Combination therapy provided no further increase in spirometry compared with that of single-agent therapy. One study did report an early discharge from the ED with the addition of ipratropium. Most studies did not use large doses of beta-agonists or evaluate the effect of repeated doses. Many studies allowed concomitant therapy. Most did not include outcome measurements, such as ED length of stay, admission rates, hospital stay, or incidence of relapse.

CONCLUSIONS:

Dose—response studies in patients with stable disease suggest that doses of albuterol powder up to 1 mg may be tolerated safely, although use of repeated larger doses has not been well studied. Beta-agonists given by MDIS or NEB are equally effective in this setting. There is no apparent advantage to combined use of beta-agonist and ipratropium in the acute setting. Future research in this area should evaluate the use of larger or repeated doses of beta-agonists in the acute setting. Optimizing concurrent therapy and evaluating various patient outcomes should receive special attention in further investigations.
Pharmacists' Attitudes toward Adverse Drug Reaction Reporting in Hong Kong
Authors: Lee Kenneth K.C. , Chan Thomas Y.K. , Raymond Kenneth , Critchley Julian A.J.H.
Published: January 2017

OBJECTIVE:

To study the attitudes and knowledge of pharmacists in Hong Kong toward the reporting of adverse drug reactions (ADRs).

METHODS:

In December 1993, all pharmacists who were working in retail shops (n=230), hospitals (n=44), or outpatient clinics (n=12) in Hong Kong were sent a questionnaire as well as a letter explaining the purpose of the survey.

RESULTS:

One hundred and twenty-nine pharmacists (retail pharmacies 40.4 percent, hospitals 68.2 percent, outpatient clinics 50 percent) responded. Although 93 percent of the pharmacists in this survey agreed that it is necessary to report ADRs, a much smaller proportion (14.7 percent) had actually done so in the previous 12 months. Most pharmacists (87.4 percent) were not aware of any ADR reporting system in Hong Kong. There did not appear to be a relationship between ADR reporting and the length or place of practice, workload, or patient contact time. Severe or unusual ADRs and ADRs to new products were perceived to be significant enough to report.

CONCLUSIONS:

The great majority of pharmacists in Hong Kong agreed on the necessity of reporting ADRs. The lack of knowledge of an ADR reporting program might have led to nonreporting in the past. It is important that there be continuing efforts to promote ADR reporting programs.
Cyclosporine and Vancomycin Disposition During Continuous Venovenous Hemodiafiltration
Authors: Munar Myrna Y , Doyle Ian C , Meyer Mary M
Published: January 2017

Objective:

To report cyclosporine and vancomycin disposition during continuous venovenous hemodiafiltration (CVVHD) in a 41—year-old heart transplant patient while in the intensive care unit at a primary and tertiary care teaching hospital.

Case Summary:

The patient received a 60—mg infusion of cyclosporine over 24 hours and vancomycin 1 g over 1 hour. Blood samples subsequently were collected and analyzed using whole blood monoclonal radioimmunoassay and fluorescence polarization immunoassay, respectively. Blood samples were measured every hour from the arterial and venous lines of the apparatus, as were ultrafiltrate drug concentrations. Drug clearance rates into the ultrafiltrate subsequently were calculated.

Discussion:

Measurements of ultrafiltrate detected no cyclosporine. A slight variation existed between arterial and venous drug concentrations, which was not statistically significant (p > 0.05, paired Student's t-test). Analysis of vancomycin samples revealed a steady decline of drug concentration, with 4.75% of the dose eliminated in the ultrafiltrate. Vancomycin arterial and venous concentrations decreased from 24.4 and 23.3 mg/L to 15.7 and 12.3 mg/L, respectively.

Conclusions:

Vancomycin is eliminated by CVVHD and it may be necessary for these patients to receive the drug more frequently. In contrast, cyclosporine is not removed effectively by CVVHD; therefore, replacement doses are not warranted.
Clinafloxacin-Theophylline Drug Interaction
Authors: Matuschka Paul R , Vissing Richard S
Published: January 2017

Objective:

To report an apparent pharmacokinetic interaction between clinafloxacin and theophylline in a patient with chronic obstructive pulmonary disease (COPD).

Case Summary:

A patient with a history of COPD was admitted for a fracture of the right femoral neck. Admission medications included extended-release theophylline 400 mg bid. The initial serum theophylline concentration was 81.03 µmol/L (normal 55—110). A subsequent concentration was subtherapeutic (46.62 µmol/L) and the theophylline dosage was increased to 300 mg tid. Therapeutic steady-state concentrations were achieved. The patient later developed pneumonia and was enrolled in a study of nosocomial acquired pneumonia involving clinafloxacin versus ceftazidime. He was randomized to receive clinafloxacin 200 mg iv ql2h. After clinafloxacin therapy was initiated, the serum theophylline concentration increased into the toxic range (155.96 µmol/L). Theophylline administration was held for 2 doses and the dosage then reduced to 200 mg tid. Serum concentrations decreased to within the therapeutic range.

Discussion:

The fluoroquinolones have been shown to interact with the hepatic metabolism of theophylline and increase serum theophylline concentrations. The quinolone metabolite, 4-oxo-quinolone, inhibits the N-demethylation of theophylline, leading to a decrease in the clearance of theophylline. The resultant rise in theophylline concentrations corresponds with the decrease in clearance and possible toxicity. In our patient, careful monitoring of theophylline concentrations and dosage adjustments resulted in the restoration of therapeutic serum concentrations.

Conclusions:

The observation of this drug interaction between clinafloxacin and theophylline suggests a need for prudent monitoring of theophylline concentrations. Dosage adjustments may be warranted when this combination of medications is used. Such action may prevent significant toxicities and prolonged hospitalization. Further controlled clinical trials in healthy volunteers are needed to substantiate the interaction between clinafloxacin and theophylline.
Sinus Arrest After Administration of Intravenous Metoclopramide
Authors: Malkoff Marc D , Ponzillo John J , Myles Geraldine L , Gomez Camilo R , Cruz-Flores Salvador
Published: January 2017

Background:

Sinus arrest is a rare complication of metoclopramide administration.

Case Description:

A 51-year-old woman developed Guillain-Barre syndrome and severe dysautonomia. Metoclopramide was administered for the treatment of gastroparesis. Sinus arrest followed drug administration on several occasions and on rechallenge.

Conclusions:

After reviewing the literature and discussing possible etiologies for this unusual adverse drug reaction in this setting, we recommend that metoclopramide be used with caution in patients prone to develop bradyarrythmias, particularly those with dysautonomias and Guillain-Barre syndrome.
Torsemide: A Pyridine-Sulfonylurea Loop Diuretic
Authors: Blose Jamie S , Adams Kirkwood F , Patterson J Herbert
Published: January 2017

Objective:

To review the clinical pharmacology of torsemide and to compare it with currently available loop diuretics, particularly furosemide.

Data Sources:

An English-language MEDLINE search, 1985 to October 1994, was used to identify pertinent literature, including review articles.

Data Extraction:

Data from scientific literature were extracted, evaluated, and summarized for presentation. Pivotal and representative studies are discussed relating to the pharmacology, pharmacokinetics, and use of torsemide in patients with congestive heart failure, renal disease, hepatic disease, and hypertension.

Data Synthesis:

Torsemide is a loop diuretic of the pyridine-sulfonylurea class. The bioavailability of torsemide is approximately 80%, with little first-pass metabolism, and torsemide can be given without regard to meals. The serum concentration reaches its peak within 1 hour after oral administration and diuresis lasts approximately 6—8 hours. Torsemide is eliminated both hepatically (80%) and renally (20%) as unchanged drug with an elimination half-life of about 3.5 hours. Because of the high bioavailability, oral and intravenous doses are therapeutically equivalent. Torsemide, and other loop diuretics such as furosemide, are indicated for the treatment of edema associated with congestive heart failure, renal disease, and hepatic disease. They also are indicated for the treatment of hypertension alone or in combination with other antihypertensive agents. Depending on the indication, the recommended initial adult dosage of torsemide is between 5 and 20 mg once daily orally or intravenously. Special dosage adjustments in the elderly are not necessary.

Conclusions:

Torsemide is a loop diuretic similar to furosemide, with similar indications. Torsemide is characterized by good bioavailability and once-daily dosing and, compared with furosemide, provides generally equivalent therapeutic efficacy.