Crisis management strategies.

This paper discusses the different facets of crisis as experienced within the pharmaceutical industry but which are also prevalent throughout other industries. It highlights the importance of early identification and management of crises and issues, which in return are strongly intertwined with a fundamental positive internal corporate climate. A corporate philosophy should always embrace crisis management with the attitude of 'when' and not 'if'; therefore, a company should act today and not tomorrow once a crisis is on its doorstep. Preparation is of utmost importance and there are several items that can be addressed even before a crisis has arisen. Further, this paper also provides guidance on how to deal with the media, what to do and what not to do, and how to appoint the appropriate spokesperson. In this era of fast exchange of information, crisis, which previously may have stayed behind corporate doors, may not do so any longer. Image is very important and should therefore not be risked. Crisis and issue management should therefore be integrated in every company's philosophy and standard operating procedures.     

A clinical database management system.

The processing of Case Report Form data collected in clinical trials is a data processing task unlike any other. Conventional systems approaches to clinical data management are not responsive to user demands and require excessive amounts of manpower to support. The Clinical Data Management System implemented at Merck utilizes Infodata 's Inquire database management software, IBM's CICS communications software, IBM's VSAM file management software, and SAS Institute's SAS software. System flexibility was the paramount consideration when the CDMS was designed. Clinical data at Merck is now processed on a system that provides on-line ad hoc retrieval capabilities through a user friendly query language, and allows for drug specific database designs coupled with a common update and retrieval mechanism.     

Orlistat: new preparation. No hurry . .

(1) Treatments for obesity are disappointing. None has yet shown an effect on morbidity and mortality. Non drug treatments are poorly assessed. Stable long-term weight loss necessitates long-term management. (2) Orlistat, a gastrointestinal lipase inhibitor, is indicated, in combination with a low-calorie diet, for the management of obesity. (3) The assessment file is rather bulky and methodologically sound, at least in terms of the "weight loss" end point. (4) During medium-term trials (12-24 months), orlistat administered at a dose of 120 mg three times a day and combined with dietary intervention had a moderate positive impact on body weight (-3.5 kg on average). (5) No longer-term trials have been done. (6) It is not known whether this drug affects morbidity and mortality linked to obesity. (7) In clinical trials there was an increase in the frequency of breast cancer among patients treated with orlistat. This potential risk is currently being assessed in a specific trial. (8) Gastrointestinal adverse effects are frequent. (9) Treatment is costly.     

Pain management content in curricula of U.S. schools of pharmacy

OBJECTIVES: To identify individuals in schools of pharmacy in the United States who are responsible for covering the topic of pain management in courses for doctor of pharmacy students and to describe how and at what depth pain management is covered in pharmacy school curricula. DESIGN: One-time qualitative assessment. SETTING: Schools of pharmacy in the United States. PARTICIPANTS Twenty-eight faculty members with the rank of professor, associate professor, or assistant professor who had been employed in their current positions for at least 2 years and who were directly involved in preparing and teaching didactic courses that address pain management. INTERVENTION: In-depth telephone interviews. MAIN OUTCOME MEASURES: Qualitative responses to open-ended interview questions. RESULTS: While pain management was included in the curricula of all 28 schools of pharmacy, it was generally covered in a fragmented way, usually as part of presentations on diseases with pain as a prominent feature (e.g., cancer pain addressed during oncology lectures) or as part of discussions of analgesics. Only two schools offered stand-alone courses in pain management, and both of those courses were electives that were taken by an average of 15 students per year. Three-fourths of respondents believed that pain was being given too little emphasis in their schools' curricula. Palliative care and the use of medications in the treatment of cancer pain was not presented in a standardized manner, and respondents were unsure of how the subject was covered in pharmacy law classes. Instruction about the diagnosis of pain, patient assessment, and physical examination was reported as "minimal" by most respondents. Respondents perceived a need for a single, complete reference and teaching resource that would address the entire spectrum of pain management as it applies to pharmacy. CONCLUSION: The topic of pain management is poorly presented and inadequately developed in the curricula of many U.S. schools of pharmacy.     

Mammary cancers and pregnancy.

Uncertainties persist about management and prognosis of mammary cancers that occur during and after pregnancy and during lactation. Pathological features of mammary cancers occurring during pregnancy are the same as those in non-pregnant women and survival rates are comparable. Management should be the same as in non-pregnant patients. Termination of pregnancy does not improve survival but it should be advised if the prognosis is poor. Mastectomy apparently presents little danger to the fetus, though treatment such as chemotherapy and irradiation should be avoided. Women who have received treatment for mammary cancer need not be advised against subsequent pregnancy. Routine ovarian radiation in non-pregnant premenopausal women is not generally to be recommended, since it does not prolong survival and would deprive some of the chance of further pregnancy. In lactating women who develop mammary cancers survival is apparently not adversely affected. Lactation should be suppressed initially and followed by mastectomy. Regimens of immunotherapy, chemotherapy, or radiotherapy may then be begun. Until results of current trials of combined treatments of mammary cancers associated with pregnancy are available, management should be neither aggressive nor tentative. It should be based on a well-balanced concept of applying all available treatments, as in non-pregnant patients.     

Managing antipsychotic-induced parkinsonism.

Notwithstanding the advent of clozapine and other 'atypical' antipsychotic agents, the conventional ('typical') antipsychotic agents remain in widespread use. Antipsychotic-induced parkinsonism is a highly prevalent adverse effect that may result in increased morbidity and noncompliance. Bedside examination is generally sufficient for the detection of the onset of parkinsonism and should be carried out frequently in the first 3 months of treatment. In addition to decreasing patient discomfort, monitoring for antipsychotic-induced parkinsonism also serves to identify the minimally effective dosage required for the individual patient. Several strategies are utilised in the management of antipsychotic-induced parkinsonism including dosage reduction, switching to other antipsychotic agents and the use of antiparkinsonian drugs such as anticholinergic agents and amantadine. Anticholinergic agents remain the mainstay of the pharmacological management of antipsychotic-induced parkinsonism in younger patients. Amantadine is a better tolerated agent for elderly patients, with similar efficacy to the anticholinergic agents. The routine use of prophylactic anticholinergics is not recommended and is clearly contraindicated in the elderly. An individualised risk-benefit assessment is necessary for the younger patient in whom prophylactic use of anticholinergic drugs is considered.     

Postoperative pain management with a patient-controlled transdermal delivery system for fentanyl.

PURPOSE: The efficacy and safety of fentanyl hydrochloride patient-controlled trans-dermal system (PCTS) for management of acute postoperative pain are discussed. SUMMARY: Fentanyl hydrochloride PCTS is a self-contained, needle-free, credit-card-sized fentanyl-delivery system that is worn on the patient's arm or chest. The system uses iontophoretic technology to actively deliver preprogrammed doses of fentanyl into the systemic circulation when activated by the patient on demand. PCTS is as safe and effective as i.v. morphine patient-controlled analgesia and superior to placebo for managing acute postoperative pain. Fentanyl absorption from PCTS is clinically insignificant when the device is not activated. This contrasts with the transdermal fentanyl patch, which delivers fentanyl continuously for 72 hours via passive absorption and is indicated only for use in the management of chronic pain. CONCLUSION: Fentanyl hydrochloride PCTS is a self-contained iontophoretic fentanyl-delivery system that provides patients control over pain management and consistent management of pain without analgesic peaks and troughs.     

Current approaches to the management of osteoporosis in men.

PURPOSE: The epidemiology, pathophysiology, diagnosis, and management of osteoporosis in men are reviewed. SUMMARY: Men with osteoporosis account for approximately one fifth of all patients with osteoporosis, and their morbidity and mortality rates from this disease are higher than in other patients. Guidelines specifically addressing the management of osteoporosis in men are not available. Lifestyle modifications, including smoking cessation, limited alcohol consumption, routine exercise, and fall prevention strategies, are beneficial to maintain bone health. Appropriate calcium and vitamin D intakes are critical components of any osteoporosis management strategy. Drug therapy should be initiated in all men at high risk for fracture. Alendronate is indicated for the treatment of osteoporosis. It is considered first-line therapy because of its efficacy and safety profiles. Teriparatide is indicated for the management of osteoporosis in high-risk men, but the drug's cost, complex administration schedule, and potential risks have caused it to be restricted to a second-line therapy. Other options reserved for select patients include calcitonin and testosterone. Further studies are needed to better understand the distinctive features and management strategies for men with osteoporosis. CONCLUSION: While the rate of osteoporosis in men is lower than in women, the consequences are possibly more devastating. Evaluation of secondary causes, especially hypogonadism, is important, as they can play a significant role in the development of osteoporosis in men. All men should be educated to improve modifiable risk factors and maintain recommended daily intakes of calcium and vitamin D. Bone mineral density should be evaluated in high-risk men using central dual energy x-ray absorptiometry, and drug treatment should be considered in those with a history of low-trauma fracture or significant bone loss.     

Cholesterol risk management: a systematic examination of the gap from evidence to practice.

Hypercholesterolemia is a major risk factor for coronary heart disease, and data indicate that aggressive cholesterol reduction decreases mortality and morbidity associated with this disease. Many patients with hypercholesterolemia, however, are not screened, prescribed appropriate lipid-lowering therapy, or treated to target cholesterol levels. Practice patterns are particularly inadequate for those patients at highest risk for having a cardiac event. We performed a literature search to identify studies of practice patterns in the management of patients with hypercholesterolemia with regard to screening, implementing lipid-lowering therapy, and treating to lipid goals. The findings highlight the potential for substantial opportunities to improve patient outcomes. Future studies should evaluate reasons for suboptimal cholesterol management as well as provide steps to improve management.     

Data quality management in pharmacovigilance.

Pharmacovigilance relies on information gathered from the collection of individual case safety reports and other pharmacoepidemiological data. Even given the inherent limitations of spontaneous reports, the usefulness of this data source can be improved with good data quality management. Although under-reporting cannot be remedied this way, the negative impact of incomplete reports, which is another serious problem in pharmacovigilance, can be reduced.Quality management consists of quality planning, quality control, quality assurance and quality improvements. The pharmacovigilance data processing cycle starts with data collection and, in computerised systems, data entry; the next step is data storage and maintenance; followed by data selection, retrieval and manipulation. The resulting data output is analysed and assessed. Finally, conclusions are drawn and decisions made. The increased knowledge feeds back into the data processing cycle. Focussing on the first three steps of the data processing cycle, the different quality dimensions associated with these steps are described in this review, together with examples relevant to pharmacovigilance data. Functioning, well documented, and transparent quality management systems will benefit not only those involved in data collection, management and output production, but, ultimately, also the pharmacovigilance end users, the patients.     

Role of i.v. allopurinol and rasburicase in tumor lysis syndrome.

The role of i.v. allopurinol and rasburicase in tumor lysis syndrome (TLS) is described. The current standard management for TLS consists of oral allopurinol in conjunction with i.v. hydration with or without alkalinization. Despite this standard prophylactic regimen, some high-risk patients may still develop urate nephropathy from TLS. Recently, i.v. allopurinol and rasburicase became available for the management of TLS. Available data on i.v. allopurinol indicate that the administration schedule and the adverse-effect profile will be similar to the oral formulation. The primary advantage of i.v. allopurinol is the flexibility of administration for patients who cannot take anything by mouth, since there are no data indicating the superiority of the i.v. to the oral product. Rasburicase is the first agent that will oxidize uric acid to allantoin, a metabolite with 5-10-fold greater solubility than uric acid, and reduces serum uric acid (SUA) levels within four hours of administration. Rasburicase is considerably more expensive than standard management strategies and should be reserved for patients with either renal dysfunction, significant elevations in SUA values, or large tumor burdens. Preliminary evidence indicates that rasburicase offers cost savings in the treatment of TLS and is cost-effective as a strategy for preventing TLS for many cancer patients. Both i.v. allopurinol and rasburicase offer additional flexibility in the management of TLS and may allow for further avoidance of the consequences of inadequate management of this syndrome.     

Crystal-associated rheumatic disease. Current management considerations

Safe, effective treatment is available for acute crystal-associated arthropathy. It is time for some older remedies, phenylbutazone and perhaps colchicine, to give way to more modern regimens of combined NSAID therapy and intra-articular steroid injection. Hypouricaemic agents have revolutionised the management of gout but are not without their dangers, and there is a need for re-emphasis on the value of dietary measures and control of alcohol and diuretic use. At present only symptomatic management is available for chronic pyrophosphate- and hydroxyapatite-associated disease.     

Clinical research: regulatory issues.

The regulatory issues faced by institutions performing clinical research are described. Many institutions do not have on staff an expert who understands the regulatory issues involved in managing investigational new drug research and who knows the institution's obligations under the federal rules. Because pharmacists understand the FDA regulations that apply to the management of drugs in clinical research, institutions are asking pharmacists to expand their role and manage clinical research offices. Many authorities govern various aspects of investigational drug research. FDA has published regulations for good clinical practice (GCP), and the International Conference on Harmonisation is developing an international standard for the proper management of clinical trials. The guidelines published by the Joint Commission on Accreditation of Healthcare Organizations aim to protect patients who are in the institution to receive health care and also participate in clinical trials. The Social Security Administration Acts specifically state that only items and services that are reasonable and necessary for the diagnosis and treatment of injury or disease can be billed to the government; research-related billings are excluded from coverage. Proper management of drug research is crucial to the success of a research program that is integrated with patient care.     

Open questions on bioequivalence: some problems and some solutions.

This paper focuses on some specific situations where bioequivalence requires careful attention and tailored protocols in order to overcome intrinsic difficulties either marginally covered or fully neglected by operating guidelines. Some problems congregate with serious difficulties, namely high variability, very poorly absorbed drugs and endogenous substances with their own baseline. With endogenous substances, the dilemma faced is whether to subtract baseline from post-dose values in assessing bioequivalence. Either approach has intrinsic problems and is somewhat puzzling. In an attempt to resolve other existing problems, the most appropriate approach should be selected on a case-by-case basis, ensuring that the adopted procedure does not conflict with operating guidelines and scientific literature on the matter. Problematic cases include the management of trials with a predominant active metabolite, the absence of a reliable analytical bioassay, the availability of various strengths of the same drug on the market, a wide acceptability titre range, the management of studies on topical drugs that are devoid of systemic activity, the management of drugs that cannot be given for ethical reasons to healthy subjects or that may cause adverse events, especially when a steady state design is required. The parallel group study design appears to be more appropriate than the cross-over or the individual bioequivalence design in assessing drugs with a long half-life. Some pharmacokinetic and statistical analysis-related issues are also discussed such as the sequence/period interaction sometimes encountered in these trials, which, in the absence of the carry-over effect, does not bias the bioequivalence results and the need to process data with non-compartmental pharmacokinetic analysis.     

Recent developments in the management of acute respiratory distress syndrome in adults.

PURPOSE: Recent developments in the management of acute respiratory distress syndrome (ARDS) in adults are reviewed. SUMMARY: Corticosteroids have been extensively studied in ARDS; however, they have not demonstrated clear benefit in patients with ARDS. Some trials have found increased complications and mortality related to corticosteroid use. The use of conservative fluid management has been associated with significant reductions in morbidity, highlighting the need to avoid fluid over-administration in patients with ARDS. A number of ventilatory strategies have also been studied. Studies have found that higher positive end-expiratory pressure settings do not appear to be harmful in patients with ARDS. In an effort to prevent alveolar overdistention, low tidal volume and plateau pressure ventilation is increasingly being used in patients with acute lung injury (ALI). Given the increasing evidence supporting the use of lower tidal volume ventilation, this strategy has become the new standard of care in patients with suspected ALI and ARDS. No clear benefit has been shown in the treatment of ARDS with nitric oxide and surfactant. Prostaglandins and acetylcysteine are not considered useful in the treatment of ARDS, while no conclusions can be drawn regarding the benefits of albuterol on mortality in patients with ARDS. The use of prone positioning should be discouraged in the treatment of ARDS based on its associated risks. CONCLUSION: Early administration of moderate-dosage corticosteroids likely helps decrease the time of ventilator dependence and duration of intensive care unit stay. Conservative fluid management and low tidal volume ventilation are becoming increasingly widespread in the management of patients with ARDS. Nitric oxide, surfactant, prostaglandins, albuterol, acetylcysteine, and prone positioning have not been shown to be beneficial in the treatment of ARDS.     

Cancer--an ayurvedic perspective.

An integrated approach is needed to manage cancer using the growing body of knowledge gained through scientific developments. Thousands of herbal and traditional compounds are being screened worldwide to validate their use as anti-cancerous drugs. The science of Ayurveda is supposed to add a step on to the curative aspects of cancers that have resemblance with clinical entities of arbuda and granthi mentioned in Sushrutha samhita. Hence, an attempt is made in this review to discuss about the pathology and therapeutic management of various cancers described in Ayurveda. Review of literature on anticancer drugs of plant origin revealed identification of newer ayurvedic drugs that are not mentioned in the ancient texts. These new findings add up to ayurvedic science that has been developed through ages. In addition, details of experimental and clinical studies conducted on single and compound ayurvedic preparations for their anticancer efficacy strongly emphasize ayurvedic therapy as a scientifically driven one and not simply unconventional.