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Drug Regimens (drug + regimen)
Selected AbstractsAn Approach to Postmenopausal Osteoporosis Treatment: A Case Study ReviewJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 12 2003Cathy Kessenich DSN Purpose To review and discuss the clinical evaluation and therapeutic options for a postmenopausal woman with osteoporosis. Data Sources Review of scientific literature, practice guidelines, and a case study. Conclusions To prevent and treat postmenopausal osteoporosis, women should be encouraged to per-form weight-bearing exercise, to not smoke, and to optimize calcium and vitamin D intake through diet and supplements. Drug regimens are effective and well tolerated in post-menopausal women with osteoporosis. Implications for Practice Drugs currently approved by the U.S. Food and Drug Administration for the treatment of postmenopausal osteoporosis include the bisphosphonates risedronate and alendronate; the selective estrogen receptor modulator, raloxifene; and intranasal calcitonin-salmon spray. Bisphosphonates have demonstrated the most impressive fracture risk reduction in prospective clinical trials of women with post-menopausal osteoporosis. Risedronate has consistently demonstrated significant reductions in vertebral fracture risk at 1 year and in vertebral and nonvertebral fracture risk at 3 years. Alendronate has demonstrated significant reductions in vertebral and nonvertebral fracture risk after 3 years. [source] Metabolic consequences of pancreatic systemic or portal venous drainage in simultaneous pancreas-kidney transplant recipientsDIABETIC MEDICINE, Issue 6 2006P. Petruzzo Abstract Aims The aim was to investigate pancreatic B-cell function and insulin sensitivity in simultaneous pancreas-kidney (SPK) recipients with systemic or portal venous drained pancreas allograft using simple and easy tests. Methods The study included 44 patients with Type 1 diabetes and end-stage renal disease who had undergone SPK transplantation: 20 recipients received a pancreas allograft with systemic venous drainage (S-SPK) and 24 with portal venous drainage (P-SPK). We studied only recipients with functioning grafts, with normal serum glucose, HbA1c and serum creatinine values, on a stable drug regimen. The subjects were studied at 6, 12, 24, 36, 48 and 60 months after transplantation. Insulin sensitivity and B-cell function indices were derived from blood samples and oral glucose tolerance tests. Results All patients from both groups had normal fasting glucose, body mass index and HbA1c values by selection. The homeostatic model (HOMA) ,-cell index was significantly lower in P-SPK recipients at several points of the follow-up. HOMA-IR was significantly higher in S-SPK recipients at 6 and 24 months after transplantation and was positively correlated with fasting insulin values, but never exceeded 3.2. There was no significant difference in QUICKI index values between the two groups. Although all patients from both groups always had normal glucose tolerance, the area under the insulin curve was higher in the S-SPK group. Cholesterol, low-density lipoprotein-cholesterol and triglycerides were higher in the P-SPK group. Conclusions The results suggest sustained long-term endocrine function in both groups and show that portal venous drainage does not offer major metabolic advantages. [source] Outcome after hemispherectomy in hemiplegic adult patients with refractory epilepsy associated with early middle cerebral artery infarctsEPILEPSIA, Issue 6 2009Arthur Cukiert Summary Purpose:, To study the outcome after hemispherectomy (HP) in a homogeneous adult patient population with refractory hemispheric epilepsy. Methods:, Fourteen adult patients submitted to HP were studied. Patients had to be at least 18 years old, and have refractory epilepsy, clearly focal lateralized seizures and unilateral porencephalus consistent with early middle cerebral artery infarct on magnetic resonance imaging (MRI). All patients were submitted to functional hemispherectomy. We analyzed age of seizure onset, age by the time of surgery, gender, seizure type and frequency, interictal and ictal electroencephalography (EEG) findings, MRI and IQ scores preoperatively; seizure frequency, drug regimen, and IQ outcome were studied postoperatively. Results:, Mean follow-up was 64 months. All patients had frequent daily seizures preoperatively. All patients had unilateral simple partial motor seizures (SPS); 11 patients had secondarily generalized tonic,clonic (GTC) seizures and five patients had complex partial seizures (CPS), preoperatively. All patients had hemiplegia and hemianopsia. Twelve patients had unilateral EEG findings, and in two epileptic discharges were seen exclusively over the apparently normal hemisphere. Twelve patients were seizure-free after surgery and two patients had at least 90% improvement in seizure frequency. Pre- and postoperative mean general IQ was 84 and 88, respectively. Five of the twelve Engel I patients were receiving no drugs at last follow-up. There was no mortality or major morbidity. Conclusions:, Our results suggest that well-selected adult patients might also get good results after HP. Although good results were obtained in our adult series, the same procedure yielded a much more striking result if performed earlier in life. [source] Focal Semiologic and Electroencephalographic Features in Patients with Juvenile Myoclonic EpilepsyEPILEPSIA, Issue 10 2005Naotaka Usui Summary:,Purpose: A few reports have described focal electroencephalographic or clinical features or both of juvenile myoclonic epilepsy (JME), but without video-EEG documentation. We examined focal clinical and EEG features in patients with JME who underwent video-EEG monitoring. Methods: Twenty-six patients (nine males and 17 females) who had seizures recorded during video-EEG monitoring were included. Age at seizure onset was 0 to 22 years (mean, 12.3 years), and age at monitoring was 12 to 44 years (mean, 26.5 years). In one patient with left parietooccipital epilepsy, primary generalized tonic,clonic seizures developed after resection of the parietal tumor. Two patients had both temporal lobe epilepsy and JME. Videotaped seizures in each patient were analyzed. Interictal and ictal EEG also were analyzed for any focal features. Results: Focal semiologic features were observed in 12 (46%) of 26 patients. Six patients had focal myoclonic seizures, and two had Figure 4 sign: one with version to the left, and another had left version followed by Figure 4 sign, and left arm clonic seizure. Their ictal EEGs were generalized at onset but with a lateralized evolution over the right hemisphere. The patient who had both JME and left parietooccipital epilepsy, right arm clonic seizure, and Figure 4 sign was seen during a generalized EEG seizure. Interictally, one patient had temporal sharp waves, and another had run of spikes in the right frontal region. Conclusions: Fourteen (54%) of 26 patients with JME exhibited focal semiologic or electroencephalographic features or both. Video-EEG was essential in reaching a correct diagnosis and choosing an appropriate antiepileptic drug regimen. [source] Multifactorial approach and adherence to prescribed oral medications in patients with type 2 diabetes,INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2006J. F. Mateo Summary The aims of this study were to assess adherence to oral hypoglycaemic/cardiovascular drugs and determine non-adherence predictors in type 2 diabetes patients. It was designed as a population-based cross-sectional study in which 90 patients from a primary care setting were studied. Pill count and self-report methods were used to measure adherence. Logistic regression analysis was performed to predict factors related to non-adherence. Adequate adherence to all drugs was found in 29 patients (35.4%; 95% confidence interval (CI) 25.0,45.7). Variables associated with non-adherence were HbA1c odds ratio (OR) 2.32 (95% CI: 1.09,4.95), systolic blood pressure OR 1.68 (95% CI: 1.08,2.62), total cholesterol OR 1.34 (95% CI: 1.08,1.66), number of pills OR 1.80 (95% CI: 1.26,2.55) and duration of disease OR 0.44 (CI 95%: 0.24,0.83). In conclusion, one in three patients had adequate adherence. Factors associated with non-adherence were duration of disease, complexity of drug regimen and inadequate control of cardiovascular risk factors. [source] A study of dietary advice and care provided to HIV positive patients referred for lipid lowering: as part of a service improvement initiativeJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 4 2008N.A. Billing Background:, Combination antiretroviral therapy (ART) has dramatically reduced mortality in HIV-infected patients. As life expectancy of HIV infected patients has increased, concerns about the long-term effects of treatment grow (Sax, 2006). HIV positive patients have a greater risk of myocardial infarction (MI) and ART has been associated with a 26% increase in the rate of MI per year of exposure (DAD Study Group, 2003). The aim of this study was to evaluate provision of dietetic care to patients referred for lipid lowering advice and identify potential areas for service improvement. Methods:, Departmental activity statistics identified 117 new clients referred for lipid lowering advice in the previous 11 months. The biochemical data and dietetic record cards were screened, of the initial sample 30 were excluded as they did not have follow up biochemistry after their dietetic consultation and a further seven were excluded as they were seen primarily for other conditions. The remaining cards (n = 80) had their dietetic record cards audited to check dietary topics discussed, risk factors identified length before follow up and clinical outcomes. Results:, There were 68 men and 12 women in this sample with a mean age of 46 years and mean body mass index (BMI) of 25.4 kg m,2 (3.7 kg m,2). Of the clients referred, only 48.8% of the sample had high density lipoprotein (HDL): cholesterol ratios taken to calculate cardiovascular risk and most patients were seen an average of 30.7 days (35.3 days) after high was identified. Following their dietetic consultation, 77% of clients had a reduction in their cholesterol levels and 61% had a reduction in triglyceride levels. This sample's average percentage change in cholesterol was ,10% (16%) and triglyceride was ,6% (32%). The most popular dietary advice was reducing saturated fat intake (90%), increasing fibre intake (76%), benefits of plant stanols (40%), importance of regular meals (29%), exercise (26%) and benefits of omega three (11%). Additional risk factors identified 11% of clients seen were smokers, however most records (66%) did not have documentation on whether smoking behaviour was discussed. Only 20% of clients had a follow up appointments and not all were seen within 3 months with average time between follow up being 14.9 weeks (13.2 weeks). Discussion:, Improvement in biochemical results were comparable to a study by Henry et al., (1998) which showed that in HIV infected clients receiving ART, diet modification and increased exercise were successful in reducing cholesterol levels by 11% and triglyceride levels by 21%. The level of smoking was considerably lower than other studies (DAD Study Group, 2003) which reported 56% of HIV positive clients to be smokers. A large number of clients were lost to follow up and were not seen within 3 months. Lazzaretti et al., (2007) showed in a randomized trial that seeing patients at regular 3 month intervals for dietary intervention prevented an increase in lipid blood levels in individuals who start ART. Conclusions:, Not all clients are having their cardiovascular risk calculated before referral for dietary advice. Clients are not being seen at regular intervals by dietitians, some are lost to follow up and smoking status is not regularly documented during dietetic consultation. References, Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group. (2003) Combination antiretroviral therapy and the risk of myocardial infarction. N. Engl. J. Med.349, 1993,2003. Friis-Moller, N., Weber, R., Reiss, P., Thiebaut, R., Kirk, O., d'Arminio, M.A. et al. (2003) Cardiovascular disease risk factors in HIV patients' association with antiretroviral therapy. Results from the DAD study. AIDS17, 1179,1193. Henry, K., Melroe, H., Huebesch, J., Hermundson, J. & Simpson, J. (1998) Atorvastatin and gemfibrozil for protease inhibitor-related lipid abnormalities. Lancet352, 1031,1032. Sax, P.E. (2006)Strategies for management and treatment of dyslipidemia in HIV/AIDS. AIDS Care 18, 149,157. Lazzaretti, R., Pinto-Ribeiro, J., Kummer, R., Polanczyk, C. & Sprinz, E. (2007) Dietary intervention when starting HAART prevents the increase in lipids independently of drug regimen: a randomized trial. Oral abstract session: 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention: Abstract no.WEAB303. [source] Use of Malaria Prevention Measures by North American and European Travelers to East AfricaJOURNAL OF TRAVEL MEDICINE, Issue 4 2001Hans O. Lobel Background: The use of preventive measures, including effective chemoprophylaxis, is essential for protection against malaria among travelers. However, data have shown that travelers and medical advisors are confused by the lack of uniform recommendations and numerous prophylactic regimens of varying effectiveness that are used. Methods: To assess the use and type of preventive measures against malaria, we conducted a cross-sectional study in 1997 among travelers departing from the Nairobi and Mombasa airports in Kenya with European destinations. Results: Seventy-five percent of the travelers studied were residents of Europe and 25% were residents of North America; all stayed less than 1 year, and visited malarious areas. Most travelers, 97.1%, were aware of the risk and 91.3% sought pretravel medical advice. Although 95.4% used chemoprophylaxis and/or antimosquito measures, only 61.7% used both regular chemoprophylaxis and two or more antimosquito measures. Compliance with chemoprophylaxis was lowest amongst those who used a drug with a daily, as opposed to, a weekly dosing schedule, stayed more than 1 month, attributed an adverse health event to the chemoprophylaxis, and were less than 40 years of age. Among US travelers, 94.6% of those taking chemoprophylaxis were taking an effective regimen, that is, mefloquine or doxycycline. Only 1.9% used a suboptimal drug regimen, such as chloroquine/proguanil. Among European travelers, 69% used mefloquine or doxycycline, and 25% used chloroquine/proguanil. Notably, 45.3% of travelers from the UK used chloroquine/proguanil. Adverse events were noted by 19.7% of mefloquine users and 16.4% of travelers taking chloroquine/proguanil. Neuropsychologic adverse events were reported by 7.8% of users of mefloquine and 1.9% of those taking chloroquine/proguanil. The adverse events, however, had a lesser impact on compliance than frequent dosing schedule. Conclusions: Health information should be targeted to travelers who are likely to use suboptimal chemoprophylaxis or may be noncompliant with prophylaxis. Uniform recommendations for effective chemoprophylaxis with simple dosing schedules are necessary to reduce rates of malaria among travelers to Africa. [source] Evaluating provider prescribing practices for the treatment of tuberculosis in Virginia, 1995 to 1998: An assessment of educational needTHE JOURNAL OF CONTINUING EDUCATION IN THE HEALTH PROFESSIONS, Issue 3 2000Nicole L. Richardson BA Abstract Background: Although the use of epidemiologic studies to demonstrate learning needs appears to be infrequent, this study addressed the discrepancies in the prescribing practices for the initial treatment of tuberculosis in Virginia between public and private clinicians, comparing them with the treatment regimens recommended by the Centers for Disease Control and Prevention and the American Thoracic Society (CDC-ATS). Methods: Data examined were the 1995 to 1998 reported cases of tuberculosis within the Commonwealth of Virginia. The study population consisted of 770 laboratory-confirmed tuberculosis cases, living in Virginia, whose isolates were tested for isoniazid susceptibility and were prescribed an initial drug regimen. Prevalence rates, prevalence odds ratios, and logistic regression were used to determine the estimated risk for receipt of the CDC-ATS treatment regimen. Results: Of the 770 cases, 28.7% did not receive the CDC-ATS recommended drug regimen. Prevalence rates and odds for not receiving the recommended regimen were highest among persons of United States origin, Caucasians, females, persons under age 15, and persons from the southwest region of Virginia. Logistic regression indicated a slight increase in the estimated risk of not receiving the CDC-ATS regimen from a private physician (OR: 1.40; CI: 0.97, 2.04) when compared to a public physician. Findings: Private tuberculosis care providers were less compliant with CDC-ATS guidelines than public tuberculosis care providers. Because providers did not follow the recommended treatment guidelines universally, it is advised that all tuberculosis care providers in Virginia would benefit from increased education regarding adequate treatment regimens for tuberculosis and the prevention of multidrug-resistant tuberculosis. [source] In vivo microfocal computed tomography and micro,magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the ratARTHRITIS & RHEUMATISM, Issue 9 2010Michael D. Jones Objective To determine whether treatment with an antiresorptive drug in combination with an antiinflammatory drug reduces periarticular bone and soft tissue adaptations associated with the progression of posttraumatic secondary osteoarthritis (OA). Methods We used in vivo microfocal computed tomography (micro-CT) to map bony adaptations and in vivo micro,magnetic resonance imaging (micro-MRI) to examine joint inflammation in a rat model of surgically induced OA secondary to knee triad injury. We examined the arthroprotective effects of the bisphosphonates alendronate and risedronate and the nonsteroidal antiinflammatory drug (NSAID) meloxicam. Results Micro-CT revealed reduced levels of periarticular trabecular bone loss in animals with knee triad injury treated with the bisphosphonate drugs alendronate or risedronate, or the NSAID meloxicam, compared with untreated animals. Alendronate treatment reduced bony osteophyte development. While risedronate as a monotherapy did not positively impact osteophytogenesis, combination therapy with risedronate and meloxicam reduced osteophyte severity somewhat. Micro-MRI revealed an increased, diffuse water signal in the epiphyses of untreated rats with knee triad injury 8 weeks after surgery, suggestive of a bone marrow lesion,like stimulus. In contrast, meloxicam-treated rats showed a significant reduction in fluid signal compared with both bisphosphonate-treated groups 8 weeks after surgery. Histologic analysis qualitatively confirmed the chondroprotective effect of both bisphosphonate treatments, showing fewer degradative changes compared with untreated rats with knee triad injury. Conclusion Our findings indicate that select combinations of bisphosphonate and NSAID drug therapy in the early stages of secondary OA preserve trabecular bone mass and reduce the impact of osteophytic bony adaptations and bone marrow lesion,like stimulus. Bisphosphonate and NSAID therapy may be an effective disease-modifying drug regimen if administered early after the initial injury. [source] Epitope-specific immunotherapy of rheumatoid arthritis: Clinical responsiveness occurs with immune deviation and relies on the expression of a cluster of molecules associated with T cell tolerance in a double-blind, placebo-controlled, pilot phase II trial,ARTHRITIS & RHEUMATISM, Issue 11 2009Eva C. Koffeman Objective Induction of immune tolerance to maintain clinical control with a minimal drug regimen is a current research focus in rheumatoid arthritis (RA). Accordingly, we are developing a tolerization approach to dnaJP1, a peptide part of a pathogenic mechanism that contributes to autoimmune inflammation in RA. We undertook this study to test 2 hypotheses: 1) that mucosal induction of immune tolerance to dnaJP1 would lead to a qualitative change from a proinflammatory phenotype to a more tolerogenic functional phenotype, and 2) that immune deviation of responses to an inflammatory epitope might translate into clinical improvement. Methods One hundred sixty patients with active RA and with immunologic reactivity to dnaJP1 were enrolled in a pilot phase II trial. They received oral doses of 25 mg of dnaJP1 or placebo daily for 6 months. Results The dnaJP1 peptide was safe and well-tolerated. In response to treatment with dnaJP1, there was a significant reduction in the percentage of T cells producing tumor necrosis factor , and a corresponding trend toward an increased percentage of T cells producing interleukin-10. Coexpression of a cluster of molecules (programmed death 1 and its ligands) associated with T cell regulation was also found to be a prerequisite for successful tolerization in clinical responders. Analysis of the primary efficacy end point (meeting the American College of Rheumatology 20% improvement criteria at least once on day 112, 140, or 168) showed a difference between treatment groups that became significant in post hoc analysis using generalized estimating equations. Differences in clinical responses were also found between treatment groups on day 140 and at followup. Post hoc analysis showed that the combination of dnaJP1 and hydroxychloroquine (HCQ) was superior to the combination of HCQ and placebo. Conclusion Tolerization to dnaJP1 leads to immune deviation and a trend toward clinical efficacy. Susceptibility to treatment relies on the coexpression of molecules that can down-regulate adaptive immunity. [source] PERSONAL DIGITAL VIDEO: A METHOD TO MONITOR DRUG REGIMEN ADHERENCE DURING HUMAN CLINICAL INVESTIGATIONSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2006Chad C Carroll SUMMARY 1Maintaining patient adherence to a drug regimen has proven to be difficult. Missed doses can impact drug efficacy and disease control, leading to increased health-care costs. 2During clinical drug trials, poor adherence could lead to false conclusions regarding drug efficacy. Therefore, the purpose of the present study was to determine the feasibility of using personal digital video cameras to monitor adherence to a medication regimen during a clinical investigation. 3Older men and women (60,78 years) participated in a double-blind, placebo-controlled trial to determine the effect of ibuprofen or paracetamol on skeletal muscle adaptations to chronic resistance exercise training. Patients took three daily doses of either a placebo or the maximal daily over-the-counter dose of ibuprofen (1.2 g/day) or paracetamol (4.0 g/day) for 12 weeks. Prior to beginning the study, subjects were trained to use a personal digital video camera to record their drug consumption. 4Subjects correctly recorded 4956 of 5375 doses, resulting in an average camera compliance rate of 92% (71,100%). 5We describe a method of monitoring adherence to a prescribed drug regimen during a clinical investigation. Camera compliance rates, which directly confirm drug consumption, were higher than what is typically obtained with other methods of monitoring adherence. This camera compliance method provides the investigator with a simple and convenient means to generate direct evidence of drug consumption. [source] Therapy of HIV infectionDERMATOLOGIC THERAPY, Issue 6 2004Yuchi C. Chang ABSTRACT:, HIV is a devastating disease caused by the human immunodeficiency virus. Symptoms of illness can manifest in every organ system, including the skin. Although there is no definitive cure, the creation of antiretroviral drugs and aggressive treatment regimens have dramatically altered disease morbidity and mortality. However, the precise drug selection is often difficult and intimidating given the sheer abundance of drug therapies available. In this article, the HIV disease course is reviewed and different classes of antiretroviral medications are presented with emphasis on initial drug regimens, potential adverse effects, particularly those of dermatologic nature, possible drug interactions, patient compliance, and the emergence of drug resistance. [source] Interactions between microvascular and macrovascular disease in diabetes: pathophysiology and therapeutic implicationsDIABETES OBESITY & METABOLISM, Issue 6 2007Andrew J. Krentz Convention partitions the complications of diabetes into two main subtypes. First are the diabetes-specific microvascular complications of retinopathy, nephropathy and neuropathy; second are the atherothrombotic macrovascular complications that account for the majority of premature deaths. Pathological interactions between microvascular and macrovascular complications, for example, nephropathy and macrovascular disease, are common. Similar mechanisms and shared risk factors drive the development and progression of both small and large vessel disease. This concept has therapeutic implications. Mounting evidence points to the need for multifactorial strategies to prevent vascular complications in subjects with diabetes and/or the metabolic syndrome. We advocate a combined therapeutic approach that addresses small and large vessel disease. Preferential use should be made of drug regimens that (i) maximize vascular protection, (ii) reduce the risk of iatrogenic vascular damage and (iii) minimize the increasing problem of polypharmacy. [source] Immune tolerance induction in patients with haemophilia A with inhibitors: a systematic reviewHAEMOPHILIA, Issue 4 2003J. Wight Summary., In some patients with haemophilia A, therapeutically administered factor VIII (FVIII) comes to stimulate the production of antibodies (inhibitors) which react with FVIII to render it ineffective. As a result, FVIII cannot be used prophylactically and patients become liable to recurrent bleeds. There are two elements to the management of patients with inhibitors: the treatment of bleeding episodes, and attempts to abolish inhibitor production through the induction of immune tolerance. This paper reports a systematic review of the best available evidence of clinical effectiveness in relation to immune tolerance induction (ITI) in patients with haemophilia A with inhibitors. Owing to the lack of randomized controlled trials on this topic, broad inclusion criteria with regard to study design were applied in order to assess the best available evidence for each intervention. As a result of the clinical and methodological heterogeneity of the evidence, it was not appropriate to pool data across studies; instead, data were synthesized using tabulation and qualitative narrative assessment. The International Registry provides the most reliable estimate of the proportion of successful cases of ITI [48.7%, 95% confidence interval (CI) 42.6,52.7%]. The duration of effect is unclear, but relapses appear to be infrequent. The International Registry shows a rate of relapse of 15% at 15 years. The comparative effectiveness of different protocols is uncertain, as no trials have been undertaken which compare them directly. However, the evidence suggests that the Bonn protocol may be more effective than the Malmö or low-dose protocols. There is no good evidence that immunosuppressive drug regimens are effective. [source] Efficacy of splenectomy for hypersplenic patients with advanced hepatocellular carcinomaHEPATOLOGY RESEARCH, Issue 12 2008Masashi Hirooka Aim:, Chemotherapy for advanced hepatocellular carcinoma (HCC) patients with hypersplenism is generally unsatisfactory, as a lower-dose therapy is usually administered. Splenectomy may represent a better approach to overcoming the complication due to hypersplenism in patients with advanced HCC. This retrospective study was conducted to evaluate whether HCC patients who undergo splenectomy show improved prognosis. Methods:, We examined 34 HCC patients. Twenty-two had thrombocytopenia and/or leucopenia and underwent laparoscopic splenectomy. The completion rate of full-dose drug regimens, the response rate, the toxicity of chemotherapy and the cumulative survival rate were compared between the splenectomy and non-splenectomy groups. Results:, The response rate and the cumulative survival rate in the splenectomy group were significantly better than that in the non-splenectomy group. Conclusions:, Splenectomy is an efficient method for advanced HCC patients with hypersplenism treated by chemotherapy. [source] Evidence for prolonged clinical benefit from initial combination antiretroviral therapy: Delta extended follow-upHIV MEDICINE, Issue 3 2001Delta Coordinating Committee Background The findings from therapeutic trials in HIV infection with surrogate endpoints based on laboratory markers are only partially relevant for clinical decisions on treatment. Although the collection of clinical follow-up data from such a trial would be relatively straightforward, this rarely occurs. An important reason for this may be the perception that such data have little value because the number of participants remaining on their original allocated therapy has usually fallen substantially. Methods Delta was an international, multicentre trial in which 3207 HIV infected individuals were randomly allocated to treatment with zidovudine (ZDV) alone, ZDV combined with didanosine (ddI) or ZDV combined with zalcitabine (ddC). Although the trial closed in September 1995, information on vital status, AIDS events, treatment changes and CD4 counts was still collected every 12 months until at least March 1997. This has allowed analyses of the longer term clinical effect of treatment. Results The median follow-up to date of death or last known vital status was 43 months (10th percentile 18 months; 90th percentile 55 months). The proportion of participants remaining on their allocated treatment fell steadily over time; by 4 years after trial entry, 3% remained on ZDV, 20% on ZDV + ddI and 21% on ZDV + ddC. Changes mainly involved the stopping, addition or switching of a nucleoside reverse transcriptase inhibitor (NRTIs). There was little use of protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) before the third year of the trial. Between the third and fourth years, regimens included a drug from one of these classes for approximately 17% of person-time in all treatment groups. Relative to ZDV monotherapy, the beneficial effects of combination therapy on mortality and disease progression rates increased significantly with time since randomization. The maximum effects on mortality were observed between 2 and 3 years, with a 48% reduction for ZDV + ddI and a 26% reduction for ZDV + ddC. These rates were observed when the original allocated treatment was received 42% and 47% of the time in the ZDV + ddI and ZDV + ddC groups, respectively. The mean CD4 count remained significantly higher (approximately 50 cells/,L) in the combination therapy groups 4 years after randomization, suggesting a projection of a clinical benefit beyond this time point. Conclusions The sustained clinical effect of the initial allocation to combination therapy, particularly ZDV + ddI, was remarkable in light of the convergence of drug regimens actually received across the three treatment groups. Interpretation of this finding is not straightforward. One of the possible explanations is that the effectiveness of ddI and ddC is diminished if first used later in infection or with greater prior exposure to ZDV, although the data do not clearly support either hypothesis. This analysis highlights the value of long-term clinical follow-up of therapeutic trials in HIV infection, which should be considered in the planning of all new studies. [source] Detection of Cryptosporidium parvum in lettuceINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 4 2007John E. Moore Summary Human cryptosporidiosis has emerged as an important gastrointestinal infection in the 1990s as a result of the ingestion of mainly contaminated water and to a lesser extent foodstuffs containing the protozoan parasite, Cryptosporidium parvum. This pathogen has particular clinical significance for immunocompromised persons, including AIDS patients and cancer patients receiving toxic chemotherapeutic drug regimens. There have been a limited number of studies performed examining the occurrence of the parasite on vegetables, including lettuce. Detection rates are very dependent on the laboratory isolation technique employed and has ranged from 1.2% to 14.5%. Current best practice of laboratory recovery, isolation and detection methods include detergent removal, oocysts concentration by immunomagnetic separation, followed by a combination of immunofluorescent microscopy and a nested PCR approach. Employment of contaminated non-potable water in the production of vegetables, particularly lettuce, may represent an important potential source of entry of pathogens into food processing and the human food chain. Given that lettuce is an important constituent of hamburger dressing, and the size of the fast-food industry, where lettuce is an important constituent, horticultural producers of lettuce should therefore place special emphasis on developing suitable and efficient Hazard Analysis Critical Control Point strategies for the critical control of oocysts depending on the type of unit operation employed and vegetable being processed. This review aims to examine (i) the incidence of C. parvum in vegetables, particularly lettuce and (ii) laboratory detection methods for the isolation and identification of this parasite from lettuce. [source] Risk factors for drug-induced gingival overgrowthJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 4 2000R. A. Seymour Abstract Background/Aims: Drug-induced gingival overgrowth remains a significant problem for the periodontologist. Many patients medicated with the drugs implicated in this unwanted effect experience significant, recurrent gingival problems that require repeated surgical excisions. In this review, we attempt to identify and quantify the various "risk factors" associated with both the development and expression of the drug-induced gingival changes. Method: The risk factors appraised include age, sex, drug variables, concomitant medication, periodontal variables and genetic factors. Elucidation of such factors may help to identify "at risk patients" and then develop appropriate treatment strategies. Results: Of the factors identified, the only one that can be affected by the periodontologist is the patents' periodontal condition. However, drug variables and concomitant medication do impact upon the expression of gingival overgrowth. Conclusion: The identificatioin of risk factors associated with both the prevalence and severity of drug-induced gingival overgrowth is important for all parties involved with this unwanted effect. Both periodontologist and patient have an important rôle to play in improving oral hygiene and gingival health. Likewise, there is always an opportinity to establish a close liaison between the patient's physician and the periodontologist to try and identify alternative drug regimens that can help reduce the impact of this unwanted effect. [source] The efficacy of orally dosed ketamine and ketamine/medetomidine compared with intramuscular ketamine in rhesus macaques (Macaca mulatta) and the effects of dosing route on haematological stress markersJOURNAL OF MEDICAL PRIMATOLOGY, Issue 3 2008Andrew N Winterborn Abstract Background, This study compared the efficacy of two orally-dosed (PO) anaesthetic regimens for chemical immobilization in rhesus macaques (Macaca mulatta), versus the standard protocol of intramuscular (TM) ketamine. In addition, the effects of dosing route on haematological stress markers were evaluated. Methods, Testing was conducted on 18 chronically housed animals. Animals were trained to accept oral dosing and then randomly assigned to one of three drug regimens: (1) ketamine IM, (2) ketamine PO, (3) Ketamine/medetomidine PO. Sedation levels for each regimen were evaluated. Results, Oral dosing alone was not sufficient to achieve a plane of sedation that allowed for safe handling. Serum cortisol and glucose levels were unchanged across groups, although differences were observed in the leukogram profiles. Conclusion, The oral dosages used in this study fell short in providing adequate sedation for safe handling for routine veterinary procedures. Leukogram profiles indicated that orally dosed animals experienced a higher level of stress. [source] Malaria in Brazilian Military Personnel Deployed to AngolaJOURNAL OF TRAVEL MEDICINE, Issue 5 2000COL L. Jose Sanchez Background: Malaria represents one of the most important infectious disease threats to deployed military forces; most personnel from developed countries are nonimmune personnel and are at high risk of infection and clinical malaria. This is especially true for forces deployed to highly-endemic areas in Africa and Southeast Asia where drug-resistant malaria is common. Methods: We conducted an outbreak investigation of malaria cases in Angola where a total of 439 nonimmune Brazilian troops were deployed for a 6-month period in 1995,1996. A post-travel medical evaluation was also performed on 338 (77%) of the 439 soldiers upon return to Brazil. Questionnaire, medical record, thick/thin smear, and serum anti- Plasmodium falciparum antibody titer (by IFA) data were obtained. Peak serum mefloquine (M) and methylmefloquine (MM) metabolite levels were measured in a subsample of 66 soldiers (42 cases, 24 nonmalaria controls) who were taking weekly mefloquine prophylaxis (250 mg). Results: Seventy-eight cases of malaria occurred among the 439 personnel initially interviewed in Angola (attack rate = 18%). Four soldiers were hospitalized, and 3 subsequently died of cerebral malaria. Upon return to Brazil, 63 (19%) of 338 soldiers evaluated were documented to have had clinical symptoms and a diagnosis of malaria while in Angola. In addition, 37 (11%) asymptomatically infected individuals were detected upon return (< 1% parasitemia). Elevated, post-travel anti- P. falciparum IFA titers (, 1:64) were seen in 101 (35%) of 292 soldiers tested, and was associated with a prior history of malaria in-country (OR = 3.67, 95% CI 1.98,6.82, p < .001). Noncompliance with weekly mefloquine prophylaxis (250 mg) was associated with a malaria diagnosis in Angola (OR = 3.75, 95% CI 0.97,17.41, p = .03) but not with recent P. falciparum infection (by IFA titer). Mean peak levels (and ratios) of serum M and MM were also found to be lower in those who gave a history of malaria while in Angola. Conclusions: Malaria was a significant cause of morbidity among Brazilian Army military personnel deployed to Angola. Mefloquine prophylaxis appeared to protect soldiers from clinical, but not subclinical, P. falciparum infections. Mefloquine noncompliance and an erratic chemoprophylaxis prevention policy contributed to this large outbreak in nonimmune personnel. This report highlights the pressing need for development of newer, more efficacious and practical, prophylactic drug regimens that will reduce the malaria threat to military forces and travelers. [source] Medication Quantification Scale Version III: Internal Validation of Detriment Weights Using a Chronic Pain PopulationPAIN PRACTICE, Issue 1 2008Michael Gallizzi MS ,,Abstract Introduction: We report an internal validation of the Medication Quantification Scale (MQS III) using a chronic pain population. The MQS was designed as a methodology of quantifying different drug regimens in 1992, updated in 1998 (MQS II), and again updated in 2003 (MQS III) using "detriment" weights determined by surveying physician members of the American Pain Society. The MQS has been used as a unitary clinical and research outcome. Methods: A retrospective chart review was collected from 400 patients in an interdisciplinary outpatient chronic pain clinic. A linear regression equation was developed using the patients' composite MQS III score, and those values were used in a Pearson correlation analysis. Results: The correlation between the subjects' computed regression detriment weights and the corresponding MQS III detriment weights yielded a significant result (r = 0.962, P < 0.01; two-tailed). Discussion: Our chronic pain sample-derived detriment weights did differ in some drug classes from that of the physician consensus, most notably the selective serotonin reuptake inhibitor, Opioid Schedule II, and NSAID class detriment. It is necessary to periodically resurvey large groups of physicians in order to control and modify the detriment weights of our categories in light of new information about detrimental effects (eg, COX-2 inhibitors), or to accommodate medical or political changes in prescribing habits (eg, more liberal opioid prescribing in the later years). This work suggests it may also be important to assess patients' perspective on detriment, as well as statistical and empiric use patterns.,, [source] Refill adherence and polypharmacy among patients with type 2 diabetes in general practicePHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 11 2009Rykel van Bruggen PhD Abstract Background and Aims Non-adherence is considered a major barrier to better outcomes of diabetes care. A relationship has been established between polypharmacy and patients' adherence. This study aims to investigate the occurrence of polypharmacy and non-adherence in general practice, their mutual relationship and the association between adherence and the intermediate outcomes of diabetes care. Materials and Methods We used the baseline and follow-up data of a randomised controlled trial (RCT) that compared usual care with care in accordance with a locally adapted national guideline. This study took place in the Netherlands and involved 30 general practices and 1283 patients. We obtained a complete medication profile of all participants and calculated the number of prescribed drugs and the adherence indices (AI) for oral blood glucose, blood pressure and cholesterol lowering drugs. Patients with an adherence index <,0.8 were considered non-adherent. Clustering at practice level and case-mix were taken into account. Results Approximately 80% of the participating patients demonstrated an adherence index ,,0.8 for oral blood glucose, blood pressure and cholesterol lowering drugs. In the intervention group, increase of drug prescriptions exceeded that of controls (1.1,±,2.0 vs. 0.6,±,1.5, p,<,0.001, adjusted p,<,0.05). There was evidence of an inverse relationship between the number of drugs that had been prescribed during the last 6 months of the study and patients' adherence to blood pressure lowering medications (adjusted OR 0.84, 95%CI 0.78,0.91). After one year, HbA1c and total cholesterol levels were significantly lower in adherent patients. Conclusion During the intervention the mean number of drug prescriptions increased in both the study groups. This did not result in a lower adherence to blood glucose and cholesterol lowering medications. Given the relationship between the number of medications and patients' adherence to blood pressure lowering drugs, it may be wise to discuss adherence before prescribing multiple drug regimens. Copyright © 2009 John Wiley & Sons, Ltd. [source] Antituberculosis drugs and hepatotoxicityRESPIROLOGY, Issue 6 2006Wing Wai YEW Abstract: Isoniazid, pyrazinamide and rifampicin have hepatotoxic potential, and can lead to such reactions during antituberculosis chemotherapy. Most of the hepatotoxic reactions are dose-related; some are, however, caused by drug hypersensitivity. The immunogenetics of antituberculosis drug-induced hepatotoxicity, especially inclusive of acetylaor phenotype polymorphism, have been increasingly unravelled. Other principal clinical risk factors for hepatotoxicity are old age, malnutrition, alcoholism, HIV infection, as well as chronic hepatitis B and C infections. Drug-induced hepatic dysfunction usually occurs within the initial few weeks of the intensive phase of antituberculosis chemotherapy. Vigilant clinical (including patient education on symptoms of hepatitis) and biochemical monitoring are mandatory to improve the outcomes of patients with drug-induced hepatotoxicity during antituberculosis chemotherapy. Some fluoroquinolones like ofloxacin/levofloxacin may have a role in constituting non-hepatotoxic drug regimens for management of tuberculosis (TB) in the presence of hepatic dysfunction. Isoniazid administration is currently the standard therapy for latent TB infection. Rifamycins like rifampicin or rifapentine, alone or in combination with isoniazid, may also be considered as alternatives, pending accumulation of further clinical data. During treatment of latent TB infection, regular follow up is essential to ensure adherence to therapy and facilitate clinical monitoring for hepatic dysfunction. Monitoring of liver chemistry is also required for those patients at risk of drug-induced hepatotoxicity. [source] Postoperative pain relief using thoracic epidural analgesia: outstanding success and disappointing failuresANAESTHESIA, Issue 1 2001G. A. McLeod Six hundred and forty patients received epidural analgesia for postoperative pain relief following major surgery in the 6-year period 1993,1998. Although satisfactory pain relief was achieved in over two-thirds of patients for a median duration of 44 h after surgery, one-fifth of patients (133 individuals) still experienced poor pain relief. Almost one out of three patients (194 individuals) had a problem with their epidural. Eighty-three patients (13%) suffered a technical failure and 84 (13%) patients had their epidurals removed at night time when pain-free because of pressure on beds. Seven patients had their epidural replaced and subsequently experienced excellent pain relief for a median of 77 h. Lack of resources prevented a further 480 patients from receiving the potential benefits of epidural analgesia. These results would suggest that the practical problems of delivering an epidural service far outweigh any differences in drug regimens or modes of delivery of epidural solutions. [source] Older age predicts a decline in adjuvant chemotherapy recommendations for patients with breast carcinomaCANCER, Issue 9 2003Evidence from a tertiary care cohort of chemotherapy-eligible patients Abstract BACKGROUND The appropriate use of adjuvant chemotherapy for elderly women with breast carcinoma remains controversial. Efficacy data in women age , 70 years are scarce, resulting in a lack of clear guidelines for patients in this age group. Although several studies have demonstrated decreasing use of chemotherapy with age, none specifically examined its use in an elderly cohort of patients who were deemed eligible for such therapy based on consensus guidelines, simultaneously examining the impact of comorbidity and previous history of malignant disease on these recommendations. METHODS The authors examined adjuvant chemotherapy use among chemotherapy-eligible patients age , 50 years who were evaluated in a tertiary care cancer center. Associations between patient age and 1) physician recommendation for adjuvant chemotherapy, 2) recommended treatment regimen, and 3) patient acceptance of the treatment plan recommended were examined, adjusting for the impact of aggressive tumor characteristics, medical comorbidity, previous history of malignant disease, and features of the treatment setting. RESULTS Of the 208 chemotherapy-eligible patients who were studied, 74% overall were recommended chemotherapy. Chemotherapy was recommended to 92% of women age 50,59 years compared with 77% of women age 60,69 years and 23% of women age , 70 years. Increasing age was associated strongly with a decreasing likelihood of receiving a recommendation in favor of chemotherapy. After adjusting for estrogen receptor status, previous history of malignant disease, comorbidity score, and prognostic group, the odds of receiving a recommendation in favor of chemotherapy fell by 22% per year or 91% per 10-year interval, and the rate of decline did not change significantly at age , 70 years. We found no age-related differences in either the drug regimens recommended or patient acceptance rates for adjuvant therapy. CONCLUSIONS Age was associated strongly and independently with physician recommendation for adjuvant chemotherapy among a group of older women who were eligible specifically for such therapy. Medical comorbidity and a history of previous malignant disease did not alter this correlation significantly, although the latter was a significant predictor of chemotherapy use. Further studies clearly are needed to determine the underlying reasons for this strong age effect and to explore strategies that will optimize the utilization of this potentially curative therapy in the elderly. Cancer 2003;97:2150,9. © 2003 American Cancer Society. DOI 10.1002/cncr.11338 [source] Treatment of hepatitis C virus infection in intravenous drug usersACTA NEUROPSYCHIATRICA, Issue 5 2006Matthew L Cowan Background:, Hepatitis C virus (HCV) infection is common among intravenous drug users, and because of the long latent period, HCV liver disease is set to increase. Objectives:, We sought to examine practice guidelines regarding treatment of HCV in drug users and to review the evidence for current practices. Methods:, A structured search of the Pubmed database, websites of the National Institute for Clinical Excellence and national and international expert groups and opinion of independent experts in the field. Results and Conclusions:, All those infected with HCV need to be assessed to ascertain whether they have active ongoing viral replication and the extent of liver damage. HCV-infected individuals should be educated about the modes of transmission and means of reducing the risk of infecting others. They should also be advised to avoid cofactors (especially alcohol) that accelerate the progression of liver disease. Specific treatment with antivirals can cause viral clearance and prevent the progression of liver disease. Therapy is effective in those on opiate-replacement treatments and also in motivated individuals who continue to use intravenous drugs. The decision whether to treat drug users should be made jointly by specialists in the management of viral hepatitis and addiction on a case-by-case basis. Current combination drug regimens are expensive but are claimed to be cost-effective, and are certainly much less costly than managing end-stage liver disease. In addition to satisfactory sustained viral response rates, other benefits such as a beneficial effect on drug habit, self-esteem and rehabilitation have been reported. Encouraging suitable drug users to take-up and comply with treatment seems to be more easily achieved in supportive drug dependency unit settings (rather than the more formal surroundings of a hospital clinic). [source] Antifungal pharmacokinetics and pharmacodynamics: bridging from the bench to bedsideCLINICAL MICROBIOLOGY AND INFECTION, Issue 7 2009W. W. Hope Abstract This review considers a way in which experimental data can be used to identify safe and effective antifungal regimens for humans. The process begins with experimental models of invasive fungal infections that enable definition of optimal dosages and schedules of antifungal drug administration to be defined. These preclinical models also enable the identification of drug exposure targets that are associated with therapeutic outcomes of interest. Human pharmacokinetic variability results in a considerable range of drug exposures following the use of fixed antifungal drug regimens. This variability can be quantified using population pharmacokinetic modeling techniques. Monte Carlo simulation can then be used to simulate pharmacokinetic variability and thereby estimate the proportion of patients with a therapeutic outcome of interest. Effective and safe regimens can thus be studied appropriately in clinical settings. This approach can, and should, be used to optimize antifungal therapy for a large number of clinical scenarios. [source] Hypoglycaemia in Type 2 diabetesDIABETIC MEDICINE, Issue 3 2008S. A. Amiel Abstract The primary cause of hypoglycaemia in Type 2 diabetes is diabetes medication,in particular, those which raise insulin levels independently of blood glucose, such as sulphonylureas (SUs) and exogenous insulin. The risk of hypoglycaemia is increased in older patients, those with longer diabetes duration, lesser insulin reserve and perhaps in the drive for strict glycaemic control. Differing definitions, data collection methods, drug type/regimen and patient populations make comparing rates of hypoglycaemia difficult. It is clear that patients taking insulin have the highest rates of self-reported severe hypoglycaemia (25% in patients who have been taking insulin for > 5 years). SUs are associated with significantly lower rates of severe hypoglycaemia. However, large numbers of patients take SUs in the UK, and it is estimated that each year > 5000 patients will experience a severe event caused by their SU therapy which will require emergency intervention. Hypoglycaemia has substantial clinical impact, in terms of mortality, morbidity and quality of life. The cost implications of severe episodes,both direct hospital costs and indirect costs,are considerable: it is estimated that each hospital admission for severe hypoglycaemia costs around £1000. Hypoglycaemia and fear of hypoglycaemia limit the ability of current diabetes medications to achieve and maintain optimal levels of glycaemic control. Newer therapies, which focus on the incretin axis, may carry a lower risk of hypoglycaemia. Their use, and more prudent use of older therapies with low risk of hypoglycaemia, may help patients achieve improved glucose control for longer, and reduce the risk of diabetic complications. [source] | |||||||||||||||||||||||||