Immunogenicity and protective efficacy of a live, oral cholera vaccine formulation stored outside-the-cold-chain for 140 days.

BACKGROUND: Cholera, an acute watery diarrhoeal disease caused by Vibrio cholerae serogroup O1 and O139 across the continents. Replacing the existing WHO licensed killed multiple-dose oral cholera vaccines that demand 'cold chain supply' at 2-8 °C with a live, single-dose and cold chain-free vaccine would relieve the significant bottlenecks and cost determinants in cholera vaccination campaigns. In this direction, a prototype cold chain-free live attenuated cholera vaccine formulation (LACV) was developed against the toxigenic wild-type (WT) V. cholerae O139 serogroup. LACV was found stable and retained its viability (5 × 106 CFU/mL), purity and potency at room temperature (25 °C ± 2 °C, and 60% ± 5% relative humidity) for 140 days in contrast to all the existing WHO licensed cold-chain supply (2-8 °C) dependent killed oral cholera vaccines. RESULTS: The LACV was evaluated for its colonization potential, reactogenicity, immunogenicity and protective efficacy in animal models after its storage at room temperature for 140 days. In suckling mice colonization assay, the LACV recorded the highest recovery of (7.2 × 107 CFU/mL) compared to those of unformulated VCUSM14P (5.6 × 107 CFU/mL) and the WT O139 strain (3.5 × 107 CFU/mL). The LACV showed no reactogenicity even at an inoculation dose of 104-106 CFU/mL in a rabbit ileal loop model. The rabbits vaccinated with the LACV or unformulated VCUSM14P survived a challenge with WT O139 and showed no signs of diarrhoea or death in the reversible intestinal tie adult rabbit diarrhoea (RITARD) model. Vaccinated rabbits recorded a 275-fold increase in anti-CT IgG and a 15-fold increase in anti-CT IgA antibodies compared to those of rabbits vaccinated with unformulated VCUSM14P. Vibriocidal antibodies were increased by 31-fold with the LACV and 14-fold with unformulated VCUSM14P. CONCLUSION: The vaccine formulation mimics a natural infection, is non-reactogenic and highly immunogenic in vivo and protects animals from lethal wild-type V. cholerae O139 challenge. The single dose LACV formulation was found to be stable at room temperature (25 ± 2 °C) for 140 days and it would result in significant cost savings during mass cholera vaccination campaigns.

Effects of pre and post-treatments with dipyridamole in gentamicin-induced acute nephrotoxicity in the rat.

This study investigated the pretreatment and post-treatment effects of dipyridamole (20 mg/kg/day, p.o.) in gentamicin-induced acute nephrotoxicity in rats. Rats were administered gentamicin (100 mg/kg/day, i.p.) for 8 days. Gentamicin-administered rats exhibited renal structural and functional changes as assessed in terms of a significant increase in serum creatinine and urea and kidney weight to body weight ratio as compared to normal rats. Renal histopathological studies revealed a marked incidence of acute tubular necrosis in gentamicin-administered rats. These renal structural and functional abnormalities in gentamicin-administered rats were accompanied with elevated serum uric acid level, and renal inflammation as assessed in terms of decrease in interleukin-10 levels. Dipyridamole pretreatment in gentamicin-administered rats afforded a noticeable renoprotection by markedly preventing renal structural and functional abnormalities, renal inflammation and serum uric acid elevation. On the other hand, dipyridamole post-treatment did not significantly prevent uric acid elevation and renal inflammation, and resulted in comparatively less protection on renal function although it markedly reduced the incidence of tubular necrosis. In conclusion, uric acid elevation and renal inflammation could play key roles in gentamicin-nephrotoxicity. Dipyridamole pretreatment markedly prevented gentamicin-induced acute nephrotoxicity, while its post-treatment resulted in comparatively less renal functional protection.

Are parents' knowledge and practice regarding immunization related to pediatrics' immunization compliance? a mixed method study.

BACKGROUND: Immunization rate is one of the best public health outcome and service indicators of the last 100 years. Parental decisions regarding immunization are very important to improve immunization rate. The aim of this study was to evaluate the correlation between parental knowledge-practices (KP) and children's immunization completeness. METHODS: A mixed method has been utilized in this study: a retrospective cohort study was used to evaluate immunization completeness; a prospective cross-sectional study was used to evaluate immunization KP of parents. 528 children born between 1 January 2003 and 31 June 2008 were randomly selected from five public health clinics in Mosul, Iraq. Immunization history of each child was collected retrospectively from their immunization record/card. RESULTS: About half of studied children (n = 286, 56.3%) were immunized with all vaccination doses; these children were considered as having had complete immunization. 66.1% of the parents was found to have adequate KP scores. A significant association of immunization completeness with total KP groups (p < 0.05) was found. CONCLUSIONS: Future efforts are required to improve immunization rate and parents' knowledge and practice. The study results reinforce recommendations for the periodic assessment of immunization rate and the use of educational programmes to improve the immunization rate, knowledge and practice.

Factors underlying inadequate parents' awareness regarding pediatrics immunization: findings of cross-sectional study in Mosul- Iraq.

BACKGROUND: Since last 100 years, immunization rate is one of the best public health outcome and service indicators. However, the immunization system is still imperfect; there are many countries that still have unvaccinated children. Parental decisions regarding immunization are very important to improve immunization rate. The aim of this study is to evaluate the association between parental knowledge-practice (KP) regarding immunization with family and immunization providers' factors. METHODS: This is a prospective cross-sectional study design. Immunization knowledge and practices among 528 Iraqi parents were evaluated through validated questionnaire. Familial data and immunization provider's characteristics were collected from parents through interview. RESULTS: More than half of respondents/study population (66.1%) have adequate knowledge- practice scores. Significant associations were noted for knowledge-practice groups with father's education level, mother's education level, mother's age at delivery, number of preschool children, parents gender, family income, provider types, and birth place (p < 0.05). CONCLUSION: Immunization campaigns and awareness are required to improve parents' knowledge and practice regarding immunization. The study results reinforce recommendations for use of educational programmes to improve the immunization knowledge and practice.

An RP-HPLC-UV method with SPE for cefotaxime in all-in-one total parenteral nutritional admixtures: application to stability studies.

A simple and selective RP-HPLC-UV method with SPE was developed and validated for the quantification of cefotaxime in all-in-one total parenteral nutrition (AIO-TPN) admixtures. Chromatographic separation was achieved on a 5 pm particle size C18 DB column (250 x 4.6 mm id) using the mobile phase ammonium acetate (25 mM, pH 4.0)-50% acetonitrile in methanol (80 + 20, v/v). The flow rate was 0.9 mL/min and the detection wavelength was 254 nm. The analyte was extracted from AIO-TPN admixtures by means of an SPE method. The cefotaxime calibration curve was linear over a concentration range of 100-1400 microg/mL with a correlation coefficient of > or = 0.9994. The intraday accuracy and precision for cefotaxime were < or = -3.15 and < or = 3.08%, respectively, whereas the interday accuracy and precision were < or = -2.48 and < or = 2.25%, respectively. The method was successfully applied to stability studies of cefotaxime in the presence of micronutrients together with low and high concentrations of macronutrients in AIO-TPN admixtures. Cefotaxime was degraded by 13.00 and 26.05% at room temperature (25 +/- 2 degrees C) after 72 h in low and high macronutrient concentration formulations of AIO-TPN admixtures, respectively. The values of cefotaxime degradation rates for low and high macronutrient concentration formulations of AIO-TPN admixtures were -0.164 and -0.353, respectively. These results indicated that there was a higher rate of degradation in the AIO-TPN admixture formulations containing high concentrations of macronutrients.

Selected pharmacokinetic issues of the use of antiepileptic drugs and parenteral nutrition in critically ill patients.

OBJECTIVES: To conduct a systematic review for the evidence supporting or disproving the reality of parenteral nutrition- antiepileptic drugs interaction, especially with respect to the plasma protein-binding of the drug. METHODS: The articles related to the topic were identified through Medline and PubMed search (1968-Feburary 2010) for English language on the interaction between parenteral nutrition and antiepileptic drugs; the search terms used were anti-epileptic drugs, parenteral nutrition, and/or interaction, and/or in vitro. The search looked for prospective randomized and nonrandomized controlled studies; prospective nonrandomized uncontrolled studies; retrospective studies; case reports; and in vitro studies. Full text of the articles were then traced from the Universiti Sains Malaysia (USM) library subscribed databases, including Wiley-Blackwell Library, Cochrane Library, EBSCOHost, OVID, ScienceDirect, SAGE Premier, Scopus, SpringerLINK, and Wiley InterScience. The articles from journals not listed by USM library were traced through inter library loan. RESULTS: There were interactions between parenteral nutrition and drugs, including antiepileptics. Several guidelines were designed for the management of illnesses such as traumatic brain injuries or cancer patients, involving the use of parenteral nutrition and antiepileptics. Moreover, many studies demonstrated the in vitro and in vivo parenteral nutrition -drugs interactions, especially with antiepileptics. CONCLUSIONS: There was no evidence supporting the existence of parenteral nutrition-antiepileptic drugs interaction. The issue has not been studied in formal researches, but several case reports and anecdotes demonstrate this drug-nutrition interaction. However, alteration in the drug-free fraction result from parenteral nutrition-drug (i.e. antiepileptics) interactions may necessitate scrupulous reassessment of drug dosages in patients receiving these therapies. This reassessment may be particularly imperative in certain clinical situations characterized by hypoalbuminemia (e.g., burn patients).

Potential drug-herb interaction with antiplatelet/anticoagulant drugs.

This is a cross-sectional survey evaluating the use of herbal medicines in medical wards patients that may interfere with the effect of antiplatelet or anticoagulant therapy. Among the 250 patients participated, 42.4% (n=106) were taking herbs with 76 patients (71.7%) using herbs for the past 12 months. Overall, almost 31% (n=23, N=76) of patients were taking one or more of the specified herbal medicines [ginseng (Panax ginseng), garlic (Allium sativum), ginkgo (Gingko biloba) thought to interact with antiplatelet or anticoagulant therapy. The study showed that 21% (n=16, N=76) of patients co-ingested specified herbs with antiplatelet or anticoagulant therapy, of which half of them were at risk of potential drug-herb interactions. A large proportion of respondents involved in potential drug-herb interaction were elderly people (62.5%, n=5). However, more than 90% of herbal users did not disclose the use of herbal medicine to their health professionals. It is thus prudent for all care givers to be aware of the possibility of drug-herb interaction and inquire about herbal use from patients.

Practices associated with serum antiepileptic drug level monitoring at a pediatric neurology clinic: a Malaysian experience.

OBJECTIVES: To assess the practices associated with the application of therapeutic drug monitoring (TDM) for antiepileptic drugs (AEDs) in the management of children with structural-metabolic epilepsy. METHODS: It was a retrospective chart review and included children aged ≥2 years old with structural-metabolic epilepsy, treated with AEDs, and received TDM. The data were extracted from the medical records. RESULTS: Thirty-two patients were identified with 50 TDM assays. In two thirds of the assays, "check level" and "recheck level" were the reasons behind the requesting of serum level monitoring of AEDs. Knowledge of serum AED levels led to alterations in the management in 60% of the assays. Thirty-two (76%) pediatrician's actions were consistent with the recommendation of TDM pharmacist. Forty-nine (98%) levels were appropriately indicated. In relation to the appropriateness of sampling time, 9 (18%) levels were not assessed due to missing data. Twenty-seven (54%) levels were appropriately sampled. CONCLUSIONS: More studies should be designed to improve the component of the current TDM request form, especially in the reason section. By the same token, the number of pointless assays and the costs to the health care system can be reduced both by enhancing and improving the educational standards of the requesting neurologists.

Cost-effectiveness analysis for the use of serum antiepileptic drug level monitoring in children diagnosed with structural-metabolic epilepsy.

Treatment with antiepileptic drugs is commonly guided by serum level monitoring. Such monitoring requires expensive laboratory equipment and products. However, well-conducted studies on the cost-effectiveness of therapeutic drug monitoring for antiepileptic drugs are lacking particularly in patients with structural-metabolic epilepsy. The study aims to assess the cost-effectiveness of serum level monitoring services in the management of children with structural-metabolic epilepsy during the first year of diagnosis. A retrospective cost-effectiveness analysis was conducted from the provider perspective. It included patients attended a paediatric neurology clinic. The effectiveness measures used in this analysis were the number of patients that achieved ≥50% reduction in seizure frequency, and the number of patients with 3-month seizure free. Medical records of the patients were reviewed for the required information. Medical chart/billing data obtained from the hospital were collected to estimate the resources used (One Malaysian Ringgit MYR is equivalent to 0.31 USD). The recruited children were followed for one year following their first visit. The average cost effectiveness ratio for the monitored patients (MYR 2735 per patient that achieved a ≥50% reduction in seizure frequency) was lower than that for non-monitored patients (MYR 2921 per patients that achieved a ≥50% reduction in seizure frequency), with incremental cost-effectiveness ratio of MYR 2357 per one additional patient that achieved a ≥50% reduction in seizure frequency. The average cost effectiveness ratios for monitored and non-monitored group were MYR 8279 and MYR 6433 per patient with a 3-month seizure-free period, respectively, with incremental cost-effectiveness ratio of MYR 29,666 per one additional patient with a 3-month seizure-free period. In terms of the effectiveness measures used, serum level monitoring of antiepileptic drugs was found to be cost-effective. However, the incremental cost-effectiveness ratio was found to be sensitive to the cost of management.

Estimation of immunization providers' activities cost, medication cost, and immunization dose errors cost in Iraq.

The immunization status of children is improved by interventions that increase community demand for compulsory and non-compulsory vaccines, one of the most important interventions related to immunization providers. The aim of this study is to evaluate the activities of immunization providers in terms of activities time and cost, to calculate the immunization doses cost, and to determine the immunization dose errors cost. Time-motion and cost analysis study design was used. Five public health clinics in Mosul-Iraq participated in the study. Fifty (50) vaccine doses were required to estimate activities time and cost. Micro-costing method was used; time and cost data were collected for each immunization-related activity performed by the clinic staff. A stopwatch was used to measure the duration of activity interactions between the parents and clinic staff. The immunization service cost was calculated by multiplying the average salary/min by activity time per minute. 528 immunization cards of Iraqi children were scanned to determine the number and the cost of immunization doses errors (extraimmunization doses and invalid doses). The average time for child registration was 6.7 min per each immunization dose, and the physician spent more than 10 min per dose. Nurses needed more than 5 min to complete child vaccination. The total cost of immunization activities was 1.67 US$ per each immunization dose. Measles vaccine (fifth dose) has a lower price (0.42 US$) than all other immunization doses. The cost of a total of 288 invalid doses was 744.55 US$ and the cost of a total of 195 extra immunization doses was 503.85 US$. The time spent on physicians' activities was longer than that spent on registrars' and nurses' activities. Physician total cost was higher than registrar cost and nurse cost. The total immunization cost will increase by about 13.3% owing to dose errors.

Medical care costs of newly diagnosed children with structural-metabolic epilepsy: a one year prevalence-based approached.

PURPOSE: Aims of this study were to estimate the first-year medical care costs of newly diagnosed children with structural-metabolic epilepsy and to determine the cost-driving factors in the selected population. METHOD: This was a prevalence-based retrospective chart review that included patients who attended a pediatric neurology clinic in a tertiary referral center in Malaysia. The total first-year medical care costs were estimated from the provider (i.e., hospital) perspective, using a bottom-up, microcosting analysis. Medical chart/billing data (i.e., case reports) obtained from the hospital (i.e., provider) were collected to determine the resources used. Prices or cost data were standardized for the year 2010 (One Malaysian Ringgit MYR is equivalent to 0.26 Euro or 0.32 USD). RESULTS: The most expensive item in the costs list was antiepileptic drugs, whereas ultrasound examination represented the cheapest item. Hospitalization and the use of non-antiepileptic drugs were the second and third most costly items, respectively. The cost of therapeutic drug monitoring comprised only a small proportion of the total annual expenditure. None of the demographic variables (i.e., gender, race, and age) significantly impacted the first-year medical care costs. Similarly, child development, seizure type, therapy type (i.e., polytherapy versus monotherapy), and therapeutic drug monitoring utilization were also not associated with the cost of management. The first-year medical care costs positively correlated with seizure frequency (r(s)=0.294, p=0.001). However, the only variable that significantly predict the first-year medical care costs was the type of antiepileptic drugs (R(2)=0.292, F=7.772, p<0.001). CONCLUSION: This investigation was the first cost analysis study of epilepsy in Malaysia. The total first-year medical care costs for 120 patients with structural-metabolic epilepsy were MYR 202,816 (i.e., MYR 1690.13 per patient per year). The study findings highlight the importance of optimizing seizure control in reducing the cost of management.

Exploring community pharmacists' views on generic medicines: a nationwide study from Malaysia.

OBJECTIVE: To evaluate the Malaysian community pharmacists' views on generic medicines. SETTING: A sample of 1419 Malaysian community pharmacies with resident pharmacists. METHOD: A cross-sectional nationwide survey using a self-completed mailing questionnaire. MAIN OUTCOME MEASURE: Pharmacists' views on generic medicines including issues surrounding efficacy, safety, quality and bioequivalence. RESULTS: Responses were received from 219 pharmacies (response rate 15.4%). Only 50.2% of the surveyed pharmacists agreed that all products that are approved as generic equivalents can be considered therapeutically equivalent with the innovator medicines. Around 76% of respondents indicated that generic substitution of narrow therapeutic index medicines is inappropriate. The majority of the pharmacists understood that a generic medicine must contain the same amount of active ingredient (84.5%) and must be in the same dosage form as the innovator brand (71.7%). About 21% of respondents though that generic medicines are of inferior quality compared to innovator medicines. Most of the pharmacists (61.6%) disagreed that generic medicines produce more side-effects than innovator brand. Pharmacists graduated from Malaysian universities, twinning program and overseas universities were not differed significantly in their views on generic medicines. Additionally, the respondents appeared to have difficulty in ascertaining the bioequivalent status of the marketed generic products in Malaysia. CONCLUSION: The Malaysian pharmacists' have lack of information and/or trust in the generic manufacturing and/or approval system in Malaysia. This issue should be addressed by pharmacy educators and relevant government agencies.

A nationwide study on generic medicines substitution practices of Australian community pharmacists and patient acceptance.

OBJECTIVES: This study evaluated Australian community pharmacists' rate of generic medicine substitution, patient acceptance of generic substitution and cost-savings achieved for patients from substitution. METHOD: A national stratified sample of 500 Australian pharmacies was randomly selected from different geographical areas. The data of the first 25 original PBS prescription items dispensed on one working day eligible for generic substitution were collected from each pharmacy. RESULTS: Responses were received from 82 pharmacies with a response rate of 16.4%. The pharmacists recommended generics for 96.4% (1461/1515) of the prescription items which were eligible for substitution. The generic substitution recommendation rate in urban (98.7%) and rural areas (98.0%) was significantly higher than remote areas (91.6%). Conversely, patients' acceptance in remote areas (84.5%) was significantly higher than rural (78.6%) and urban areas (73.2%). Patients with chronic diseases demonstrated significantly lower acceptability (72.4%) than patients with acute conditions (81.6%). Through acceptance of substitution, the patients' medicines expenditure reduced by around 21%. CONCLUSION: Australian community pharmacists demonstrated a high rate of recommending generic substitution. However, to optimize the generic medicines utilization, patients' acceptance requires further improvement.

Evaluating community pharmacists' perceptions of future generic substitution policy implementation: a national survey from Malaysia.

OBJECTIVES: This study aims to provide baseline data to support the implementation of generic substitution policy in Malaysia by evaluating the community pharmacists' perceptions and opinions on generic substitution and current substitution practices. METHODS: A cross-sectional descriptive study involving the entire population of Malaysian community pharmacies (n=1419) was undertaken using a self-completed anonymous mail questionnaire. RESULTS: A total of 219 responses were received for a response rate of 15.4%. Majority of the respondents (93.6%) agreed that pharmacists should have generic substitution rights. Almost all pharmacists (96.8%) viewed Poison Class C (pharmacist only medicine) as most suitable class of controlled medicines for substitution. About half (51.6%) of the pharmacists preferred a policy which allowed substitution on any prescription. The pharmacists prefer to consult the physician when substituting narrow therapeutic index medicines (88.1%) and prescription only medicines (51.3%). Less than 25.0% of the pharmacists routinely keep the medication records and follow-up the patients who received substitution. Monitoring the efficacy (79.2%) and patient's satisfaction with the generic medicines (74.9%) were the main reasons for following-up the patient if substitution occurs. CONCLUSIONS: Malaysian community pharmacists are generally in favour of generic substitution policy implementation.

A pilot study on generic medicine substitution practices among community pharmacists in the State of Penang, Malaysia.

PURPOSE: The purpose of this study was to evaluate the generic substitution (GS) practices undertaken by community pharmacists in the State of Penang, Malaysia with a focus on the extent of communication between pharmacists and prescribers on issues related to GS, consumer's acceptance on the GS and estimation of cost saving achieved for patients opted for GS. METHOD: A cross-sectional descriptive study for a period of 2 months using a specific questionnaire as a data collection tool was undertaken with a random sample of 40 community pharmacies located in the State of Penang. RESULTS: By the end of the study period, 34 out of 40 pharmacies contacted participated in the study. Forty-seven per cent of pharmacists consulted prescribers while promoting GS to their consumers. Majority of the prescribers (84.4%) when contacted by the pharmacists accepted the suggestion for substitution. From consumers' perspective, 88% (n = 156) of the consumers involved in this study accepted pharmacist's recommendation to generically substitute their prescribed medications. Through acceptance of GS, it has been estimated that the overall consumers' expenses on drugs can be reduced to a total of RM6137 (US$1615; US$1 = RM3.80) and this corresponds to a cost saving of 61.1%. CONCLUSIONS: The outcome of the present study showed that through GS recommendation by community pharmacist, consumers can save the expenditure of their prescribed medications.