Applying value-based strategies to accelerate access to novel cancer medications: guidance from the Oncology Health Economics Expert Panel in Qatar (Q-OHEP).

BACKGROUND: In line with global trends, cancer incidence and mortality may have decreased for specific types of cancer in Qatar. However, the cancer-related burden on patients, healthcare systems, and the economy is expected to expand; thus, cancer remains a significant public healthcare issue in Qatar. Qatar's free access to cancer care represents a considerable economic burden. Ensuring the best utilization of financial resources in the healthcare sector is important to provide unified and fair access to cancer care for all patients. Experts from the Qatar Oncology Health Economics Expert Panel (Q-OHEP) aimed to establish a consistent and robust base for evaluating oncology/hematology medications; involve patients' insights to accelerate access to cutting-edge medications; increase the value of cancer care; and reach a consensus for using cost-effective strategies and efficient methodologies in cancer treatment. METHODS: The Q-OHEP convened on 30 November 2021 for a 3-hour meeting to discuss cancer management, therapeutics, and health economics in Qatar, focusing on four domains: (1) regulatory, (2) procurement, (3) treatment, and (4) patients. Discussions, guided by a moderator, focused on a list of suggested open-ended questions. RESULTS: Some of the salient recommendations included the development of a formal, fast-track, preliminary approval pathway for drugs needed by patients with severe disease or in critical condition; and encouraging and promoting the conduct of local clinical trials and real-world observational studies using existing registry data. The Q-OHEP also recommended implementing a forecast system using treatment center data based on the supply/demand of formulary oncology drugs to detect treatment patterns, estimate needs, expedite procurement, and prevent shortages/delays. Furthermore, the panel discussed the needs to define value concerning cancer treatment in Qatar, implement value-based models for reimbursement decision-making such as health technology assessment and multiple-criteria decision analysis, and promote patient education and involvement/feedback in developing and implementing cancer management guidelines. CONCLUSION: Herein, we summarize the first Q-OHEP consensus recommendations, which aim to provide a solid basis for evaluating, registering, and approving new cancer medications to accelerate patient access to novel cancer treatments in Qatar; promote/facilitate the adoption and collection of patient-reported outcomes; and implement value-based cancer care in Qatar.

Epidemiology, clinical characteristics, and associated cost of acute poisoning: a retrospective study.

Introduction: Poisoning is a major public health issue and a leading cause of admission to the emergency department (ED). There is a paucity of data describing the epidemiology and cost of acute poisoning. Therefore, this study investigated the epidemiology, patterns, and associated costs of acute poisoning in emergency department of the largest tertiary care healthcare centre in Qatar. Method: This study was a retrospective review of the health records of patients admitted to the ED due to poisoning between January 2015 and December 2019. Incidence, clinical characteristics, and costs associated with acute poisoning were assessed. Frequency and percentages were calculated for categorical variables and mean and SD for continuous variables. The relationship between sociodemographic characteristics and poisoning profile was assessed using the chi-square test. A micro-costing approach using the cost of each resource was applied for cost calculations. Result: The incidence of acute poisoning was 178 cases per 100,000 patients. Females (56%) and children below 14 years (44.3%) accounted for the largest proportion. Most of the exposures were accidental involving therapeutic agents (64.2%). The mean length of hospital stay was found to be 1.84 ± 0.81 days, and most patients (76.6%) were discharged within the first 8 h. A statistically significant difference was found between age groups and type of toxin (χ2 = 23.3, p < 0.001), cause and route of exposure (χ2 = 42.2, p < 0.001), and length of hospital stay (χ2 = 113.16, p < 0.001). Admission to intensive care units had the highest cost expenditure (USD 326,008), while general wards accounted for the least (USD 57,709). Conclusion: Unintentional poisoning by pharmacological agents is common in infants and children. This study will assist in the development of educational and preventive programmes to minimise exposure to toxic agents. Further studies are required to explore the impact of medical toxicology services, and post discharge monitoring of poisoning.

The cost associated with the development of the antimicrobial stewardship program in the adult general medicine setting in Qatar.

Objective: To estimate the economic impact of the developed antimicrobial stewardship program (ASP) versus the preliminary ASP use, in the adults' general medicine settings in Qatar. Methods: Patient records were retrospectively reviewed during two periods: preliminary ASP was defined as the 12 months following ASP implementation (i.e. May 2015-April 2016), and developed ASP was defined as the last 12 months of a 5-year ASP implementation in Hamad Medical Corporation (HMC) (i.e. February 2019-January 2020). The economic impact was the overall cost savings in resource use, including operational costs, plus the cost avoidance associated with ASP. Results: A total of 500 patients were included in the study. The operational costs decreased with the developed ASP. Whereas antimicrobial consumption and resource utilisation, and their associated costs, appear to have declined with the developed ASP, with a cost saving of QAR458 (US$125) per 100-patient beds, the avoided cost was negative, by QAR4,807 (US$1,317) per 100-patient beds, adding to a total QAR4,224 (US$1,160) increase in the 100-patient beds cost after ASP development. Conclusions: Despite that the developed ASP attained a total cost saving QAR458 (US$125) per 100-patient beds, the avoided cost was QAR-4,807 (US$-1,317) per 100-patient beds, which exceeded the cost savings achieved.

Investigating physicians' views on non-formulary prescribing: a qualitative study using the theoretical domains framework.

BACKGROUND: Well-designed and well-maintained drug formularies serve as a reliable resource to guide prescribing decisions; they are associated with improved medicine safety and increased efficiency, while also serving as a cost-effective tool to help manage and predict medicine expenditure. Multiple studies have investigated the inappropriate prescribing of non-formulary drugs (NFDs) with statistics indicating that up to 70% of NFD usage being inappropriate or not following the ascribed NFD policies. AIM: To explore physicians' views and influences on their prescribing of non-formulary drugs. METHOD: Data collection and analysis were underpinned using the Theoretical Domains Framework (TDF). Thirteen semi-structured interviews were conducted within Hamad Medical Corporation, the main provider of secondary and tertiary healthcare in Qatar, with physicians who had submitted a NFD request in the preceding 12 months. RESULTS: Three overarching themes were identified: providing evidence-based care for individual patients; influences of others; and formulary management issues. Subthemes were mapped to specific TDF domains: environmental context and resources; social influences; professional role and identity; beliefs about consequences; goals; intentions. CONCLUSION: The behavioral influences identified in this study can be mapped to behavior change strategies facilitating the development of an intervention to promote appropriate prescribing of NFDs with implications for medicine safety and healthcare efficiency.

A scoping review of theories used to investigate clinician adherence to clinical practice guidelines.

BACKGROUND: Routine utilization of evidence-based clinical practice guidelines (CPGs) is an effective strategy to optimize patient care and reduce practice variation. Healthcare professionals' failure to adhere to CPGs introduces risks to both patients and the sustainability of healthcare systems. The integration of theory to investigate adherence provides greater insight into the often complex reasons for suboptimal behaviors. AIM: To determine the coverage of literature surrounding the use of theory in studies of CPG adherence, report the key findings and identify the knowledge gaps. METHOD: In April 2021, three bibliographic databases were searched for studies published since January 2010, adopting theory to investigate health professionals' adherence to CPGs. Two reviewers independently screened the articles for eligibility and charted the data. A narrative approach to synthesis was employed. RESULTS: The review includes 12 articles. Studies were limited to primarily investigations of physicians, quantitative designs, single disease states and few countries. The use of behavioral theories facilitated pooling of data of barriers and facilitators of adherence. The domains and constructs of a number of the reported theories are captured within the Theoretical Domains Framework (TDF); the most common barriers aligned with the TDF domain of environmental context and resources, fewer studies reported facilitators. CONCLUSION: There is emerging use of behavioral theories investigating physicians' adherence to CPGs. Although limited in number, these studies present specific insight into common barriers and facilitators, thus providing valuable evidence for refining existing and future implementation strategies. Similar investigations of other health professionals are warranted.

Patterns and outcomes of paracetamol poisoning management in Hamad Medical Corporation, Qatar: A retrospective cohort study.

We aimed to investigate the characteristics and clinical outcomes of paracetamol poisoning and paracetamol overdose in Qatar. This retrospective cohort study included patients admitted to the emergency department (ED). We included patients who presented with excessive paracetamol ingestion, between December 2018 and September 2019. The primary outcomes were describing the characteristics and outcomes of paracetamol overdose (from a suicidal overdose or accidental overdose, dose ≤ 150 mg/kg, when serum levels of <60 mmol/L) or dose ingested (≤75 mg/kg) with staggered ingestion poisoning due to suicidal attempt or accidental attempt, defined as the dose ingested (>150 mg/kg), acute ingestion, nomogram level more than the treatment line, or dose ingested (>75 mg/kg) with staggered ingestion, and assessing the management of excessive paracetamol ingestion. Secondary outcomes included evaluation of the time difference between ingestion and time of administration, hospitalization, and adverse drug events. Significant differences were detected between patients who presented with paracetamol overdose and those who presented with paracetamol toxicity. A total of 69 patients were analyzed, of whom 43 received paracetamol overdose (mean age 27.5 ± 11.1 years) and 26 had paracetamol poisoning (mean age 25 ± 6.22 years). Paracetamol poisoning was identified in 26% of the patients with a 24.3% history of psychiatric illness, compared to 18.6% with paracetamol overdose. More patients presented with paracetamol toxicity in the time between ingestion and obtaining serum levels compared to the overdose group. A significantly longer length of hospitalization was observed in the toxicity group. A significantly higher number of patients in the toxicity group received N-acetylcysteine (NAC). More hypotension and rashes were observed among those who received NAC in the toxicity group. Patients presenting to the ED due to paracetamol toxicity are not uncommon, and most cases occur in young adults, and few in patients with a history of psychiatric illness, suggesting that preventive approaches are highly required.

A theoretically informed, mixed-methods study of pharmacists' aspirations and readiness to implement pharmacist prescribing.

Background Studies have highlighted advancing clinical pharmacy practice in Qatar. Objective To explore pharmacists' aspirations and readiness to implement pharmacist prescribing. Setting Hamad Medical Corporation (HMC), the main provider of secondary and tertiary care. Method A sequential explanatory mixed-methods design. Questionnaire items were derived from the Consolidated Framework of Implementation Research (CFIR), in domains of: awareness/support; readiness; implementation; and facilitators and barriers. Following piloting, all pharmacists (n = 554) were invited to participate. Questionnaire data were analysed using descriptive and inferential statistics with principal component analysis of attitudinal items. Focus groups were recorded, transcribed and analysed using the Framework Approach. Main outcome measure Aspirations and readiness to implement pharmacist prescribing. Results The response rate was 62.8% (n = 348), with respondents highly supportive of implementation in Qatar (median 4, scale 0-5, extremely supportive). The majority (64.9%, n = 226) considered themselves ready, particularly those more senior (p < 0.05) and classifying themselves innovative (p < 0.01). Outpatient (72.9%, n = 221 agreeing) and inpatient (71.1%, n = 218 agreeing) HMC settings were those perceived as being most ready. PCA identified 2 components, with 'personal attributes' being more positive than 'prescribing support'. Facilitators were access to records, organizational/management support and the practice environment, with physician resistance and scope of practice as barriers. Focus groups provided explanation, with themes in CFIR domains of innovation characteristics, characteristics of individuals and the inner setting. Conclusion HMC pharmacists largely aspire, and consider themselves ready, to be prescribers with inpatient and outpatient settings most ready. CFIR domains and constructs identified as facilitators and barriers should be focus for implementation.

Pregnancy-related issues in women with multiple sclerosis: an evidence-based review with practical recommendations.

Objective: To review the current evidence regarding pregnancy-related issues in multiple sclerosis (MS) and to provide recommendations specific for each of them. Research design and methods: A systematic review was performed based on a comprehensive literature search. Results: MS has no effect on fertility, pregnancy or fetal outcomes, and pregnancies do not affect the long-term disease course and accumulation of disability. There is a potential risk for relapse after use of gonadotropin-releasing hormone agonists during assisted reproduction techniques. At short-term, pregnancy leads to a reduction of relapses during the third trimester, followed by an increased risk of relapses during the first three months postpartum. Pregnancies in MS are not per se high risk pregnancies, and MS does not influence the mode of delivery or anesthesia unless in the presence of significant disability. MRI is not contraindicated during pregnancy; however, gadolinium contrast media should be avoided whenever possible. It is safe to use pulse dose methylprednisolone infusions to manage acute disabling relapses during pregnancy and breastfeeding. However, its use during the first trimester of pregnancy is still controversial. Women with MS should be encouraged to breastfeed with a possible favorable effect of exclusive breastfeeding. Disease-modifying drugs can be classified according to their potential for pregnancy-associated risk and impact on fetal outcome. Interferon beta (IFNß) and glatiramer acetate (GA) may be continued until pregnancy is confirmed and, after consideration of the individual risk-benefit if continued, during pregnancy. The benefit of continuing natalizumab during the entire pregnancy may outweigh the risk of recurring disease activity, particularly in women with highly active MS. GA and IFNß are considered safe during breastfeeding. The use of natalizumab during pregnancy or lactation requires monitoring of the newborn. Conclusions: This review provides current evidence and recommendations for counseling and management of women with MS preconception, during pregnancy and postpartum.

Severe rebound disease activity after fingolimod withdrawal in a pregnant woman with multiple sclerosis managed with rituximab: A case study.

Although pregnancy is potentially protective against relapses of multiple sclerosis, severe rebound of disease activity after withdrawal of fingolimod may occur. We report a woman with multiple sclerosis who discontinued fingolimod in the first month of her pregnancy. She developed severe disease rebound which responded poorly to steroids. She was started on rituximab, which was continued during the rest of her pregnancy and beyond. Rituximab appeared safe and well tolerated by both mother and infant, and could be considered in pregnancy for those patients with multiple sclerosis who are at high risk of gestational and postpartum relapse.

Oral disease-modifying therapies for multiple sclerosis in the Middle Eastern and North African (MENA) region: an overview.

BACKGROUND: The introduction of new disease-modifying therapies (DMTs) for remitting-relapsing multiple sclerosis (RRMS) has considerably transformed the landscape of therapeutic opportunities for this chronic disabling disease. Unlike injectable drugs, oral DMTs promote patient satisfaction and increase therapeutic adherence. REVIEW: This article reviews the salient features about the mode of action, efficacy, safety, and tolerability profile of approved oral DMTs in RRMS, and reviews their place in clinical algorithms in the Middle East and North Africa (MENA) region. A systematic review was conducted using a comprehensive search of MEDLINE, PubMed, Cochrane Database of Systematic Reviews (period January 1, 1995-January 31, 2018). Additional searches of the American Academy of Neurology and European Committee for Treatment and Research in Multiple Sclerosis abstracts from 2012-2017 were performed, in addition to searches of the Food and Drug Administration and European Medicines Agency websites, to obtain relevant safety information on these DMTs. CONCLUSIONS: Four oral DMTs: fingolimod, teriflunomide, dimethyl fumarate, and cladribine have been approved by the regulatory agencies. Based on the number needed to treat (NNT), the potential role of these DMTs in the management of active and highly active or rapidly evolving RRMS is assessed. Finally, the place of the oral DMTs in clinical algorithms in the MENA region is reviewed.

A rare and unsuspected complication of Clostridium difficile infection.

OBJECTIVE: To report the occurrence of abdominal compartment syndrome (ACS) due to infection with Clostridium difficile. DESIGN: Case report. SETTING: Trauma intensive care unit (TICU) of Hamad General Hospital, a teaching hospital in Doha, Qatar. PATIENT: A 36-year-old man involved in a motor vehicle accident had severe traumatic brain injury and received ceftriaxone. On day 7, he developed severe abdominal distension and diarrhoea followed by paralytic ileus with oliguria, hyperkalaemia, and intra-abdominal hypertension. The patient's stool sample was positive for C. difficile toxin A and B MEASUREMENTS AND RESULTS: An ACS was diagnosed. The patient was successfully treated in the TICU by stopping the offending antibiotic and starting metronidazole plus neostigmine as a prokinetic agent. The fluid status was guided by pulse-induced continuous cardiac output, and frusemide was added to the treatment. With this aggressive management the abdominal pressure decreased and the renal function improved, with full recovery of renal function by day 21. Unfortunately the patient's Glasgow coma score (GCS) deteriorated, so percutaneous tracheostomy was performed. He was transferred to the neurosurgical ward on day 35. A week later he was shifted to the rehabilitation unit for further management. CONCLUSIONS: C. difficile colitis can cause intra-abdominal hypertension (IAH) and ACS. Rapid diagnosis, early aggressive supportive care, metronidazole and prokinetics are necessary to lower the morbidity and mortality of C. difficile colitis associated with IAH and ACS.

Neurogenic stunned myocardium following hemorrhagic cerebral contusion.

Neurogenic stunned myocardium (NSM) is a well-known complication of subarachnoidal hemorrhage, but has been reported rarely in association with other central nervous system disorders. A case of NSM is described in a patient with hemorrhagic brain contusion associated with cerebral edema. An 18-year-old man was admitted with severe cranial trauma following a car roll-over. Six days after admission, he developed findings suggestive for NSM. The troponin T and creatine kinase-MB level were elevated and echocardiogram showed apical and inferoposterior hypokinesis and diffuse left ventricular akinesis with severely reduced ejection fraction (18%). Invasive measurements confirmed low cardiac output. His cardiac function resolved completely within 6 days after decompressive craniotomy. This case supports the presumed unifying role of the increased intracranial pressure, probably triggering a vigorous sympathetic outflow hyperactivity leading to NSM.

Optimization and stratification of multiple sclerosis treatment in fast developing economic countries: a perspective from Qatar.

OBJECTIVE: The introduction of disease-modifying therapies (DMTs) - with varying degrees of efficacy for reducing annual relapse rate and disability progression - has considerably transformed the therapeutic landscape of relapsing-remitting multiple sclerosis (RRMS). We aim to develop rational evidence-based treatment recommendations and algorithms for the management of clinically isolated syndrome (CIS) and RRMS that conform to the healthcare system in a fast-developing economic country such as Qatar. RESEARCH DESIGN AND METHODS: We conducted a systematic review using a comprehensive search of MEDLINE, PubMed, and Cochrane Database of Systematic Reviews (1 January 1990 through 30 September 2016). Additional searches of the American Academy of Neurology and European Committee for Treatment and Research in Multiple Sclerosis abstracts from 2012 through 2016 were performed, in addition to searches of the Food and Drug Administration and European Medicines Agency websites to obtain relevant safety information on these DMTs. RESULTS: For each of the DMTs, the mode of action, efficacy, safety and tolerability are briefly discussed. To facilitate the interpretation, the efficacy data of the pivotal phase III trials are expressed by their most clinically useful measure of therapeutic efficacy, the number needed to treat (NNT). In addition, an overview of head-to-head trials in RRMS is provided as well as a summary of the several different RRMS management strategies (lateral switching, escalation, induction, maintenance and combination therapy) and the potential role of each DMT. Finally, algorithms were developed for CIS, active and highly active or rapidly evolving RRMS and subsequent breakthrough disease or suboptimal treatment response while on DMTs. The benefit-to-risk profiles of the DMTs, taking into account patient preference, allowed the provision of rational and safe patient-tailored treatment algorithms. CONCLUSIONS: Recommendations and algorithms for the management of CIS and RRMS have been developed relevant to the healthcare system of this fast-developing economic country.

Improving oral medicine administration in patients with swallowing problems and feeding tubes.

BACKGROUND: Correct administration of oral medicines in patients with swallowing problems and feeding tubes remains a challenge. OBJECTIVE: To improve drug administration in patients with swallowing problems and feeding tubes in a 1600 bed tertiary referral center in the State of Qatar. METHODS: A questionnaire was used to evaluate the knowledge and practice of nursing staff from 6 different intensive care units (ICU). Questions assessed the respondents' knowledge of the purpose of controlled-release (CR) preparations, codes used for CR medication, the consequences of crushing these preparations, and their interactions with enteral feeds and feeding tubes. Based on the results of the questionnaire, a 2 day training program was conducted for a core group of 34 staff nurses from all units (ICU and non-ICU) and 3 nursing instructors. Following the principle of "training the trainers," the core group and the nursing instructors would widen the scope of education by running programs in the future. Lecture sessions for pharmacy staff and a monitoring tool to evaluate the practice were also developed. RESULTS: Overall knowledge of CR codes increased from 0% to 40%, correct crushing of solid preparations from 35% to 90%, and knowledge of possible interactions with the enteral feed or feeding tubes from 51% to 88%. Correct administration of medication in patients with feeding tubes improved from 32% to 83%. The quality and value of the 2 day training course received a mean score of 96%. CONCLUSIONS: While most nurses were aware of the purpose of CR formulations, little was known about the different codes used by drug companies and the consequences of crushing these preparations. Interactions with enteral feeds and feeding tubes were mostly overlooked. A 2 day training course followed by continuous in-service training, a lecture to pharmacy staff, and provision of supportive educational material greatly improved the overall medicine administration process in patients with swallowing problems and feeding tubes.

Efficacy and tolerability of antiepileptic drugs in an Omani epileptic population.

OBJECTIVE: The aim of this hospital-based study is to get an insight into the efficacy and tolerability of antiepileptic drugs (AED) in Omani epileptic patients. PATIENTS AND METHODS: All Omani patients (aged 14 years and above) suffering from epileptic seizures for at least 2 years and followed-up by board-certified neurologists in Sultan Qaboos University Hospital (SQUH) were evaluated. The treatment retention rate since first visit at SQUH and over the last 2 years was used as primary efficacy measure of AED therapy. Change in seizure-frequency and side effect profiles were also assessed. RESULTS: In this population of 203 confirmed epileptic patients, generalized tonic-clonic (40%) and partial seizures (39%) were most commonly observed, idiopathic/cryptogenic origin (81%) being the most frequent encountered origin. Sixty one percent of the patients were controlled with an AED in monotherapy and overall 34% of patients could be successfully maintained on monotherapy during the whole follow-up period at SQUH (median 6 years). The treatment retention rates for carbamazepine (CBZ) at a daily dose of 400-600 mg, sodium valproate (VPA) at a daily dose of 500-1000 mg, and phenytoin (PHT) at a daily dose of 300 mg, in monotherapy over the total follow-up period was 51, 50, and 21%, respectively. In contrast, over the last 2 years these rates were highest for VPA (91%) followed by CBZ (83%) and PHT (73%). Adverse drug reactions were recorded in 67% of patients, and were most commonly encountered with VPA. CONCLUSIONS: Despite a higher adverse effect profile for VPA, long-term treatment with CBZ and VPA appeared to be equally effective in terms of treatment retention rates and seizure control.

"Man-in-the-barrel" syndrome as delayed manifestation of extrapontine and central pontine myelinolysis: beneficial effect of intravenous immunoglobulin.

"Man-in-the-barrel" syndrome has been rarely described following osmotic myelinolysis. We report a case of a 45-year-old woman admitted with septicemia and severe hyponatremia. She presented with a "man-in-the-barrel" syndrome which developed more than 10 days after rapid correction of the hyponatremia. There was radiological evidence of central pontine and extrapontine myelinolysis. Three days after completing a course of intravenous immunoglobulin therapy (0.4 g/kg body weight/day for 5 days) there was considerable improvement (Expanded Disability Status Scale score improved 30%). This case, reported for its peculiar mode of development, unusual presentation and challenging therapeutic response to intravenous immunoglobulin, highlights the enigmatic and unpredictable aspects of osmotic myelinolysis.

Organophosphate poisoning in pregnancy: a case report.

A 42-year-old pregnant woman (26 weeks of gestation, G(4)P(0+3)) presented at the emergency department with a two-hour history of dizziness, blurred vision and repeated vomiting. These symptoms started during the use of an undiluted insecticide liquid (diazinon 60 EC) while cleaning a small non-aired bathroom. After clinical and laboratory confirmation for organophosphate poisoning (plasma pseudocholinesterase levels 161 U/l), treatment with atropine and pralidoxime was started. She recovered within 7 days and delivered a healthy baby 12 weeks later (Apgar score 9 and 10) by elective cesarean section. The child showed no signs or symptoms of organophospate, atropine or pralidoxime exposure.

Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson's disease.

Current research in Parkinson's disease (PD) focuses on symptomatic therapy and neuroprotective interventions. Drugs that have been used for symptomatic therapy are levodopa, usually combined with a peripheral decarboxylase inhibitor, synthetic dopamine receptor agonists, centrally-acting antimuscarinic drugs, amantadine, monoamine oxidase-B (MAO-B) inhibitors and catechol-O-methyltransferase (COMT) inhibitors. Drugs for which there is at least some evidence for neuroprotective effect are certain dopamine agonists, amantadine and MAO-B inhibitors (selegiline). Levodopa remains the most effective drug for the treatment of PD. Several factors contribute to the complex clinical pharmacokinetics of levodopa: erratic absorption, short half-life, peripheral O-methylation and facilitated transport across the blood-brain barrier. In patients with response fluctuations to levodopa, the concentration-effect curve becomes steeper and shifts to the right compared with patients with stable response. Pharmacokinetic-pharmacodynamic modelling can affect decisions regarding therapeutic strategies. The dopamine agonists include ergot derivatives (bromocriptine, pergolide, lisuride and cabergoline), non-ergoline derivatives (pramipexole, ropinirole and piribedil) and apomorphine. Most dopamine agonists have their specific pharmacological profile. They are used in monotherapy and as an adjunct to levodopa in early and advanced PD. Few pharmacokinetic and pharmacodynamic data are available regarding centrally acting antimuscarinic drugs. They are characterised by rapid absorption after oral intake, large volume of distribution and low clearance relative to hepatic blood flow, with extensive metabolism. The mechanism of action of amantadine remains elusive. It is well absorbed and widely distributed. Since elimination is primarily by renal clearance, accumulation of the drug can occur in patients with renal dysfunction and dosage reduction must be envisaged. The COMT inhibitors entacapone and tolcapone dose-dependently inhibit the formation of the major metabolite of levodopa, 3-O-methyldopa, and improve the bioavailability and reduce the clearance of levodopa without significantly affecting its absorption. They are useful adjuncts to levodopa in patients with end-of-dose fluctuations. The MAO-B inhibitor selegiline may have a dual effect: reducing the catabolism of dopamine and limiting the formation of neurotoxic free radicals. The pharmacokinetics of selegiline are highly variable; it has low bioavailability and large volume of distribution. The oral clearance is many-fold higher than the hepatic blood flow and the drug is extensively metabolised into several metabolites, some of them being active. Despite the introduction of several new drugs to the antiparkinsonian armamentarium, no single best treatment exists for an individual patient with PD. Particularly in the advanced stage of the disease, treatment should be individually tailored.

Subcutaneous apomorphine : an evidence-based review of its use in Parkinson's disease.

Apomorphine, a short-acting dopamine D1 and D2 receptor agonist, was the first dopamine receptor agonist used to treat Parkinson's disease. Subcutaneous apomorphine is currently used for the management of sudden, unexpected and refractory levodopa-induced 'off' states in fluctuating Parkinson's disease either as intermittent rescue injections or continuous infusions. Other indications include the challenge test for determining the dopaminergic responsiveness and finding the appropriate dose of the drug in intermittent subcutaneous administration. Except for a rapid on- and offset of the antiparkinsonian response with subcutaneous apomorphine, the magnitude and pattern of the motor response to single dose of subcutaneously administered apomorphine is qualitatively comparable to that of oral levodopa. Seventy-five percent of patients achieve a clinically significant improvement with a dose of apomorphine 4mg. The efficacy of intermittent subcutaneous apomorphine injections as an add-on to levodopa therapy in advanced Parkinson's disease was explored in one short-term, randomised, double-blind, placebo-controlled trial, one short-term and six long-term, open-label, uncontrolled studies, including a total of 195 patients. These studies provide evidence that this mode of administration was successful in aborting 'off' periods and improving Parkinson's disease motor scores, but tended to increase dyskinesias. No levodopa-sparing effect was observed. Eleven long-term, open-label, uncontrolled studies, including a total of 233 patients evaluated the efficacy of continuous subcutaneous apomorphine infusions in monotherapy or as an add-on to levodopa therapy in advanced Parkinson's disease. These studies proved that subcutaneous apomorphine infusions are successful in aborting 'off' periods, reducing dyskinesias and improving Parkinson's disease motor scores with the added benefit of a substantial levodopa-sparing effect. The apomorphine challenge test has at least 80% overall predictive ability to clinically diagnose Parkinson's disease across the different stages of the disease and parkinsonian syndromes. Similarly, those data also indicate that the apomorphine challenge test has a >80% ability to predict dopaminergic responsiveness across all stages of Parkinson's disease. Adverse events are usually mild and consist predominantly of cutaneous reactions and neuropsychiatric adverse effects. The incidence of adverse effects is higher in patients receiving continuous infusion than in those receiving intermittent pulsatile administration. Based on the results of these studies it is recommended that subcutaneous apomorphine either as intermittent injections or continuous infusions should be offered to any suitable Parkinson's disease patient who has difficulties in his/her management with conventional therapy. Low-dose levodopa therapy in combination with waking-day hours subcutaneous apomorphine infusion would probably be the most efficient treatment. Continuous subcutaneous apomorphine infusions should be evaluated before more invasive measures or neurosurgical interventions are contemplated.

Annual direct medical cost and contributing factors to total cost of epilepsy in Oman.

OBJECTIVES: To describe the pharmaceutical use, health care resource utilisation patterns, and annual direct medical cost of epilepsy as well as determining the impact of various demographic and clinical characteristics on total costs of epilepsy in Oman. METHODS: Medical and pharmacy data were collected for 6 months on all patients aged > or =13 years attending the Sultan Qaboos University Hospital. Unit pharmacy and medical costs were retrieved for each patient, and multiple linear regression was utilised to analyse the impact of various demographic and clinical characteristics on total cost. RESULTS: A total of 486 patients were seen over the study period. Annual direct medical costs of epilepsy amounted to 1,426 US dollars. In-patient care, the antiepileptic drug (AED) lamotrigine and specialist visits, respectively, were the first, second and third most significant predictors of total cost. Age was associated positively, and was the most significant predictor of total costs among demographic and clinical parameters. CONCLUSIONS: This analysis, the first economic study of epilepsy in Oman, could assist in health care allocation of scarce resources and in pharmacoeconomic analysis of AEDs. Besides in-patient admission, our findings demonstrate that the newer drugs are significant predictors of total cost, and hence any incremental benefits derived from them must be rigorously assessed for their cost-effectiveness.