Cost-effectiveness of rimegepant oral lyophilisate compared to best supportive care for the acute treatment of migraine in the UK.

AIMS: Migraine is the most common disabling headache disorder and is characterized by recurrent throbbing head pain and symptoms of photophobia, phonophobia, nausea, and vomiting. Rimegepant 75 mg, an oral lyophilisate calcitonin gene-related peptide antagonist, is the first treatment approved for both the acute and preventative treatment of migraine, and the first acute therapy approved in over 20-years. The objective was to assess the cost-utility of rimegepant compared with best supportive care (BSC) in the UK, for the acute treatment of migraine in the adults with inadequate symptom relief after taking at least 2 triptans, or for whom triptans are contraindicated or not tolerated. MATERIALS AND METHODS: A de novo model was developed to estimate incremental costs and quality-adjusted life years (QALYs), structured as a decision tree followed by Markov model. Patients received rimegepant or BSC for a migraine attack and were assessed for response (pain relief at 2-h). Responders and non-responders followed different pain trajectories over 48-h cycles. Non-responders discontinued treatment while responders continued treatment for subsequent attacks, with a proportion discontinuing over time. Data sources included a post-hoc pooled analysis of the phase 3 acute rimegepant trials (NCT03235479, NCT03237845, NCT03461757), and a long-term safety study (NCT03266588). The analysis was conducted from the perspective of the UK National Health Service and Personal Social Services over a 20-year time horizon. RESULTS: Rimegepant resulted in an incremental cost-utility ratio (ICUR) of £10,309 per QALY gained vs BSC, which is cost-effectiveness at a willingness to pay threshold of £30,000/QALY. Rimegepant generated +0.44 incremental QALYs and higher incremental lifetime costs (£4,492). Improved QALYs for rimegepant were a result of less time spent with severe and moderate headache pain. CONCLUSION: This study highlights the economic value of rimegepant which was found to be cost-effective for the acute treatment of migraine in adults unsuitable for triptans.

Rotarix in developing countries: paving the way for inclusion in national childhood immunization programs in Africa.

Rotavirus gastroenteritis causes more than half a million deaths annually among children aged <5 years, the great majority of which occur in Africa and Asia. Vaccination is considered to be the most effective public health strategy to prevent rotavirus disease and to reduce the significant global burden of rotavirus gastroenteritis. Rotarix (GlaxoSmithKline Biologicals) is an oral, live attenuated rotavirus vaccine derived from a human G1P[8] rotavirus strain. Results of phase III studies in Europe, Latin America, and Asia have shown that Rotarix offers sustained high protection against severe rotavirus gastroenteritis during the first 2 years of life, when disease burden is highest, with broad protection demonstrated against each of the 5 main rotavirus types that circulate globally (G1, G2, G3, G4, and G9). Coupled with the availability of local burden of disease data and promising interim efficacy data from an ongoing study in Malawi and South Africa, this further reinforces the case for introduction of this rotavirus vaccine in national childhood immunization programs in Africa, where rotavirus-related mortality is significant.

Multicenter prospective study on the burden of rotavirus gastroenteritis in Turkey, 2005-2006: a hospital-based study.

Rotavirus is the main cause of gastroenteritis and dehydration requiring hospitalization among infants and children. Despite the high diarrhea-related mortality rate, there are limited studies describing the prevalence of rotavirus in Turkey. The disease burden of rotavirus gastroenteritis in Turkey was assessed by active, prospective surveillance conducted in accordance with a modified World Health Organization generic protocol from 1 June 2005 through 1 June 2006. A total of 411 children aged <5 years who were hospitalized for gastroenteritis in 4 centers were enrolled. Rotavirus was identified in 53% of samples from the 338 children tested; the range for individual centers was 32.4%-67.4%. Overall, 83.8% of rotavirus-positive children were aged <2 years. Rotavirus gastroenteritis occurred year-round but peaked in the winter. G1P[8] was the most widely prevalent strain (76% of strains), followed by G2P[4] (12.8%). G9P[8] was reported in samples from 3.9% of children. These data support the need for a rotavirus vaccine in Turkey.

Multi-Criteria Decision Analysis to Develop an Efficacy-Safety Profile of Parenteral Analgesics Used in the Treatment of Postoperative Pain.

BACKGROUND: Identifying the optimal treatment in an acute postoperative setting remains a challenge. Multiple analgesic options are available, but comparing outcomes is limited by a lack of head-to-head trials. In addition, decisions based on efficacy only do not take drug safety into account. In such cases, multi-criteria decision analysis (MCDA) can be utilized to quantify and compare the efficacy and safety data of various drugs. METHODOLOGY: The efficacy-safety profiles of eight parenteral, postoperative analgesics (acetaminophen, diclofenac, ketorolac, metamizole, morphine, nefopam, parecoxib, tramadol) widely used in Europe were evaluated using an MCDA model that included 17 criteria: three for efficacy and 14 for safety. Each drug was scored on each criterion on a scale from 0 (worst) to 100 (best), according to published data and the judgment of an expert panel. A weighting process was then applied to standardize the impact of each criterion and adjust drugs' preference scores accordingly, normalizing them on the 0-100 scale. Sensitivity analyses were also performed, including a model in which analgesic profiles were compared when opioid sparing effect was set at a zero value for all drugs. RESULTS: In the primary model, efficacy and safety had relative weightings of 64% and 36%, respectively. Efficacy and safety criteria with the highest values were pain relief (relative weight, 29%) and gastrointestinal effects (12%). Parecoxib received the highest overall score (93), followed by diclofenac (80), and ketorolac (75). Morphine scored the lowest (57), due to the lack of an opioid sparing effect. When opioid sparing was given a zero rating, parecoxib remained the highest scoring analgesic (93), followed by diclofenac (80), metamizole (76), and morphine (76). Parecoxib remained the most preferred analgesic in several other sensitivity analyses. CONCLUSION: This MCDA-based assessment suggests that parecoxib has the most favorable efficacy-safety profile among the assessed postoperative analgesics.

Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa.

BACKGROUND: The epidemics of HIV-1 and tuberculosis in South Africa are closely related. High mortality rates in co-infected patients have improved with antiretroviral therapy, but drug-resistant tuberculosis has emerged as a major cause of death. We assessed the prevalence and consequences of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis in a rural area in KwaZulu Natal, South Africa. METHODS: We undertook enhanced surveillance for drug-resistant tuberculosis with sputum culture and drug susceptibility testing in patients with known or suspected tuberculosis. Genotyping was done for isolates resistant to first-line and second-line drugs. RESULTS: From January, 2005, to March, 2006, sputum was obtained from 1539 patients. We detected MDR tuberculosis in 221 patients, of whom 53 had XDR tuberculosis. Prevalence among 475 patients with culture-confirmed tuberculosis was 39% (185 patients) for MDR and 6% (30) for XDR tuberculosis. Only 55% (26 of 47) of patients with XDR tuberculosis had never been previously treated for tuberculosis; 67% (28 of 42) had a recent hospital admission. All 44 patients with XDR tuberculosis who were tested for HIV were co-infected. 52 of 53 patients with XDR tuberculosis died, with median survival of 16 days from time of diagnosis (IQR 6-37) among the 42 patients with confirmed dates of death. Genotyping of isolates showed that 39 of 46 (85%, 95% CI 74-95) patients with XDR tuberculosis had similar strains. CONCLUSIONS: MDR tuberculosis is more prevalent than previously realised in this setting. XDR tuberculosis has been transmitted to HIV co-infected patients and is associated with high mortality. These observations warrant urgent intervention and threaten the success of treatment programmes for tuberculosis and HIV.

Multisectoral responses to HIV/AIDS: applying research to policy and practice.

The KwaZulu-Natal Enhancing Care Initiative is a program developed by a consortium of members who represent 4 sectors: academia, government, nongovernmental and community-based organizations, and the business sector. The Initiative was formed to develop a plan for improved care and support for people with HIV/AIDS and who live in resource-constrained settings in the province of KwaZulu-Natal, South Africa. A needs analysis helped to determine the following priorities in prevention, treatment, care, and support: training, grant-seeking, prevention, and care and treatment, including provision of antiretroviral therapy. A partnership approach resulted in better access to a wider community of people, information, and resources, and facilitated rapid program implementation. Creative approaches promptly translated research into policy and practice.

Gastroenteritis attributable to rotavirus in hospitalized Saudi Arabian children in the period 2007-2008.

PURPOSE: Rotavirus (RV) is a leading cause of severe gastroenteritis (GE) in children across the world. As there is a lack of epidemiological data for RV gastroenteritis (RVGE) in Saudi Arabia, this hospital-based study was designed to estimate the disease burden of RVGE and assess the prevalent RV types in Saudi children younger than 5 years of age. PATIENTS AND METHODS: Children hospitalized for acute GE were enrolled at four pediatric referral hospitals in Saudi Arabia. The study was conducted from February 2007 to March 2008 and used the World Health Organization's generic protocol for RVGE surveillance. The Vesikari severity scale was used to assess the severity of RVGE. Stool samples were tested for RV using an enzyme-linked immunosorbent assay. Samples were further typed by reverse transcriptase-polymerase chain reaction and hybridization assay for determining the G and P types. RESULTS: A total of 1,007 children were enrolled; the final analysis included 970 children, of whom 395 were RV positive, 568 were RV negative, and seven had unknown RV status. The proportion of RVGE among GE hospitalizations was 40.7% (95% confidence interval: 37.6-43.9). The highest percentage of RVGE hospitalizations (83.1%) was seen in children younger than 2 years of age. The highest proportion of RV among GE hospitalizations was in June 2007 with 57.1%. The most common RV types detected were G1P[8] (49.3%), G1G9P[8] (13.2%), and G9P[8] (9.6%). Before hospitalization, severe GE episodes occurred in 88.1% RV-positive and 79.6% RV-negative children. Overall, 94% children had recovered by the time they were discharged. Two children (one RV positive and one RV negative) died due to GE complications. CONCLUSION: RVGE is responsible for a high proportion of hospitalizations in Saudi children younger than 5 years of age. Routine RV vaccination has therefore been introduced into the national immunization program and may help reduce the morbidity, mortality, and disease burden associated with RVGE in Saudi Arabia.

Meningococcal disease in the Middle East and North Africa: an important public health consideration that requires further attention.

This paper reviews the epidemiological data describing meningococcal disease in the Middle East and North Africa (MENA). While meningococcal disease remains an important cause of endemic and epidemic disease in many MENA countries, existing published epidemiological data appear limited, fragmented, and collected via disparate methodologies. Children aged 5 years and younger are predominantly affected, though outbreaks of the disease often affect older age groups. Whilst serogroup A remains a main cause of meningococcal disease in the region, cases of serogroup B, W-135, and Y have been increasingly reported over the last two decades in some countries. The Hajj pilgrimage is a key factor influencing outbreaks and transmission, and the use of vaccines has minimized the effects on the home countries of the pilgrims and has decreased global dissemination of disease. Wider use of available polyvalent meningococcal conjugate vaccines may provide broader protection against the range of serogroups causing disease or posing a threat in the region. In addition, strengthening regional surveillance systems and regularly publishing reports with reliable estimates of disease incidence, carriage, disease-related mortality, and sequelae may facilitate the development of appropriate interventions and public health strategies regarding meningococcal disease within the region.

Successful integration of tuberculosis and HIV treatment in rural South Africa: the Sizonq'oba study.

BACKGROUND: Tuberculosis (TB) is the leading cause of death among HIV-infected patients worldwide. In KwaZulu-Natal, South Africa, 80% of TB patients are HIV coinfected, with high treatment default and mortality rates. Integrating TB and HIV care may be an effective strategy for improving outcomes for both diseases. METHODS: Prospective operational research study treating TB/HIV-coinfected patients in rural KwaZulu-Natal with once-daily antiretroviral (ARV) therapy concurrently with TB therapy by home-based, modified directly observed therapy. Patients were followed for 12 months after ARV initiation. RESULTS: Of 119 TB/HIV-coinfected patients enrolled, 67 (56%) were female, mean age was 34.0 years, and median CD4 count was 78.5 cells per cubic millimeter. After 12 months on ARVs, mean CD4 count increase was 211 cells per cubic millimeter, and 88% had an undetectable viral load; 84% completed TB treatment. Thirteen patients (11%) died; 10 (77%) with multidrug-resistant or extensively drug-resistant TB. There were few severe adverse events or immune reconstitution events. Adherence was high with 93% of study visits attended and 99% of ARV doses taken. CONCLUSIONS: Integration of TB and HIV treatment in a rural setting using concurrent home-based therapy resulted in excellent adherence and TB and HIV outcomes. This model may result in successful management of both diseases in other rural resource-poor settings.