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The Cochrane Database of Systematic... Nov 2019Sickle cell disease (SCD) is a group of inherited disorders of haemoglobin (Hb) structure in a person who has inherited two mutant globin genes (one from each parent),... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sickle cell disease (SCD) is a group of inherited disorders of haemoglobin (Hb) structure in a person who has inherited two mutant globin genes (one from each parent), at least one of which is always the sickle mutation. It is estimated that between 5% and 7% of the world's population are carriers of the mutant Hb gene, and SCD is the most commonly inherited blood disorder. SCD is characterized by distorted sickle-shaped red blood cells. Manifestations of the disease are attributed to either haemolysis (premature red cell destruction) or vaso-occlusion (obstruction of blood flow, the most common manifestation). Shortened lifespans are attributable to serious comorbidities associated with the disease, including renal failure, acute cholecystitis, pulmonary hypertension, aplastic crisis, pulmonary embolus, stroke, acute chest syndrome, and sepsis. Vaso-occlusion can lead to an acute, painful crisis (sickle cell crisis, vaso-occlusive crisis (VOC) or vaso-occlusive episode). Pain is most often reported in the joints, extremities, back or chest, but it can occur anywhere and can last for several days or weeks. The bone and muscle pain experienced during a sickle cell crisis is both acute and recurrent. Key pharmacological treatments for VOC include opioid analgesics, non-opioid analgesics, and combinations of drugs. Non-pharmacological approaches, such as relaxation, hypnosis, heat, ice and acupuncture, have been used in conjunction to rehydrating the patient and reduce the sickling process.
OBJECTIVES
To assess the analgesic efficacy and adverse events of pharmacological interventions to treat acute painful sickle cell vaso-occlusive crises in adults, in any setting.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, Embase via Ovid and LILACS, from inception to September 2019. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries.
SELECTION CRITERIA
Randomized, controlled, double-blind trials of pharmacological interventions, of any dose and by any route, compared to placebo or any active comparator, for the treatment (not prevention) of painful sickle cell VOC in adults.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio (RR) and number needed to treat for one additional event, using standard methods. Our primary outcomes were participant-reported pain relief of 50%, or 30%, or greater; Patient Global Impression of Change (PGIC) very much improved, or much or very much improved. Our secondary outcomes included adverse events, serious adverse events, and withdrawals due to adverse events. We assessed GRADE and created three 'Summary of findings' tables.
MAIN RESULTS
We included nine studies with data for 638 VOC events and 594 participants aged 17 to 42 years with SCD presenting to a hospital emergency department in a painful VOC. Three studies investigated a non-steroidal anti-inflammatory drug (NSAID) compared to placebo. One study compared an opioid with a placebo, two studies compared an opioid with an active comparator, two studies compared an anticoagulant with a placebo, and one study compared a combination of three drugs with a combination of four drugs. Risk of bias across the nine studies varied. Studies were primarily at an unclear risk of selection, performance, and detection bias. Studies were primarily at a high risk of bias for size with fewer than 50 participants per treatment arm; two studies had 50 to 199 participants per treatment arm (unclear risk). Non-steroidal anti-inflammatory drugs (NSAID) compared with placebo No data were reported regarding participant-reported pain relief of 50% or 30% or greater. The efficacy was uncertain regarding PGIC very much improved, and PGIC much or very much improved (no difference; 1 study, 21 participants; very low-quality evidence). Very low-quality, uncertain results suggested similar rates of adverse events across both the NSAIDs group (16/45 adverse events, 1/56 serious adverse events, and 1/56 withdrawal due to adverse events) and the placebo group (19/45 adverse events, 2/56 serious adverse events, and 1/56 withdrawal due to adverse events). Opioids compared with placebo No data were reported regarding participant-reported pain relief of 50% or 30%, PGIC, or adverse events (any adverse event, serious adverse events, and withdrawals due to adverse events). Opioids compared with active comparator No data were reported regarding participant-reported pain relief of 50% or 30% or greater. The results were uncertain regarding PGIC very much improved (33% of the opioids group versus 19% of the placebo group). No data were reported regarding PGIC much or very much improved. Very low-quality, uncertain results suggested similar rates of adverse events across both the opioids group (9/66 adverse events, and 0/66 serious adverse events) and the placebo group (7/64 adverse events, 0/66 serious adverse events). No data were reported regarding withdrawal due to adverse events. Quality of the evidence We downgraded the quality of the evidence by three levels to very low-quality because there are too few data to have confidence in results (e.g. too few participants per treatment arm). Where no data were reported for an outcome, we had no evidence to support or refute (quality of the evidence is unknown).
AUTHORS' CONCLUSIONS
This review identified only nine studies, with insufficient data for all pharmacological interventions for analysis. The available evidence is very uncertain regarding the efficacy or harm from pharmacological interventions used to treat pain related to sickle cell VOC in adults. This area could benefit most from more high quality, certain evidence, as well as the establishment of suitable registries which record interventions and outcomes for this group of people.
Topics: Acute Pain; Analgesics; Analgesics, Opioid; Anemia, Sickle Cell; Anti-Inflammatory Agents, Non-Steroidal; Humans; Pain Management; Pain Measurement; Peripheral Vascular Diseases; Randomized Controlled Trials as Topic
PubMed: 31742673
DOI: 10.1002/14651858.CD012187.pub2 -
Medicine Jul 2020Thalassemia is a hereditary disease, which caused economic burden in developing countries. This study evaluated the cost utility of new formulation of deferasirox... (Comparative Study)
Comparative Study
OBJECTIVES
Thalassemia is a hereditary disease, which caused economic burden in developing countries. This study evaluated the cost utility of new formulation of deferasirox (Jadenu) vs deferoxamine (Desferal) among B-Thalassemia-major patients from payer perspective in Iran.
METHODS
An economic-evaluation through Markov model was performed. A systematic review was conducted in order to evaluate the clinical effectiveness of comparators. Because of chelating therapy is weight-dependent, patients were assumed to be 2 years-old at initiation in first and 18 years-old in second scenario, and model was estimated lifetime costs and utilities. Costs were calculated to the Iran healthcare system through payer perspective and measured effectiveness using quality-adjusted life years (QALYs). One-way sensitivity analysis and budget impact analysis was also employed.
RESULTS
The 381 studies were retrieved from systematic searching through databases. After eliminating duplicate and irrelevant studies, 2 studies selected for evaluating the effectiveness. Jadenu was associated with an incremental cost-effectiveness ratio (ICER) of 1470.6 and 2544.7 US$ vs Desferal in first and second scenario respectively. The estimated ICER for Jadenu compared to generic deferoxamine was 2837.0 and 6924.1 US$ for first and second scenario respectively. For all scenarios Jadenu is presumed as cost-effective option based on calculated ICER which was lower than 1 gross domestic product per capita in Iran. Sensitivity analysis showed that different parameters except discount rate and indirect cost did not have impact on results. Based on budget impact analysis the estimated cost for patients using Desferal (based on the market share of brand) was 44,021,478 US$ in 3 years vs 42,452,606 US$ in replacing 33% of brand market share with Jadenu. This replacement corresponded to the cost saving of almost 1,568,872 US$ for the payers in 3 years. The calculated cost of using generic deferoxamine in all patients was 68,948,392 US$. The increase in the cost of using Jadenu for 10% of all patients in this scenario would be 934,427 US$ (1.36%) US$ at the first year.
CONCLUSIONS
Based on this analysis, film-coated deferasirox appeared to be cost-effective treatment in comparison with Desferal for managing child and adult chronic iron overload in B-thalassemia major patients of Iran.
Topics: Cost-Benefit Analysis; Deferasirox; Deferoxamine; Humans; Iran; Iron Chelating Agents; Tablets; beta-Thalassemia
PubMed: 32664096
DOI: 10.1097/MD.0000000000020949