BACKGROUND: The optimal duration of antiplatelet therapy (APT) after coronary stenting in patients at high bleeding risk (HBR) presenting with an acute coronary syndrome remains unclear. OBJECTIVES: The objective of this study was to investigate the safety and efficacy of an abbreviated APT regimen after coronary stenting in an HBR population presenting with acute or recent myocardial infarction. METHODS: In the MASTER DAPT trial, 4,579 patients at HBR were randomized after 1 month of dual APT (DAPT) to abbreviated (DAPT stopped and 11 months single APT or 5 months in patients with oral anticoagulants) or nonabbreviated APT (DAPT for minimum 3 months) strategies. Randomization was stratified by acute or recent myocardial infarction at index procedure. Coprimary outcomes at 335 days after randomization were net adverse clinical outcomes events (NACE); major adverse cardiac and cerebral events (MACCE); and type 2, 3, or 5 Bleeding Academic Research Consortium bleeding. RESULTS: NACE and MACCE did not differ with abbreviated vs nonabbreviated APT regimens in patients with an acute or recent myocardial infarction (n = 1,780; HR: 0.83; 95% CI: 0.61-1.12 and HR: 0.86; 95% CI: 0.62-1.19, respectively) or without an acute or recent myocardial infarction (n = 2,799; HR: 1.03; 95% CI: 0.77-1.38 and HR: 1.13; 95% CI: 0.80-1.59; Pinteraction = 0.31 and 0.25, respectively). Bleeding Academic Research Consortium 2, 3, or 5 bleeding was significantly reduced in patients with or without an acute or recent myocardial infarction (HR: 0.65; 95% CI: 0.46-0.91 and HR: 0.71; 95% CI: 0.54-0.92; Pinteraction = 0.72) with abbreviated APT. CONCLUSIONS: A 1-month DAPT strategy in patients with HBR presenting with an acute or recent myocardial infarction results in similar NACE and MACCE rates and reduces bleedings compared with a nonabbreviated DAPT strategy. (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020).
- MeSH
- antikoagulancia terapeutické užití MeSH
- dimaprit analogy a deriváty MeSH
- infarkt myokardu * farmakoterapie MeSH
- inhibitory agregace trombocytů škodlivé účinky MeSH
- kombinovaná farmakoterapie MeSH
- koronární angioplastika * metody MeSH
- krvácení chemicky indukované epidemiologie MeSH
- lidé MeSH
- polymery MeSH
- stenty MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Nonadherence to antiplatelet therapy after percutaneous coronary intervention (PCI) is common, even in clinical trials. OBJECTIVES: The purpose of this study was to investigate the impact of nonadherence to study protocol regimens in the MASTER DAPT (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen) trial. METHODS: At 1-month after PCI, 4,579 high bleeding risk patients were randomized to single antiplatelet therapy (SAPT) for 11 months (or 5 months in patients on oral anticoagulation [OAC]) or dual antiplatelet therapy (DAPT) for ≥2 months followed by SAPT. Coprimary outcomes included net adverse clinical events (NACE), major adverse cardiac and cerebral events (MACE), and major or clinically relevant nonmajor bleeding (MCB) at 335 days. Inverse probability-of-censoring weights were used to correct for nonadherence Academic Research Consortium type 2 or 3. RESULTS: In total, 464 (20.2%) patients in the abbreviated-treatment and 214 (9.4%) in the standard-treatment groups incurred nonadherence Academic Research Consortium type 2 or 3. At inverse probability-of-censoring weights analyses, NACE (HR: 1.01; 95% CI: 0.88-1.27) or MACE (HR: 1.07; 95% CI: 0.83-1.40) did not differ, and MCB was lower with abbreviated compared with standard treatment (HR: 0.51; 95% CI: 0.60-0.73) consistently across OAC subgroups; among OAC patients, SAPT discontinuation 6 months after PCI was associated with similar MACE and lower MCB (HR: 0.47; 95% CI: 0.22-0.99) compared with SAPT continuation. CONCLUSIONS: In the MASTER DAPT adherent population, 1-month compared with ≥3-month DAPT was associated with similar NACE or MACE and lower MCB. Among OAC patients, SAPT discontinuation after 6 months was associated with similar MACE and lower MCB than SAPT continuation (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020).
- MeSH
- adherence k farmakoterapii MeSH
- inhibitory agregace trombocytů terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- koronární angioplastika * metody MeSH
- krvácení chemicky indukované farmakoterapie epidemiologie MeSH
- lidé MeSH
- polymery MeSH
- stenty uvolňující léky * škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.
- MeSH
- Aspirin aplikace a dávkování škodlivé účinky MeSH
- časové faktory MeSH
- dvojitá slepá metoda MeSH
- gastrointestinální krvácení chemicky indukované prevence a kontrola MeSH
- hodnocení rizik MeSH
- inhibitory agregace trombocytů aplikace a dávkování škodlivé účinky MeSH
- inhibitory faktoru Xa aplikace a dávkování škodlivé účinky MeSH
- inhibitory protonové pumpy aplikace a dávkování škodlivé účinky MeSH
- kardiovaskulární nemoci diagnóza farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- onemocnění periferních arterií diagnóza farmakoterapie MeSH
- pantoprazol aplikace a dávkování škodlivé účinky MeSH
- prospektivní studie MeSH
- pseudomembranózní enterokolitida chemicky indukované mikrobiologie MeSH
- rivaroxaban aplikace a dávkování škodlivé účinky MeSH
- rizikové faktory MeSH
- rozvrh dávkování léků MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528). CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.
- MeSH
- antikoagulancia aplikace a dávkování škodlivé účinky MeSH
- aplikace orální MeSH
- Aspirin aplikace a dávkování škodlivé účinky MeSH
- dvojitá slepá metoda MeSH
- gastrointestinální krvácení chemicky indukované epidemiologie prevence a kontrola MeSH
- inhibitory protonové pumpy aplikace a dávkování MeSH
- kardiovaskulární nemoci prevence a kontrola MeSH
- kombinovaná farmakoterapie škodlivé účinky metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- pantoprazol aplikace a dávkování MeSH
- peptický vřed chemicky indukované epidemiologie prevence a kontrola MeSH
- rivaroxaban aplikace a dávkování škodlivé účinky MeSH
- rozvrh dávkování léků MeSH
- senioři MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications. METHODS: This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS: Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043). INTERPRETATION: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding. FUNDING: Bayer AG.
- MeSH
- amputace statistika a číselné údaje MeSH
- Aspirin aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- cévní mozková příhoda epidemiologie etiologie prevence a kontrola MeSH
- dolní končetina krevní zásobení chirurgie MeSH
- dvojitá slepá metoda MeSH
- incidence MeSH
- infarkt myokardu epidemiologie etiologie prevence a kontrola MeSH
- inhibitory agregace trombocytů aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- inhibitory faktoru Xa aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- kardiovaskulární nemoci mortalita prevence a kontrola MeSH
- kombinovaná farmakoterapie MeSH
- krvácení chemicky indukované MeSH
- lidé středního věku MeSH
- lidé MeSH
- morbidita MeSH
- nemoci arterie carotis komplikace farmakoterapie epidemiologie MeSH
- onemocnění periferních arterií komplikace farmakoterapie epidemiologie MeSH
- rivaroxaban aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- rozvrh dávkování léků MeSH
- senioři MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. AIMS: We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. METHODS: We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. RESULTS: Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. CONCLUSIONS: NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research.
- MeSH
- Aspirin terapeutické užití MeSH
- cévní mozková příhoda diagnóza farmakoterapie epidemiologie MeSH
- dvojitá slepá metoda MeSH
- fibrinolytika terapeutické užití MeSH
- inhibitory agregace trombocytů terapeutické užití MeSH
- inhibitory faktoru Xa terapeutické užití MeSH
- intrakraniální embolie diagnóza farmakoterapie epidemiologie MeSH
- komorbidita MeSH
- lidé středního věku MeSH
- lidé MeSH
- rasové skupiny MeSH
- rivaroxaban terapeutické užití MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sexuální faktory MeSH
- tranzitorní ischemická ataka diagnóza farmakoterapie epidemiologie MeSH
- věkové faktory MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
BACKGROUND: Long-term aspirin prevents vascular events but is only modestly effective. Rivaroxaban alone or in combination with aspirin might be more effective than aspirin alone for vascular prevention in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). Rivaroxaban as well as aspirin increase upper gastrointestinal (GI) bleeding and this might be prevented by proton pump inhibitor therapy. METHODS: Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) is a double-blind superiority trial comparing rivaroxaban 2.5 mg twice daily combined with aspirin 100 mg once daily or rivaroxaban 5 mg twice daily vs aspirin 100 mg once daily for prevention of myocardial infarction, stroke, or cardiovascular death in patients with stable CAD or PAD. Patients not taking a proton pump inhibitor were also randomized, using a partial factorial design, to pantoprazole 40 mg once daily or placebo. The trial was designed to have at least 90% power to detect a 20% reduction in each of the rivaroxaban treatment arms compared with aspirin and to detect a 50% reduction in upper GI complications with pantoprazole compared with placebo. RESULTS: Between February 2013 and May 2016, we recruited 27,395 participants from 602 centres in 33 countries; 17,598 participants were included in the pantoprazole vs placebo comparison. At baseline, the mean age was 68.2 years, 22.0% were female, 90.6% had CAD, and 27.3% had PAD. CONCLUSIONS: COMPASS will provide information on the efficacy and safety of rivaroxaban, alone or in combination with aspirin, in the long-term management of patients with stable CAD or PAD, and on the efficacy and safety of pantoprazole in preventing upper GI complications in patients receiving antithrombotic therapy.
- MeSH
- antikoagulancia terapeutické užití MeSH
- kardiovaskulární nemoci prevence a kontrola MeSH
- lidé MeSH
- randomizované kontrolované studie jako téma metody MeSH
- směrnice pro lékařskou praxi jako téma * MeSH
- trombolytická terapie normy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
This paper examines the impact of demographic change resulting from AIDS deaths on the population of Nigeria. The population of Nigeria is increasing annually at a growth rate of 3.2% and also with the increase in prevalence rate of HIV/AIDS. The purpose of this paper is to use a demographic dynamic microsimulation method to look at the impact of death resulting from AIDS given the fact that demographic variables such as fertility, mortality, migration and life expectancy influence population growth rate significantly. In order to determine the impact of birth and death rates resulting from HIV/AIDS and other causes on the population structure over time, a dynamic microsimulation model is used to capture these demographic trends. Dynamic microsimulation models focus on the simulation of behaviour over time. Micro-units are dynamically aged according to a life-cycle behavioural model. Each year individuals are born, become educated, leave home, obtain employment, cohabit and marry, have children, sometimes divorce, and die. Whenever one of these demographic events occurs in a given period, it affects the likelihood of subsequent events happening. From the result we observed that the impact of HIV/AIDS on the population is considerable. It is about 2% under the without HIV/AIDS and with HIV/AIDS scenarios. We also observed an increase in the number of women aged in their 30s giving birth and an increase in the dependency ratio of the old people to 4.2% by 2015. Finally we observed no significant change among the working age population.
- Klíčová slova
- mikrosimulační model,
- MeSH
- AIDS * MeSH
- bezpečný sex MeSH
- demografie * MeSH
- HIV infekce * MeSH
- lidé MeSH
- mortalita MeSH
- populační předpověď MeSH
- populační růst MeSH
- porodnost MeSH
- rizikové faktory MeSH
- sexuální chování MeSH
- socioekonomické faktory MeSH
- věkové faktory MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Geografické názvy
- Nigérie MeSH
INTRODUCTION: The aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe. METHODS: This was an international, prospective, multi-centre one-month study. Patients who suffered an OHCA during October 2014 who were attended and/or treated by an Emergency Medical Service (EMS) were eligible for inclusion in the study. Data were extracted from national, regional or local registries. RESULTS: Data on 10,682 confirmed OHCAs from 248 regions in 27 countries, covering an estimated population of 174 million. In 7146 (66%) cases, CPR was started by a bystander or by the EMS. The incidence of CPR attempts ranged from 19.0 to 104.0 per 100,000 population per year. 1735 had ROSC on arrival at hospital (25.2%), Overall, 662/6414 (10.3%) in all cases with CPR attempted survived for at least 30 days or to hospital discharge. CONCLUSION: The results of EuReCa ONE highlight that OHCA is still a major public health problem accounting for a substantial number of deaths in Europe. EuReCa ONE very clearly demonstrates marked differences in the processes for data collection and reported outcomes following OHCA all over Europe. Using these data and analyses, different countries, regions, systems, and concepts can benchmark themselves and may learn from each other to further improve survival following one of our major health care events.
- MeSH
- analýza přežití MeSH
- incidence MeSH
- kardiopulmonální resuscitace statistika a číselné údaje MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- registrace MeSH
- senioři MeSH
- urgentní zdravotnické služby statistika a číselné údaje MeSH
- zástava srdce mimo nemocnici mortalita terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa epidemiologie MeSH