Comparative efficacy and safety of warfarin care bundles and novel oral anticoagulants in patients with atrial fibrillation: a systematic review and network meta-analysis.

Warfarin care bundles (e.g. genotype-guided warfarin dosing, patient's self-testing [PST] or patient's self-management [PSM] and left atrial appendage closure) are based on the concept of combining several interventions to improve anticoagulation care. NOACs are also introduced for stroke prevention in atrial fibrillation (SPAF). However, these interventions have not been compared in head-to-head trials yet. We did a network meta-analysis based on a systematic review of randomized controlled trials comparing anticoagulant interventions for SPAF. Studies comparing these interventions in adults, whether administered alone or as care bundles were included in the analyses. The primary efficacy outcome was stroke and the primary safety outcome was major bleeding. Thirty-seven studies, involving 100,142 patients were assessed. Compared to usual care, PSM significantly reduced the risk of stroke (risk ratio [RR] 0.24, 95% CI 0.08-0.68). For major bleeding, edoxaban 60 mg (0.80, 0.71-0.90), edoxaban 30 mg (0.48, 0.42-0.56), and dabigatran 110 mg (0.81, 0.71-0.94) significantly reduced the risk of major bleeding compared with usual warfarin care. Cluster rank plot incorporating stroke and major bleeding outcomes indicates that some warfarin care bundles perform as well as NOACs. Both interventions are therefore viable options to be considered for SPAF. Additional studies including head-to-head trials and cost-effectiveness evaluation are still warranted.

Cost-effectiveness of warfarin care bundles and novel oral anticoagulants for stroke prevention in patients with atrial fibrillation in Thailand.

INTRODUCTION: Novel oral anticoagulants (NOACs) and warfarin care bundles (e.g. genotyping, patient self-testing or self-management) are alternatives to usual warfarin care for stroke prevention in patients with atrial fibrillation (AF). We aim to evaluate the cost-effectiveness of NOACs and warfarin care bundles in patients with AF in a middle-income country, Thailand. MATERIALS AND METHODS: A Markov model was used to evaluate the economic and treatment outcomes of warfarin care bundles and NOACs compared with usual warfarin care. Cost-effectiveness was assessed from a societal perspective over a lifetime horizon with 3% discount rate in a hypothetical cohort of 65-year-old atrial fibrillation patients. Input parameters were derived from published literature, meta-analysis and local data when available. The outcome measure was incremental cost per quality-adjusted life years (QALY) gained (ICER). RESULTS: Using USD5104 as the threshold of willingness-to-pay per QALY, patient's self-management of warfarin was cost-effective when compared to usual warfarin care, with an ICER of USD1395/QALY from societal perspective. All NOACs were not cost-effective in Thailand, with ICER ranging from USD8678 to USD14,247/QALY. When compared to the next most effective intervention, patient's self-testing and genotype-guided warfarin dosing were dominated. In the cost-effectiveness acceptability curve, patient's self-management had the highest probability of being cost-effective in Thailand, approximately 78%. Results were robust over a range of inputs in sensitivity analyses. CONCLUSIONS: In Thailand, NOACs were unlikely to be cost-effective at current prices. Conversely, patient's self-management is a highly cost-effective intervention and may be considered for adoption in developing regions with resource-limited healthcare systems.

Animal-assisted therapy for dementia.

BACKGROUND: Dementia is a chronic condition which progressively affects memory and other cognitive functions, social behaviour, and ability to carry out daily activities. To date, no treatment is clearly effective in preventing progression of the disease, and most treatments are symptomatic, often aiming to improve people's psychological symptoms or behaviours which are challenging for carers. A range of new therapeutic strategies has been evaluated in research, and the use of trained animals in therapy sessions, termed animal-assisted therapy (AAT), is receiving increasing attention. OBJECTIVES: To evaluate the efficacy and safety of animal-assisted therapy for people with dementia. SEARCH METHODS: We searched ALOIS: the Cochrane Dementia and Cognitive Improvement Group's Specialised Register on 5 September 2019. ALOIS contains records of clinical trials identified from monthly searches of major healthcare databases, trial registries, and grey literature sources. We also searched MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCOhost), ISI Web of Science, ClinicalTrials.gov, and the WHO's trial registry portal. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster-randomised trials, and randomised cross-over trials that compared AAT versus no AAT, AAT using live animals versus alternatives such as robots or toys, or AAT versus any other active intervention. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of Cochrane Dementia. Two review authors independently assessed the eligibility and risk of bias of the retrieved records. We expressed our results using mean difference (MD), standardised mean difference (SMD), and risk ratio (RR) with their 95% confidence intervals (CIs) where appropriate. MAIN RESULTS: We included nine RCTs from 10 reports. All nine studies were conducted in Europe and the US. Six studies were parallel-group, individually randomised RCTs; one was a randomised cross-over trial; and two were cluster-RCTs that were possibly related where randomisation took place at the level of the day care and nursing home. We identified two ongoing trials from trial registries. There were three comparisons: AAT versus no AAT (standard care or various non-animal-related activities), AAT using live animals versus robotic animals, and AAT using live animals versus the use of a soft animal toy. The studies evaluated 305 participants with dementia. One study used horses and the remainder used dogs as the therapy animal. The duration of the intervention ranged from six weeks to six months, and the therapy sessions lasted between 10 and 90 minutes each, with a frequency ranging from one session every two weeks to two sessions per week. There was a wide variety of instruments used to measure the outcomes. All studies were at high risk of performance bias and unclear risk of selection bias. Our certainty about the results for all major outcomes was very low to moderate. Comparing AAT versus no AAT, participants who received AAT may be slightly less depressed after the intervention (MD -2.87, 95% CI -5.24 to -0.50; 2 studies, 83 participants; low-certainty evidence), but they did not appear to have improved quality of life (MD 0.45, 95% CI -1.28 to 2.18; 3 studies, 164 participants; moderate-certainty evidence). There were no clear differences in all other major outcomes, including social functioning (MD -0.40, 95% CI -3.41 to 2.61; 1 study, 58 participants; low-certainty evidence), problematic behaviour (SMD -0.34, 95% CI -0.98 to 0.30; 3 studies, 142 participants; very-low-certainty evidence), agitation (SMD -0.39, 95% CI -0.89 to 0.10; 3 studies, 143 participants; very-low-certainty evidence), activities of daily living (MD 4.65, 95% CI -16.05 to 25.35; 1 study, 37 participants; low-certainty evidence), and self-care ability (MD 2.20, 95% CI -1.23 to 5.63; 1 study, 58 participants; low-certainty evidence). There were no data on adverse events. Comparing AAT using live animals versus robotic animals, one study (68 participants) found mixed effects on social function, with longer duration of physical contact but shorter duration of talking in participants who received AAT using live animals versus robotic animals (median: 93 seconds with live versus 28 seconds with robotic for physical contact; 164 seconds with live versus 206 seconds with robotic for talk directed at a person; 263 seconds with live versus 307 seconds with robotic for talk in total). Another study showed no clear differences between groups in behaviour measured using the Neuropsychiatric Inventory (MD -6.96, 95% CI -14.58 to 0.66; 78 participants; low-certainty evidence) or quality of life (MD -2.42, 95% CI -5.71 to 0.87; 78 participants; low-certainty evidence). There were no data on the other outcomes. Comparing AAT using live animals versus a soft toy cat, one study (64 participants) evaluated only social functioning, in the form of duration of contact and talking. The data were expressed as median and interquartile ranges. Duration of contact was slightly longer in participants in the AAT group and duration of talking slightly longer in those exposed to the toy cat. This was low-certainty evidence. AUTHORS' CONCLUSIONS: We found low-certainty evidence that AAT may slightly reduce depressive symptoms in people with dementia. We found no clear evidence that AAT affects other outcomes in this population, with our certainty in the evidence ranging from very-low to moderate depending on the outcome. We found no evidence on safety or effects on the animals. Therefore, clear conclusions cannot yet be drawn about the overall benefits and risks of AAT in people with dementia. Further well-conducted RCTs are needed to improve the certainty of the evidence. In view of the difficulty in achieving blinding of participants and personnel in such trials, future RCTs should work on blinding outcome assessors, document allocation methods clearly, and include major patient-important outcomes such as affect, emotional and social functioning, quality of life, adverse events, and outcomes for animals.

Systematic review of cost-effectiveness studies of human papillomavirus (HPV) vaccination: 9-Valent vaccine, gender-neutral and multiple age cohort vaccination.

BACKGROUND: The success of human papillomavirus (HPV) national immunization program depends on effective strategies in optimizing the uptake of HPV vaccine. Given the increasing number of economic evaluations, this review was conducted to update the economic evidence on HPV vaccination, by focusing on: (i) 9-valent vaccine compared to bi- or quadrivalent vaccine; (ii) gender-neutral vaccination compared to female only vaccination; and (iii) multiple age cohort immunization compared to single age cohort immunization. METHODS: Searches were performed until June 2016 using 4 databases: PubMed; Embase; Cochrane Library; and LILACS. The combined WHO, Drummond and CHEERS checklist were used to evaluate the quality of included studies. RESULTS: Thirty-four studies were included in the review and most of them were conducted in high-income countries. The inclusion of adolescent boys in vaccination program was found to be cost-effective if vaccine price and coverage was low. When coverage for female was above 75%, gender-neutral vaccination was less cost-effective than when targeting only girls aged 9-18 years. Current evidence does not show conclusive proof of greater cost-effectiveness of 9-valent vaccine compared to the older HPV vaccines as the price for 9-valent vaccine was still uncertain. Multicohort immunization strategy was cost-effective in the age range 9-14 years but the upper age limit at which vaccination was no longer cost-effective needs to be further investigated. Key influential parameters identified were duration of vaccine protection, vaccine price, coverage, and discounting rates. CONCLUSIONS: These findings are expected to support policy-makers in making recommendations for HPV immunization programs on either switching to the 9-valent vaccine or inclusion of adolescent boys' vaccination or extending the age of vaccination.

Interventions and Strategies to Improve Oral Anticoagulant Use in Patients with Atrial Fibrillation: A Systematic Review of Systematic Reviews.

INTRODUCTION: Anticoagulation therapy is the fundamental approach for stroke prevention in atrial fibrillation (AF) patients. Numerous systematic reviews comparing anticoagulation strategies have been published. We aim to summarize the efficacy and safety evidence of these strategies in AF patients from previously published systematic reviews. METHODS: We searched PubMed, EMBASE and Cochrane library from inception to Feb 24th, 2017, to identify systematic reviews and meta-analyses of randomized controlled trials that assessed interventions or strategies to improve oral anticoagulant use in AF patients. RESULTS: Thirty-four systematic reviews were eligible for inclusion but only 11 were included in the qualitative analyses, corresponding to 40 unique meta-analyses, as the remaining systematic reviews had overlapping primary studies. There was insufficient evidence to support the efficacy of genotype-guided dosing and pharmacist-managed anticoagulation clinics for stroke prevention in AF patients. Conversely, patient's self-management and novel oral anticoagulants (NOACs), in general were superior to warfarin for preventing stroke and reducing mortality. All interventions showed comparable risk of major bleeding with warfarin. CONCLUSION: Findings from this overview support the superiority of NOACs and patient's self-management for preventing stroke in AF patients. However, uncertainties remain on the benefits of genotype-guided dosing and pharmacist-managed anticoagulation clinics due to poor quality evidence, and future research is warranted.