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BMC Medicine May 2013The role of drug-eluting balloons (DEB) is unclear. Increasing evidence has shown a benefit for the treatment of in-stent restenosis. Its effect on de novo coronary... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The role of drug-eluting balloons (DEB) is unclear. Increasing evidence has shown a benefit for the treatment of in-stent restenosis. Its effect on de novo coronary lesions is more controversial. Several smaller randomized trials found conflicting results.
METHODS
This is a systematic review and meta-analysis of randomized controlled trials (RCT) evaluating the effect of local Paclitaxel delivery/drug eluting balloons (DEB) (+/- bare metal stent) compared to current standard therapy (stenting) to treat de novo coronary lesions. Data sources for RCT were identified through a literature search from 2005 through 28 December 2012. The main endpoints of interest were target lesion revascularization (TLR), major adverse cardiac events (MACE), binary in-segment restenosis, stent thrombosis (ST), myocardial infarction (MI), late lumen loss (LLL) and mortality. A random effects model was used to calculate the pooled relative risks (RR) with 95% confidence intervals.
RESULTS
Eight studies (11 subgroups) and a total of 1,706 patients were included in this analysis. Follow-up duration ranged from 6 to 12 months. Overall, DEB showed similar results to the comparator treatment. The relative risk (RR) for MACE was 0.95 (0.64 to 1.39); P = 0.776, for mortality it was 0.79 (0.30 to 2.11), P = 0.644, for stent thrombosis it was 1.45 (0.42 to 5.01), P = 0.560, for MI it was 1.26 (0.49 to 3.21), P = 0.629, for TLR it was 1.09 (0.71 to 1.68); P = 0.700 and for binary in-stent restenosis it was 0.96 (0.48 to 1.93), P = 0.918. Compared to bare metal stents (BMS), DEB showed a lower LLL (- 0.26 mm (-0.51 to 0.01)) and a trend towards a lower MACE risk (RR 0.66 (0.43 to 1.02)).
CONCLUSION
Overall, drug-eluting balloons (+/- bare metal stent) are not superior to current standard therapies (BMS or drug eluting stent (DES)) in treating de novo coronary lesions. However, the performance of DEB seems to lie in between DES and BMS with a trend towards superiority over BMS alone. Therefore, DEB may be considered in patients with contraindications for DES. The heterogeneity between the included studies is a limitation of this meta-analysis; different drug-eluting balloons have been used.
Topics: Cardiovascular Agents; Coronary Artery Disease; Drug Delivery Systems; Humans; Paclitaxel; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 23657123
DOI: 10.1186/1741-7015-11-123 -
Health Technology Assessment... Jun 2020Impacted third molars are third molars that are blocked, by soft tissue or bone, from fully erupting through the gum. This can cause pain and disease. The treatment...
BACKGROUND
Impacted third molars are third molars that are blocked, by soft tissue or bone, from fully erupting through the gum. This can cause pain and disease. The treatment options for people with impacted third molars are removal or retention with standard care. If there are pathological changes, the current National Institute for Health and Care Excellence guidance states that the impacted third molar should be removed.
OBJECTIVE
The objective of this study was to appraise the clinical effectiveness and cost-effectiveness of the prophylactic removal of impacted mandibular third molars compared with retention of, and standard care for, impacted third molars.
METHODS
Five electronic databases were searched (1999 to 29 April 2016) to identify relevant evidence [The Cochrane Library (searched 4 April 2016 and 29 April 2016), MEDLINE (searched 4 April 2016 and 29 April 2016), EMBASE (searched 4 April 2016 and 29 April 2016), EconLit (searched 4 April 2016 and 29 April 2016) and NHS Economic Evaluation Database (searched 4 April 2016)]. Studies that compared the prophylactic removal of impacted mandibular third molars with retention and standard care or studies that assessed the outcomes from either approach were included. The clinical outcomes considered were pathology associated with retention, post-operative complications following extraction and adverse effects of treatment. Cost-effectiveness outcomes included UK costs and health-related quality-of-life measures. In addition, the assessment group constructed a de novo economic model to compare the cost-effectiveness of a prophylactic removal strategy with that of retention and standard care.
RESULTS
The clinical review identified four cohort studies and nine systematic reviews. In the two studies that reported on surgical complications, no serious complications were reported. Pathological changes due to retention of asymptomatic impacted mandibular third molars were reported by three studies. In these studies, the extraction rate for retained impacted mandibular third molars varied from 5.5% to 31.4%; this variation can be explained by the differing follow-up periods (i.e. 1 and 5 years). The findings from this review are consistent with the findings from previous systematic reviews. Two published cost-effectiveness studies were identified. The authors of both studies concluded that, to their knowledge, there is currently no economic evidence to support the prophylactic removal of impacted mandibular third molars. The results generated by the assessment group's lifetime economic model indicated that the incremental cost-effectiveness ratio per quality-adjusted life-year gained for the comparison of a prophylactic removal strategy with a retention and standard care strategy is £11,741 for people aged 20 years with asymptomatic impacted mandibular third molars. The incremental cost per person associated with prophylactic extraction is £55.71, with an incremental quality-adjusted life-year gain of 0.005 per person. The base-case incremental cost-effectiveness ratio per quality-adjusted life-year gained was found to be robust when a range of sensitivity and scenario analyses were carried out.
LIMITATIONS
Limitations of the study included that no head-to-head trials comparing the effectiveness of prophylactic removal of impacted mandibular third molars with retention and standard care were identified with the assessment group model that was built on observational data. Utility data on impacted mandibular third molars and their symptoms are lacking.
CONCLUSIONS
The evidence comparing the prophylactic removal of impacted mandibular third molars with retention and standard care is very limited. However, the results from an exploratory assessment group model, which uses available evidence on symptom development and extraction rates of retained impacted mandibular third molars, suggest that prophylactic removal may be the more cost-effective strategy.
FUTURE WORK
Effectiveness evidence is lacking. Head-to-head trials comparing the prophylactic removal of trouble-free impacted mandibular third molars with retention and watchful waiting are required. If this is not possible, routine clinical data, using common definitions and outcome reporting methods, should be collected.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42016037776.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 30. See the NIHR Journals Library website for further project information.
Topics: Cost-Benefit Analysis; Humans; Molar, Third; Treatment Outcome; United Kingdom
PubMed: 32589125
DOI: 10.3310/hta24300 -
Global Spine Journal Jun 2023Primary objectives were outcomes comparison of instrumented surgery used for de-novo spinal infections in terms of infection recurrence, reoperations, primary failure,... (Review)
Review
OBJECTIVES
Primary objectives were outcomes comparison of instrumented surgery used for de-novo spinal infections in terms of infection recurrence, reoperations, primary failure, mortality, and length of stay relative to non-instrumented surgery. Secondary objectives were outcomes for surgical and non-surgical treatment of de-novo spinal infections regarding recurrence of infection, mortality, quality of life, and length-of-stay.
METHODS
A systematic literature review was performed using the PubMed database. Studies comparing outcome variables of patients with de-novo spinal infections (DNSI) treated with and without instrumentation and surgical versus non-surgical treatment were included. Studies primarily focusing on epidural abscesses or non-de-novo infections were excluded. A meta-analysis was performed for infection recurrence, reoperation, primary treatment failure, mortality, and quality-of-life parameters.
RESULTS
A total of 17 retrospective studies with 2.069 patients met the inclusion criteria. 1.378 patients received surgical treatment with or without instrumentation; 676 patients were treated non-surgically. For the comparison of instrumented to non-instrumented surgery Odds-Ratios were .98 (P = .95) for infection recurrence, .83 (P = .92) for primary failure, .53 (P = .02) for mortality and .32 (P = .05) for reoperation. For the comparison of non-surgical to surgical treatment, Odds-Ratios were .98 (P = .95) for infection recurrence, and 1.05 (P = .89) for mortality.
CONCLUSION
Available data support that instrumented surgery can be performed safely without higher rates of infection recurrence or primary failure and lower reoperation and mortality rates compared to nonsurgical treatment for DNSI. Furthermore, spine surgical treatment may generally be performed without higher risk of infection recurrence and mortality and better quality-of-life outcomes compared to generic non-surgical treatment.
PubMed: 36510352
DOI: 10.1177/21925682221145603 -
Health Technology Assessment... Jan 2024Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the age of 5 years, but it can develop at any age. Atopic dermatitis is characterised by dry, inflamed skin accompanied by intense itchiness (pruritus).
OBJECTIVES
To appraise the clinical and cost effectiveness of abrocitinib, tralokinumab and upadacitinib within their marketing authorisations as alternative therapies for treating moderate-to-severe atopic dermatitis compared to systemic immunosuppressants (first-line ciclosporin A or second-line dupilumab and baricitinib).
DATA SOURCES
Studies were identified from an existing systematic review (search date 2019) and update searches of electronic databases (MEDLINE, EMBASE, CENTRAL) to November 2021, from bibliographies of retrieved studies, clinical trial registers and evidence provided by the sponsoring companies of the treatments under review.
METHODS
A systematic review of the clinical effectiveness literature was carried out and a network meta-analysis undertaken for adults and adolescents at different steps of the treatment pathway. The primary outcome of interest was a combined response of Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4; where this was consistently unavailable for a step in the pathway, an analysis of Eczema Area and Severity Index 75 was conducted. A de novo economic model was developed to assess cost effectiveness from the perspective of the National Health Service in England. The model structure was informed through systematic review of the economic literature and by consulting clinical experts. Effectiveness data were obtained from the network meta-analysis. Costs and utilities were obtained from the evidence provided by sponsoring companies and standard UK sources.
RESULTS
Network meta-analyses indicate that abrocitinib 200 mg and upadacitinib 30 mg may be more effective, and tralokinumab may be less effective than dupilumab and baricitinib as second-line systemic therapies. Abrocitinib 100 mg and upadacitinib 15 mg have a more similar effectiveness to dupilumab. Upadacitinib 30 and 15 mg are likely to be more effective than ciclosporin A as a first-line therapy. Upadacitinib 15 mg, abrocitinib 200 and 100 mg may be more effective than dupilumab in adolescents. The cost effectiveness of abrocitinib and upadacitinib for both doses is dependent on the subgroup of interest. Tralokinumab can be considered cost-effective as a second-line systemic therapy owing to greater cost savings per quality-adjusted life-year lost.
CONCLUSIONS
The primary strength of the analysis of the three new drugs compared with current practice for each of the subpopulations is the consistent approach to the assessment of clinical and cost effectiveness. However, the conclusions are limited by the high uncertainty around the clinical effectiveness and lack of data for the primary outcome for comparisons with baricitinib and for the adolescent and adult first-line populations.
FUTURE WORK AND LIMITATIONS
The most significant limitation that Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4 could not be obtained for the adolescent and adult first-line systemic treatment populations is due to a paucity of data for dupilumab and ciclosporin A. A comparison of the new drugs against one another in addition to current practice would be beneficial to provide a robust view on which treatments are the most cost-effective.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42021266219.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: 135138) and is published in full in ; Vol. 28, No. 4. See the NIHR Funding and Awards website for further award information.
Topics: Child; Adult; Adolescent; Humans; Child, Preschool; Dermatitis, Atopic; Cyclosporine; State Medicine; Treatment Outcome; Cost-Benefit Analysis; Eczema; Antibodies, Monoclonal; Purines; Heterocyclic Compounds, 3-Ring; Sulfonamides; Pyrazoles; Pyrimidines; Azetidines
PubMed: 38343072
DOI: 10.3310/LEXB9006 -
Experimental and Clinical... Feb 2022Our aim was to perform a comprehensive literature review on the pathogenesis of squamous anal cancerin patients after solid-organ transplant. Medical databases were... (Review)
Review
Our aim was to perform a comprehensive literature review on the pathogenesis of squamous anal cancerin patients after solid-organ transplant. Medical databases were consulted until June 1, 2020, for potentially relevant publications.All studies on pathogenesis of de novo anal squamous cell carcinoma in solid-organ transplant recipients were included. Two researchers independently performed study selection, quality assessment, and data extraction and analysis. Twenty-one studies were included.None ofthe selected papers had been solely focused on carcinogenesis. Most ofthe studies identified human papillomavirus infection and immunosuppression to be significantly correlated with the development of de novo anal cancer in adult solid organ transplant recipients. CD4+ T-cell depletion and inactivation oftumor suppressor pathways were mainly implicated. All solid-organ transplant recipients, especially those who were human papillomavirus positive, were shown to be at increased risk for the development of posttransplant anal cancer. Further studies are needed to determine the specific mechanisms of pathogenesis according to different solid-organ transplant populations.
Topics: Adult; Anus Neoplasms; Carcinogenesis; Carcinoma, Squamous Cell; Humans; Organ Transplantation; Transplant Recipients; Treatment Outcome
PubMed: 35282809
DOI: 10.6002/ect.2021.0412 -
Cancers Mar 2021Immunosuppressive therapy after solid organ transplantation leads to the development of cancer in many recipients. Analysis of the occurrence of different types of de... (Review)
Review
Immunosuppressive therapy after solid organ transplantation leads to the development of cancer in many recipients. Analysis of the occurrence of different types of de novo carcinomas in relation to specific immunosuppressive drugs may give insight into their carcinogenic process and carcinogenesis in general. Therefore, a systematic search was performed in Embase and PubMed. Studies describing over five de novo carcinomas in patients using immunosuppressive drugs after solid organ transplantation were included. Incidence per 1000 person-years was calculated with DerSimonian-Laird random effects model and odds ratio for developing carcinomas with the Mantel-Haenszel test. Following review of 5606 papers by title and abstract, a meta-analysis was conducted of 82 studies. The incidence rate of de novo carcinomas was 8.41. Patients receiving cyclosporine developed more de novo carcinomas compared to tacrolimus (OR1.56, 95%CI 1.00-2.44) and mycophenolate (OR1.26, 95%CI 1.03-1.56). Patients receiving azathioprine had higher odds to develop de novo carcinomas compared to mycophenolate (OR3.34, 95%CI 1.29-8.65) and head and neck carcinoma compared to tacrolimus (OR3.78, 95%CI 1.11-12.83). To conclude, patients receiving immunosuppressive drugs after solid organ transplantation have almost a 20-fold increased likelihood of developing carcinomas, with the highest likelihood for patients receiving cyclosporine A and azathioprine. Looking into altered immune pathways affected by immunosuppressive drugs might lead to better understanding of carcinogenesis in general.
PubMed: 33807849
DOI: 10.3390/cancers13051122 -
Health Technology Assessment... Dec 2022Malnutrition worsens the health of frail older adults. Current treatments for malnutrition may include prescribed oral nutritional supplements, which are multinutrient... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malnutrition worsens the health of frail older adults. Current treatments for malnutrition may include prescribed oral nutritional supplements, which are multinutrient products containing macronutrients and micronutrients.
OBJECTIVE
To assess the effectiveness and cost-effectiveness of oral nutritional supplements (with or without other dietary interventions) in frail older people who are malnourished or at risk of malnutrition.
DATA SOURCES
MEDLINE, EMBASE, Cochrane Library, Scopus, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and grey literature were searched from inception to 13 September 2021.
REVIEW METHODS
A systematic review and meta-analysis was conducted to evaluate the effectiveness and cost-effectiveness of oral nutritional supplements in frail older people (aged ≥ 65 years) who are malnourished or at risk of malnutrition (defined as undernutrition as per National Institute for Health and Care Excellence guidelines). Meta-analysis and network meta-analysis were undertaken, where feasible, along with a narrative synthesis. A cost-effectiveness review was reported narratively. A de novo model was developed using effectiveness evidence identified in the systematic review to estimate the cost-effectiveness of oral nutritional supplements.
RESULTS
Eleven studies ( = 822 participants) were included in the effectiveness review, six of which were fully or partly funded by industry. Meta-analyses suggested positive effects of oral nutritional supplements compared with standard care for energy intake (kcal) (standardised mean difference 1.02, 95% confidence interval 0.15 to 1.88; very low quality evidence) and poor mobility (mean difference 0.03, < 0.00001, 95% confidence interval 0.02 to 0.04; very low quality evidence) but no evidence of an effect for body weight (mean difference 1.31, 95% confidence interval -0.05 to 2.66; very low quality evidence) and body mass index (mean difference 0.54, 95% confidence interval -0.03 to 1.11; very low quality evidence). Pooled results for other outcomes were statistically non-significant. There was mixed narrative evidence regarding the effect of oral nutritional supplements on quality of life. Network meta-analysis could be conducted only for body weight and grip strength; there was evidence of an effect for oral nutritional supplements compared with standard care for body weight only. Study quality was mixed; the randomisation method was typically poorly reported. One economic evaluation, in a care home setting, was included. This was a well-conducted study showing that oral nutritional supplements could be cost-effective. Cost-effectiveness analysis suggested that oral nutritional supplements may only be cost-effective for people with lower body mass index (< 21 kg/m) using cheaper oral nutritional supplements products that require minimal staff time to administer.
LIMITATIONS
The review scope was narrow in focus as few primary studies used frailty measures (or our proxy criteria). This resulted in only 11 included studies. The small evidence base and varied quality of evidence meant that it was not possible to determine accurate estimates of the effectiveness or cost-effectiveness of oral nutritional supplements. Furthermore, only English-language publications were considered.
CONCLUSIONS
Overall, the review found little evidence of oral nutritional supplements having significant effects on reducing malnutrition or its adverse outcomes in frail older adults.
FUTURE WORK
Future research should focus on independent, high-quality, adequately powered studies to investigate oral nutritional supplements alongside other nutritional interventions, with longer-term follow-up and detailed analysis of determinants, intervention components and cost-effectiveness.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42020170906.
FUNDING
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 26, No. 51. See the NIHR Journals Library website for further project information.
Topics: Aged; Humans; Frail Elderly; Quality of Life; Malnutrition; Cost-Benefit Analysis; Body Weight
PubMed: 36541454
DOI: 10.3310/CCQF1608 -
Frontiers in Immunology 2020The impact of anti-HLA donor-specific alloantibodies (DSA) which develop after long-term liver transplantation (LT) remains controversial and unclear. The aim of this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The impact of anti-HLA donor-specific alloantibodies (DSA) which develop after long-term liver transplantation (LT) remains controversial and unclear. The aim of this study was to investigate the role of DSAs on the outcome in LT.
METHODS
We did a systematic review and meta-analysis of observational studies published until Dec 31, 2019, that reported DSA outcome data (≥1 year of follow-up) after liver transplant. A literature search in the MEDLINE/PubMed, EMBASE, Cochrane Library, Scopus and Web of Science Core Collection databases was performed.
RESULTS
Of 5,325 studies identified, 15 fulfilled our inclusion criteria. The studies which reported 2016 liver transplant recipients with DSAs showed an increased complication risk, i.e. graft loss and chronic rejection (OR 3.61; 95% CI 1.94-6.71, < 0.001; I 58.19%), and allograft rejection alone (OR 6.43; 95% CI: 3.17-13.04; < 0.001; I 49.77%); they were compared to patients without DSAs. The association between DSAs and overall outcome failure was consistent across all subgroups and sensitivity analysis.
CONCLUSIONS
Our study suggested that DSAs had a significant deleterious impact on the liver transplant risk of rejection. The routine detection of DSAs may be beneficial as noninvasive biomarker-guided risk stratification.
Topics: Animals; Graft Rejection; Humans; Isoantibodies; Liver Transplantation; Observational Studies as Topic; Tissue Donors
PubMed: 33424868
DOI: 10.3389/fimmu.2020.613128 -
Advances in Radiation Oncology 2021Stereotactic body radiation therapy (SBRT) for de novo (previously untreated) head and neck cancers (HNCs) is increasingly being used in medically unfit patients. A...
PURPOSE
Stereotactic body radiation therapy (SBRT) for de novo (previously untreated) head and neck cancers (HNCs) is increasingly being used in medically unfit patients. A systematic review of SBRT was conducted for previously untreated HNCs.
METHODS AND MATERIALS
Medline (PubMed), excerpta medica database, and Cochrane Library databases were queried from inception until July 2020. Comparative outcome data were extracted where available up to 5 years. Results from random-effect models were presented in forest plots, with between-study heterogeneity evaluated by I statistics and Q-tests.
RESULTS
Nine studies met inclusion criteria, representing 157 patients. Local control rates at 1, 2, and 3 years were as follows: 90.7% (95% confidence interval, 80.6%-95.6%), 81.8% (67.2%-90.7%), and 73.5% (40.4%-90.5%), respectively. Overall survival at 1, 2, and 3 years was 75.9% (75.1%-76.6%), 61.1% (60.3%-61.9%), and 50.0% (48.8%-51.4%), respectively. Late grade 3 to 4 toxicity rate was 3.3% (0.2%-10.2%), and late grade 5 toxicity rate was 0.1% (0.0%-1.0%).
CONCLUSIONS
SBRT for de novo HNC is safe and effective in providing locoregional control, with acceptable toxicities in most subsites. This finding warrants broader validation to guide its scope.
PubMed: 33665492
DOI: 10.1016/j.adro.2020.11.013 -
Breast (Edinburgh, Scotland) Aug 2021Locoregional therapy (LRT) in de novo metastatic disease is controversial with inconsistent results from randomized control trials (RCTs). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Locoregional therapy (LRT) in de novo metastatic disease is controversial with inconsistent results from randomized control trials (RCTs).
METHODS
RCTs comparing LRT and systemic therapy to standard therapy alone in de novo metastatic breast cancer were identified. Hazard ratios (HRs) and their associated 95% confidence intervals (CIs) were computed and pooled in a meta-analysis using generic inverse variance. Overall survival (OS) and time to locoregional progression data were extracted for the intention to treat (ITT) population. Data on OS for pre-specified subgroups defined by tumor subtype and by site of metastases were also extracted.
RESULTS
Analyses included 4 trials comprising 970 patients. LRT included standard surgery to the primary breast tumor in all studies, and adjuvant radiation per standard of care was required in 3 studies. Compared to standard treatment, LRT was not associated with improved OS in the ITT population (HR 0.97, 95% CI 0.72-1.29, p = 0.81). However, LRT was associated with improved time to locoregional progression (HR 0.36, 95% CI 0.14-0.95, p = 0.04). LRT was not associated with improved OS in any tumor subtypes, including hormone receptor positive (HR 0.96, 95% CI 0.65-1.43), triple negative (HR 1.4, 95% CI 0.50-3.91) and human epidermal growth factor receptor 2 positive disease (HR 0.93, 95% CI 0.68-1.28). Additionally, LRT did not improve OS in bone only disease (HR 0.97, 95% CI 0.58-1.62) and in visceral disease (HR = 1.02, 95% CI 0.77-1.35). Our critical appraisal has identified some methodological problems in the design and conduct of the studies included that could affect the meta-analysis result.
CONCLUSIONS
LRT in de novo metastatic breast cancer is not associated with improved OS. Results are consistent among different breast cancer subgroups. However, this conclusion should be interpreted with caution in view of the limitations identified in meta-analysis.
Topics: Breast Neoplasms; Female; Humans; Proportional Hazards Models; Radiotherapy, Adjuvant; Survival Rate
PubMed: 34158167
DOI: 10.1016/j.breast.2021.05.003