-
Advances in Therapy Sep 2023Achondroplasia is the most common form of skeletal dysplasia. Recent advances in therapeutic options have highlighted the need for understanding the burden and treatment... (Review)
Review
BACKGROUND
Achondroplasia is the most common form of skeletal dysplasia. Recent advances in therapeutic options have highlighted the need for understanding the burden and treatment landscape of the condition. This systematic literature review (SLR) aimed to identify health-related quality of life (HRQoL)/utilities, healthcare resource use (HCRU), costs, efficacy, safety and economic evaluation data in achondroplasia and to identify gaps in the research.
METHODS
Searches of MEDLINE, Embase, the University of York Centre for Reviews and Dissemination (CRD), the Cochrane Library and grey literature were performed. Articles were screened against pre-specified eligibility criteria by two individuals and study quality was assessed using published checklists. Additional targeted searches were conducted to identify management guidelines.
RESULTS
Fifty-nine unique studies were included. Results demonstrated a substantial HRQoL and HCRU/cost-related burden of achondroplasia on affected individuals and their families throughout their lifetimes, particularly in emotional wellbeing and hospitalisation costs and resource use. Vosoritide, growth hormone (GH) and limb lengthening all conferred benefits for height or growth velocity; however, the long-term effects of GH therapy were unclear, data for vosoritide were from a limited number of studies, and limb lengthening was associated with complications. Included management guidelines varied widely in their scope, with the first global effort to standardise achondroplasia management represented by the International Achondroplasia Consensus Statement published at the end of 2021. Current evidence gaps include a lack of utility and cost-effectiveness data for achondroplasia and its treatments.
CONCLUSIONS
This SLR provides a comprehensive overview of the current burden and treatment landscape for achondroplasia, along with areas where evidence is lacking. This review should be updated as new evidence becomes available on emerging therapies.
Topics: Humans; Quality of Life; Achondroplasia; Human Growth Hormone; Cost-Benefit Analysis
PubMed: 37382866
DOI: 10.1007/s12325-023-02549-3 -
Annals of Internal Medicine Sep 2023Artificial intelligence computer-aided detection (CADe) of colorectal neoplasia during colonoscopy may increase adenoma detection rates (ADRs) and reduce adenoma miss... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Artificial intelligence computer-aided detection (CADe) of colorectal neoplasia during colonoscopy may increase adenoma detection rates (ADRs) and reduce adenoma miss rates, but it may increase overdiagnosis and overtreatment of nonneoplastic polyps.
PURPOSE
To quantify the benefits and harms of CADe in randomized trials.
DESIGN
Systematic review and meta-analysis. (PROSPERO: CRD42022293181).
DATA SOURCES
Medline, Embase, and Scopus databases through February 2023.
STUDY SELECTION
Randomized trials comparing CADe-assisted with standard colonoscopy for polyp and cancer detection.
DATA EXTRACTION
Adenoma detection rate (proportion of patients with ≥1 adenoma), number of adenomas detected per colonoscopy, advanced adenoma (≥10 mm with high-grade dysplasia and villous histology), number of serrated lesions per colonoscopy, and adenoma miss rate were extracted as benefit outcomes. Number of polypectomies for nonneoplastic lesions and withdrawal time were extracted as harm outcomes. For each outcome, studies were pooled using a random-effects model. Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework.
DATA SYNTHESIS
Twenty-one randomized trials on 18 232 patients were included. The ADR was higher in the CADe group than in the standard colonoscopy group (44.0% vs. 35.9%; relative risk, 1.24 [95% CI, 1.16 to 1.33]; low-certainty evidence), corresponding to a 55% (risk ratio, 0.45 [CI, 0.35 to 0.58]) relative reduction in miss rate (moderate-certainty evidence). More nonneoplastic polyps were removed in the CADe than the standard group (0.52 vs. 0.34 per colonoscopy; mean difference [MD], 0.18 polypectomy [CI, 0.11 to 0.26 polypectomy]; low-certainty evidence). Mean inspection time increased only marginally with CADe (MD, 0.47 minute [CI, 0.23 to 0.72 minute]; moderate-certainty evidence).
LIMITATIONS
This review focused on surrogates of patient-important outcomes. Most patients, however, may consider cancer incidence and cancer-related mortality important outcomes. The effect of CADe on such patient-important outcomes remains unclear.
CONCLUSION
The use of CADe for polyp detection during colonoscopy results in increased detection of adenomas but not advanced adenomas and in higher rates of unnecessary removal of nonneoplastic polyps.
PRIMARY FUNDING SOURCE
European Commission Horizon 2020 Marie Skłodowska-Curie Individual Fellowship.
Topics: Humans; Artificial Intelligence; Colorectal Neoplasms; Computers; Colonoscopy; Databases, Factual
PubMed: 37639719
DOI: 10.7326/M22-3678 -
Jornal de Pediatria 2024To compare LISA with INSURE technique for surfactant administration in preterm with gestational age (GA) < 36 weeks with RDS in respect to the incidence of pneumothorax,... (Meta-Analysis)
Meta-Analysis Review
Less invasive surfactant administration versus intubation-surfactant-extubation in the treatment of neonatal respiratory distress syndrome: a systematic review and meta-analyses.
OBJECTIVES
To compare LISA with INSURE technique for surfactant administration in preterm with gestational age (GA) < 36 weeks with RDS in respect to the incidence of pneumothorax, bronchopulmonary dysplasia (BPD), need for mechanical ventilation (MV), regional cerebral oxygen saturation (rSO2), peri‑intraventricular hemorrhage (PIVH) and mortality.
METHODS
A systematic search in PubMed, Embase, Lilacs, CINAHL, SciELO databases, Brazilian Registry of Randomized Clinical Trials (ReBEC), Clinicaltrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) was performed. RCTs evaluating the effects of the LISA technique versus INSURE in preterm infants with gestational age < 36 weeks and that had as outcomes evaluation of the rates of pneumothorax, BPD, need for MV, rSO2, PIVH, and mortality were included in the meta-analysis. Random effects and hazard ratio models were used to combine all study results. Inter-study heterogeneity was assessed using Cochrane Q statistics and Higgin's I2 statistics.
RESULTS
Sixteen RCTs published between 2012 and 2020 met the inclusion criteria, a total of 1,944 preterms. Eleven studies showed a shorter duration of MV and CPAP in the LISA group than in INSURE group. Two studies evaluated rSO2 and suggested that LISA and INSURE transiently affect brain autoregulation during surfactant administration. INSURE group had a higher risk for MV in the first 72 h of life, pneumothorax, PIVH and mortality in comparison to the LISA group.
CONCLUSION
This systematic review and meta-analyses provided evidence for the benefits of the LISA technique in the treatment of RDS, decreasing CPAP time, need for MV, BPD, pneumothorax, PIVH, and mortality when compared to INSURE.
Topics: Infant; Infant, Newborn; Humans; Infant, Premature; Surface-Active Agents; Airway Extubation; Pneumothorax; Pulmonary Surfactants; Intubation; Respiratory Distress Syndrome, Newborn; Cerebral Hemorrhage
PubMed: 37353207
DOI: 10.1016/j.jped.2023.05.008 -
Lancet (London, England) Mar 2024Infants and young children born prematurely are at high risk of severe acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV). In this... (Meta-Analysis)
Meta-Analysis
Global disease burden of and risk factors for acute lower respiratory infections caused by respiratory syncytial virus in preterm infants and young children in 2019: a systematic review and meta-analysis of aggregated and individual participant data.
BACKGROUND
Infants and young children born prematurely are at high risk of severe acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV). In this study, we aimed to assess the global disease burden of and risk factors for RSV-associated ALRI in infants and young children born before 37 weeks of gestation.
METHODS
We conducted a systematic review and meta-analysis of aggregated data from studies published between Jan 1, 1995, and Dec 31, 2021, identified from MEDLINE, Embase, and Global Health, and individual participant data shared by the Respiratory Virus Global Epidemiology Network on respiratory infectious diseases. We estimated RSV-associated ALRI incidence in community, hospital admission, in-hospital mortality, and overall mortality among children younger than 2 years born prematurely. We conducted two-stage random-effects meta-regression analyses accounting for chronological age groups, gestational age bands (early preterm, <32 weeks gestational age [wGA], and late preterm, 32 to <37 wGA), and changes over 5-year intervals from 2000 to 2019. Using individual participant data, we assessed perinatal, sociodemographic, and household factors, and underlying medical conditions for RSV-associated ALRI incidence, hospital admission, and three severity outcome groups (longer hospital stay [>4 days], use of supplemental oxygen and mechanical ventilation, or intensive care unit admission) by estimating pooled odds ratios (ORs) through a two-stage meta-analysis (multivariate logistic regression and random-effects meta-analysis). This study is registered with PROSPERO, CRD42021269742.
FINDINGS
We included 47 studies from the literature and 17 studies with individual participant-level data contributed by the participating investigators. We estimated that, in 2019, 1 650 000 (95% uncertainty range [UR] 1 350 000-1 990 000) RSV-associated ALRI episodes, 533 000 (385 000-730 000) RSV-associated hospital admissions, 3050 (1080-8620) RSV-associated in-hospital deaths, and 26 760 (11 190-46 240) RSV-attributable deaths occurred in preterm infants worldwide. Among early preterm infants, the RSV-associated ALRI incidence rate and hospitalisation rate were significantly higher (rate ratio [RR] ranging from 1·69 to 3·87 across different age groups and outcomes) than for all infants born at any gestational age. In the second year of life, early preterm infants and young children had a similar incidence rate but still a significantly higher hospitalisation rate (RR 2·26 [95% UR 1·27-3·98]) compared with all infants and young children. Although late preterm infants had RSV-associated ALRI incidence rates similar to that of all infants younger than 1 year, they had higher RSV-associated ALRI hospitalisation rate in the first 6 months (RR 1·93 [1·11-3·26]). Overall, preterm infants accounted for 25% (95% UR 16-37) of RSV-associated ALRI hospitalisations in all infants of any gestational age. RSV-associated ALRI in-hospital case fatality ratio in preterm infants was similar to all infants. The factors identified to be associated with RSV-associated ALRI incidence were mainly perinatal and sociodemographic characteristics, and factors associated with severe outcomes from infection were mainly underlying medical conditions including congenital heart disease, tracheostomy, bronchopulmonary dysplasia, chronic lung disease, or Down syndrome (with ORs ranging from 1·40 to 4·23).
INTERPRETATION
Preterm infants face a disproportionately high burden of RSV-associated disease, accounting for 25% of RSV hospitalisation burden. Early preterm infants have a substantial RSV hospitalisation burden persisting into the second year of life. Preventive products for RSV can have a substantial public health impact by preventing RSV-associated ALRI and severe outcomes from infection in preterm infants.
FUNDING
EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe.
Topics: Infant; Child; Infant, Newborn; Humans; Child, Preschool; Infant, Premature; Global Burden of Disease; Respiratory Tract Infections; Hospitalization; Respiratory Syncytial Virus Infections; Pneumonia; Respiratory Syncytial Virus, Human; Risk Factors
PubMed: 38367641
DOI: 10.1016/S0140-6736(24)00138-7 -
Reviews in Endocrine & Metabolic... Dec 2023Fibrous dysplasia (FD) is a rare skeletal disorder in which normal bone is replaced by a fibro-osseous tissue, resulting in possible deformities and fractures. The aim... (Meta-Analysis)
Meta-Analysis Review
Fibrous dysplasia (FD) is a rare skeletal disorder in which normal bone is replaced by a fibro-osseous tissue, resulting in possible deformities and fractures. The aim of this systematic review and meta-analysis was to synthesize the available evidence on the use of antiresorptive drugs in FD in terms of changes in bone turnover markers (BTMs), bone mineral density (BMD), and reducing pain. Three databases were searched in October 2022, with an update in July 2023. Of the 1037 studies identified, 21 were retained after eligibility assessment. A random-effects model was used to calculate global effect size and the corresponding standard error. Pamidronate and Denosumab were the most reported drugs in a total of 374 patients assessed. The initiation of treatments was accompanied by an average reduction of 40.5% [CI -51.6, -29.3] in the bone resorption parameters, and 22.0% [CI -31.9, -12.1] in the parameters of bone formation after 6-12 months. BMD was increased in both FD lesions and in the unaffected skeleton. Pain was reduced by 32.7% [CI -52.7, -12.6] after 6-12 months of treatment, and by 44.5% [CI -65.3, -23.6] after a mean 41.2 months of follow-up. The variation in pain was highly correlated to variation in bone resorption (R = 0.08, p < 0.0001) and formation parameters (R = 0.17, p < 0.0001). This study supports the overall efficacy of antiresorptive therapies in terms of reducing bone remodeling, improving bone density, and pain in FD.
Topics: Humans; Bone Density Conservation Agents; Fibrous Dysplasia, Polyostotic; Diphosphonates; Fibrous Dysplasia of Bone; Bone Resorption; Pain
PubMed: 37632645
DOI: 10.1007/s11154-023-09832-2 -
The Journal of Clinical Endocrinology... Aug 2023Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism, and electrolyte disturbances. KCS1 and KCS2 are caused by...
CONTEXT
Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism, and electrolyte disturbances. KCS1 and KCS2 are caused by pathogenic variants in TBCE and FAM111A, respectively. Clinically the phenotypes are difficult to distinguish.
OBJECTIVE
The objective was to determine and expand the phenotypic spectrum of KCS1 and KCS2 in order to anticipate complications that may arise in these disorders.
METHODS
We clinically and genetically analyzed 10 KCS2 patients from 7 families. Because we found unusual phenotypes in our cohort, we performed a systematic review of genetically confirmed KCS cases using PubMed and Scopus. Evaluation by 3 researchers led to the inclusion of 26 papers for KCS1 and 16 for KCS2, totaling 205 patients. Data were extracted following the Cochrane guidelines and assessed by 2 independent researchers.
RESULTS
Several patients in our KCS2 cohort presented with intellectual disability (3/10) and chronic kidney disease (6/10), which are not considered common findings in KCS2. Systematic review of all reported KCS cases showed that the phenotypes of KCS1 and KCS2 overlap for postnatal growth retardation (KCS1: 52/52, KCS2: 23/23), low parathyroid hormone levels (121/121, 16/20), electrolyte disturbances (139/139, 24/27), dental abnormalities (47/50, 15/16), ocular abnormalities (57/60, 22/23), and seizures/spasms (103/115, 13/16). Symptoms more prevalent in KCS1 included intellectual disability (74/80, 5/24), whereas in KCS2 bone cortical thickening (1/18, 16/20) and medullary stenosis (7/46, 27/28) were more common.
CONCLUSION
Our case series established chronic kidney disease as a new feature of KCS2. In the literature, we found substantial overlap in the phenotypic spectra of KCS1 and KCS2, but identified intellectual disability and the abnormal bone phenotype as the most distinguishing features.
Topics: Humans; Intellectual Disability; Hyperostosis, Cortical, Congenital; Phenotype; Electrolytes; Hypoparathyroidism
PubMed: 36916904
DOI: 10.1210/clinem/dgad147 -
The Knee Oct 2023Treatment of patellar instability remains up for debate, and a combination of tibial tubercle osteotomy and medial patellofemoral ligament reconstruction (MPFLr) of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Treatment of patellar instability remains up for debate, and a combination of tibial tubercle osteotomy and medial patellofemoral ligament reconstruction (MPFLr) of the medial patellofemoral ligament (MPFL) has become the mainstay treatment for recurrent lateral patellar dislocation. Due to limited small studies, there remains a variety of surgical techniques still being practiced. The use of MPFL reconstruction, in isolation, has demonstrated promise.
PURPOSE
The purpose of this systematic review and meta-analysis is to investigate if isolated medial patellofemoral ligament reconstruction (iMPFLr) can safely and efficaciously restore knee stability and to present the patient demographics, surgical techniques, graft choices, clinical outcomes, and complications after iMPFLr for recurrent patellar dislocation (RPD).
METHODS
A review of the current literature according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, yielded 299 abstracts. Twenty-seven articles met the inclusion/exclusion criteria accounting for 1200 patients. Data was pooled and analyzed focusing on patient demographics, graft type used, Kujala, International Knee Documentation Committee (IKDC), Lysholm, Tegner, and complications.
RESULTS
Across all studies the weighted mean age was found to be an average of 24.5 years, BMI was 24.9 kg/m, follow-up was 47.3 months, as 67% were female, TT-TG distance was 15.3 mm, and Caton Deschamps index 1.11. The pooled effect size difference of pre versus post assessment of Kujala was -2.8, IKDC was -4.5, Lysholm was -6.4, and Tegner was -0.74. The pooled complication rate was found to be 8% across all included studies. A subgroup analysis was also performed, specifically looking at how single bundle, double bundle, gracilis, semitendinosus and knee angle during fixation effect outcome data.
CONCLUSION
This systematic review and meta-analysis demonstrates that isolated MPFL reconstruction is a safe and effective treatment for recurrent patellar dislocations. Given the efficacy of isolated MPFL reconstruction, future investigations should aim to uncover the exact TT-TG distance, trochlear dysplasia, and patella alta grade for selecting patients to undergo this procedure. Furthermore, more primary research needs to be conducted on this topic due to the overall lack of published data from randomized controlled studies and no broad standardization of outcome measurements.
LEVEL OF EVIDENCE
(4) Systematic Review and Meta-Analysis.
Topics: Humans; Female; Young Adult; Adult; Male; Patellar Dislocation; Patellofemoral Joint; Joint Instability; Knee Joint; Joint Dislocations; Ligaments, Articular; Patella
PubMed: 37531844
DOI: 10.1016/j.knee.2023.07.003 -
BMJ Paediatrics Open Oct 2023To estimate the prevalence of developmental dysplasia of the hip (DDH) in infants with a systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To estimate the prevalence of developmental dysplasia of the hip (DDH) in infants with a systematic review and meta-analysis.
METHOD
A literature search was conducted in April 2023, using databases such as Cochrane Library, PubMed, MEDLINE, CNKI, and SinoMed, without language restrictions. Eligible studies included cross-sectional studies reporting the prevalence of DDH among infants aged 0-12 months. Two independent reviewers manually selected and coded the studies, with any disagreements resolved by a third reviewer. Meta-analysis was performed using a random-effects model to calculate the prevalence of DDH. Regression analysis examined the trend of DDH prevalence, and stratification analysis explored heterogeneity between studies.
RESULTS
A total of 65 studies involving 3 451 682 infants were included in the meta-analysis. None of the studies were classified as high quality, four were medium-to-high quality, 50 were low-to-medium quality, and eight were low quality. The pooled prevalence of DDH was 1.40% (95% CI: 0.86 to 2.28, I=100%), and prevalence of dysplasia, subluxation, and dislocation was 1.45% (95% CI: 0.93 to 2.24, I=97%), 0.37% (95% CI: 0.22 to 0.60, I=94%), and 0.21% (95% CI: 0.13 to 0.34, I=92%), respectively. Notably, the overall prevalence has a slight upward trend in the last three decades (β=0.24, p=0.35), but the dysplasia was downward trend (β=-0.48, p<0.01). Girls have higher risk of DDH than boys (1.46% vs 0.66%; Q=5.83, df=1, p=0.02). There were no significant differences based on gender, country, setting, or screening technique.
CONCLUSION
The prevalence of DDH among infants is approximately one in a 100, with girls being at higher risk. Though the prevalence of dysplasia has decreased, there is a slight upward trend in overall DDH. Therefore, routine screening for DDH in infants is recommended to prevent more serious developmental problems.
Topics: Male; Female; Humans; Infant; Prevalence; Cross-Sectional Studies; Developmental Dysplasia of the Hip; Hip Dislocation, Congenital; Mass Screening
PubMed: 37879719
DOI: 10.1136/bmjpo-2023-002080 -
Journal of Laparoendoscopic & Advanced... Dec 2023Gastroesophageal reflux disease is a common gastrointestinal disorder with one of its most feared complications being Barrett's esophagus (BE). Currently, most of the...
Gastroesophageal reflux disease is a common gastrointestinal disorder with one of its most feared complications being Barrett's esophagus (BE). Currently, most of the recommendations of BE management are driven by the level of dysplasia. However, the length of BE might also be related to the risk of dysplasia/malignant transformation. We aimed to determine the appropriate management of BE based on its length. A systematic literature review was conducted with searches made on PubMed, Embase, and Cochrane databases. Long-segment BE (LSBE) was defined as 3 cm or longer and short-segment BE (SSBE) as under 3 cm. Studies evaluating the behavior and management of SSBE and/or LSBE were included for analysis. LSBE have greater risk of dysplasia or progression to esophageal adenocarcinoma compared to SSBE. Despite this greater risk, LSBE and SSBE are currently managed similarly based on the presence and degree of dysplasia. Endoscopic and ablative techniques may have higher level of success and less complications in SSBE, compared to LSBE. Decreasing time interval between surveillance may be a viable option for managing LSBE. Although many algorithms of monitoring and treatment of BE remain the same regardless of segment length, current evidence suggests that more aggressive management for LSBE might be needed due to its higher risk of malignant progression.
Topics: Humans; Barrett Esophagus; Esophageal Neoplasms; Adenocarcinoma; Gastroesophageal Reflux; Endoscopy
PubMed: 37796531
DOI: 10.1089/lap.2023.0321 -
Bronchopulmonary dysplasia prediction models: a systematic review and meta-analysis with validation.Pediatric Research Jul 2023Prediction models could identify infants at the greatest risk of bronchopulmonary dysplasia (BPD) and allow targeted preventative strategies. We performed a systematic... (Meta-Analysis)
Meta-Analysis
Prediction models could identify infants at the greatest risk of bronchopulmonary dysplasia (BPD) and allow targeted preventative strategies. We performed a systematic review and meta-analysis with external validation of identified models. Studies using predictors available before day 14 of life to predict BPD in very preterm infants were included. Two reviewers assessed 7628 studies for eligibility. Meta-analysis of externally validated models was followed by validation using 62,864 very preterm infants in England and Wales. A total of 64 studies using 53 prediction models were included totalling 274,407 infants (range 32-156,587/study). In all, 35 (55%) studies predated 2010; 39 (61%) were single-centre studies. A total of 97% of studies had a high risk of bias, especially in the analysis domain. Following meta-analysis of 22 BPD and 11 BPD/death composite externally validated models, Laughon's day one model was the most promising in predicting BPD and death (C-statistic 0.76 (95% CI 0.70-0.81) and good calibration). Six models were externally validated in our cohort with C-statistics between 0.70 and 0.90 but with poor calibration. Few BPD prediction models were developed with contemporary populations, underwent external validation, or had calibration and impact analyses. Contemporary, validated, and dynamic prediction models are needed for targeted preventative strategies. IMPACT: This review aims to provide a comprehensive assessment of all BPD prediction models developed to address the uncertainty of which model is sufficiently valid and generalisable for use in clinical practice and research. Published BPD prediction models are mostly outdated, single centre and lack external validation. Laughon's 2011 model is the most promising but more robust models, using contemporary data with external validation are needed to support better treatments.
Topics: Infant; Infant, Newborn; Humans; Infant, Premature; Bronchopulmonary Dysplasia; Infant, Very Low Birth Weight; Infant, Premature, Diseases; England
PubMed: 36624282
DOI: 10.1038/s41390-022-02451-8