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Head and Neck Pathology Mar 2022The 5 edition of the World Health Organization (WHO) Classification of Head and Neck Tumours (2022) comes out only five years after the previous edition, however it...
The 5 edition of the World Health Organization (WHO) Classification of Head and Neck Tumours (2022) comes out only five years after the previous edition, however it presents important updates that run in parallel with the rapid progression involving the increasingly sophisticated molecular investigation and its interpretation, some of which already have therapy-related impact. This manuscript provides an overview of the leading changes introduced in the classification of Odontogenic and Maxillofacial Bone Tumours that encompasses cysts of the jaws, odontogenic tumours, giant cell lesions and bone cysts, and bone and cartilage tumours. This is the first edition that Essential and Desirable Diagnostic Features were added for each entity, so that the most important clinical, microscopic and/or radiologic features were encapsulated and briefly highlighted. Surgical ciliated cyst was added to the group of odontogenic cysts, adenoid ameloblastoma was a newly recognized benign epithelial odontogenic tumour, and segmental odontomaxillary dysplasia was introduced in the group of fibro-osseous tumours and dysplasia. In addition, rhabdomyosarcoma with TFCP2 rearrangement, was introduced into the group of malignant jawbone tumours. The unique genetic aberrations distinguish it from other types of rhabdomyosarcomas. On the other hand, melanotic neuroectodermal tumour of infancy and osteoid osteoma were deleted from the benign bone and cartilageneous tumours, as was the hematolymphoid tumour of solitary plasmacytoma of bone. We systematically reviewed each entity in this chapter and provided important updated findings for selected topics that can further aid in the diagnostic process for challenging cases, broaden insights on the logic of the present classification, and finally, emphasize the potential that some of the molecular results may have in the near future to set new treatment approaches.
Topics: Bone Neoplasms; DNA-Binding Proteins; Head and Neck Neoplasms; Humans; Odontogenic Cysts; Odontogenic Tumors; Transcription Factors; World Health Organization
PubMed: 35312978
DOI: 10.1007/s12105-021-01404-7 -
Lancet (London, England) Aug 2019More than 10 years have elapsed since human papillomavirus (HPV) vaccination was implemented. We did a systematic review and meta-analysis of the population-level impact... (Meta-Analysis)
Meta-Analysis
BACKGROUND
More than 10 years have elapsed since human papillomavirus (HPV) vaccination was implemented. We did a systematic review and meta-analysis of the population-level impact of vaccinating girls and women against human papillomavirus on HPV infections, anogenital wart diagnoses, and cervical intraepithelial neoplasia grade 2+ (CIN2+) to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination.
METHODS
In this updated systematic review and meta-analysis, we used the same search strategy as in our previous paper. We searched MEDLINE and Embase for studies published between Feb 1, 2014, and Oct 11, 2018. Studies were eligible if they compared the frequency (prevalence or incidence) of at least one HPV-related endpoint (genital HPV infections, anogenital wart diagnoses, or histologically confirmed CIN2+) between pre-vaccination and post-vaccination periods among the general population and if they used the same population sources and recruitment methods before and after vaccination. Our primary assessment was the relative risk (RR) comparing the frequency (prevalence or incidence) of HPV-related endpoints between the pre-vaccination and post-vaccination periods. We stratified all analyses by sex, age, and years since introduction of HPV vaccination. We used random-effects models to estimate pooled relative risks.
FINDINGS
We identified 1702 potentially eligible articles for this systematic review and meta-analysis, and included 65 articles in 14 high-income countries: 23 for HPV infection, 29 for anogenital warts, and 13 for CIN2+. After 5-8 years of vaccination, the prevalence of HPV 16 and 18 decreased significantly by 83% (RR 0·17, 95% CI 0·11-0·25) among girls aged 13-19 years, and decreased significantly by 66% (RR 0·34, 95% CI 0·23-0·49) among women aged 20-24 years. The prevalence of HPV 31, 33, and 45 decreased significantly by 54% (RR 0·46, 95% CI 0·33-0·66) among girls aged 13-19 years. Anogenital wart diagnoses decreased significantly by 67% (RR 0·33, 95% CI 0·24-0·46) among girls aged 15-19 years, decreased significantly by 54% (RR 0·46, 95% CI 0.36-0.60) among women aged 20-24 years, and decreased significantly by 31% (RR 0·69, 95% CI 0·53-0·89) among women aged 25-29 years. Among boys aged 15-19 years anogenital wart diagnoses decreased significantly by 48% (RR 0·52, 95% CI 0·37-0·75) and among men aged 20-24 years they decreased significantly by 32% (RR 0·68, 95% CI 0·47-0·98). After 5-9 years of vaccination, CIN2+ decreased significantly by 51% (RR 0·49, 95% CI 0·42-0·58) among screened girls aged 15-19 years and decreased significantly by 31% (RR 0·69, 95% CI 0·57-0·84) among women aged 20-24 years.
INTERPRETATION
This updated systematic review and meta-analysis includes data from 60 million individuals and up to 8 years of post-vaccination follow-up. Our results show compelling evidence of the substantial impact of HPV vaccination programmes on HPV infections and CIN2+ among girls and women, and on anogenital warts diagnoses among girls, women, boys, and men. Additionally, programmes with multi-cohort vaccination and high vaccination coverage had a greater direct impact and herd effects.
FUNDING
WHO, Canadian Institutes of Health Research, Fonds de recherche du Québec - Santé.
Topics: Adolescent; Adult; Age Distribution; Condylomata Acuminata; Endpoint Determination; Female; Humans; Incidence; Male; Mass Vaccination; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; Prevalence; Uterine Cervical Neoplasms; Young Adult; Uterine Cervical Dysplasia
PubMed: 31255301
DOI: 10.1016/S0140-6736(19)30298-3 -
BMJ (Clinical Research Ed.) Aug 2022To explore the efficacy of human papillomavirus (HPV) vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To explore the efficacy of human papillomavirus (HPV) vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment.
DESIGN
Systematic review and meta-analysis DATA SOURCES: PubMed (Medline), Scopus, Cochrane, Web of Science, and ClinicalTrials.gov were screened from inception to 31 March 2021.
REVIEW METHODS
Studies reporting on the risk of HPV infection and recurrence of disease related to HPV infection after local surgical treatment of preinvasive genital disease in individuals who were vaccinated were included. The primary outcome measure was risk of recurrence of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) after local surgical treatment, with follow-up as reported by individual studies. Secondary outcome measures were risk of HPV infection or other lesions related to HPV infection. Independent and in duplicate data extraction and quality assessment were performed with ROBINS-I and RoB-2 tools for observational studies and randomised controlled trials, respectively. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was implemented for the primary outcome. Observational studies and randomised controlled trials were analysed separately from post hoc analyses of randomised controlled trials. Pooled risk ratios and 95% confidence intervals were calculated with a random effects meta-analysis model. The restricted maximum likelihood was used as an estimator for heterogeneity, and the Hartung-Knapp-Sidik-Jonkman method was used to derive confidence intervals.
RESULTS
22 articles met the inclusion criteria of the review; 18 of these studies also reported data from a non-vaccinated group and were included in the meta-analyses (12 observational studies, two randomised controlled trials, and four post hoc analyses of randomised controlled trials). The risk of recurrence of CIN2+ was reduced in individuals who were vaccinated compared with those who were not vaccinated (11 studies, 19 909 participants; risk ratio 0.43, 95% confidence interval 0.30 to 0.60; I=58%, τ=0.14, median follow-up 36 months, interquartile range 24-43.5). The effect estimate was even stronger when the risk of recurrence of CIN2+ was assessed for disease related to HPV subtypes HPV16 or HPV18 (six studies, 1879 participants; risk ratio 0.26, 95% confidence interval 0.16 to 0.43; I=0%, τ=0). Confidence in the meta-analysis for CIN2+ overall and CIN2+ related to HPV16 or HPV18, assessed by GRADE, ranged from very low to moderate, probably because of publication bias and inconsistency in the studies included in the meta-analysis. The risk of recurrence of CIN3 was also reduced in patients who were vaccinated but uncertainty was large (three studies, 17 757 participants; 0.28, 0.01 to 6.37; I=71%, τ=1.23). Evidence of benefit was lacking for recurrence of vulvar, vaginal, and anal intraepithelial neoplasia, genital warts, and persistent and incident HPV infections, although the number of studies and participants in each outcome was low.
CONCLUSION
HPV vaccination might reduce the risk of recurrence of CIN, in particular when related to HPV16 or HPV18, in women treated with local excision. GRADE assessment for the quality of evidence indicated that the data were inconclusive. Large scale, high quality randomised controlled trials are required to establish the level of effectiveness and cost of HPV vaccination in women undergoing treatment for diseases related to HPV infection.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021237350.
Topics: Alphapapillomavirus; Female; Human papillomavirus 16; Humans; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; Uterine Cervical Neoplasms; Vaccination; Uterine Cervical Dysplasia
PubMed: 35922074
DOI: 10.1136/bmj-2022-070135 -
Orphanet Journal of Rare Diseases Oct 2022The objective of this systematic review was to determine the orthodontic and dentofacial orthopedic treatments carried out in patients with ectodermal dysplasia to... (Review)
Review
OBJECTIVE
The objective of this systematic review was to determine the orthodontic and dentofacial orthopedic treatments carried out in patients with ectodermal dysplasia to facilitate functional and aesthetic rehabilitation.
METHODS
The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. We systematically searched PubMed, Web of Science, Scopus, Scielo, LILACS, EBSCOhost and Embase databases up to 6 January 2022. We included articles describing patients with any type of ectodermal dysplasia who received orthodontic or dentofacial orthopedic treatment to facilitate functional and aesthetic oral rehabilitation. The search was not restricted by language or year of publication. The quality of the studies was assessed using the Joanna Briggs Institute Quality Assessment Scale of the University of Adelaide for case series and case reports. The review was registered at the University of York Centre for reviews (CRD42021288030).
RESULTS
Of the initial 403 studies found, 29 met the inclusion criteria. After applying the quality scale, 23 were left for review-21 case reports and 2 case series. The initial age of patients ranged from 34 months to 24 years. Thirteen studies were on hypohidrotic and/or anhidrotic ectodermal dysplasia, of which two were X-chromosome linked. In one study, the patient had Wiktop syndrome, and in nine the type of ectodermal dysplasia was not specified. The duration of treatment was 7 weeks to 10 years. The treatments described were: fixed orthodontic appliances or simple acrylic plates designed for tooth movement, including leveling and aligning, closing of diastemata, retraction of impacted teeth in the dental arch; clear aligners; fixed and/or removable appliances for the correction of skeletal and/or dentoalveolar relationships; palatal expanders in combination with face masks for orthopedic traction of the maxilla; and orthognathic surgery. Only three studies provided cephalometric data.
CONCLUSION
The level of evidence of the articles reviewed was low and most orthopedic and dentofacial orthodontic treatments described were focused on correcting dental malpositioning and jaw asymmetries and not on stimulating growth from an early age. Studies with greater scientific evidence are needed to determine the best treatment for these patients.
Topics: Child, Preschool; Ectodermal Dysplasia; Ectodermal Dysplasia 1, Anhidrotic; Humans; Tooth Movement Techniques
PubMed: 36253866
DOI: 10.1186/s13023-022-02533-0 -
Nutrients May 2018This systematic review and meta-analysis synthesised the post-1990 literature examining the effect of human milk on morbidity, specifically necrotising enterocolitis... (Comparative Study)
Comparative Study Meta-Analysis Review
This systematic review and meta-analysis synthesised the post-1990 literature examining the effect of human milk on morbidity, specifically necrotising enterocolitis (NEC), late onset sepsis (LOS), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD) and neurodevelopment in infants born ≤28 weeks' gestation and/or publications with reported infant mean birth weight of ≤1500 g. Online databases including Medline, PubMed, CINAHL, Scopus, and the Cochrane Central Register of Controlled Trials were searched, and comparisons were grouped as follows: exclusive human milk (EHM) versus exclusive preterm formula (EPTF), any human milk (HM) versus EPTF, higher versus lower dose HM, and unpasteurised versus pasteurised HM. Experimental and observational studies were pooled separately in meta-analyses. Risk of bias was assessed for each individual study and the GRADE system used to judge the certainty of the findings. Forty-nine studies (with 56 reports) were included, of which 44 could be included in meta-analyses. HM provided a clear protective effect against NEC, with an approximate 4% reduction in incidence. HM also provided a possible reduction in LOS, severe ROP and severe NEC. Particularly for NEC, any volume of HM is better than EPTF, and the higher the dose the greater the protection. Evidence regarding pasteurisation is inconclusive, but it appears to have no effect on some outcomes. Improving the intake of mother's own milk (MOM) and/or donor HM results in small improvements in morbidity in this population.
Topics: Enteral Nutrition; Enterocolitis, Necrotizing; Evidence-Based Medicine; Humans; Infant; Infant Formula; Infant Nutritional Physiological Phenomena; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Milk, Human; Neonatal Sepsis; Neurodevelopmental Disorders; Premature Birth; Severity of Illness Index
PubMed: 29857555
DOI: 10.3390/nu10060707 -
JAMA Pediatrics Jun 2021The safety of postnatal corticosteroids used for prevention of bronchopulmonary dysplasia (BPD) in preterm neonates is a controversial matter, and a risk-benefit balance... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The safety of postnatal corticosteroids used for prevention of bronchopulmonary dysplasia (BPD) in preterm neonates is a controversial matter, and a risk-benefit balance needs to be struck.
OBJECTIVE
To evaluate 14 corticosteroid regimens used to prevent BPD: moderately early-initiated, low cumulative dose of systemic dexamethasone (MoLdDX); moderately early-initiated, medium cumulative dose of systemic dexamethasone (MoMdDX); moderately early-initiated, high cumulative dose of systemic dexamethasone (MoHdDX); late-initiated, low cumulative dose of systemic dexamethasone (LaLdDX); late-initiated, medium cumulative dose of systemic dexamethasone (LaMdDX); late-initiated, high cumulative dose of systemic dexamethasone (LaHdDX); early-initiated systemic hydrocortisone (EHC); late-initiated systemic hydrocortisone (LHC); early-initiated inhaled budesonide (EIBUD); early-initiated inhaled beclomethasone (EIBEC); early-initiated inhaled fluticasone (EIFLUT); late-initiated inhaled budesonide (LIBUD); late-initiated inhaled beclomethasone (LIBEC); and intratracheal budesonide (ITBUD).
DATA SOURCES
PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, World Health Organization's International Clinical Trials Registry Platform (ICTRP), and CINAHL were searched from inception through August 25, 2020.
STUDY SELECTION
In this systematic review and network meta-analysis, the randomized clinical trials selected included preterm neonates with a gestational age of 32 weeks or younger and for whom a corticosteroid regimen was initiated within 4 weeks of postnatal age. Peer-reviewed articles and abstracts in all languages were included.
DATA EXTRACTION AND SYNTHESIS
Two independent authors extracted data in duplicate. Network meta-analysis used a bayesian model.
MAIN OUTCOMES AND MEASURES
Primary combined outcome was BPD, defined as oxygen requirement at 36 weeks' postmenstrual age (PMA), or mortality at 36 weeks' PMA. The secondary outcomes included 15 safety outcomes.
RESULTS
A total of 62 studies involving 5559 neonates (mean [SD] gestational age, 26 [1] weeks) were included. Several regimens were associated with a decreased risk of BPD or mortality, including EHC (risk ratio [RR], 0.82; 95% credible interval [CrI], 0.68-0.97); EIFLUT (RR, 0.75; 95% CrI, 0.55-0.98); LaHdDX (RR, 0.70; 95% CrI, 0.54-0.87); MoHdDX (RR, 0.64; 95% CrI, 0.48-0.82); ITBUD (RR, 0.73; 95% CrI, 0.57-0.91); and MoMdDX (RR, 0.61; 95% CrI, 0.45-0.79). Surface under the cumulative ranking curve (SUCRA) value ranking showed that MoMdDX (SUCRA, 0.91), MoHdDX (SUCRA, 0.86), and LaHdDX (SUCRA, 0.76) were the 3 most beneficial interventions. ITBUD (RR, 4.36; 95% CrI, 1.04-12.90); LaHdDX (RR, 11.91; 95% CrI, 1.64-44.49); LaLdDX (RR, 6.33; 95% CrI, 1.62-18.56); MoHdDX (RR, 4.96; 95% CrI, 1.14-14.75); and MoMdDX (RR, 3.16; 95% CrI, 1.35-6.82) were associated with more successful extubation from invasive mechanical ventilation. EHC was associated with a higher risk of gastrointestinal perforation (RR, 2.77; 95% CrI, 1.09-9.32). MoMdDX showed a higher risk of hypertension (RR, 3.96; 95% CrI, 1.10-30.91). MoHdDX had a higher risk of hypertrophic cardiomyopathy (RR, 5.94; 95% CrI, 1.95-18.11).
CONCLUSIONS AND RELEVANCE
This study suggested that MoMdDX may be the most appropriate postnatal corticosteroid regimen for preventing BPD or mortality at a PMA of 36 weeks, albeit with a risk of hypertension. The quality of evidence was low.
Topics: Bronchopulmonary Dysplasia; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature
PubMed: 33720274
DOI: 10.1001/jamapediatrics.2020.6826 -
The Cochrane Database of Systematic... Oct 2017Damage caused by lung overdistension (volutrauma) has been implicated in the development of bronchopulmonary dysplasia (BPD). Modern neonatal ventilation modes can... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Damage caused by lung overdistension (volutrauma) has been implicated in the development of bronchopulmonary dysplasia (BPD). Modern neonatal ventilation modes can target a set tidal volume as an alternative to traditional pressure-limited ventilation (PLV) using a fixed inflation pressure. Volume-targeted ventilation (VTV) aims to produce a more stable tidal volume in order to reduce lung damage and stabilise the partial pressure of carbon dioxide (pCO).
OBJECTIVES
To determine whether VTV compared with PLV leads to reduced rates of death and death or BPD in newborn infants and to determine whether use of VTV affected outcomes including air leak, cranial ultrasound findings and neurodevelopment.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 12), MEDLINE via PubMed (1966 to 13 January 2017), Embase (1980 to 13 January 2017) and CINAHL (1982 to 13 January 2017). We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We contacted the principal investigators of studies to obtain supplementary information.
SELECTION CRITERIA
Randomised and quasi-randomised trials comparing VTV versus PLV in infants of less than 44 weeks' postmenstrual age and reporting clinically relevant outcomes.
DATA COLLECTION AND ANALYSIS
We assessed risk of bias for each trial using Cochrane methodology. We evaluated quality of evidence for each outcome using GRADE criteria. We tabulated mortality, rates of BPD, short-term clinical outcomes and long-term developmental outcomes.
STATISTICS
for categorical outcomes, we calculated typical estimates for risk ratios (RR), risk differences (RD) and number needed to treat for an additional beneficial outcome (NNTB). For continuous variables, we calculated typical estimates for mean differences (MD). We used 95% confidence intervals (CI) and assumed a fixed-effect model for meta-analysis.
MAIN RESULTS
Twenty randomised trials met our inclusion criteria; 16 parallel trials (977 infants) and four cross-over trials (88 infants). No studies were blinded and the quality of evidence for outcomes assessed varied from moderate to low.We found no difference in the primary outcome, death before hospital discharge, between VTV modes versus PLV modes (typical RR 0.75, 95% CI 0.53 to 1.07; low quality evidence). However, there was moderate quality evidence that the use of VTV modes resulted in a reduction in the primary outcome, death or BPD at 36 weeks' gestation (typical RR 0.73, 95% CI 0.59 to 0.89; typical NNTB 8, 95% CI 5 to 20) and the following secondary outcomes: rates of pneumothorax (typical RR 0.52, 95% CI 0.31 to 0.87; typical NNTB 20, 95% CI 11 to 100), mean days of mechanical ventilation (MD -1.35 days, 95% CI -1.83 to -0.86), rates of hypocarbia (typical RR 0.49, 95% CI 0.33 to 0.72; typical NNTB 3, 95% CI 2 to 5), rates of grade 3 or 4 intraventricular haemorrhage (typical RR 0.53, 95% CI 0.37 to 0.77; typical NNTB 11, 95% CI 7 to 25) and the combined outcome of periventricular leukomalacia with or without grade 3 or 4 intraventricular haemorrhage (typical RR 0.47, 95% CI 0.27 to 0.80; typical NNTB 11, 95% CI 7 to 33). VTV modes were not associated with any increased adverse outcomes.
AUTHORS' CONCLUSIONS
Infants ventilated using VTV modes had reduced rates of death or BPD, pneumothoraces, hypocarbia, severe cranial ultrasound pathologies and duration of ventilation compared with infants ventilated using PLV modes. Further studies are needed to identify whether VTV modes improve neurodevelopmental outcomes and to compare and refine VTV strategies.
Topics: Bronchopulmonary Dysplasia; Humans; Infant, Newborn; Infant, Premature; Intermittent Positive-Pressure Ventilation; Pressure; Randomized Controlled Trials as Topic; Tidal Volume
PubMed: 29039883
DOI: 10.1002/14651858.CD003666.pub4 -
The Cochrane Database of Systematic... Aug 2017Cervical cancer screening has traditionally been based on cervical cytology. Given the aetiological relationship between human papillomavirus (HPV) infection and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cervical cancer screening has traditionally been based on cervical cytology. Given the aetiological relationship between human papillomavirus (HPV) infection and cervical carcinogenesis, HPV testing has been proposed as an alternative screening test.
OBJECTIVES
To determine the diagnostic accuracy of HPV testing for detecting histologically confirmed cervical intraepithelial neoplasias (CIN) of grade 2 or worse (CIN 2+), including adenocarcinoma in situ, in women participating in primary cervical cancer screening; and how it compares to the accuracy of cytological testing (liquid-based and conventional) at various thresholds.
SEARCH METHODS
We performed a systematic literature search of articles in MEDLINE and Embase (1992 to November 2015) containing quantitative data and handsearched the reference lists of retrieved articles.
SELECTION CRITERIA
We included comparative test accuracy studies if all women received both HPV testing and cervical cytology followed by verification of the disease status with the reference standard, if positive for at least one screening test. The studies had to include women participating in a cervical cancer screening programme who were not being followed up for previous cytological abnormalities.
DATA COLLECTION AND ANALYSIS
We completed a 2 x 2 table with the number of true positives (TP), false positives (FP), true negatives (TN), and false negatives for each screening test (HPV test and cytology) used in each study. We calculated the absolute and relative sensitivities and the specificities of the tests for the detection of CIN 2+ and CIN 3+ at various thresholds and computed sensitivity (TP/(TP + TN) and specificity (TN/ (TN + FP) for each test separately. Relative sensitivity and specificity of one test compared to another test were defined as sensitivity of test-1 over sensitivity of test-2 and specificity of test-1 over specificity of test-2, respectively. To assess bias in the studies, we used the Quality Assessment of Diagnostic test Accuracy Studies (QUADAS) tool. We used a bivariate random-effects model for computing pooled accuracy estimates. This model takes into account the within- and between-study variability and the intrinsic correlation between sensitivity and specificity.
MAIN RESULTS
We included a total of 40 studies in the review, with more than 140,000 women aged between 20 and 70 years old. Many studies were at low risk of bias. There were a sufficient number of included studies with adequate methodology to perform the following test comparisons: hybrid capture 2 (HC2) (1 pg/mL threshold) versus conventional cytology (CC) (atypical squamous cells of undetermined significance (ASCUS)+ and low-grade squamous intraepithelial lesions (LSIL)+ thresholds) or liquid-based cytology (LBC) (ASCUS+ and LSIL+ thresholds), other high-risk HPV tests versus conventional cytology (ASCUS+ and LSIL+ thresholds) or LBC (ASCUS+ and LSIL+ thresholds). For CIN 2+, pooled sensitivity estimates for HC2, CC and LBC (ASCUS+) were 89.9%, 62.5% and 72.9%, respectively, and pooled specificity estimates were 89.9%, 96.6%, and 90.3%, respectively. The results did not differ by age of women (less than or greater than 30 years old), or in studies with verification bias. Accuracy of HC2 was, however, greater in European countries compared to other countries. The results for the sensitivity of the tests were heterogeneous ranging from 52% to 94% for LBC, and 61% to 100% for HC2. Overall, the quality of the evidence for the sensitivity of the tests was moderate, and high for the specificity.The relative sensitivity of HC2 versus CC for CIN 2+ was 1.52 (95% CI: 1.24 to 1.86) and the relative specificity 0.94 (95% CI: 0.92 to 0.96), and versus LBC for CIN 2+ was 1.18 (95% CI: 1.10 to 1.26) and the relative specificity 0.96 (95% CI: 0.95 to 0.97). The relative sensitivity of HC2 versus CC for CIN 3+ was 1.46 (95% CI: 1.12 to 1.91) and the relative specificity 0.95 (95% CI: 0.93 to 0.97). The relative sensitivity of HC2 versus LBC for CIN 3+ was 1.17 (95% CI: 1.07 to 1.28) and the relative specificity 0.96 (95% CI: 0.95 to 0.97).
AUTHORS' CONCLUSIONS
Whilst HPV tests are less likely to miss cases of CIN 2+ and CIN 3+, these tests do lead to more unnecessary referrals. However, a negative HPV test is more reassuring than a negative cytological test, as the cytological test has a greater chance of being falsely negative, which could lead to delays in receiving the appropriate treatment. Evidence from prospective longitudinal studies is needed to establish the relative clinical implications of these tests.
Topics: Adult; Aged; Early Detection of Cancer; Female; Humans; Middle Aged; Papillomavirus Infections; Polymerase Chain Reaction; Precancerous Conditions; Sensitivity and Specificity; Uterine Cervical Neoplasms; Vaginal Smears; Uterine Cervical Dysplasia
PubMed: 28796882
DOI: 10.1002/14651858.CD008587.pub2 -
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 -
BMJ (Clinical Research Ed.) Feb 2018To estimate the regression, persistence, and progression of untreated cervical intraepithelial neoplasia grade 2 (CIN2) lesions managed conservatively as well as... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To estimate the regression, persistence, and progression of untreated cervical intraepithelial neoplasia grade 2 (CIN2) lesions managed conservatively as well as compliance with follow-up protocols.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1 January 1973 to 20 August 2016.
ELIGIBILITY CRITERIA
Studies reporting on outcomes of histologically confirmed CIN2 in non-pregnant women, managed conservatively for three or more months.
DATA SYNTHESIS
Two reviewers extracted data and assessed risk of bias. Random effects model was used to calculate pooled proportions for each outcome, and heterogeneity was assessed using I statistics.
MAIN OUTCOME MEASURES
Rates of regression, persistence, or progression of CIN2 and default rates at different follow-up time points (3, 6, 12, 24, 36, and 60 months).
RESULTS
36 studies that included 3160 women were identified (seven randomised trials, 16 prospective cohorts, and 13 retrospective cohorts; 50% of the studies were at low risk of bias). At 24 months, the pooled rates were 50% (11 studies, 819/1470 women, 95% confidence interval 43% to 57%; I=77%) for regression, 32% (eight studies, 334/1257 women, 23% to 42%; I=82%) for persistence, and 18% (nine studies, 282/1445 women, 11% to 27%; I=90%) for progression. In a subgroup analysis including 1069 women aged less than 30 years, the rates were 60% (four studies, 638/1069 women, 57% to 63%; I=0%), 23% (two studies, 226/938 women, 20% to 26%; I=97%), and 11% (three studies, 163/1033 women, 5% to 19%; I=67%), respectively. The rate of non-compliance (at six to 24 months of follow-up) in prospective studies was around 10%.
CONCLUSIONS
Most CIN2 lesions, particularly in young women (<30 years), regress spontaneously. Active surveillance, rather than immediate intervention, is therefore justified, especially among young women who are likely to adhere to monitoring.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO 2014: CRD42014014406.
Topics: Conservative Treatment; Disease Progression; Female; Humans; Neoplasm Grading; Uterine Cervical Dysplasia
PubMed: 29487049
DOI: 10.1136/bmj.k499