Category: Statistics

Cochrane Database Syst Rev. 2022 Jun 30;6:CD005996. doi: 10.1002/14651858.CD005996.pub4.

ABSTRACT

BACKGROUND: The use of peri-implantation glucocorticoids has been advocated to improve embryo implantation during assistive reproductive technology (ART) cycles such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). It has been proposed that glucocorticoids may improve the intrauterine environment by acting as immunomodulators to reduce the uterine natural killer (NK) cell count and activity, normalising the cytokine expression profile in the endometrium and by suppression of endometrial inflammation.

OBJECTIVES: To evaluate the effectiveness and safety of glucocorticoids versus no glucocorticoids administered around the time of anticipated implantation in women undergoing IVF or ICSI.

SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group specialised register, CENTRAL (now also containing output from two trial registers and CINAHL), MEDLINE and Embase, on 20 December 2021, together with reference checking, contact with experts in the field and relevant conference proceedings to identify additional studies. This review is an update of the review first published in 2007 and last updated in 2012.

SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the efficacy of supplementary systemic administration of glucocorticoids in the peri-implantation period with a placebo or no glucocorticoids in subfertile women undergoing IVF or ICSI were included.

DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary review outcomes were live birth rate and multiple pregnancy.

MAIN RESULTS: We included 16 RCTs (2232 couples analysed). We are uncertain whether glucocorticoids improved live birth rates (odds ratio (OR) 1.37, 95% confidence interval (CI) 0.69 to 2.71; 2 RCTs, n = 366; I² = 7%; very low-certainty evidence). This suggests that if the chance of live birth following no glucocorticoids/placebo is assumed to be 9%, the chance following glucocorticoids would be between 6% and 21%. We are also uncertain whether there was a difference between peri-implantation glucocorticoids on multiple pregnancy rates per couple (OR 0.86, 95% CI 0.33 to 2.20; 4 RCTs, n = 504; I² = 53%; very low-certainty evidence). The I² of 53% may represent moderate statistical heterogeneity and results have to be interpreted with caution. With regard to pregnancy rates, we are uncertain whether there was a difference between ongoing pregnancy rates after glucocorticoids versus no glucocorticoids/placebo (OR 1.19, 95% CI 0.80 to 1.76; 3 RCTs, n = 476; I² = 0%; very low-certainty evidence) and clinical pregnancy rates after glucocorticoids versus no glucocorticoids/placebo (OR 1.17, 95% CI 0.95 to 1.44; 13 RCTs, n = 1967; I² = 0%; low-certainty evidence). This suggests that if the chance of clinical pregnancy following no glucocorticoids/placebo is assumed to be 25%, the chance following glucocorticoids would be between 24% and 32%. Furthermore, we are also uncertain whether peri-implantation glucocorticoids influenced miscarriage rates per couple (OR 1.09, 95% CI 0.63 to 1.87; 6 RCTs, n = 821; I² = 0%; very low-certainty evidence), the incidence of ectopic pregnancies per couple (OR 2.28, 95% CI 0.33 to 15.62; 3 RCTs, n = 320; I² = 0%; very low-certainty evidence) and ovarian hyperstimulation syndrome (OHSS) per couple (OR 1.07, 95% CI 0.60 to 1.90; 3 RCTs, n = 370; I² = 0%; very low-certainty evidence) compared to no glucocorticoids/placebo. The evidence was very low to low certainty: the main limitations were serious risk of bias due to poor reporting of study methods, and serious imprecision.

AUTHORS’ CONCLUSIONS: Overall, there was insufficient evidence that administration of peri-implantation glucocorticoids in IVF/ICSI cycles influenced clinical outcomes. These findings were limited to the routine use of glucocorticoids in subfertile women undergoing IVF or ICSI.

PMID:35771604 | DOI:10.1002/14651858.CD005996.pub4

JAMA Netw Open. 2022 Jun 1;5(6):e2219651. doi: 10.1001/jamanetworkopen.2022.19651.

ABSTRACT

IMPORTANCE: Substance use disorders (SUDs) are major contributors to morbidity and mortality globally, but they are often underrecognized and underdiagnosed, particularly in some sociodemographic subgroups. Understanding the extent to which clinical diagnoses underestimate these conditions within subgroups is imperative to achieving equitable treatment, regardless of race, ethnicity, gender, or age, and to informing and improving performance monitoring.

OBJECTIVE: To compare clinically documented diagnosis rates of alcohol use disorder (AUD), drug use disorder (DUD), and total SUD (AUD and/or DUD) with the prevalence of these disorders as reported in surveys-based on structured, validated diagnostic assessments-across demographic subgroups.

DESIGN, SETTING, AND PARTICIPANTS: A telephone-based survey was conducted from January 8, 2018, to April 30, 2019, among 5995 Veterans Health Administration (VHA) outpatients who were randomly sampled from 30 VHA facilities and were 18 years of age or older, could complete the survey in English, and had a valid address and telephone number. Survey data were linked to electronic health record (EHR) data for all participants. Statistical analysis was performed between January 29, 2020, and April 20, 2021.

EXPOSURES: Demographic subgroups based on self-report: gender (male or female), age (18-34, 35-49, 50-64, 65-74, and ≥75 years), and race and ethnicity (Black non-Hispanic, Hispanic, multiracial, other [Asian or Asian-American, American Indian or Alaskan Native, Native Hawaiian or Pacific Islander, and any other race endorsed by the participant], and White non-Hispanic).

MAIN OUTCOMES AND MEASURES: Survey-based prevalence rates of AUD, DUD, and SUD were assessed using the Mini International Neuropsychiatric Interview, version 7.0, the only validated instrument available at study outset that measured Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for past 12-month diagnoses. Clinically documented diagnosis rates were measured using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses from VHA EHR data. Analyses compared survey-based prevalence rates of AUD, DUD, and SUD with diagnosis rates using sensitivity and specificity and difference-in-difference analysis. All analyses were weighted with survey weights to account for nonresponse.

RESULTS: Of 5995 participants, 4115 (68.6%) were White non-Hispanic, and 5429 (91.1%) were male; the mean (SD) age was 61.5 (15.3) years. The survey-based prevalence rates of AUD, DUD, and SUD were higher than the diagnosis rates among all patients (AUD, 608 [10.1%] vs 360 [6.0%]; DUD, 282 [4.7%] vs 275 [4.6%]; SUD, 768 [12.8%] vs 515 [8.6%]). Survey-based prevalence rates of AUD and SUD exceeded the diagnosis rates in every demographic subgroup. Gaps between diagnosis rates and survey-based prevalence rates for AUD and SUD were largest among patients aged 18 to 34 years (AUD diagnosis rate, 27 [6.9%; 95% CI, 4.8%-9.9%] vs AUD prevalence rate, 88 [22.4%; 95% CI, 17.3%-28.5%]; SUD diagnosis rate, 41 [10.5%; 95% CI, 8.1%-13.4%] vs SUD prevalence rate, 109 [27.7%; 95% CI, 22.6%-33.3%]) and Hispanic and Latinx patients (AUD diagnosis rate, 31 [7.6%; 95% CI, 5.3%-10.8%] vs AUD prevalence rate, 72 [17.7%; 95% CI, 14.0%-22.1%]; and SUD diagnosis rate, 48 [11.7%; 95% CI, 7.9%-16.9%] vs SUD prevalence rate, 88 [21.6%; 95% CI, 18.0%-25.8%]). For DUD, only patients aged 18 to 34 years had a true prevalence rate that significantly exceeded the diagnosis rate (diagnosis rate, 21 [5.4%; 95% CI, 3.7%-7.8%] vs prevalence rate, 40 [10.1%; 95% CI, 7.2%-14.0%]).

CONCLUSIONS AND RELEVANCE: The results of this survey study suggest that existing diagnostic procedures and tools are insufficient to capture SUD prevalence rates, particularly among younger patients and Hispanic and Latinx patients. Clinics and health systems should implement standardized SUD assessments to ensure the provision of equitable care and the optimal identification of underlying conditions for performance monitoring.

PMID:35771574 | DOI:10.1001/jamanetworkopen.2022.19651

JAMA Netw Open. 2022 Jun 1;5(6):e2219657. doi: 10.1001/jamanetworkopen.2022.19657.

NO ABSTRACT

PMID:35771578 | DOI:10.1001/jamanetworkopen.2022.19657

JAMA Netw Open. 2022 Jun 1;5(6):e2219678. doi: 10.1001/jamanetworkopen.2022.19678.

ABSTRACT

IMPORTANCE: Many older adults with depression do not experience remission with antidepressant treatment, and markers of cellular senescence in late-life depression (LLD) are associated with greater severity of depression, greater executive dysfunction, and higher medical illness burden. Since these clinical characteristics are associated with remission in LLD, molecular and cellular senescence abnormalities could be a possible biological mechanism underlying poor treatment response in this population.

OBJECTIVE: To examine whether the senescence-associated secretory phenotype (SASP) index was associated with the likelihood of remission from a depressive episode in older adults.

DESIGN, SETTING, AND PARTICIPANTS: A nonrandomized, open-label clinical trial was conducted between August 2009 and August 2014 in Pittsburgh, Pennsylvania; St Louis, Missouri; and Toronto, Ontario, Canada, with older adults in a current major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) diagnostic criteria. Data from biomarker analyses were reported according to the clinical trial archived plasma samples run in March 2021. Data were analyzed from June to November 2021.

EXPOSURE: Venlafaxine extended release (dose ranging from 37.5 mg to 300 mg daily) for up to 12 weeks.

MAIN OUTCOMES AND MEASURES: The association between a composite biomarker-based index (SASP index) and treatment remission in older adults with major depression was measured using clinical data and blood samples.

RESULTS: There were 416 participants with a mean (SD) age of 60.02 (7.13) years; 64% (265 participants) were self-reported female, and the mean (SD) Montgomery-Asberg Depression Rating Scale score was 26.6 (5.7). Higher SASP index scores were independently associated with higher rates of nonremission, with an increase of 1 unit in the SASP index score increasing the odds of nonremission by 19% (adjusted odds ratio, 1.19; 95% CI, 1.05-1.35; P = .006). In contrast, no individual SASP factors were associated with remission in LLD.

CONCLUSIONS AND RELEVANCE: Using clinical data and blood samples from a nonrandomized clinical trial, the results of this study suggest that molecular and cellular senescence, as measured with the SASP index, is associated with worse treatment outcomes in LLD. Combining this index score reflecting interrelated biological processes with other molecular, clinical, and neuroimaging markers may be useful in evaluating antidepressant treatment outcomes. These findings inform a path forward for geroscience-guided interventions targeting senescence to improve remission rates in LLD.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00892047.

PMID:35771573 | DOI:10.1001/jamanetworkopen.2022.19678

JAMA Netw Open. 2022 Jun 1;5(6):e2219814. doi: 10.1001/jamanetworkopen.2022.19814.

ABSTRACT

IMPORTANCE: The ability of computed tomography (CT) to distinguish between benign congenital lung malformations and malignant cystic pleuropulmonary blastomas (PPBs) is unclear.

OBJECTIVE: To assess whether chest CT can detect malignant tumors among postnatally detected lung lesions in children.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter case-control study used a consortium database of 521 pathologically confirmed primary lung lesions from January 1, 2009, through December 31, 2015, to assess diagnostic accuracy. Preoperative CT scans of children with cystic PPB (cases) were selected and age-matched with CT scans from patients with postnatally detected congenital lung malformations (controls). Statistical analysis was performed from January 18 to September 6, 2020. Preoperative CT scans were interpreted independently by 9 experienced pediatric radiologists in a blinded fashion and analyzed from January 24, 2019, to September 6, 2020.

MAIN OUTCOMES AND MEASURES: Accuracy, sensitivity, and specificity of CT in correctly identifying children with malignant tumors.

RESULTS: Among 477 CT scans identified (282 boys [59%]; median age at CT, 3.6 months [IQR, 1.2-7.2 months]; median age at resection, 6.9 months [IQR, 4.2-12.8 months]), 40 cases were extensively reviewed; 9 cases (23%) had pathologically confirmed cystic PPB. The median age at CT was 7.3 months (IQR, 2.9-22.4 months), and median age at resection was 8.7 months (IQR, 5.0-24.4 months). The sensitivity of CT for detecting PPB was 58%, and the specificity was 83%. High suspicion for malignancy correlated with PPB pathology (odds ratio, 13.5; 95% CI, 2.7-67.3; P = .002). There was poor interrater reliability (κ = 0.36 [range, 0.06-0.64]; P < .001) and no significant difference in specific imaging characteristics between PPB and benign cystic lesions. The overall accuracy rate for distinguishing benign vs malignant lesions was 81%.

CONCLUSIONS AND RELEVANCE: This study suggests that chest CT, the current criterion standard imaging modality to assess the lung parenchyma, may not accurately and reliably distinguish PPB from benign congenital lung malformations in children. In any cystic lung lesion without a prenatal diagnosis, operative management to confirm pathologic diagnosis is warranted.

PMID:35771571 | DOI:10.1001/jamanetworkopen.2022.19814

Am J Respir Crit Care Med. 2022 Jun 30. doi: 10.1164/rccm.202109-2166OC. Online ahead of print.

ABSTRACT

RATIONALE: A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in SARS-CoV-2 infection and disease severity is unclear.

OBJECTIVES: To assess whether rs35705950-T confers differential risk for clinical outcomes associated with COVID-19 infection among participants in the Million Veteran Program (MVP).

METHODS: The MUC5B rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by trans-ancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (BMI, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease and IPF) and associations with post-COVID-19 pneumonia were performed in MVP subjects.

MEASUREMENTS AND MAIN RESULTS: The rs35705950-T allele was associated with fewer COVID-19 hospitalizations (Ncases=4,325/, Ncontrols=507,640; OR=0.89 [0.82-0.97], p=6.86 x 10-03) in trans-ancestry meta-analysis within MVP and joint meta-analyses with the HGI (Ncases=13,320, Ncontrols=1,508,841; OR=0.90 [0.86-0.95], p =8.99 x 10-05). The rs35705950-T allele was not associated reduced COVID-19 positivity in trans-ancestry meta-analysis within MVP (Ncases=19,168/Ncontrols=492,854; OR=0.98 [0.95-1.01], p=0.06) but was nominally significant (p<0.05) in the joint meta-analysis with HGI (Ncases=44,820/Ncontrols=1,775,827; OR=0.97 [0.95-1]; p=0.03). We did not observe associations with severe outcomes or mortality. Among MVP individuals of European ancestry, rs35705950-T was associated with fewer post-COVID-19 pneumonia events (OR=0.82 [0.72-0.93], p=0.001).

CONCLUSIONS: The MUC5B variant rs35705950-T may confer protection in COVID-19 hospitalizations. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

PMID:35771531 | DOI:10.1164/rccm.202109-2166OC

J Consult Clin Psychol. 2022 Jun;90(6):503-512. doi: 10.1037/ccp0000739.

ABSTRACT

OBJECTIVE: Prolonged exposure (PE) therapy is a first-line posttraumatic stress disorder (PTSD) treatment, but the manualized 90-min session format constitutes a barrier to adopting PE in most settings because they use 60-min sessions for scheduling and billing. We examined whether 60-min PE sessions were as effective and efficient as 90-min PE sessions.

METHOD: In total, 160 active-duty military personnel with PTSD were randomized to 8-15 sessions of 60- or 90-min PE sessions and assessed pre- and posttreatment, and 3- and 6-month posttreatment, using the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual for Mental Disorders, 5th edition [DSM-5] (CAPS-5). Participants were also assessed weekly during treatment using the PTSD Checklist for DSM-5 (PCL-5). A 60-min PE was hypothesized to be noninferior to 90-min PE based on preliminary studies.

RESULTS: Using intent-to-treat analyses, the 95% CI for the difference between 60- and 90-min PE was less than the noninferiority margin (4.69 for the CAPS-5 and 7.38 for the PCL-5) at all three endpoints, suggesting that the efficacy of 60-min PE was noninferior to that of 90-min PE. Similarly, the rate of improvement per session for 60-min PE was noninferior to the rate for 90-min sessions for the PCL-5. Sensitivity analyses and Bayes factors were consistent with these results.

CONCLUSIONS: 60-min sessions of PE are noninferior to 90-min sessions with regard to both efficacy and efficiency. Thus, PE can be effectively delivered in shorter sessions, making it easier for behavioral health providers to implement within the military health system and in other mental health systems that use 60-min session appointments. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PMID:35771512 | DOI:10.1037/ccp0000739

J Fam Psychol. 2022 Jun 30. doi: 10.1037/fam0001006. Online ahead of print.

ABSTRACT

Parenting is known to impact children’s executive function (EF) skills. However, nearly all the evidence comes from analyses of mother-child interaction. Using the National Longitudinal Study of Child Development and Care Database in Taiwan, the relations between both mother-child and father-child interaction and 3-year-olds’ EF were investigated in 2,164 families. The results showed that mothers interacted with their children differently from fathers in terms of time distribution. Mothers were more equally involved in all aspects of parental involvement, whereas fathers spent more time in play. In addition, both mother-child and father-child play contributed to children’s EF; however, the mediating effect of child motor skills was more prominent for father-child play. This study not only suggests a potential distinct and complementary role of fathers in young children’s EF development but also indicates a unique mediating effect of motor skills in the path from parent-child play to child EF. Implications for parent education are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PMID:35771502 | DOI:10.1037/fam0001006

Med Sci Monit Basic Res. 2022 Jun 15;28:e936675. doi: 10.12659/MSMBR.936675.

ABSTRACT

BACKGROUND A hermetic seal at the apical terminus is required for healthy periradicular tissue. Root canal obturation sealers that are used in endodontics are based on zinc oxide eugenol, calcium hydroxide, resins, glass ionomers, silicone, or bioceramics, but no optimal sealer material has been identified to date. Therefore, the aim of this in vitro study was to evaluate apical leakage after crown-down preparation and root canal obturation with Endomethasone N, glass ionomer cement, and EndoRez sealers. MATERIAL AND METHODS For this in vitro study, we tested 92 extracted human teeth, which were divided into 3 groups after a preparation technique and obturation with Endomethasone N sealer, glass ionomer cement, and EndoRez sealer in combination with Thermafil obturator. Apical leakage was evaluated and compared among the tested groups using a dye leakage method through a stereomicroscope. The values were measured from the apex to the coronal extent of dye penetration. For statistical analysis, the t test was used for comparison of the arithmetic averages of tested groups. RESULTS After preparation with rotary files, tested groups obturated with Thermafil obturator in combination with Endomethasone sealer showed higher average dye penetration than tested groups obturated with EndoRez and glass ionomer sealer. CONCLUSIONS Although all experimental groups showed dye leakage, the glass ionomer sealer in combination with Thermafil showed the least leakage, compared with EndoRez and Endomethason N.

PMID:35771493 | DOI:10.12659/MSMBR.936675

Pharmacoeconomics. 2022 Jun 30. doi: 10.1007/s40273-022-01162-6. Online ahead of print.

ABSTRACT

OBJECTIVES: As obesity-associated events impact long-term survival, health economic (HE) modelling is commonly applied, but modelling approaches are diverse. This research aimed to compare the events simulation and the HE outcomes produced by different obesity modelling approaches.

METHODS: An external validation, using the Swedish obesity subjects (SOS) study, of three main structural event modelling approaches was performed: (1) continuous body mass index (BMI) approach; (2) risk equation approach; and (3) categorical BMI-related approach. Outcomes evaluated were mortality, cardiovascular events, and type 2 diabetes (T2D) for both the surgery and the control arms. Concordance between modelling results and the SOS study were investigated by different state-of-the-art measurements, and categorized by the grade of deviation observed (grades 1-4 expressing mild, moderate, severe, and very severe deviations). Furthermore, the costs per quality-adjusted life-year (QALY) gained of surgery versus controls were compared.

RESULTS: Overall and by study arm, the risk equation approach presented the lowest average grade of deviation (overall grade 2.50; control arm 2.25; surgery arm 2.75), followed by the continuous BMI approach (overall 3.25; control 3.50; surgery 3.00) and by the categorial BMI approach (overall 3.63; control 3.50; surgery 3.75). Considering different confidence interval limits, the costs per QALY gained were fairly comparable between all structural approaches (ranging from £2,055 to £6,206 simulating a lifetime horizon).

CONCLUSION: None of the structural approaches provided perfect external event validation, although the risk equation approach showed the lowest overall deviations. The economic outcomes resulting from the three approaches were fairly comparable.

PMID:35771486 | DOI:10.1007/s40273-022-01162-6