Sufficient Follow-up Research Articles

P-785 Assisted reproduction techniques and the risk of ovarian tumors

Abstract Study question Are fertility treatments associated with increased risk of subsequent development of ovarian tumors? Summary answer Results from recent studies have been primarily reassuring. However, further investigation is needed to determine whether fertility drug use increases the risk of ovarian tumors. What is known already In the last decades, the number of fertility treatments is rising worldwide due to postponing childbearing to a later age. The increasing exposure to fertility drugs has brought probable long term sequelae into focus, notably correlation with gynaecological malignancies. Two theories on the association between fertility drugs and ovarian cancer have been proposed, the “incessant ovulation” and the “elevated gonadotropin levels” theory. Use of assisted reproduction techniques (ART) is highly associated with many factors that are known to affect ovarian cancer risk such as parity. Study design, size, duration Summary of relevant clinical literature and review of all research studies that address the possible relation of assisted reproductive treatments with ovarian tumors. Participants/materials, setting, methods Published literature in PubMed, Medline and Google Scholar databases from 2011 to 2021 was screened using the following keywords: assisted reproductive techniques, in vitro fertilization, fertility drugs, ovarian cancer, and borderline ovarian tumors. Articles that were written in non- Latin alphabet were excluded for translational reasons. At least two review authors independently evaluated articles for eligibility. Main results and the role of chance Sixteen cohort and three case-control studies were selected. The majority of included studies reported no increase in ovarian cancer risk among subfertile women treated with ART, compared to either general population or subfertile non-treated women. In eight cohort and one case control studies, the type of fertility drug was clearly reported, including clomiphene citrate, gonadotropins, GnRH (gonadotropin releasing hormone) analogues, alone or in mixed protocols, while in the rest, the type of drug was not specified. Some studies showed a trend for a causative role of increasing dosage or number of IVF (in vitro fertilization) cycles, though statistically insignificant. Based on existing data, genetically vulnerable BRCA mutation carriers should not be excluded from use of ART, although extensive information of the potential association of ovarian stimulating drugs with ovarian tumors should be provided. Data on the association of fertility drug use with borderline ovarian tumors were contradictory. All included studies adjusted or matched for one or more possible confounding factors, such as age, parity and oral contraceptive use. Stratification by cause of infertility, showed an increased risk of ovarian cancer in treated women, with female factor infertility, which was more prominent in case of endometriosis. Limitations, reasons for caution High clinical and methodological heterogeneity of the included studies, with adjustment for varying confounding factors, relatively short follow–up periods and small samples sizes were noticed. Wider implications of the findings Ovarian cancer is the deadliest among all gynaecological malignancies. Considering the increasing use of ART worldwide, further clarification of the association between the two is crucial. For this reason larger, prospective studies are needed with sufficient follow-up exceeding 20years so that treated women will reach the ovarian cancer age range. Trial registration number not applicable

The Impact of Juvenile Drug Treatment Courts on Substance Use, Mental Health, and Recidivism: Results from a Multisite Experimental Evaluation.

Juvenile Drug Treatment Courts (JDTC) emerged in the mid-1990s as a potential solution to concern about substance use among youth in the juvenile justice system (JJS). Despite substantial research, findings on the JDTC effectiveness for reducing recidivism and substance use remain inconsistent, hampered by methodological problems. In 2016, the Office of Juvenile Justice and Delinquency Prevention published research-based JDTC Guidelines for best practices, and funded technical assistance for implementation and a multisite national outcomes study among JDTCs implementing the Guidelines. Ten sites were originally selected for this study, with a JDTC and Traditional Juvenile Court (TJC) participating. In two sites, moderate- to high-risk youth were randomized to JDTC or TJC, and in eight sites, a regression discontinuity design assigned moderate- to high-risk youth to JDTC, and other youth to TJC. Findings from four sites with sufficient cases and follow-up rates indicated that JDTCs reduced cannabis use, increased access to mental health services, and reduced recidivism. However, the effects were small to moderate, with positive impacts mainly observed among high-risk youth. The impacts of JDTCs may have been attenuated because Guidelines implementation was inconsistent across courts, and some TJCs implemented elements of the Guidelines, blurring the distinction between JDTCs and TJCs.

Abstract 5767: Landscape of concomitant driver mutations in EGFR-mutated NSCLCs

Abstract Background While most oncogenic driver mutations are mutually exclusive, next-generation sequencing (NGS) has led to the identification of concomitant driver alterations in non-small cell lung cancer (NSCLC). However, the landscape of concomitant drivers and the clinical relevance remain to be explored. Methods: We profiled concomitant driver alterations, including EGFR, KRAS, ALK, RET, ROS1, MET, BRAF and ERBB2 from baseline tumor tissues of 22,610 NSCLC patients by using targeted NGS. The associated genomic and clinical features were analyzed and validated in a TCGA dataset of 136 EGFR+ NSCLC patients. Results: The overall frequency of concomitant driver mutations in EGFR+ patients was 3.09% (334/10,801). EGFR activating mutations most commonly co-occurred with KRAS mutations (2.42%), followed by ERBB2 (1.09%), MET (0.75%) and BRAF (0.15%). A total of six EGFR+ patients were identified with co-occurring ALK (n=2), RET (n=1), or ROS1 (n=3) fusions. Patients with dual EGFR/KRAS mutations were more likely to carry the p.G13D (6.1% vs. 2.9%, P<.05), p.G12S (6.1% vs. 2.3%, P<.01), p.A146T (8.3% vs. 0.9%, P<.0001), p.A146V (3.9% vs. 0.5%, P<.001)variants in KRAS, whereas those with single KRAS were enriched with p.G12C (15.0% vs. 33.0%, P<.0001) and p.G12A (3.9% vs. 8.5%, P<.05) variants. Patients with dual EGFR/MET alterations had a higher frequency of MET amplification (71.4% vs. 43.3%) and lower exon 14 skipping mutations (28.6% vs. 56.7%, P=.0001) than MET single drivers. Patients with dual EGFR/ERBB2 alterations had higher ERBB2 amplification (40.7% vs. 16.5%, P<.0001) and p.S310F/Y mutations (44.4% vs. 4.3%, P<.0001), and lower ERBB2 exon 20 insertions (9.9%, vs. 70.6%, P<.0001). In addition, dual drivers had higher frequencies of TP53 (P<.01), RB1 (P<.05), ARID2 (P<.05), NTRK1 (P<.01), TSC2 (P<.001), and BRIP1 (P<.01) alterations than single drivers. At the genomic level, dual drivers had higher mutational load than those with only EGFR mutations (median 4 vs. 2 muts, P<.01). In 75% of dual drivers, EGFR mutant allele frequency (MAF) was higher than that of the other concomitant driver. In patients with sufficient clinical follow-up, dual drivers were associated with unfavorable PFS outcomes compared with single drivers (HR=2.87, P=.04) following first-line first-generation EGFR TKIs, which was mainly attributed to the presence of MET amplification or PIK3CA mutations. In addition, in dual EGFR/KRAS and EGFR/BRAF drivers, a higher MAF of EGFR than that of the respective co-occurring driver was associated with a trend towards prolonged PFS (11.0 vs. 8.1m, HR= 0.21, P=.15), likely suggesting clonal advantage of EGFR sensitizing mutations in response to first-generation TKIs. Conclusion: In our large cohort study, we present the landscape of EGFR+ dual drivers and their associated clinical and genomic features and survival outcomes, which could aid in therapeutic decisions and facilitate the development of combination therapies. Citation Format: Xiaonan Wang, Junli Zhang, Chuqiao Liang, Jiani C. Yin, Yang Shao. Landscape of concomitant driver mutations in EGFR-mutated NSCLCs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5767.

Rho kinase inhibitor for primary open-angle glaucoma and ocular hypertension.

Rho kinase inhibitor for primary open-angle glaucoma and ocular hypertension.

Post-radiation cisplatin and etoposide as systemic treatment in newly diagnosed adult medulloblastomas: A retrospective, single institution, longitudinal evaluation of clinical outcomes and toxicity.

e14046 Background: Medulloblastomas are malignancies of the posterior fossa with metastatic potential to the central nervous system. While a common pediatric malignancy, they are rare in adults. Extrapolating treatment regimens from pediatrics to adults is fraught as adults can developmentally tolerate higher radiation doses, but have less bone marrow reserve and therefore risk higher myelosuppressive toxicities with adjuvant systemic therapy. A standard systemic regimen for adults has not been delineated, though craniospinal radiation alone is likely insufficient in most cases. In the absence of well-established guidelines, our institution has historically used a combination of cisplatin (60 mg/m2 on Day 1) and etoposide (60-120 mg/m2 on Days 1-3 or 1-5) repeated in three-week cycles for three to a maximum of six cycles, but the literature to support this regimen is scant. Methods: In this retrospective chart evaluation, we reviewed the medical information of patients who were seen for newly diagnosed adult medulloblastoma between 1995 and 2020 at Johns Hopkins Hospitals. Those who met our pre-specified criteria (adjuvant treatment with etoposide/cisplatin within six months of craniospinal irradiation, sufficient data on toxicity before and after radiation, during chemotherapy, and one month after completion of the regimen, as well as sufficient clinical follow-up) were included in the analysis. Hematological toxicities were graded by NCI CTCAE guidelines. Follow-up for progression and survival were calculated from the end of the last chemotherapy administration and plotted on swimmers plots. Results: Ten out of 74 total adult medulloblastoma patients had adequate data about the tolerability of the regimen and clinical follow-up. Median time to follow-up was 46 months (range 4.5-164 months). Eight patients experienced Grade 3 and 4 hematological toxicities. Seven patients completed their planned treatment course, while two patients discontinued treatment prematurely because of hematological toxicities and one due to ototoxicity and fatigue. Three out of the ten patients progressed post-chemotherapy at 1 month, 24.5 months, and 44 months. Both early-progression patients died (7 and 29.5 months respectively), while the remaining eight are alive without evidence of progression. Conclusions: The data suggest a combination regimen of cisplatin and etoposide after craniospinal radiation in newly diagnosed adult medulloblastoma patients has acceptable toxicity and survival outcomes in this small patient cohort and compare favorably to other limited datasets in the literature. Further study is warranted to validate this as a recommended regimen.

Hearing Benefits of Clinical Management for Meniere's Disease.

Meniere’s disease is a progressive hearing–disabling condition. Patients can benefit from strict clinical management, including lifestyle and dietary counseling, and medical treatment. A prospective cohort study was carried out with 154 patients with definite Meniere’s disease, with an average age of 43.53 ± 11.40, and a male to female ratio of 0.97:1. The pure-tone thresholds of all 165 affected ears, over a one-year clinical management period, were analyzed. After one year, 87.27% of patients had improved or preserved their hearing at a low frequency, and 71.51% at a high frequency. The hearing threshold at frequencies from 250 Hz to 2000 Hz had improved significantly (p < 0.001, p < 0.001, p < 0.001, p < 0.01), and deteriorated slightly at 8000 Hz (p < 0.05). Of all the patients, 40.00% had a hearing average threshold that reached ≤25 dB HL after the clinical management period, among whom 27.27% were patients in stage 3. The restoration time was 2.5 (1.0, 4.125) months, with a range of 0.5–11.0 months, and the restoration time was longer for stage 3 than for stages 1 and 2 (u = −2.542, p < 0.05). The rising curves improved the most (p < 0.05), with most becoming peaks, whereas most peaks and flats remained the same. Patients who were initially in the earlier stages (95% CI 1.710~4.717, OR 2.840, p < 0.001), have an increased odds ratio of hearing by an average of ≤25 dB HL. Age (95% CI 1.003~1.074, OR 1.038, p = 0.031), peak curve (95% CI 1.038~5.945, OR = 2.484, p = 0.041), and flat curve (95% CI 1.056~19.590, OR = 4.549, p = 0.042), compared with the rising curve, increase the odds ratio of hearing on average by >25 dB HL. Most patients can have their hearing preserved or improved through strict clinical management, and sufficient follow-up is also essential. Stage 3 patients also have the potential for hearing improvement, although the restoration time is longer than in the early stages. The initial hearing stage, age, and audiogram pattern are related to the hearing benefits.

Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: Update of a living systematic review and meta-analysis.

Debate about the level of asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection continues. The amount of evidence is increasing and study designs have changed over time. We updated a living systematic review to address 3 questions: (1) Among people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? (2) What is the infectiousness of asymptomatic and presymptomatic, compared with symptomatic, SARS-CoV-2 infection? (3) What proportion of SARS-CoV-2 transmission in a population is accounted for by people who are asymptomatic or presymptomatic? The protocol was first published on 1 April 2020 and last updated on 18 June 2021. We searched PubMed, Embase, bioRxiv, and medRxiv, aggregated in a database of SARS-CoV-2 literature, most recently on 6 July 2021. Studies of people with PCR-diagnosed SARS-CoV-2, which documented symptom status at the beginning and end of follow-up, or mathematical modelling studies were included. Studies restricted to people already diagnosed, of single individuals or families, or without sufficient follow-up were excluded. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with a bespoke checklist and modelling studies with a published checklist. All data syntheses were done using random effects models. Review question (1): We included 130 studies. Heterogeneity was high so we did not estimate a mean proportion of asymptomatic infections overall (interquartile range (IQR) 14% to 50%, prediction interval 2% to 90%), or in 84 studies based on screening of defined populations (IQR 20% to 65%, prediction interval 4% to 94%). In 46 studies based on contact or outbreak investigations, the summary proportion asymptomatic was 19% (95% confidence interval (CI) 15% to 25%, prediction interval 2% to 70%). (2) The secondary attack rate in contacts of people with asymptomatic infection compared with symptomatic infection was 0.32 (95% CI 0.16 to 0.64, prediction interval 0.11 to 0.95, 8 studies). (3) In 13 modelling studies fit to data, the proportion of all SARS-CoV-2 transmission from presymptomatic individuals was higher than from asymptomatic individuals. Limitations of the evidence include high heterogeneity and high risks of selection and information bias in studies that were not designed to measure persistently asymptomatic infection, and limited information about variants of concern or in people who have been vaccinated. Based on studies published up to July 2021, most SARS-CoV-2 infections were not persistently asymptomatic, and asymptomatic infections were less infectious than symptomatic infections. Summary estimates from meta-analysis may be misleading when variability between studies is extreme and prediction intervals should be presented. Future studies should determine the asymptomatic proportion of SARS-CoV-2 infections caused by variants of concern and in people with immunity following vaccination or previous infection. Without prospective longitudinal studies with methods that minimise selection and measurement biases, further updates with the study types included in this living systematic review are unlikely to be able to provide a reliable summary estimate of the proportion of asymptomatic infections caused by SARS-CoV-2. Open Science Framework (https://osf.io/9ewys/).

Risk Factors for Postischemic Stroke Epilepsy in Young Adults: A Nationwide Population-Based Study in Taiwan.

BackgroundThe incidence of ischemic stroke has been increasing in the young population over the past 20 years. Poststroke epilepsy (PSE) is a common complication after stroke. However, few population-based studies with sufficient follow-up have investigated factors associated with PSE, especially factors related to comorbidities and unhealthy lifestyles in the modern young population. Accordingly, this study aimed to determine the long-term incidence and these risk factors for PSE young adults.MethodsThis cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) from 2002 to 2018. All patients aged between 19 and 44 years and diagnosed with ischemic stroke from 2002 to 2015 were retrospectively enrolled with a follow-up of at least 3 years. Multivariable Cox regression models were performed to identify predictors of PSE, including patients' demographics, baseline conditions, stroke severity, etiologies, comorbidities, and unhealthy behaviors.ResultsAmong 6,512 ischemic stroke patients, 402 cases (6.2%) developed PSE who were with a mean follow-up period of 8.3 years (SD = 4.3 years). During the overall follow-up, stroke severity and manifestations were associated with PSE, including National Institutes of Health Stroke Scale (NIHSS) score ≥10 (aHR, 1.98; 95% CI, 1.50–2.61), seizure at first stroke admission [adjusted hazard ratio (aHR), 57.39; 95% confidence interval (CI), 43.02–76.55], length of hospital stay ≥14 days (aHR, 1.60; 95% CI, 1.26–2.02), recurrent stroke (aHR, 2.32; 95% CI, 1.85–2.90), aphasia (aHR, 1.77; 95% CI, 1.20–2.60), and malignancy (aHR, 2.05; 95% CI, 1.30–3.24). Furthermore, stroke patients with drug abuse were 2.90 times more likely to develop PSE than those without (aHR, 2.90; 95% CI, 1.53–5.50). By contrast, statin use (aHR, 0.62; 95% CI, 0.48–0.80) was associated with a lower risk of PSE. The risk factors at 1-year and 5-year PSE were similar to that of an overall follow-up.ConclusionsStroke severity, aphasia, malignancy, and drug abuse were associated increased risk of PSE and statin use may protect against PSE in young adults. Reducing the severity of stroke, statin use and controlling unhealthy behaviors might be able to decrease the development of PSE. Since PSE is associated with poor outcomes, early identification or intervention of PSE based on the risk factors might reduce the harmful effects of PSE.

Low function and frequent readmission in nursing home patients with persistent resistant gram-negative bacterial colonization

Background: Persistent colonization with resistant gram-negative bacteria (R-GNB) increases risk of clinical infection and intra-facility transmission among nursing home (NH) patients. Limited data exist on the roles of age and function on duration of R-GNB colonization. Methods: Secondary data analysis was performed from a cohort study of patients admitted to 6 Michigan NHs between November 2013 and May 2018. Swabs obtained upon enrollment, day 14, day 30, then monthly until NH discharge from 6 anatomical sites were cultured for GNB. R-GNB were defined as resistant to ciprofloxacin, ceftazidime, or imipenem. Positive R-GNB culture from a single visit followed by negative cultures for the same organism from ≥2 subsequent visits were defined as transient R-GNB colonization. All other patients with positive R-GNB cultures from multiple visits were considered persistently colonized. Demographic data, antibiotic use, device use, and physical self-maintenance scales (PSMSs) were obtained upon enrollment. Characteristics were compared between patients with transient versus persistent R-GNB and uncolonized patients using multinomial logistic regression. Results: We recruited 896 patients (median age, 75 years; 41% male; 46% nonwhite) and followed them for 2,437 total visits. Of 896 patients, 407 (45.4%) were colonized with ≥1 R-GNB during their stay. Of 171 patients with ≥ 2 follow-up visits after R-GNB detection, 94 (55%) remained persistently colonized with the same R-GNB (Table 1). Escherichia coli (30%) and Proteus mirabilis (22%) were the most frequently identified R-GNB. The most common anatomical colonization sites were perirectal (368 [24.3%] of 1,147) groin (340 [14.3%] of 2,046), and hands (115 [4.8%] of 2283). Compared to uncolonized patients, patients with persistent (1.09; 95% CI, 1.00–1.19, P = .048) and transient R-GNB colonization (1.13; 95% CI, 1.04–1.23; P = .003) had lower PSMS (Tables 2 and 3). Compared to uncolonized and transiently colonized patients, patients with persistent R-GNB colonization had prolonged lengths of NH stay (1.01; 95% CI, 1.00–1.01; P = .003). Conclusions: R-GNB colonization in vulnerable NH patients is common (407 [45.5%] of 896 and often persistent (94 [55%] of 171 patients with sufficient follow-up to assess persistence). Patients with persistent R-GNB had lower functional status, longer LOS, and higher readmission rates than those without. R-GNB decolonization should be investigated as a strategy to potentially improve outcomes among NH patients.Funding: NoneDisclosures: None

Real-world data: Assessing electronic health records and medical claims data to support regulatory decision-making for drug and biological products.

Real-world data: Assessing electronic health records and medical claims data to support regulatory decision-making for drug and biological products.

Endosteal plating in proximal humerus fractures: a novel technique and alternative to fibular strut allograft for medial column support

The purpose of this retrospective study is to investigate the clinical and radiographic outcomes associated with the use of a standard metal plate as an endosteal implant in combination with a lateral locking plate to treat 4 patients with displaced proximal humerus fractures. A retrospective case series study design was utilized, and the medical records of 4 patients with displaced, 3-part proximal humerus fractures treated using this technique between January 2019 and July 2021 were reviewed for this study. The mean age was 52 years (range, 44-57 years). The radiographic outcome of interest was humeral neck-shaft angle preoperatively, intraoperatively, and at the latest follow-up. The average follow-up duration was 62 weeks (range, 12-161 weeks). All fractures healed without loss of reduction or neurovascular deficits. Avascular necrosis was not observed in the 2 patients with sufficient follow-up time to make such an evaluation. The average neck-shaft angles preoperatively, intraoperatively, and at the latest follow-up were 104.8°, 139.8°, and 137°, respectively. Locking plate technology augmented with an endosteal plate provided stable reduction and restoration of physiologic alignment in a small number of patients with displaced proximal humerus fractures. This construct creates a second column of fixation, providing medial column support, and could be removed in the event of a future revision to a reverse shoulder arthroplasty.

Automated Spontaneity Assessment after Smile Reanimation: A Machine Learning Approach.

Recreation of a spontaneous, emotional smile remains a paramount goal of smile reanimation surgery. However, optimal techniques to reliably restore spontaneity remain unknown. Dual automated machine-learning tools were used to develop an objective tool to analyze spontaneous smiling. The feasibility of this tool was tested in a sample of functional free muscle transfers. Validated humorous videos were used to elicit spontaneous smiles. Automated facial landmark recognition (Emotrics) and emotion detection software (Affdex) were used to analyze video clips of spontaneous smiling in nine normal subjects and 39 facial reanimation cases. Emotionality quotient was used to quantify the ability of spontaneous smiles to express joy. The software could analyze spontaneous smiling in all subjects. Spontaneous smiles of normal subjects exhibited median 100 percent joy and 0 percent negative emotion (emotional quotient score, +100/0). Spontaneous smiles of facial palsy patients after smile reanimation, using cross-facial nerve graft, masseteric nerve, and dual innervation, yielded median emotional quotient scores of +82/0, 0/-48, and +10/-24 respectively (joy, p = 0.006; negative emotion, p = 0.034). Computer vision software can objectively quantify spontaneous smiling outcomes. Of the retrospective sample of cases reviewed in this study, cross-facial nerve graft-innervated gracilis functional free muscle transfer achieved a greater degree of emotionality during spontaneous smiling than masseteric or dually innervated transfer. Quantification of spontaneous smiling from standard video clips could facilitate future, blinded, multicenter trials with sufficient long-term follow-up to definitively establish the rates of spontaneity from a range of reanimation procedures. Diagnostic, IV.

The surgical outcomes of reconstruction for the treatment of ureteral stricture after holmium laser lithotripsy: The comprehensive experiences

ObjectiveTo analyze the characteristics of ureteral stricture after ureteroscopic holmium laser lithotripsy and summarize our experience with the reconstructive strategies. MethodsThis study retrospectively reviewed 42 patients with ureteral stricture after ureteroscopic holmium laser lithotripsy between December 2009 and December 2019. Patient demographics, laboratory data, imaging studies, perioperative variables, complications, and follow-up data were recorded. Surgical success was defined as relief of symptoms, improved/stabilized hydronephrosis, and stable renal function. ResultsThe upper, middle, and lower thirds of the ureter were affected in 27, 6, and 7 cases, respectively. Multiple ureteral strictures were found in 2 patients. The median length of the stricture was 3.5 cm (range 1–30 cm). In the upper ureteral strictures, lingual mucosal ureteroplasty (8/27, 29.6%) is the most commonly used treatment method for stricture longer than 3 cm but shorter than 6 cm, followed by appendiceal onlay ureteroplasty (5/27, 18.5%). Four lower ureteral strictures ranging from 3 to 8 cm were repaired with Boari flap. Reconstructive strategies of the middle ureteral strictures included Boari flap, appendiceal onlay ureteroplasty and ureteroureterostomy. Patients with the length of the stricture longer than 8 cm or multiple strictures underwent ileal ureter replacement. The median follow-up was 27.3 ± 17.2 months. The overall success rate was 97.6%. ConclusionUpper ureter is more vulnerable in ureteroscopic holmium laser lithotripsy. Sufficient follow-up and appropriate examination are necessary for diagnosis. Different treatment strategies need to be flexibly selected according to the location and length of the injury.

Identifying possible inaccuracy in reported birth head circumference measurements among infants in the US Zika Pregnancy and Infant Registry.

The US Zika Pregnancy and Infant Registry (USZPIR) monitors infants born to mothers with confirmed or possible Zika virus infection during pregnancy. The surveillance case definition for Zika-associated birth defects includes microcephaly based on head circumference (HC). We assessed birth and follow-up data from infants with birth HC measurements <3rd percentile and birthweight ≥10th percentile to determine possible misclassification of microcephaly. We developed a schema informed by literature review and expert opinion to identify possible HC measurement inaccuracy using HC growth velocity and longitudinal HC measurements between 2 and 12 months of age. Two or more HC measurements were required for assessment. Inaccuracy in birth HC measurement was suspected if growth velocity was >3 cm/month in the first 3 months or HC was consistently >25th percentile during follow-up. Of 6,799 liveborn infants in USZPIR, 351 (5.2%) had Zika-associated birth defects, of which 111 had birth HC measurements <3rd percentile and birthweight ≥10th percentile. Of 84/111 infants with sufficient follow-up, 38/84 (45%) were classified as having possible inaccuracy of birth HC measurement, 19/84 (23%) had HC ≥3rd percentile on follow-up without meeting criteria for possible inaccuracy, and 27/84 (32%) had continued HC <3rd percentile. After excluding possible inaccuracies, the proportion of infants with Zika-associated birth defects including microcephaly decreased from 5.2% to 4.6%. About one-third of infants in USZPIR with Zika-associated birth defects had only microcephaly, but indications of possible measurement inaccuracy were common. Implementation of this schema in longitudinal studies can reduce misclassification of microcephaly.

Coming Soon: Ability to Orgasm After Gender Affirming Vaginoplasty

Many patients have goals related to sexual health when seeking gender-affirming vaginoplasty, and previous investigations have only studied the ability to orgasm at cross-sectional timepoints. Our aim is to quantify the time to orgasm postoperative gender-affirming vaginoplasty and describe potential correlative factors, including preoperative orgasm, to improve preoperative counseling. A retrospective chart review was utilized to extract factors thought to influence pre and postoperative orgasm in patients undergoing robotic peritoneal flap vaginoplasty. Mean days to orgasm plus one standard deviation above that mean was used to define the time at which patients would be considered anorgasmic. Orgasm was documented as a categorical variable on the basis of surgeon interviews during pre and postoperative appointments while time to orgasm was measured as days from surgery to first date documented as orgasmic in the medical record. A total of 199 patients underwent surgery from September 2017 to August 2020. The median time to orgasm was 180 days. 178 patients had completed 1 year or greater of follow-up, and of these patients, 153 (86%) were orgasmic and 25 patients (14%) were not. Difficulty in preoperative orgasm was correlated only with older age (median age 45.9 years vs 31.7, P=.03). Postoperative orgasm was not significantly correlated with preoperative orgasm. The only factor related to postoperative orgasm was smoking history: 12 of 55 patients (21.8%) who had a positive smoking history and sufficient follow-up reported anorgasmia (P-value .046). Interventions for anorgasmic patients include testosterone replacement, pelvic floor physical therapy, and psychotherapy. Preoperative difficulty with orgasm improves with gender-affirming robotic peritoneal flap vaginoplasty, while smoking had a negative impact on postoperative orgasm recovery despite negative cotinine test prior to surgery. This investigation is the first effort to determine a timeline for the return of orgasmic function after gender-affirming vaginoplasty. It is limited by retrospective review methodology and lack of long-term follow-up. The association of smoking with postoperative orgasm despite universal nicotine cessation prior to surgery may indicate prolonged smoking cessation improves orgasmic outcomes or that underlying, unmeasured exposures correlated with smoking may be the factor inhibiting recovery of orgasm. The majority of patients were orgasmic at their 6-month follow-up appointments, however, patients continued to become newly orgasmic in appreciable numbers more than 1 year after surgery. Blasdel G, Kloer C, Parker A, et al. Coming Soon: Ability to Orgasm After Gender Affirming Vaginoplasty. J Sex Med 2022;19:781-788.

Combination Therapy Should Be Reserved as Second-Line Treatment of Onychomycosis: A Systematic Review of Onychomycosis Clinical Trials.

Onychomycosis is the most common nail disease encountered in clinical practice. Its importance extends well beyond aesthetics, often causing pain, difficulty with ambulation and performing daily activities, and impairing quality of life. Many patients fail to achieve cure with antifungal monotherapy and recurrences are common. Combination therapy has therefore gained considerable interest, given the potential for drug synergy and prevention of antifungal resistance, but it has not been well studied. A systematic review of onychomycosis medication only, as well as medication and procedural (laser, debridement, photodynamic therapy), clinical or randomized controlled trials evaluating combination vs. monotherapies was performed. After exclusions, 30 studies were included in the final analysis. There were conflicting results for medication-only trials, with some showing significant benefit of combination therapy over monotherapy, however, trials were not robustly designed and lacked sufficient follow-up. Procedural studies also lacked long-term follow-up, and failed to demonstrate efficacy in some severe onychomycosis cases. Considering the high cure rates demonstrated in pivotal antifungal monotherapy trials, and conflicting results, costs, and safety concerns associated with combination therapy, we recommend that combination therapy be reserved as second-line treatment options in patients with poor prognostic factors or for those who failed monotherapy for onychomycosis.

Early rituximab treatment is associated with increased and sustained remission in pemphigus patients: A retrospective cohort of 99 patients.

Rituximab is the front-line therapy for pemphigus disease. Although very effective, relapse rates are high. We assessed factors associated with disease remission and early relapse following the first rituximab cycle. A single center, retrospective cohort study of patients with pemphigus treated with rituximab (1000 mg0, 14 days) at the Autoimmune Bullous Disease Clinic of the Division of Dermatology in Rabin Medical Center, Israel, between January 1, 1995 and March 31, 2020. The cohort included 99 patients with a median follow-up of 37 months (range 12-155). After a single rituximab cycle, 74 patients (75%) achieved remission. Increased time to rituximab was associated with decreased remission rates (OR, 0.98 per month; 95% CI, 0.97-0.998). Of patients in remission with sufficient follow-up, 15/69 (22%) experienced an early relapse (≤12 months from remission). Prolonged time to rituximab and increased baseline disease severity, were associated with early relapse (OR, 1.02 per month; 95% CI, 1.001-1.04; OR, 1.04 per point; 95% CI, 1.01-1.08, accordingly). Initiating rituximab early following diagnosis is recommended. Maintenance rituximab infusions, especially for patients with severe baseline disease, should be further investigated.

Pediatric and Adolescent Fractures of the Acetabulum Treated With ORIF: What Are Their Functional Outcomes?

To evaluate the functional outcomes of pediatric and adolescent patients (<18 year old) who sustained acetabulum fractures that were treated with open reduction internal fixation (ORIF). Retrospective cohort. Level 1 trauma center. Thirty-four pediatric and adolescent patients underwent acetabulum fracture ORIF between 2001 and 2018. Of the operatively treated patients, 21 patients had sufficient follow-up (>6 months), one died after fixation secondary to other traumatic injuries, and 12 patients were lost to follow-up. Acetabulum fracture ORIF. The SF-36 Health Survey and Short Musculoskeletal Functional Assessment (SMFA) were compared with population norms. The modified Merle d'Aubigné clinical hip score, Matta radiologic outcome, and postoperative complications were also documented. Functional outcome data were available at a mean of 5 years 2 months. Mean SF-36 scores were 44.8 and 50.1 for the physical component score and mental component scores, respectively, which did not differ significantly from US population norms (physical component score mean: 50, P = 0.061 and mental component score mean: 50, P = 0.973). Furthermore, the mean SMFA Bother Index score was 18.6, which is not significantly different from the population norm mean of 13.8 (P = 0.268). However, the function index mean was 31.9, which was significantly worse than the population norm mean of 12.7 (P = 0.001). Two patients with a delayed reduction (>6 hours) of an acetabulum fracture dislocation had poor outcomes related to the development of avascular necrosis and post-traumatic osteoarthritis. In this small cohort, 86% (18/21) of these patients had a favorable functional outcome with the exception of the SMFA Functional Index that was significantly less than population norms. Although long-term follow-up is needed, we advocate for operative management of pediatric and adolescent acetabulum fractures when adult displacement and instability criteria are present. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

E-health interventions targeting STIs, sexual risk, substance use and mental health among men who have sex with men: four systematic reviews

BackgroundHuman immunodeficiency virus/sexually transmitted infections, sexual risk, substance (alcohol and other legal and illegal drugs) use and mental ill health constitute a ‘syndemic’ of mutually reinforcing epidemics among men who have sex with men. Electronic health (e-health) interventions addressing these epidemics among men who have sex with men might have multiplicative effects. To our knowledge, no systematic review has examined the effectiveness of such interventions on these epidemics among men who have sex with men.ObjectiveThe objective was to synthesise evidence addressing the following: (1) What approaches and theories of change do existing e-health interventions employ to prevent human immunodeficiency virus/sexually transmitted infections, sexual risk, alcohol/drug use or mental ill health among men who have sex with men? (2) What factors influence implementation? (3) What are the effects of such interventions on the aforementioned epidemics? (4) Are such interventions cost-effective?Data sourcesA total of 24 information sources were searched initially (October–November 2018) [the following sources were searched: ProQuest Applied Social Sciences Index and Abstracts; Campbell Library; EBSCO Cumulative Index to Nursing and Allied Health Literature Plus, Wiley Online Library The Cochrane Library; Centre for Reviews and Dissemination databases (the Database of Abstracts of Reviews of Effects and the NHS Economic Evaluation Database); the Health Technology Assessment database; Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre) database of health promotion research (Bibliomap); ProQuest Dissertations &amp; Theses Global; OvidSP EconLit; OvidSP EMBASE; OvidSP Global Health; OvidSP Health Management Information Consortium; ProQuest International Bibliography of the Social Sciences; Ovid MEDLINE ALL; OvidSP PsycINFO; Web of Science Science Citation Index Expanded; Elsevier Scopus; OvidSP Social Policy &amp; Practice; Web of Science Social Sciences Citation Index Expanded; ProQuest Sociological Abstracts; ClinicalTrials.gov; World Health Organization International Clinical Trials Registry Platform; EPPI-Centre Trials Register of Promoting Health Interventions; and the OpenGrey database], and an updated search of 19 of these was conducted in April 2020. Reference lists of included reports were searched and experts were contacted.Review methodsEligible reports presented theories of change and/or process, outcome and/or economic evaluations of e-health interventions offering ongoing support to men who have sex with men to prevent human immunodeficiency virus/sexually transmitted infections, sexual risk behaviour, alcohol/drug use and/or common mental illnesses. References were screened by title/abstract, then by full text. Data extraction and quality assessments used existing tools. Theory and process reports were synthesised using qualitative methods. Outcome and economic data were synthesised narratively; outcome data were meta-analysed.ResultsOriginal searches retrieved 27 eligible reports. Updated searches retrieved 10 eligible reports. Thirty-seven reports on 28 studies of 23 interventions were included: 33 on theories of change, 12 on process evaluations, 16 on outcome evaluations and one on an economic evaluation. Research question 1: five intervention types were identified – ‘online modular’, ‘computer games’ and ‘non-interactive’ time-limited/modular interventions, and open-ended interventions with ‘content organised by assessment’ and ‘general content’. Three broad types of intervention theories of change were identified, focusing on ‘cognitive/skills’, ‘self-monitoring’ and ‘cognitive therapy’. Research question 2: individual tailoring based on participant characteristics was particularly acceptable, and participants valued intervention content reflecting their experiences. Research question 3: little evidence was available of effects on human immunodeficiency virus or sexually transmitted infections. The analysis did not suggest that interventions were effective in reducing instances of human immunodeficiency virus or sexually transmitted infections. The overall meta-analysis for sexually transmitted infections reported a small non-significant increase in sexually transmitted infections in the intervention group, compared with the control group. Meta-analyses found a significant impact on sexual risk behaviour. The findings for drug use could not be meta-analysed because of study heterogeneity. Studies addressing this outcome did not present consistent evidence of effectiveness. Trials did not report effects on alcohol use or mental health. Research question 4: evidence on cost-effectiveness was limited.LimitationsThe quality of the eligible reports was variable and the economic synthesis was limited to one eligible study.ConclusionsThere is commonality in intervention theories of change and factors affecting receipt of e-health interventions. Evidence on effectiveness is limited.Future workFuture trials should assess the impact of interventions on multiple syndemic factors, among them sexual risk, substance use and mental health; incorporate sufficient follow-up and sample sizes to detect the impact on human immunodeficiency virus/sexually transmitted infections; and incorporate rigorous process and economic evaluations.Study registrationThis study is registered as PROSPERO CRD42018110317.FundingThis project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full inPublic Health Research; Vol. 10, No. 4. See the NIHR Journals Library website for further project information.

Comparison of computer-assisted navigated technology and conventional technology in unicompartmental knee arthroplasty: a meta-analysis

BackgroundThough unicompartmental knee arthroplasty (UKA) is a useful procedure to treat knee osteoarthritis, it remains a great controversial point as to if navigated systems are able to achieve better accuracy of limb alignment and greater clinic results. Current meta-analysis was conducted to explore if better clinical outcomes and radiographic outcomes could be acquired in the navigated system when compared with conventional procedures.MethodsWe identified studies in the online databases, including Medline, Embase, the Cochrane Library and Web of Science before May 2021. The PRISMA guidelines in this report were strictly followed. Our research was completed via Review Manager 5.4 software.ResultsFourteen articles were included, involving 852 knees. The present meta-analysis displayed that the navigated system had remarkably improved outcomes in inliers of mechanical axis (MA) (P < 0.01), MA in the Kennedy's central zone (Zone C) (P = 0.04), inliers of the coronal femoral component (P < 0.01), inliers of the coronal tibial component (P = 0.005), inliers of the sagittal femoral component (P = 0.03), inliers of the sagittal tibial component (P = 0.002) and Range Of Motion (ROM) (P = 0.04). No significant differences were observed in Oxford Knee Score (OKS) (P = 0.15), American Knee Society Knee Score (KSS score) (P = 0.61) and postoperative complications (P = 0.73) between these 2 groups. Regarding operating time, the navigated group was 10.63 min longer in contrast to the traditional group.ConclusionBased on our research, the navigated system provided better radiographic outcomes and no significant difference in the risk of complications with longer surgical time than the conventional techniques. But no significant differences were found in functional outcomes. Because the included studies were small samples and short-term follow-up, high-quality RCTs with large patients and sufficient follow-up are required to identify the long-term effect of the navigated system.