Predicted leukocyte telomere length and risk of myeloid neoplasms.

Maintenance of telomere length has long been established to play a role in the biology of cancer and several studies suggest that it may be especially important in myeloid malignancies. To overcome potential bias in confounding and reverse causation of observational studies, we use both a polygenic risk score (PRS) and inverse-variance weighted (IVW) Mendelian randomization (MR) analyses to estimate the relationship between genetically predicted leukocyte telomere length (LTL) and acute myeloid leukemia (AML) risk in 498 cases and 2099 controls and myelodysplastic syndrome (MDS) risk in 610 cases and 1759 controls. Genetic instruments derived from four recent studies explaining 1.23-4.57% of telomere variability were considered. We used multivariable logistic regression to estimate odds ratios (OR, 95% confidence intervals [CI]) as the measure of association between individual single-nucleotide polymorphisms and myeloid malignancies. We observed a significant association between a PRS of longer predicted LTL and AML using three genetic instruments (OR = 4.03 per ~1200 base pair [bp] increase in LTL, 95% CI: 1.65, 9.85 using Codd et al. [Codd, V., Nelson, C.P., Albrecht, E., Mangino, M., Deelen, J., Buxton, J.L., Hottenga, J.J., Fischer, K., Esko, T., Surakka, I. et al. (2013) Identification of seven loci affecting mean telomere length and their association with disease. Nat. Genet., 45, 422-427 427e421-422.], OR = 3.48 per one-standard deviation increase in LTL, 95% CI: 1.74, 6.97 using Li et al. [Li, C., Stoma, S., Lotta, L.A., Warner, S., Albrecht, E., Allione, A., Arp, P.P., Broer, L., Buxton, J.L., Alves, A.D.S.C. et al. (2020) Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length. Am. J. Hum. Genet., 106, 389-404.] and OR = 2.59 per 1000 bp increase in LTL, 95% CI: 1.03, 6.52 using Taub et al. [Taub, M.A., Conomos, M.P., Keener, R., Iyer, K.R., Weinstock, J.S., Yanek, L.R., Lane, J., Miller-Fleming, T.W., Brody, J.A., Raffield, L.M. et al. (2022) Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed. Cell Genom., 2.] genetic instruments). MR analyses further indicated an association between LTL and AML risk (PIVW ≤ 0.049) but not MDS (all PIVW ≥ 0.076). Findings suggest variation in genes relevant to telomere function and maintenance may be important in the etiology of AML but not MDS.

Doxycycline versus cephalexin treatment of presumed streptococcal skin and soft tissue infection among adults presenting to the emergency department.

Among 100 propensity score-matched emergency department patients receiving ≤14 days doxycycline versus cephalexin monotherapy for outpatient treatment of nonpurulent (presumed streptococcal) skin and soft tissue infection, a low rate of 14-day clinical failure was observed [6% each group; odds ratio (OR), 1.34 (0.21-8.69); P = 0.745], defined as hospital admission, i.v. antibiotic therapy, or change in oral antibiotic. Doxycycline may represent a reasonable therapeutic alternative for this indication in regions with low tetracycline resistance.

Comparison of overall and patterns of care in patients with a malignant ovarian germ cell tumor by age in the United States: a National Cancer Database (2004-2016) analysis.

BACKGROUND: Women aged ≥40 years diagnosed with a malignant ovarian germ cell tumor are more likely to have poor outcomes than their younger counterparts (aged 15-39 years). OBJECTIVE: We used the National Cancer Database (NCDB) to evaluate patterns of care and overall survival for individuals diagnosed with one of the four most common histologic subtypes of malignant ovarian germ cell tumor by age group. METHODS: We identified women aged 15-90 diagnosed with ovarian germ cell tumors in the NCDB (2004-2016). Logistic regression was used to compare patterns of care, demographic, and disease characteristics by age group. Cox proportional hazards regression was used to evaluate associations between a range of demographic, clinical, and treatment characteristics with overall survival. RESULTS: A total of n=2998 patients who were diagnosed with one of the four most common histologic subtypes (immature teratoma, dysgerminoma, yolk sac tumor, and mixed germ cell) of ovarian germ cell tumor were included in the analysis. Patients aged ≥40 years diagnosed with ovarian germ cell tumors were more likely to have co-morbidities, a bilateral tumor, higher stage of disease, receive chemotherapy only, and have a residual tumor after resection as compared with patients aged <40 years. Moreover, women aged ≥40 years had the highest risk of death (reference: 15-24 year olds; HR=5.37, 95% CI 3.76 to 7.66) after adjustment for demographic characteristics, tumor histology, and treatment received. In stratified analyses, women aged ≥40 years had significantly worse overall survival at each disease stage and histologic subtype. CONCLUSION: Findings suggest that women aged ≥40 years who are diagnosed with ovarian germ cell tumors have worse overall survival than those aged <40, independent of stage, disease characteristics, and treatment. Our study highlights the need for future research to better understand reasons for poorer outcomes in women aged ≥40 years.

Comparison of phenobarbital-adjunct versus benzodiazepine-only approach for alcohol withdrawal syndrome in the ED.

OBJECTIVES: To compare a phenobarbital-adjunct versus benzodiazepine-only approach for the management of alcohol withdrawal syndrome in the emergency department (ED) with regard to the need for intensive care unit (ICU) admission, severity of symptoms on ED discharge, and complications. METHODS: This was a retrospective cohort study conducted in two academic EDs in the United States. Adult patients seen in the ED with a diagnosis of alcohol withdrawal syndrome were included. Patients were categorized into two groups based on whether phenobarbital was administered in the ED: 1) phenobarbital group (with or without benzodiazepines) or 2) non-phenobarbital group. The primary outcome measure was the need for ICU admission. Secondary outcomes included Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scores at ED discharge, and complications. Complications were a composite of death, need for intubation, hypotension or vasopressor use, seizures, and hospital acquired pneumonia. RESULTS: The study cohort included 209 patients (phenobarbital = 97, non-phenobarbital = 112). The mean (standard deviation) age was 49 (12) years and 85% (n = 178) were male. A similar proportion of patients in the phenobarbital (14%, n = 14) and non-phenobarbital (11%, n = 12) groups required ICU admission (p = 0.529). The median CIWA-Ar score on ED discharge was 7 (IQR 4-12) points in the phenobarbital group and 7 (IQR 4-14) points in the non-phenobarbital group (p = 0.752). The occurrence of complications was also similar in the phenobarbital (9%, n = 9) and non-phenobarbital groups (11%, n = 10). CONCLUSION: Adjunctive phenobarbital use in the ED for alcohol withdrawal syndrome did not result in decreased ICU admission, severity of symptoms, or complications.

JAK/STAT3 regulated global gene expression dynamics during late-stage reprogramming process.

BACKGROUND: The generation of induced pluripotent stem cells (iPSCs) has underdefined mechanisms. In addition, leukemia inhibitory factor (LIF) activated Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway is the master regulator for naïve-state pluripotency achievement and maintenance. However, the regulatory process to attain naïve pluripotent iPSCs is not well understood. RESULTS: We performed transcriptome analysis to dissect the genomic expression during mouse iPSC induction, with or without blocking the JAK/STAT3 activity. We describe JAK/STAT3 signaling-specific biological events such as gametogenesis, meiotic/mitotic cell cycle, and DNA repair, and JAK/STAT3-dependent expression of key transcription factors such as the naïve pluripotency-specific genes, developmental pluripotency associated (Dppa) family, along with histone modifiers and non-coding RNAs in reprogramming. We discover that JAK/STAT3 activity does not affect early phase mesenchymal to epithelial transition (MET) but is necessary for proper imprinting of the Dlk1-Dio3 region, an essential event for pluripotency achievement at late-reprogramming stage. This correlates with the JAK/STAT3-dependent stimulation of Dppa3 and Polycomb repressive complex 2 (PRC2) genes. We further demonstrate that JAK/STAT3 activity is essential for DNA demethylation of pluripotent loci including Oct4, Nanog, and the Dlk1-Dio3 regions. These findings correlate well with the previously identified STAT3 direct targets. We further propose a model of pluripotency achievement regulated by JAK/STAT3 signaling during the reprogramming process. CONCLUSIONS: Our study illustrates novel insights for JAK/STAT3 promoted pluripotency establishment, which are valuable for further improving the naïve-pluripotent iPSC generation across different species including humans.

Characteristics and knowledge synthesis approach for 456 network meta-analyses: a scoping review.

BACKGROUND: Network meta-analysis (NMA) has become a popular method to compare more than two treatments. This scoping review aimed to explore the characteristics and methodological quality of knowledge synthesis approaches underlying the NMA process. We also aimed to assess the statistical methods applied using the Analysis subdomain of the ISPOR checklist. METHODS: Comprehensive literature searches were conducted in MEDLINE, PubMed, EMBASE, and Cochrane Database of Systematic Reviews from inception until April 14, 2015. References of relevant reviews were scanned. Eligible studies compared at least four different interventions from randomised controlled trials with an appropriate NMA approach. Two reviewers independently performed study selection and data abstraction of included articles. All discrepancies between reviewers were resolved by a third reviewer. Data analysis involved quantitative (frequencies) and qualitative (content analysis) methods. Quality was evaluated using the AMSTAR tool for the conduct of knowledge synthesis and the ISPOR tool for statistical analysis. RESULTS: After screening 3538 citations and 877 full-text papers, 456 NMAs were included. These were published between 1997 and 2015, with 95% published after 2006. Most were conducted in Europe (51%) or North America (31%), and approximately one-third reported public sources of funding. Overall, 84% searched two or more electronic databases, 62% searched for grey literature, 58% performed duplicate study selection and data abstraction (independently), and 62% assessed risk of bias. Seventy-eight (17%) NMAs relied on previously conducted systematic reviews to obtain studies for inclusion in their NMA. Based on the AMSTAR tool, almost half of the NMAs incorporated quality appraisal results to formulate conclusions, 36% assessed publication bias, and 16% reported the source of funding. Based on the ISPOR tool, half of the NMAs did not report if an assessment for consistency was conducted or whether they accounted for inconsistency when present. Only 13% reported heterogeneity assumptions for the random-effects model. CONCLUSIONS: The knowledge synthesis methods and analytical process for NMAs are poorly reported and need improvement.

Minilaparotomy Versus Laparoscopic Myomectomy After Cessation of Power Morcellation: Rate of Wound Complications.

STUDY OBJECTIVE: After the US Food and Drug Administration statement warning against electronic morcellation devices, gynecologic surgeons are performing laparoscopic and robotic myomectomies with minilaparotomy incisions for tissue morcellation and removal. No data exist that focus on the superficial wound complications as a result of these larger incisions. The objective of this study is to compare the rate of wound complications for myomectomy via minilaparotomy versus laparoscopic or robotic myomectomy. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Kaiser Permanente Northern California, a large integrated healthcare delivery system. PATIENTS: Women > 18 years of age who underwent a myomectomy from either complete laparoscopic or robotic approach (LR) were compared with minilaparotomy myomectomy (MM), comprising complete minilaparotomy (ML) and laparoscopic or robotic assisted by a minilaparotomy for morcellation purposes only (LRM) from January 2011 through December 2014. INTERVENTION: Myomectomy via LR, complete ML, and LRM. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed for outcomes of interest, including superficial wound complications and surgical and demographic data. After exclusion criteria were met, 405 cases were included in the study; 270 cases were classified as MM, which included ML (n = 224), or LRM (n = 46). One hundred thirty-five cases were classified as LR. Parametric and nonparametric analyses were used to compare the 2 groups. There was no significant difference between the groups insofar as patient morbidity, including the primary outcome of wound complications and other postoperative complications; emergency visits; or readmissions. There were 2 (1.5%) wound complications in the LR group and 7 (2.6%) in the MM group (p = .72). Similarly, there were no significant differences in the subcategories of wound complications, including cellulitis, seroma, hematoma, skin separation, wound infection, or postprocedure wound complication. The distribution of estimated blood loss was significantly different between LR and MM groups with an interquartile range of 50 to 150 mL in the LR group versus 50 to 300 mL in the MM group (p < .01). The MM group experienced a shorter procedure time with a median procedure time of 125 minutes compared with 169.5 minutes in LR surgeries (p < .01). The LR group demonstrated a significantly shorter median length of hospital stay (LR 5.0 hours vs MM 23 hours; p < .01). CONCLUSION: Compared with MM, LR is associated with a shorter length of hospital stay and longer operating time but no reduction in wound complication or other patient morbidity.

Medication use trajectories of postmenopausal breast cancer survivors and matched cancer-free controls.

While adverse medical sequelae are associated with breast cancer therapies, information on breast cancer impact on medication use is limited. Therefore, we compared medication use before and after diagnosis of early stage breast cancer to medication use in matched, cancer-free controls. Of 68,132 Women's Health Initiative participants, 3726 were diagnosed with breast cancer and, after exclusions, in 1731 breast cancer cases, medication use before and >3 years after diagnosis (mean 5.3 ± 2.1 SD) was compared to use in 1731 cancer-free matched controls on similar inventory dates. The medication category number at follow-up inventory was the primary study outcome. Medication category use (n, mean, SD) was comparable at baseline and significantly increased at follow-up in both cases (2.48 ± 1.66 vs. 4.15 ± 2.13, baseline vs follow-up, respectively, P < .0001) and controls (2.44 ± 1.67 vs. 3.95 ± 2.13, respectively, P < .0001), with clinically marginal but statistically significant additional medication category use by cases (0.20 ± 2.40, P < .0001). Tamoxifen users used somewhat more selected medication categories at follow-up assessment (mean 3.40 ± 1.89 vs. 3.21 ± 1.99, respectively, P = 0.05), while aromatase inhibitor users used more medication categories (mean 4.85 ± 2.10 vs. 4.44 ± 1.94, respectively, P = 0.02). No increase in medication category was seen in cases who were not current endocrine therapy users. Breast cancer survivors having only a clinically marginal increase in medication use compared to cancer-free controls. These findings highlight the importance of incorporation of control populations in studies of cancer survivorship.

Trends, in Diagnosis and Treatment of Polycystic Ovarian Syndrome by Specialty.

OBJECTIVE: To identify trends in the diagnostic work- up of polycystic ovarian syndrome (PCOS) performed by specialists in general medicine, endocrinology, and gynecology. STUDY DESIGN: Ret- rospective electronic chart review of adolescents and young women whose workup for PCOS was initiated by specialists in endocrinology, general medicine, or gyne- cology. RESULTS: Of 530 charts reviewed, 84 patients quali- fied for inclusion. Approximately two-thirds of patients seen by generalists and endocrinologists had lipid test- ing done; no gynecologist in this study ordered lipid tests. Cortisol levels and markers of congenital adrenal hyperplasia were more often ordered for patients seen by endocrinologists than for those seen by generalists or gynecologists. There was no significant difference among specialties in the use of diagnostic criteria for PCOS, including menstrual irregularity, hyperandrogenism, ovarian imaging, or exclusion of other etiologies. Women seen by endocrinologists tended to be prescribed met- formin more often; however, there was no significant difference in the use of hormonal contraceptives, piogli- tazone, and spironolactone among specialties. CONCLUSION: Across 3 clinical practice specialties commonly evaluating menstrual irregularity and/or hirsutism in young women, patients were consistently diagnosed with PCOS based on appropriate, clinically- accepted criteria. However, no patients seen by gyne- cologists received lipid test- ing, which is considered an important screening study for cardiovascular disease risk in this population.

Synthesis and Structure-Activity Relationship Analysis of 5-HT7 Receptor Antagonists: Piperazin-1-yl Substituted Unfused Heterobiaryls.

A series of piperazin-1-yl substituted unfused heterobiaryls was synthesized as ligands of the 5-HT7 receptors. The goal of this project was to elucidate the structural features that affect the 5-HT7 binding affinity of this class of compounds represented by the model ligand 4-(3-furyl)-2-(4-methylpiperazin-1-yl)pyrimidine (2). The SAR studies included systematical structural changes of the pyrimidine core moiety in 2 to quinazoline, pyridine and benzene, changes of the 3-furyl group to other heteroaryl substituents, the presence of various analogs of the 4-methylpiperazin-1-yl group, as well as additional substitutions at positions 5 and 6 of the pyrimidine. Substitution of position 6 of the pyrimidine in the model ligand with an alkyl group results in a substantial increase of the binding affinity (note a change in position numbers due to the nomenclature rules). It was also demonstrated that 4-(3-furyl) moiety is crucial for the 5-HT7 binding affinity of the substituted pyrimidines, although, the pyrimidine core can be replaced with a pyridine ring without a dramatic loss of the binding affinity. The selected ethylpyrimidine (12) and butylpyrimidine (13) analogs of high 5-HT7 binding affinity showed antagonistic properties in cAMP functional test and varied selectivity profile-compound 12 can be regarded as a dual 5-HT7/5-HT2AR ligand, and 13 as a multi-receptor (5-HT7, 5-HT2A, 5-HT6 and D2) agent.

Emerging drugs for common conditions of sleepiness: obstructive sleep apnea and narcolepsy.

INTRODUCTION: Obstructive sleep apnea (OSA) and narcolepsy are sleep disorders associated with high prevalence and high symptomatic burden including prominent sleepiness, daytime dysfunction and poor nocturnal sleep. Both have elevated risk of poor health outcomes. Current therapies are often underutilized, cumbersome, costly or associated with residual symptoms. AREAS COVERED: This review covers current available therapies for OSA and narcolepsy as well as discusses areas for potential drug development, and agents in the therapeutic pipeline, including the cannabinoid dronabinol (OSA), the histamine inverse agonist/ antagonist pitolisant (narcolepsy), and stimulants with uncertain and/or multiple activities such as JZP-110 and JZP-386 (narcolepsy, possibly OSA). Finally it addresses new approaches and uses for therapies currently on the market such as the carbonic anhydrase inhibitor acetazolamide (OSA). EXPERT OPINION: Both OSA and narcolepsy are conditions of sleepiness for which lifelong treatments are likely to be required. In OSA, while continuous positive airway pressure will likely remain the gold standard therapy for the foreseeable future, there is plenty of room for integrating phenotypes and variants of OSA into therapeutic strategies to lead to better, more personalized disease modification. In narcolepsy, unlike OSA, drug therapy is the current mainstay of treatment. Advances using novel mechanisms to treat targeted symptoms such as sleepiness and/or novel agents that can treat more than one symptom of narcolepsy, hold promise. However, cost, convenience and side effects remain challenges.

What Guidance are Economists Given on How to Present Economic Evaluations for Policymakers? A Systematic Review.

OBJECTIVES: To systematically review health economic guidelines for information on how to present health economic evaluations and consider implications for nontechnical audiences such as policymakers. METHODS: Electronic databases and supplementary sources were searched for economic evaluation guidelines. Guidelines were critically appraised. Descriptive characteristics, standard formats, supports for nontechnical audiences, presentation approaches, and common reporting recommendations were extracted. Frequencies were tabulated and trends identified. RESULTS: Thirty-one guidelines were included. Twenty-two guidelines include a standard reporting format with some sample tables and graphs. Common presentation approaches include well-cited tables of data sources, transparent model diagrams and descriptions, disaggregated results, and tabular and graphical displays of sensitivity analyses. Despite most guidelines being funded by policymakers, only five guidelines provided advice on presenting economic evaluations to noneconomists. However, 11 guidelines included a glossary of economic terminology for nontechnical readers. Common concepts that may require further explanation include differences in economic perspectives, appropriateness of time horizons, how economic outcomes such as quality-adjusted life-years relate to their component clinical outcomes, and choice of sensitivity analyses. CONCLUSIONS: Health economists have consistent presentation formats and common reporting elements that should be considered when developing user-friendly explanations for general audiences. These overlap with policymakers' informational needs but may not be sufficient for understanding by nontechnical audiences. Developing presentation formats and tools that incorporate viewpoints of both economists and noneconomists will allow for better application of the results of economic evaluations and enhance the transparency and legitimacy of decision-making processes that are informed by economic evaluations.

Mouth breathing, "nasal disuse," and pediatric sleep-disordered breathing.

BACKGROUND: Adenotonsillectomy (T&A) may not completely eliminate sleep-disordered breathing (SDB), and residual SDB can result in progressive worsening of abnormal breathing during sleep. Persistence of mouth breathing post-T&As plays a role in progressive worsening through an increase of upper airway resistance during sleep with secondary impact on orofacial growth. METHODS: Retrospective study on non-overweight and non-syndromic prepubertal children with SDB treated by T&A with pre- and post-surgery clinical and polysomnographic (PSG) evaluations including systematic monitoring of mouth breathing (initial cohort). All children with mouth breathing were then referred for myofunctional treatment (MFT), with clinical follow-up 6 months later and PSG 1 year post-surgery. Only a limited subgroup followed the recommendations to undergo MFT with subsequent PSG (follow-up subgroup). RESULTS: Sixty-four prepubertal children meeting inclusion criteria for the initial cohort were investigated. There was significant symptomatic improvement in all children post-T&A, but 26 children had residual SDB with an AHI > 1.5 events/hour and 35 children (including the previous 26) had evidence of "mouth breathing" during sleep as defined [minimum of 44 % and a maximum of 100 % of total sleep time, mean 69 ± 11 % "mouth breather" subgroup and mean 4 ± 3.9 %, range 0 and 10.3 % "non-mouth breathers"]. Eighteen children (follow-up cohort), all in the "mouth breathing" group, were investigated at 1 year follow-up with only nine having undergone 6 months of MFT. The non- MFT subjects were significantly worse than the MFT-treated cohort. MFT led to normalization of clinical and PSG findings. CONCLUSION: Assessment of mouth breathing during sleep should be systematically performed post-T&A and the persistence of mouth breathing should be treated with MFT.

Insulins, leptin and feeding in a population of Peromyscus leucopus (white-footed mouse) with variable fertility.

This article is part of a Special Issue "Energy Balance". Natural populations display a variety of reproductive responses to environmental cues, but the underlying physiology that causes these responses is largely unknown. This study tested the hypothesis that heritable variation in reproductive traits can be described by heritable variation in concentrations of hormones critical to both energy balance and reproduction. To test this hypothesis, we used mouse lines derived from a wild population and selectively bred for response to short day photoperiod. Reproductive and metabolic traits of Peromyscus leucopus display heritable variation when held in short photoperiods typical of winter. Our two lines of mice have phenotypes spanning the full range of variation observed in nature in winter. We tested male and female mice for heritable variation in fasted serum concentrations of three hormones involved in energetic regulation: leptin, insulin-like growth factor 1 (IGF-1) and insulin, as well as the effects of exogenous leptin and a high energy diet on reproductive maturation. Exogenous leptin decreased food intake, but protected males from the reduction in testis mass caused by equivalent food restriction in pair-fed, saline-infused controls. A high energy diet resulted in calorie adjustment by the mice, and failed to alter reproductive phenotype. Concentrations of the three hormones did not differ significantly between selection lines but had correlations with measures of food intake, fertility, blood glucose, and/or body mass. There was evidence of interactions between reproductive traits and hormones related to energy balance and reproduction, but this study did not find evidence that variation in these hormones caused variation in reproductive phenotype.

Racial disparities in maternal and neonatal outcomes in HIV-1 positive mothers.

OBJECTIVE: To compare obstetric and neonatal outcomes between human immunodeficiency virus (HIV) positive (HIV+) and HIV negative (HIV-) women and to determine if racial disparities exist among pregnancies complicated by HIV infection. STUDY DESIGN: This was a retrospective analysis of data from the Consortium of Safe Labor between 2002 and 2008. Comparisons of obstetric morbidity, neonatal morbidity, and indications for cesarean delivery were examined. Included were singletons with documented HIV status, race, and antepartum admission. Chi-square, Fisher exact tests, and logistic regression were used for statistical analysis. RESULTS: Included were 178,972 patients (178,210 HIV-, 762 HIV+, 464 HIV+ black, 298 HIV+ nonblack). HIV+ women were more likely to have a cesarean delivery, preterm premature rupture of membranes, another sexually transmitted infection, and delivery at an earlier gestational age. Obstetric outcomes were similar between HIV+ black and HIV+ nonblack women. Neonates of HIV+ mothers had lower birth weights and higher rates of neonatal intensive care admissions. HIV+ black women had lower birth weight neonates than HIV+ nonblack women. CONCLUSION: HIV+ women have higher rates of obstetric complications and deliver at an earlier gestational age than HIV- mothers. Lower birth weight was the only notable complication among HIV+ black women compared with HIV+ nonblack women.

Nonsurgical improvement of severe upper airway obstruction in infants with Robin sequence and cleft palate using Stanford Orthodontic Airway Plate treatment.

STUDY OBJECTIVES: Severe respiratory distress of neonates with Robin sequence (RS) is traditionally managed by surgery. Stanford Orthodontic Airway Plate treatment (SOAP) is a nonsurgical option. The study aimed to determine if SOAP can improve polysomnography (PSG) parameters of neonates with RS. METHODS: PSG of neonates with RS treated with SOAP at a single hospital were retrospectively analyzed. Patients without PSG at all 4 time points (pre-, start of-, mid-, and post-treatment) were excluded. Data were analyzed using a linear mixed effects model. RESULTS: Sixteen patients were included. All patients had cleft palate (CP). The median age (min, max) at the start of treatment was 1.1 months (0.5, 2.3) with the treatment duration of 4.5 months (3.5, 6.0). The mean obstructive apnea-hypopnea index (95% confidence interval) decreased from 39.3 events/hour (32.9, 45.7) to 12.2 events/hour (6.7, 17.7) (P < 0.001), obstructive apnea index decreased from 14.1 (11.2, 17.0) events/hour to 1.0 (-1.5, 3.5) events/hour (P < 0.001), and oxygen nadir increased from 79.9% (77.4, 82.5) to 88.2% (85.5, 90.8) (P < 0.001) between pre- and start of treatment. Respiratory improvements were sustained during and after the treatment. All patients avoided mandibular distraction osteogenesis or tracheostomy following SOAP. CONCLUSIONS: As being a rare diagnosis, the number of participants was, as expected, low. However, the current study demonstrates that SOAP can improve PSG parameters, demonstrating its potential utility before surgical interventions for neonates with RS and CP experiencing severe respiratory distress.

The OSA patient journey: pathways for diagnosis and treatment among commercially insured individuals in the United States.

STUDY OBJECTIVES: The aims of this study were to characterize obstructive sleep apnea (OSA) care pathways among commercially insured individuals in the United States and to investigate between-groups differences in population, care delivery, and economic aspects. METHODS: We identified adults with OSA using a large, national administrative claims database (January 1, 2016-February 28, 2020). Inclusion criteria included a diagnostic sleep test on or within ≤ 12 months of OSA diagnosis (index date) and 12 months of continuous enrollment before and after the index date. Exclusion criteria included prior OSA treatment or central sleep apnea. OSA care pathways were identified using sleep testing health care procedural health care common procedure coding system/current procedural terminology codes then selected for analysis if they were experienced by ≥ 3% of the population and assessed for baseline demographic/clinical characteristics that were also used for model adjustment. Primary outcome was positive airway pressure initiation rate; secondary outcomes were time from first sleep test to initiation of positive airway pressure, sleep test costs, and health care resource utilization. Associations between pathway type and time to treatment initiation were assessed using generalized linear models. RESULTS: Of 86,827 adults with OSA, 92.1% received care in 1 of 5 care pathways that met criteria: home sleep apnea testing (HSAT; 30.8%), polysomnography (PSG; 23.6%), PSG-Titration (19.8%), Split-night (14.8%), and HSAT-Titration (3.2%). Pathways had significantly different demographic and clinical characteristics. HSAT-Titration had the highest positive airway pressure initiation rate (84.6%) and PSG the lowest (34.4%). After adjustments, time to treatment initiation was significantly associated with pathway (P < .0001); Split-night had shortest duration (median, 28 days), followed by HSAT (36), PSG (37), PSG-Titration (58), and HSAT-Titration (75). HSAT had the lowest sleep test costs and health care resource utilization. CONCLUSIONS: Distinct OSA care pathways exist and are associated with differences in population, care delivery, and economic aspects. CITATION: Wickwire EM, Zhang X, Munson SH, et al. The OSA patient journey: pathways for diagnosis and treatment among commercially insured individuals in the United States. J Clin Sleep Med. 2024;20(4):505-514.

Association of Urinary Biomarkers of Tobacco Exposure with Lung Cancer Risk in African American and White Cigarette Smokers in the Southern Community Cohort Study.

BACKGROUND: After accounting for smoking history, lung cancer incidence is greater in African Americans than Whites. In the multiethnic cohort, total nicotine equivalents (TNE) are higher in African Americans than Whites at similar reported cigarettes per day. Greater toxicant uptake per cigarette may contribute to the greater lung cancer risk of African Americans. METHODS: In a nested case-control lung cancer study within the Southern Community Cohort, smoking-related biomarkers were measured in 259 cases and 503 controls (40% White; 56% African American). TNE, the trans-3-hydroxycotinine/cotinine ratio, 4-(methylnitrosamino)-1-3-(pyridyl)-1-butanol (NNAL), mercapturic acid metabolites of volatile organic compounds, phenanthrene metabolites, cadmium (Cd), and (Z)-7-(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopenyl]hept-5-enoic acid were quantified in urine. Unconditional logistic regression was used to estimate the ORs and 95% confidence intervals (CI) for each biomarker and lung cancer risk. RESULTS: TNE, NNAL, and Cd were higher in cases than controls (adjusted for age, race, sex, body mass index, and cigarettes per day). Among cases, these levels were higher in African Americans compared with Whites. After accounting for age, sex, body mass index, and pack-years, a one-SD increase in log-TNE (OR = 1.30; 95% CI, 1.10-1.54) and log-NNAL (OR = 1.27; 95% CI, 1.03-1.58 with TNE adjustment) was associated with lung cancer risk. In this study, in which NNAL concentration is relatively high, the association for log-TNE was attenuated after adjustment for log-NNAL. CONCLUSIONS: Smoking-related biomarkers provide additional information for lung cancer risk in smokers beyond smoking pack-years. IMPACT: Urinary NNAL, TNE, and Cd concentrations in current smokers, particularly African American smokers, may be useful for predicting lung cancer risk.