False positive congenital cytomegalovirus saliva screening results with an FDA-approved assay at two institutions.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is a significant cause of childhood hearing loss and developmental delay. Congenital CMV screening was implemented at two large hospital-affiliated laboratories using the FDA-approved Alethia CMV Assay Test System. In July 2022, an increase in suspected false-positive results was noted, leading to implementation of prospective quality management strategies. METHODS: The Alethia assay was performed per manufacturer-provided instructions on saliva swab specimens. After discovery of possible elevated false-positive rates, all positive results were confirmed by repeat Alethia testing on the same specimen, orthogonal polymerase chain reaction (PCR) on the same specimen, and/or clinical adjudication. Additionally, root cause analyses were conducted to pinpoint the source of false-positive results. RESULTS: At Cleveland Clinic (CCF), 696 saliva specimens were tested after initiation of the prospective quality management strategy, of which 36 (5.2%) were positive for CMV. Five of 36 (13.9%) were confirmed CMV positive by repeat Alethia testing and orthogonal PCR. Vanderbilt Medical Center (VUMC) tested 145 specimens, of which 11 (7.6%) were positive. Two of 11 (18.2%) confirmed as positive by orthogonal PCR or clinical adjudication. The remaining specimens (31 from CCF and 9 from VUMC) were negative for CMV by repeat Alethia and/or orthogonal PCR testing. DISCUSSION: These findings suggest a false positive rate of 4.5-6.2%, higher than the 0.2% reported for this assay in FDA claims. Laboratories using Alethia CMV may consider prospective quality management to evaluate all positive results. False-positive results can lead to unnecessary follow-up care and testing, and decreased confidence in laboratory testing.

Balloon pulmonary angioplasty outcomes in patients previously treated by pulmonary endarterectomy surgery are inferior to those of inoperable patients.

Pulmonary endarterectomy (PEA) may not achieve full clearance of vascular obstructions in patients with more distal chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) may be indicated to treat these residual vascular lesions. We compared whether patients post-PEA (PP) treated by BPA derived similar benefit to those who had inoperable CTEPH (IC), and assessed predictors of BPA response after surgery. We treated 109 patients with BPA-89 with IC and 20 PP. Serial right heart catheterization performed at baseline (immediately before BPA) and 3 months after completing BPA, compared pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP) as well as change in WHO functional class and 6-minute walk distance. We also assessed the impact of total thrombus tail length (TTTL) from photographed PEA surgical specimens and PP computed tomography pulmonary angiography (CTPA)-quantified residual disease burden on BPA response. PP and IC groups did not differ significantly in terms of demographics, baseline hemodynamics or procedural characteristics. However, IC derived greater hemodynamic benefit from BPA: ΔPVR (-27.9 ± 20.2% vs. -13.9 ± 23.9%, p < 0.05) and ΔmPAP (-17.1 ± 14.4% vs. -8.5 ± 18.0%, p < 0.05). There was a negative correlation between pre-BPA PVR and TTTL (r = -0.47, p < 0.05) which persisted post-BPA. PVR, mPAP, WHO FC and 6MWD were not improved significantly post-BPA in PP patients. BPA response was not related to TTTL terciles or CTPA-quantified residual disease burden. Patients PP experienced inferior response to BPA, despite similar baseline and procedural characteristics to IC. BPA does not abolish the relationship between TTTL and postsurgical PVR in PP patients, suggesting that BPA is less effective in treating residual PH after surgery in an experienced surgical center.

Acute lung injury after balloon pulmonary angioplasty results in a similar haemodynamic response and possible clinical advantage at follow-up.

Acute lung injury (ALI) is a common but poorly defined and understood complication of balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH). Little data are available on the medium term clinical outcomes of BPA complicated by ALI. We analyzed per-procedure data from 282 procedures in 109 patients and per-patient data from 85 patients. Serial right heart catheterization at baseline, after each BPA and at 3-month follow-up measured pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP), and cardiac output (CO). ALI (ALI+) was identified by chest radiography alone (ALIr+) or in association with hypoxia clinically (ALIcr+). Procedural predictors of ALI and patient outcomes at 3-months were compared no ALI (ALI-). ALI+ occurred in 17/282 (6.0%) procedures (ALIcr+: 2.5%, ALIr+: 3.5%). Prevailing haemodynamics (PVR: p < 0.01; mPAP: p < 0.05) at a procedural and patient level, as well as number of BPA sessions (p < 0.01), total number of vessels (p < 0.05), and occlusions (p < 0.05) treated at a patient level predicted ALI+. Those with ALI had greater percentage improvement in ΔCAMPHOR symptoms score (ALI+: -63.5 ± 35.7% (p < 0.05); ALIcr+: -84.4 ± 14.5% (p < 0.01); ALI-: -27.2 ± 74.2%) and ΔNT-proBNP (ALIcr+: -78.4 ± 11.9% (p < 0.01); ALI-: -42.9 ± 36.0%) at follow-up. There was no net significant difference in haemodynamic changes in ALI+ versus ALI- at follow-up. ALI is predicted by haemodynamic severity, number of vessels treated, number of BPA sessions, and treating occlusive disease. ALI in this cohort was associated with a clinical advantage at follow-up.

Sleep disorder symptoms are associated with greater posttraumatic stress and anger symptoms in US Army service members seeking treatment for posttraumatic stress disorder.

STUDY OBJECTIVES: Characterize associations between sleep impairments and posttraumatic stress disorder (PTSD) symptoms, including anger, in service members seeking treatment for PTSD. METHODS: Ninety-three US Army personnel recruited into a PTSD treatment study completed the baseline assessment. State-of-the-science sleep measurements included 1) retrospective, self-reported insomnia, 2) prospective sleep diaries assessing sleep patterns and nightmares, and 3) polysomnography measured sleep architecture and obstructive sleep apnea-hypopnea severity. Dependent variables included self-report measures of PTSD severity and anger severity. Pearson correlations and multiple linear regression analyses examined if sleep symptoms, not generally measured in PTSD populations, were associated with PTSD and anger severity. RESULTS: All participants met PTSD, insomnia, and nightmare diagnostic criteria. Mean sleep efficiency = 70%, total sleep time = 5.5 hours, obstructive sleep apnea/hypopnea (obstructive sleep apnea-hypopnea index ≥ 5 events/h) = 53%, and clinically significant anger = 85%. PTSD severity was associated with insomnia severity (ß = .58), nightmare severity (ß = .24), nightmare frequency (ß = .31), and time spent in Stage 1 sleep (ß = .27, all P < .05). Anger severity was associated with insomnia severity (ß = .37), nightmare severity (ß = .28), and obstructive sleep apnea-hypopnea during rapid eye movement sleep (ß = .31, all P < .05). CONCLUSIONS: Insomnia and nightmares were related to PTSD and anger severity, and obstructive sleep apnea-hypopnea was related to anger. Better assessment and evidence-based treatment of these comorbid sleep impairments in service members with PTSD and significant anger should result in better PTSD, anger, and quality-of-life outcomes. CLINICAL TRIALS REGISTRATION: Registry: ClinicalTrials.gov; Name: Treatment of Comorbid Sleep Disorders and Post Traumatic Stress Disorder; Identifier: NCT02773693; URL: https://clinicaltrials.gov/ct2/show/NCT02773693. CITATION: Miles SR, Pruiksma KE, Slavis D, et al. Sleep disorder symptoms are associated with greater posttraumatic stress and anger symptoms in US Army service members seeking treatment for posttraumatic stress disorder. J Clin Sleep Med. 2022;18(6):1617-1627.

A pilot randomized controlled trial of cognitive behavioral treatment for trauma-related nightmares in active duty military personnel.

STUDY OBJECTIVES: The aim of this study was to obtain preliminary data on the efficacy, credibility, and acceptability of Exposure, relaxation, and rescripting therapy for military service members and veterans (ERRT-M) in active duty military personnel with trauma-related nightmares. METHODS: Forty participants were randomized to either 5 sessions of ERRT-M or 5 weeks of minimal contact control (MCC) followed by ERRT-M. Assessments were completed at baseline, posttreatment/postcontrol, and 1-month follow-up. RESULTS: Differences between ERRT-M and control were generally medium in size for nightmare frequency (Cohen d = -0.53), nights with nightmares (d = -0.38), nightmare severity (d = -0.60), fear of sleep (d = -0.44), and symptoms of insomnia (d = -0.52), and depression (d = -0.51). In the 38 participants who received ERRT-M, there were statistically significant, medium-sized decreases in nightmare frequency (d = -0.52), nights with nightmares (d = -0.50), nightmare severity (d = -0.55), fear of sleep (d = -0.48), and symptoms of insomnia (d = -0.59), posttraumatic stress disorder (PTSD) (d = -0.58) and depression (d = -0.59) from baseline to 1-month follow-up. Participants generally endorsed medium to high ratings of treatment credibility and expectancy. The treatment dropout rate (17.5%) was comparable to rates observed for similar treatments in civilians. CONCLUSIONS: ERRT-M produced medium effect-size reductions in nightmares and several secondary outcomes including PTSD, depression, and insomnia. Participants considered ERRT-M to be credible. An adequately powered randomized clinical trial is needed to confirm findings and to compare ERRT-M to an active treatment control. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: A Pilot Randomized Controlled Trial of Treatment for Trauma-Related Nightmares In Active Duty Military Personnel; Identifier: NCT02506595; URL: https://clinicaltrials.gov/ct2/show/NCT02506595.

Ambulatory Surgery Has Minimal Impact on Sleep Parameters: A Prospective Observational Trial.

STUDY OBJECTIVES: The presence of obstructive sleep apnea (OSA) in ambulatory surgical patients causes significant perioperative concern; however, few data exist to guide clinicians' management decisions. The objective of this study was to measure changes in perioperative sleep parameters among an ambulatory surgery population. METHODS: This study is a prospective, observational study of ambulatory patients undergoing orthopedic surgery on an extremity. Study subjects completed three unattended home sleep apnea tests: baseline before surgery, the first night after surgery (N1), and third night after surgery (N3). Anesthesia and surgical teams were blinded to study participation and patients received routine perioperative care. RESULTS: Two hundred three subjects were enrolled and 166 completed the baseline home sleep test. Sixty-six (40.0%) had OSA at baseline, 35 patients received a new diagnosis, and 31 patients had a previous diagnosis of OSA. Of those with a previous diagnosis, 20 (64.5%) were compliant with continuous positive airway pressure therapy. Respiratory event index and SpO2 nadir did not significantly change postoperatively from baseline. Cumulative percentage of time oxygen saturation < 90% significantly increased N1 as compared to baseline for all patients except for those with moderate to severe OSA. CONCLUSIONS: Ambulatory surgery had minimal effect on sleep parameters and there was no increase in adverse events among patients with either treated or untreated OSA. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Evaluation of Sleep Disordered Breathing Following Ambulatory Surgery; Identifier: NCT01851798; URL: https://clinicaltrials.gov/ct2/show/study/NCT01851798.

Amelioration of salt-induced vascular dysfunction in mesenteric arteries of Dahl salt-sensitive rats by missense mutation of extracellular superoxide dismutase.

Superoxide dismutase (SOD) enzymes, including extracellular SOD (ecSOD), are important for scavenging superoxide radicals (O2(·-)) in the vasculature. This study investigated vascular control in rats [SS-Sod(3m1Mcwi) (ecSOD(E124D))] with a missense mutation that alters a single amino acid (E124D) of ecSOD that produces a malfunctioning protein in the salt-sensitive (Dahl SS) genetic background. We hypothesized that this mutation would exacerbate endothelial dysfunction due to elevated vascular O2(·-) levels in SS, even under normal salt (NS; 0.4% NaCl) conditions. Aortas of ecSOD(E124D) rats fed standard rodent chow showed enhanced sensitivity to phenylephrine and reduced relaxation to acetylcholine (ACh) vs. SS rats. Endothelium-dependent dilation to ACh was unaffected by the mutation in small mesenteric arteries of ecSOD(E124D) rats fed NS diet, and mesenteric arteries of ecSOD(E124D) rats were protected from endothelial dysfunction during short-term (3-5 days) high-salt (HS; 4% NaCl) diet. ACh-induced dilation of mesenteric arteries of ecSOD(E124D) rats and SS rats fed NS diet was inhibited by N(G)-nitro-l-arginine methyl ester and/or by H2O2 scavenging with polyethylene glycol-catalase at higher concentrations of ACh. Total SOD activity was significantly higher in ecSOD(E124D) rats vs. SS controls fed HS diet, most likely reflecting a compensatory response to loss of a functional ecSOD isoform. These findings indicate that, contrary to its effect in the aorta, this missense mutation of ecSOD in the SS rat genome has no negative effect on vascular function in small resistance arteries, but instead protects against salt-induced endothelial dysfunction, most likely via compensatory mechanisms involving an increase in total SOD activity.

Safety of intravenous sedation administered by the operating oral surgeon: the second 7 years of office practice.

PURPOSE: This follow-up study provides an additional 7 years of data (December 2001 through November 2008) pertaining to complications that occurred in patients who received intravenous sedation in the practice of a single board-certified oral and maxillofacial surgeon. Together with the previously published 7 years of data (December 1994 through November 2001), this study summarizes the frequency of various complications encountered in patients sedated intravenously by the surgeon over a 14-year period. MATERIALS AND METHODS: The files of intravenous sedation cases from the second 7-year period were reviewed for complications. These data were then compared, contrasted, and combined with the previously published sedation cases from the first 7 years. RESULTS: A total of 3,320 sedations were performed by the surgeon during this second 7-year period, with only 1.57% of patients having complications (52 patients having 60 adverse events). These results showed a slight decline in the frequency of complications. Over the entire 14-year period of study, a total of 6,209 sedations were performed by the surgeon, with 1.96% of patients having complications (122 patients having 137 adverse events). There were no deaths, and no patients required emergency transport to a hospital. CONCLUSIONS: The results of this follow-up study confirm the previous findings. The administration of intravenous sedation by the operating surgeon for outpatient oral surgery is safe, with a low frequency of complications. Numerous patients were also made aware of previously undiagnosed medical problems, improving overall patient health.

Small cell ovarian carcinoma: a rare, aggressive tumor masquerading as constipation in a teenager with a fatal outcome.

SUMMARY: A 16-year-old female presented with symptoms consistent with constipation with no constitutional symptoms. Multiple different laxatives were attempted over 4 months and were unsuccessful. This thin female developed an impressively distended, nonacute abdomen within a 2-week period. Histology demonstrated a stage IV small cell carcinoma of the ovary. Her disease initially responded to treatment, but ultimately she relapsed and failed to respond to 2 other chemotherapy combinations, which were based on limited success found in the literature. She ultimately passed away 13 months after the diagnosis, demonstrating the poor prognosis and rapid spread of this rare disease.

Playing favorites: the influence of leaders' inner circle on group processes and performance.

Leaders frequently form stronger relationships with certain subordinates moreso than others, creating an inner circle of close friendships and an outer circle of more distant relationships. Three studies examine the effects of inner-circle membership on group dynamics and interpersonal influence in hierarchical teams. Study 1 finds that, compared to outer-circle members, inner-circle members feel safer and participate in the group discussion more, and leaders recognize them as making a greater contribution and allocate a larger bonus to them. Consequently, inner-circle members influence the groups' decisions more, and team decision quality improves when inner-circle members possess expert knowledge. Study 2 finds that leaders attended to and recalled suggestions from their inner circle more regardless of argument strength, suggesting heuristic information processing. Study 3 replicates these findings using intact teams in a large governmental agency. Implications for leadership and group decision making are discussed.