Prevalence of central sleep apnea among veterans and response rate to continuous positive airway pressure therapy.

Study Objectives: Sleep-disordered breathing (SDB) is common in the Veteran population. In this retrospective study, we investigated the prevalence of comorbid central and obstructive SDB and the response rate to PAP among Veterans. Methods: Veterans were screened from a single VA medical center who had polysomnography (PSG) study from 2017 to 2021 to ascertain the presence, severity, and type of SDB by measuring the apnea-hypopnea index (AHI) and central apnea index (CAI). Patients were excluded if they did not have complete studies (diagnostic and PAP titration studies). The inclusion criteria for these analyses were central sleep apnea (CSA) defined as AHI ≥ 10 events/hour and CAI ≥ 5 events/hour. Diagnostic "CSA only" was defined as AHI ≥ 10 events/hour and CAI ≥ 50% of AHI. "OSA only" was defined if AHI ≥ 10 events/hour and CAI < 5 events/hour. Comorbid central and obstructive sleep apnea (COSA) was defined if AHI ≥ 10 events/hour and CAI > 5 events/hour but < 50% of AHI. The responsiveness to PAP therapy was determined based on the CAI < 5 events/hour on the titration study. Results: A total of 90 patients met the inclusion criteria and from those 64 Veterans were found to have COSA (71%), 18 (20%) were CSA only, and 8 (9%) were OSA only. A total of 22 (24.4%) Veterans diagnosed with CSA or COSA were responsive to PAP therapy. Sixty days after treatment initiation, both responsive and nonresponsive groups had significant decreases in AHI and CAI (p < 0.05). Conclusions: Comorbid central and obstructive SDB is common among Veterans. The response to PAP therapy is suboptimal but improves over time.

Intensive support does not improve positive-airway pressure use in spinal cord injury/disease: a randomized clinical trial.

STUDY OBJECTIVE: Treatment of sleep-disordered breathing (SDB) with positive airway pressure (PAP) therapy has unique clinical challenges in individuals living with spinal cord injuries and diseases (spinal cord injury [SCI]/D). Interventions focused on increasing PAP use have not been studied in this population. We aimed to evaluate the benefits of a program to increase PAP use among Veterans with SCI/D and SDB. METHODS: Randomized controlled trial comparing a behavioral Intervention (n = 32) and educational control (n = 31), both including one face-to-face and five telephone sessions over 3 months. The intervention included education about SDB and PAP, goal setting, troubleshooting, and motivational enhancement. The control arm included non-directive sleep education only. RESULTS: Primary outcomes were objective PAP use (nights ≥4 hours used within 90 days) and sleep quality (Pittsburgh Sleep Quality Index [PSQI] at 3 months). These did not differ between intervention and control (main outcome timepoint; mean difference 3.5 [-9.0, 15.9] nights/week for PAP use; p = .578; -1.1 [-2.8, 0.6] points for PSQI; p = .219). Secondary outcomes included fatigue, depression, function, and quality of life. Only fatigue improved significantly more in the intervention versus the control group (p = .025). Across groups, more PAP use was associated with larger improvements in sleep quality, insomnia, sleepiness, fatigue, and depression at some time points. CONCLUSIONS: PAP use in Veterans with SCI/D and SDB is low, and a 3-month supportive/behavioral program did not show significant benefit compared to education alone. Overall, more PAP use was associated with improved symptoms suggesting more intensive support, such as in-home assistance, may be required to increase PAP use in these patients. CLINICAL TRIALS INFORMATION: Title: "Treatment of Sleep Disordered Breathing in Patients with SCI." Registration number: NCT02830074. Website: https://clinicaltrials.gov/study/NCT02830074?cond=Sleep%20Apnea&term=badr&rank=5.

Insomnia severity predicts depression, anxiety, and posttraumatic stress disorder in veterans with spinal cord injury or disease: a cross-sectional observational study.

STUDY OBJECTIVES: To assess the association of insomnia symptoms and psychiatric symptoms in patients with spinal cord injury or disease (SCI/D). METHODS: In this cross-sectional observational study, veterans with SCI/D (n = 72; mean = 59.85 ± 10.4 years; 92% male) completed baseline measures, including the Insomnia Severity Index (ISI) during the baseline phase of a clinical trial on treatment of sleep disorders in veterans with SCI/D. Depression severity was measured by the Patient Health Questionnaire (PHQ-9; sleep items excluded), anxiety severity was measured by the Generalized Anxiety Disorder screener (GAD-7), and probable posttraumatic stress disorder (PTSD) was measured by the Primary Care PTSD screener. Blocked regression was used to evaluate the impact of insomnia symptoms (ISI) on mental health measures after accounting for demographics and level of spinal cord injury/disease. RESULTS: On average, participants scored in the mild range for depression (PHQ-9 = 7.4 ± 5.9) and anxiety severity (GAD-7 = 6.1 ± 6.1). In total, 36.1% (n = 26) screened positive for probable PTSD. ISI explained 19% of the variance in PHQ-9 and 20% of the variance in GAD-7 (P < .001) over and above demographics and SCI/D level of injury/disease. Odds of probable PTSD were increased 1.22-fold for each 1 unit increase in ISI (P = .001) after accounting for demographics and level of injury/disease. CONCLUSIONS: In veterans with SCI/D, insomnia severity was linked to depression and anxiety symptom severity and risk of PTSD. Study results warrant further research to evaluate the impact of insomnia treatment on depression, anxiety, and PTSD in patients with SCI/D. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Treatment of Sleep-disordered Breathing in Patients With SCI; URL: https://clinicaltrials.gov/ct2/show/NCT02830074; Identifier: NCT02830074. CITATION: Kelly MR, Zeineddine S, Mitchell MN, et al. Insomnia severity predicts depression, anxiety, and posttraumatic stress disorder in veterans with spinal cord injury or disease: a cross-sectional observational study. J Clin Sleep Med. 2023;19(4):695-701.

Effect of Zolpidem on nocturnal arousals and susceptibility to central sleep apnea.

PURPOSE: Arousals may contribute to the pathogenesis of sleep-disordered breathing (SDB) and central sleep apnea (CSA). We aimed to determine the effect of the nonbenzodiazepine hypnotic zolpidem on the frequency of respiratory-related arousals and central apnea in patients with moderate-to-severe SDB. We hypothesized that zolpidem decreases the severity of SDB by decreasing the frequency of respiratory-related arousals. METHODS: Patients with apnea-hypopnea index ≥ 15 events/hour and central apnea-hypopnea index ≥ 5 events/hour underwent a sleep study on zolpidem 5 mg and a sleep study with no medication in a randomized order. The respiratory arousal index was compared between the two studies using a randomized crossover design. Sleep, respiratory, and physiologic parameters, including the CO2 reserve and the respiratory arousal threshold, were also compared. RESULTS: Eleven participants completed the study. Compared to no treatment, zolpidem reduced the respiratory arousal index (39.7 ± 7.7 vs. 23.3 ± 4.4 events/h, P = 0.031). Zolpidem also lowered the total apnea-hypopnea index (55.6 ± 8.5 vs. 41.3 ± 7.5 events/hour, P = 0.033) but did not affect other clinical and physiologic parameters. Compared to control, zolpidem did not widen CO2 reserve (- 0.44 ± 1.47 vs. - 0.63 ± 0.86 mmHg, P = 0.81). The respiratory arousal threshold did not show a significant change on zolpidem compared to control (- 8.72 ± 2.1 vs. - 8.25 ± 2.81 cmH2O, P = 0.41). CONCLUSION: Nocturnal arousals and overall SDB severity were reduced with a single dose of zolpidem in patients with moderate-to-severe sleep-disordered breathing with increased susceptibility for central apnea. Zolpidem did not widen the CO2 reserve or increase the arousal threshold. TRIAL REGISTRATION: Clinicaltrials.gov. Sleep and Breathing in the General Population - Chemical Stimuli (NCT04720547).

Sleep disorders, daytime symptoms, and quality of life in veterans with multiple sclerosis: preliminary findings.

Study Objectives: Multiple sclerosis (MS) is an autoimmune disease impacting the central nervous system. A hallmark symptom of MS is fatigue, which impairs daytime function and quality of life (QOL). Sleep disorders and disturbances are common in persons with MS and exacerbate fatigue. We evaluated relationships between sleep-disordered breathing (SDB), insomnia symptoms, sleep quality, and daytime functioning in veterans with MS participating in a larger study. Methods: Twenty-five veterans with clinically diagnosed MS were included (average age = 57 ± 11, 80% male). One had a co-occurring thoracic spinal cord injury. Twenty-four participants completed in-laboratory polysomnography (PSG) to measure apnea-hypopnea index (AHI) and sleep efficiency (PSG-SE). Insomnia Severity Index (ISI) and Pittsburg Sleep Quality Index (PSQI) were used to measure sleep subjectively. The Flinders Fatigue Scale (FFS), Epworth Sleepiness Scale (ESS), PHQ-9 depression scale, and GAD-7 anxiety scale assessed daytime symptoms. The World Health Organization Quality of Life (WHOQOL) was used to assess quality of life. Relationships between sleep (AHI, PSG-SE, ISI, PSQI), daytime symptoms (ESS, FFS, PHQ-9, and GAD-7), and quality of life (WHOQOL) were evaluated with bivariate correlations. Results: Higher ISI (r = 0.78, 95% CI = [0.54, 0.90], p < .001), higher PSQI (r = 0.51, 95% CI = [0.10, 0.77], p = .017), and lower PSG-SE (r = -0.45, 95% CI = [-0.74, -0.02], p = .041) were associated with worse fatigue (FFS). Higher ISI was also associated with worse WHOQOL (Physical Domain; r = -0.64, 95% CI = [-0.82, -0.32], p = .001). There were no other significant relationships. Conclusion: In veterans with MS, more severe insomnia and worse sleep quality may be associated with more fatigue and lower quality of life. Recognition and management of insomnia should be considered in future studies of sleep in MS.

Oxygen Therapy in Sleep-Disordered Breathing.

Sleep-disordered breathing (SDB) is highly prevalent in adults and leads to significant cardiovascular and neurologic sequelae. Intermittent hypoxia during sleep is a direct consequence of SDB. Administration of nocturnal supplemental oxygen (NSO) has been used as a therapeutic alternative to positive airway pressure (PAP) in SDB. NSO significantly improves oxygen saturation in OSA but is inferior to PAP in terms of reducing apnea severity and may prolong the duration of obstructive apneas. The effect of NSO on daytime sleepiness remains unclear, but NSO may improve physical function-related quality of life in OSA. Its effects on BP reduction remain inconclusive. The effects of NSO vs PAP in OSA with comorbid COPD (overlap syndrome) are unknown. NSO is effective in reducing central sleep apnea related to congestive heart failure; however, its impact on mortality and cardiovascular clinical outcomes are being investigated in an ongoing clinical trial. In conclusion, studies are inconclusive or limited regarding clinical outcomes with oxygen therapy compared with sham or PAP therapy in patients with OSA and overlap syndrome. Oxygen does mitigate central sleep apnea. This review examines the crucial knowledge gaps and suggests future research priorities to clarify the effects of optimal dose and duration of NSO, alone or in combination with PAP, on cardiovascular, sleep, and cognitive outcomes.

Treatment-Emergent Central Apnea: Physiologic Mechanisms Informing Clinical Practice.

The purpose of this review was to describe our management approach to patients with treatment-emergent central sleep apnea (TECSA). The emergence of central sleep apnea during positive airway pressure therapy occurs in approximately 8% of titration studies for OSA, and it has been associated with several demographic, clinical, and polysomnographic factors, as well as factors related to the titration study itself. TECSA shares similar pathophysiology with central sleep apnea. In fact, central and OSA pathophysiologic mechanisms are inextricably intertwined, with ventilatory instability and upper airway narrowing occurring in both entities. TECSA is a "dynamic" process, with spontaneous resolution with ongoing positive airway pressure therapy in most patients, persistence in some, or appearing de novo in a minority of patients. Management strategy for TECSA aims to eliminate abnormal respiratory events, stabilize sleep architecture, and improve the underlying contributing medical comorbidities. CPAP therapy remains a standard therapy for TECSA. Expectant management is appropriate given its transient nature in most cases, whereas select patients would benefit from an early switch to an alternative positive airway pressure modality. Other treatment options include supplemental oxygen and pharmacologic therapy.

Familial Hydrocephalus and Dysgenesis of the Corpus Callosum Associated with Xp22.33 Duplication and Stenosis of the Aqueduct of Sylvius with X-Linked Recessive Inheritance Pattern.

INTRODUCTION: X-linked recessive mutations predominantly affect male fetuses with milder or no abnormalities in female siblings. Most reports show only one affected member in the family. We are reporting a family affected with hydrocephalus, stenosis of the aqueduct of Sylvius, dysgenesis of the corpus callosum, and Xp22.33 microduplication. CASE PRESENTATION: Eighteen-year-old patient was evaluated for her 2 pregnancies; the first was a male fetus with severe hydrocephalus and the second a female fetus with mild hydrocephalus. Postnatal MRI evaluation of the male neonate revealed stenosis of the aqueduct of Sylvius, dysgenesis of the corpus callosum, and severe hydrocephalus requiring ventriculoperitoneal shunt. Postnatal MRI evaluation of the female neonate revealed mild hydrocephalus, stenosis of the aqueduct of Sylvius, and mild dysgenesis of the corpus callosum. The female baby did not require surgical intervention. Genetic testing of the mother and the 2 children revealed a 439 Kb duplication of Xp22.33. DISCUSSION: This family demonstrates typical X-linked recessive heritability. X-inactivation is a compensatory mechanism that explains the mild symptoms of the female child and the severe symptoms of the male child. This familial case shows the importance of prenatal testing and genetic counseling and testing, including karyotype and chromosomal microarray.

A Non-Lethal Osteogenesis Imperfecta Type II Mutation.

BACKGROUND: We discuss the ethical decision points in a case report that describes a novel COL1A1 mutation associated to Osteogenesis Imperfecta type II, but with a non-lethal outcome. CASE: A 33-year-old female underwent a 21-week ultrasound that revealed short bowed femurs and humeri with old fractures and bowed tibias and fibulas. Amniotic fluid testing revealed a novel COL1A1 mutation (c.1840G>A; p.Gly614Arg). OI Type II diagnosis was made. A previously reported mutation of the same gene but different locus (c.1840G>C; p.Gly614Arg) led to a lethal form of OI type II. The newborn was delivered via a cesarean delivery and intravenous bisphosphonates (Zaledronic acid) was administered every 3 months. Currently the infant is 22 months old, is growing, with mild bilateral conductive hearing loss. CONCLUSION: The unexpected clinical outcome should serve as a reminder that phenotypic variability can occur with genetic mutations. Our case shows that the diagnosis of the type of OI should be based not only on clinical findings and genetic investigations but also on the clinical course over time.

Incarcerated Uterus Presenting as Short Cervix and Placenta Previa.

INTRODUCTION: Incarcerated uterus is a rare complication of pregnancy, usually associated with retroversion. CASE: A 26-year-old woman presents at 19 4/7 weeks for evaluation of a short cervix and placenta previa. On ultrasound scan, the placenta was considered previa and the cervix was not visualized. The cervix was not identified by pelvic examination and the presumptive diagnosis of short cervix was done. The patient was followed up closely and remained asymptomatic. Retrospective analysis of the ultrasound images showed a retroverted uterus with an elongated cervix compressed towards the anterior vaginal wall. At 26 weeks of gestation, ultrasound showed a cervical length of 41 mm and a fundal placenta and the diagnosis of spontaneous correction of an incarcerated uterus was made. The patient had an uncomplicated vaginal delivery at 39 3/7 weeks. COMMENT: Identification and close follow-up of incarcerated uterus may potentially help in avoiding serious obstetrical and surgical complications.

Umbilical Artery Thrombosis with Associated Acute and Severe Fetal Growth Restriction and Transient Severe Protein S Deficiency: Report of a Case with Prenatal Ultrasound Diagnosis Allowing for Timely Intervention and Good Outcome.

BACKGROUND: Thrombosis of one of the umbilical arteries can be associated with adverse pregnancy outcomes such as stillbirth and severe intrauterine growth restriction (IUGR). CASE: A 21-year-old gravida 1 patient, with a history of 3-vessel cord at 20 weeks, presented at 29 weeks with a single umbilical artery. The estimated fetal weight measurements at 26 weeks, 29 weeks, and 31 weeks were at the 27th percentile, the 26th percentile, and less than the 5th percentile, respectively. At 33 weeks, amniotic fluid index became abnormal at 2.3 cm and fetal heart tracing revealed spontaneous prolonged decelerations, and a cesarean delivery was performed. Placental pathology showed thrombosis of one of the umbilical arteries. At birth, a transient protein S deficiency was detected (activity 13%) and resolved at two months of age (activity 66%). The baby had an uneventful clinical course since birth. CONCLUSION: The recognition of reduction of umbilical arteries from two to one allowed for timely intervention with good outcome in this case. Thrombosis of umbilical vessels may be associated with a deficiency in coagulation proteins such as protein S.

Sleep Disorders in Women Veterans.

Sleep disorders are common among women veterans and contribute to poor functioning and quality of life. Studies show that women veterans are particularly prone to insomnia, sleep-disordered breathing, and insufficient sleep. Standard cognitive behavioral therapy for insomnia (CBT-I) should be viewed as first-line therapy for insomnia disorder, and women veterans should be screened and treated for sleep-disordered breathing. Behavioral and lifestyle factors contributing to insufficient sleep should also be addressed. Challenges exist in diagnosing and treating sleep disorders in women veterans, in part because of high rates of psychiatric comorbidities, such as posttraumatic stress disorder and depression.

Is therapy with calcium and vitamin D and parathyroid autotransplantation useful in total thyroidectomy for preventing hypocalcemia?

BACKGROUND: Routine calcium and vitamin D administration and routine autotransplantation of parathyroid glands can prevent hypocalcemia after total thyroidectomy. METHODS: Routine autotransplantation of 1 or more parathyroid glands and oral calcium and vitamin D supplementation was used in 252 patients. RESULTS: One, 2, or 3 parathyroid glands were autotransplanted in 223, 27, and 2 patients, respectively. Routine oral calcium and vitamin D was administered in postoperative period in all patients. Postoperative hypocalcemia occurred in 17%, of whom 1.6% had minor symptoms related to hypocalcemia. No patient developed permanent hypocalcemia during the follow-up period. The postoperative stay was 1 day in 93.6% of the cases. The incidence of postoperative hypocalcemia and hospital stay was higher in patients who underwent autotransplantation of more than 1 parathyroid gland. CONCLUSIONS: Routine oral calcium and vitamin D supplementation and autotransplantation of at least 1 parathyroid gland effectively reduced symptomatic hypocalcemia and permanent hypoparathyroidism in total thyroidectomy.

Careful examination of thyroid specimen intraoperatively to reduce incidence of inadvertent parathyroidectomy during thyroid surgery.

OBJECTIVE: To assess the incidence and clinical relevance of inadvertent parathyroidectomy during thyroidectomy, and the possibility of reducing its occurrence. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Consecutive patients who underwent thyroidectomy from 1999 to 2005, divided into 2 groups (group 1, those with inadvertent parathyroidectomy; and group 2, those without inadvertent parathyroidectomy). Patients who underwent surgical procedures for recurrent thyroid disease, intentional parathyroidectomy, and resection of central compartment viscera were excluded. INTERVENTIONS: All pathology reports were reviewed for the presence of any parathyroid tissue in the resected specimen. Age, sex, preoperative diagnosis, thyroid hormonal status, substernal thyroid extension, number of parathyroid glands identified and spared at the time of surgery, autotransplantation of parathyroid gland, and final histologic findings were recorded. MAIN OUTCOME MEASURES: Identification of parathyroid tissue in resected specimens and postoperative symptomatic hypocalcemia. RESULTS: A total of 307 patients were included. Surgical procedures included bilateral or unilateral thyroidectomy (95% and 5% of procedures, respectively). Central neck lymph node dissection was performed in 5% of cases. Pathologic findings showed inadvertent parathyroidectomy in 12% of cases. Of these, 32% were recognized intraoperatively. The parathyroid tissue was found in extracapsular locations in 37% of cases, intracapsular locations in 39%, and intrathyroidal locations in 24%. There was no statistical difference between the 2 groups in terms of sex, preoperative diagnosis, substernal extension, extent of surgery, pathologic diagnosis, and occurrence of postoperative hypocalcemia, except for the presence of thyroiditis. CONCLUSION: Careful examination of the surgical specimen intraoperatively decreases the incidence of inadvertent parathyroidectomy during thyroidectomy.