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Tilt Table Testing

Author/s: 
Chesire, W.P., Dudenkov, D.V., Munipalli, B.

A 43-year-old woman presented with a 1-year history of recurring symptoms of sudden onset of fatigue, palpitations, dyspnea, chest pain, lightheadedness, and nausea that were associated with standing and resolved with sitting. These symptoms began 1 month after mild COVID-19 infection. At presentation, while supine, blood pressure (BP) was 123/70 mm Hg and heart rate (HR) was 90/min; while seated, BP was 120/80 and HR was 93/min; after standing for 1 minute, BP was 124/80 and HR was 119/min. Physical examination results were normal. Oxygen saturation was 98% at rest while breathing room air. She had no oxygen desaturation during a 6-minute walk test but walked only 282 m (45% predicted). Complete blood cell count, morning cortisol, and thyrotropin blood levels were normal. Electrocardiogram (ECG), chest computed tomography, pulmonary function testing, methacholine challenge, bronchoscopy, echocardiography, and cardiac catheterization findings were normal. During tilt table testing, the patient experienced lightheadedness and nausea when moved from horizontal to the upright position. Results of the tilt table test are shown in the Table and Figure.

Keywords 
tilt table testing syncope COVID-19 Dyspnea electrocardiography Echocardiography tilt table Physical Examination Cardiac Catheterization

Tilt Table Testing

Author/s: 
Chesire, W.P., Dudenkov, D.V., Munipalli, B.

A 43-year-old woman presented with a 1-year history of recurring symptoms of sudden onset of fatigue, palpitations, dyspnea, chest pain, lightheadedness, and nausea that were associated with standing and resolved with sitting. These symptoms began 1 month after mild COVID-19 infection. At presentation, while supine, blood pressure (BP) was 123/70 mm Hg and heart rate (HR) was 90/min; while seated, BP was 120/80 and HR was 93/min; after standing for 1 minute, BP was 124/80 and HR was 119/min. Physical examination results were normal. Oxygen saturation was 98% at rest while breathing room air. She had no oxygen desaturation during a 6-minute walk test but walked only 282 m (45% predicted). Complete blood cell count, morning cortisol, and thyrotropin blood levels were normal. Electrocardiogram (ECG), chest computed tomography, pulmonary function testing, methacholine challenge, bronchoscopy, echocardiography, and cardiac catheterization findings were normal. During tilt table testing, the patient experienced lightheadedness and nausea when moved from horizontal to the upright position. Results of the tilt table test are shown in the Table and Figure.

Keywords 
tilt table testing syncope COVID-19 Dyspnea electrocardiography Echocardiography tilt table Physical Examination Cardiac Catheterization

Effect of Psychological and Medication Therapies for Insomnia on Daytime Functions: A Randomized Clinical Trial

Author/s: 
Charles M Morin, Si-Jing Chen, Hans Ivers, Simon Beaulieu-Bonneau, Andrew D Krystal, Bernard Guay, Lynda Bélanger, Ann Cartwright, Bryan Simmons, Manon Lamy, Mindy Busby, Jack D Edinger

Importance: Daytime functional impairments are the primary reasons for patients with insomnia to seek treatment, yet little is known about what the optimal treatment is for improving daytime functions and how best to proceed with treatment for patients whose insomnia has not remitted.

Objectives: To compare the efficacy of behavioral therapy (BT) and zolpidem as initial therapies for improving daytime functions among patients with insomnia and evaluate the added value of a second treatment for patients whose insomnia has not remitted.

Design, setting, and participants: In this sequential multiple-assignment randomized clinical trial conducted at institutions in Canada and the US, 211 adults with chronic insomnia disorder were enrolled between May 1, 2012, and December 31, 2015, and followed up for 12 months. Statistical analyses were performed on an intention-to-treat basis in April and October 2023.

Interventions: Participants were randomly assigned to either BT or zolpidem as first-stage therapy, and those whose insomnia had not remitted received a second-stage psychological therapy (BT or cognitive therapy) or medication therapy (zolpidem or trazodone).

Main outcomes and measures: Study outcomes were daytime symptoms of insomnia, including mood disturbances, fatigue, functional impairments of insomnia, and scores on the 36-item Short-Form Health Survey (SF-36) physical and mental health components.

Results: Among 211 adults with insomnia (132 women [63%]; mean [SD] age, 45.6 [14.9] years), 104 were allocated to BT and 107 to zolpidem at the first stage. First-stage treatment with BT or zolpidem yielded significant and equivalent benefits for most of the daytime outcomes, including depressive symptoms (Beck Depression Inventory-II mean score change, -3.5 [95% CI, -4.7 to -2.3] vs -4.3 [95% CI, -5.7 to -2.9]), fatigue (Multidimensional Fatigue Inventory mean score change, -4.7 [95% CI, -7.3 to -2.2] vs -5.2 [95% CI, -7.9 to -2.5]), functional impairments (Work and Social Adjustment Scale mean score change, -5.0 [95% CI, -6.7 to -3.3] vs -5.1 [95% CI, -7.2 to -2.9]), and mental health (SF-36 mental health subscale mean score change, 3.5 [95% CI, 1.9-5.1] vs 2.5 [95% CI, 0.4-4.5]), while BT produced larger improvements for anxiety symptoms relative to zolpidem (State-Trait Anxiety Inventory mean score change, -4.1 [95% CI, -5.8 to -2.4] vs -1.2 [95% CI, -3.0 to 0.5]; P = .02; Cohen d = 0.55). Second-stage therapy produced additional improvements for the 2 conditions starting with zolpidem at posttreatment in fatigue (Multidimensional Fatigue Inventory mean score change: zolpidem plus BT, -3.8 [95% CI, -7.1 to -0.4]; zolpidem plus trazodone, -3.7 [95% CI, -6.3 to -1.1]), functional impairments (Work and Social Adjustment Scale mean score change: zolpidem plus BT, -3.7 [95% CI, -6.4 to -1.0]; zolpidem plus trazodone, -3.3 [95% CI, -5.9 to -0.7]) and mental health (SF-36 mental health subscale mean score change: zolpidem plus BT, 5.3 [95% CI, 2.7-7.9]; zolpidem plus trazodone, 2.0 [95% CI, 0.1-4.0]). Treatment benefits achieved at posttreatment were well maintained throughout the 12-month follow-up, and additional improvements were noted for patients receiving the BT treatment sequences.

Conclusions and relevance: In this randomized clinical trial of adults with insomnia disorder, BT and zolpidem produced improvements for various daytime symptoms of insomnia that were no different between treatments. Adding a second treatment offered an added value with further improvements of daytime functions.

Trial registration: ClinicalTrials.gov Identifier: NCT01651442.

Keywords 
Insomnia Insomnia medications sleep behavior therapy cognitive behavior therapy

Short-term and Long-term Rates of Postacute Sequelae of SARS-CoV-2 Infection: A Systematic Review

Author/s: 
Groff, D., Sun, A., Ssentongo, A. E., Ba, D. M., Parsons, N., Poudel, G. R., Lekoubou, A., Oh, J. S., Ericson, J. E., Ssentongo, P., Chinchilli, V. M.

Importance
Short-term and long-term persistent postacute sequelae of COVID-19 (PASC) have not been systematically evaluated. The incidence and evolution of PASC are dependent on time from infection, organ systems and tissue affected, vaccination status, variant of the virus, and geographic region.

Objective
To estimate organ system–specific frequency and evolution of PASC.

Evidence Review
PubMed (MEDLINE), Scopus, the World Health Organization Global Literature on Coronavirus Disease, and CoronaCentral databases were searched from December 2019 through March 2021. A total of 2100 studies were identified from databases and through cited references. Studies providing data on PASC in children and adults were included. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for abstracting data were followed and performed independently by 2 reviewers. Quality was assessed using the Newcastle-Ottawa Scale for cohort studies. The main outcome was frequency of PASC diagnosed by (1) laboratory investigation, (2) radiologic pathology, and (3) clinical signs and symptoms. PASC were classified by organ system, ie, neurologic; cardiovascular; respiratory; digestive; dermatologic; and ear, nose, and throat as well as mental health, constitutional symptoms, and functional mobility.

Findings
From a total of 2100 studies identified, 57 studies with 250 351 survivors of COVID-19 met inclusion criteria. The mean (SD) age of survivors was 54.4 (8.9) years, 140 196 (56%) were male, and 197 777 (79%) were hospitalized during acute COVID-19. High-income countries contributed 45 studies (79%). The median (IQR) proportion of COVID-19 survivors experiencing at least 1 PASC was 54.0% (45.0%-69.0%; 13 studies) at 1 month (short-term), 55.0% (34.8%-65.5%; 38 studies) at 2 to 5 months (intermediate-term), and 54.0% (31.0%-67.0%; 9 studies) at 6 or more months (long-term). Most prevalent pulmonary sequelae, neurologic disorders, mental health disorders, functional mobility impairments, and general and constitutional symptoms were chest imaging abnormality (median [IQR], 62.2% [45.8%-76.5%]), difficulty concentrating (median [IQR], 23.8% [20.4%-25.9%]), generalized anxiety disorder (median [IQR], 29.6% [14.0%-44.0%]), general functional impairments (median [IQR], 44.0% [23.4%-62.6%]), and fatigue or muscle weakness (median [IQR], 37.5% [25.4%-54.5%]), respectively. Other frequently reported symptoms included cardiac, dermatologic, digestive, and ear, nose, and throat disorders.

Conclusions and Relevance
In this systematic review, more than half of COVID-19 survivors experienced PASC 6 months after recovery. The most common PASC involved functional mobility impairments, pulmonary abnormalities, and mental health disorders. These long-term PASC effects occur on a scale that could overwhelm existing health care capacity, particularly in low- and middle-income countries.

Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19

Author/s: 
Taquet, M., Dercon, Q., Luciano, S., Geddes, J. R., Husain, M., Harrison, P. J.

Background
Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues.

Methods and findings
We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score–matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan–Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control.

Among COVID-19 survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza (with an overall excess incidence of 16.60% and hazard ratios between 1.44 and 2.04, all p < 0.001), co-occurred more commonly, and formed a more interconnected network. Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity. Besides the limitations inherent to EHR data, limitations of this study include that (i) the findings do not generalize to patients who have had COVID-19 but were not diagnosed, nor to patients who do not seek or receive medical attention when experiencing symptoms of long-COVID; (ii) the findings say nothing about the persistence of the clinical features; and (iii) the difference between cohorts might be affected by one cohort seeking or receiving more medical attention for their symptoms.

Conclusions
Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.

Author summary
Why was this study done?
Long-COVID has been described in recent studies. But we do not know the risk of developing features of this condition and how it is affected by factors such as age, sex, or severity of infection.
We do not know if the risk of having features of long-COVID is more likely after Coronavirus Disease 2019 (COVID-19) than after influenza.
We do not know about the extent to which different features of long-COVID co-occur.
What did the researchers do and find?
This research used data from electronic health records of 273,618 patients diagnosed with COVID-19 and estimated the risk of having long-COVID features in the 6 months after a diagnosis of COVID-19. It compared the risk of long-COVID features in different groups within the population and also compared the risk to that after influenza.
The research found that over 1 in 3 patients had one or more features of long-COVID recorded between 3 and 6 months after a diagnosis of COVID-19. This was significantly higher than after influenza.
For 2 in 5 of the patients who had long-COVID features in the 3- to 6-month period, they had no record of any such feature in the previous 3 months.
The risk of long-COVID features was higher in patients who had more severe COVID-19 illness, and slightly higher among females and young adults. White and non-white patients were equally affected.
What do these findings mean?
Knowing the risk of long-COVID features helps in planning the relevant healthcare service provision.
The fact that the risk is higher after COVID-19 than after influenza suggests that their origin might, in part, directly involve infection with SARS-CoV-2 and is not just a general consequence of viral infection. This might help in developing effective treatments against long-COVID.
The findings in the subgroups, and the fact that the majority of patients who have features of long-COVID in the 3- to 6-month period already had symptoms in the first 3 months, may help in identifying those at greatest risk.

Post COVID-19 Syndrome (Long Haul Syndrome): Description of a Multidisciplinary Clinic at the Mayo Clinic and Characteristics of the Initial Patient Cohort

Author/s: 
Vanichkachorn, G., Newcomb, R., Cowl, C. T., Trenary, M., Higgins, S., Neveau, D., Murad, M. H., Breeher, L., Miller, S.

Objective

To describe characteristics of a series of patients reporting prolonged symptoms after an infection with COVID-19.

Methods

This study describes the multidisciplinary COVID-19 Activity Rehabilitation Program (CARP), established at Mayo Clinic to evaluate and treat post-COVID-19 syndrome (PCS) patients, and reports the clinical characteristics of the first 100 patients receiving evaluation and management during the timeframe of June 1, 2020 and December 31, 2020.

Results

The cohort consisted of 100 patients (mean age 45 years, 68% women, BMI 30.2, presenting a mean of 93 days after infection). Common pre-existing conditions were respiratory (23%) and mental health, including depression and/or anxiety (34%.) The majority (75%) had not been hospitalized for COVID-19. Common presenting symptoms ware fatigue (80%), respiratory complaints (59%), and neurologic complaints (59%) followed by subjective cognitive impairment, sleep disturbance, and mental health symptoms. More than one-third of the patients (34%) reported difficulties with performing basic activities of daily living. Only 1 in 3 patients had returned to unrestricted work duty at the time of the analysis. For most patients, laboratory and imaging studies were normal or non-diagnostic despite debilitating symptoms. Most patients required physical therapy, occupational therapy, or brain rehabilitation. Face-to-face and virtual care delivery modalities were feasible.

Conclusion

Many of the patients did not experience COVID-19-related symptoms that were severe enough to require hospitalization, were younger than 65 years of age, more likely to be female, and most had no pre-existing comorbidities prior to SARS-CoV-2 infection. Symptoms including mood disorders, fatigue, and perceived cognitive impairment resulted in severe negative impacts on resumption of functional and occupational activities in patients experiencing prolonged effects.

Keywords 
COVID-19 depression anxiety fatigue,
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