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1.
J Clin Sleep Med ; 19(8): 1495-1503, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37086054

ABSTRACT

STUDY OBJECTIVES: Cognitive behavioral therapy for insomnia (CBTI) has been paired with supervised medication tapering to help hypnotic-dependent individuals discontinue their hypnotics. This study examined the hypothesis that higher participant adherence to behavioral recommendations of CBTI will predict lower odds of using sleep medications 3 months after completion of a combined CBTI/sleep medication tapering protocol. METHODS: Fifty-eight individuals who used sedative hypnotics completed four CBTI sessions followed by sleep medication tapering. Logistic regression was used to examine the association of stability of time in bed and stability of rise time (measured as the within-person standard deviation) at completion of CBTI with two outcomes at 3-month follow-up: use of sedative hypnotics and use of any medication/substance for sleep. RESULTS: Participants with more stability in their rise time after CBTI than at baseline (ie, a decrease in their within-person standard deviation) had 69.5% lower odds of using sedative hypnotics at follow-up (odds ratio = 0.305, 95% confidence interval = 0.095-0.979, P = .046) than individuals who had no change or a decrease in the stability of their rise time. Results were similar for time in bed: participants with more stability in their time in bed after CBTI than at baseline had 83.2% lower odds of using sedative hypnotics (odds ratio = 0.168, 95% confidence interval = 0.049-0.580, P = .005). Increase in stability of rise time and stability of time in bed was also associated with reduced odds of using any medication/substance for sleep at follow-up. CONCLUSIONS: Participants who implement behavioral recommendations of CBTI appear to have more success with discontinuing use of sleep medications. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: The Role of Tapering Pace and Selected Traits on Hypnotic Discontinuation; URL: https://clinicaltrials.gov/ct2/show/NCT02831894; Identifier: NCT02831894. CITATION: Edinger JD, Wamboldt FS, Johnson RL, et al. Adherence to behavioral recommendations of cognitive behavioral therapy for insomnia predicts medication use after a structured medication taper. J Clin Sleep Med. 2023;19(8):1495-1503.


Subject(s)
Cognitive Behavioral Therapy , Sleep Initiation and Maintenance Disorders , Humans , Sleep Initiation and Maintenance Disorders/drug therapy , Treatment Outcome , Cognitive Behavioral Therapy/methods , Sleep , Hypnotics and Sedatives/therapeutic use
2.
Trials ; 23(1): 806, 2022 Sep 24.
Article in English | MEDLINE | ID: mdl-36153634

ABSTRACT

BACKGROUND: Obstructive sleep apnea (OSA) and insomnia are commonly co-occurring conditions that amplify morbidity and complicates the management of affected patients. Unfortunately, previous research provides limited guidance as to what constitutes the best and most practical management approach for this comorbid patient group. Some preliminary studies show that when cognitive behavioral insomnia therapy (CBT-I) is combined with standard OSA therapies for these patients, outcomes are improved. However, the dearth of trained providers capable of delivering CBT-I has long served as a pragmatic barrier to the widespread use of this therapy in clinical practice. The emergence of sophisticated online CBT-I (OCBT-I) programs could improve access, showing promising reductions in insomnia severity. Given its putative scalability and apparent efficacy, some have argued OCBT-I should represent a 1st-stage intervention in a broader stepped care model that allocates more intensive and less assessable therapist-delivered CBT-I (TCBT-I) only to those who show an inadequate response to lower intensity OCBT-I. However, the efficacy of OCBT-I as a 1st-stage therapy within a broader stepped care management strategy for insomnia comorbid with OSA has yet to be tested with comorbid OSA/insomnia patients. METHODS/DESIGN: This dual-site randomized clinical trial will use a Sequential Multiple Assignment Randomized Trial (SMART) design to test a stepped care model relative to standard positive airway pressure (PAP) therapy and determine if (1) augmentation of PAP therapy with OCBT-I improves short-term outcomes of comorbid OSA/insomnia and (2) providing a higher intensity 2nd-stage CBT-I to patients who show sub-optimal short-term outcomes with OCBT-I+PAP improves short and longer-term outcomes. After completing baseline assessment, the comorbid OSA/insomnia patients enrolled will be randomized to a 1st-stage therapy that includes usual care PAP + OCBT-I or UC (usual care PAP + sleep hygiene education). Insomnia will be reassessed after 8 weeks. OCBT-I recipients who meet "remission" criteria (defined as an Insomnia Severity Index score < 10) will continue PAP but will not be offered any additional insomnia intervention and will complete study outcome measures again after an additional 8 weeks and at 3 and 6 month follow-ups. OCBT-I recipients classified as "unremitted" after 8 weeks of treatment will be re-randomized to a 2nd-stage treatment consisting of continued, extended access to OCBT-I or a switch to TCBT-I. Those receiving the 2nd-stage intervention as well as the UC group will be reassessed after another 8 weeks and at 3- and 6-month follow-up time points. The primary outcome will be insomnia remission. Secondary outcomes will include subjective and objective sleep data, including sleep time, sleep efficiency, fatigue ratings, PAP adherence, sleepiness ratings, sleep/wake functioning ratings, and objective daytime alertness. DISCUSSION: This study will provide new information about optimal interventions for patients with comorbid OSA and insomnia to inform future clinical decision-making processes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03109210 , registered on April 12, 2017, prospectively registered.


Subject(s)
Cognitive Behavioral Therapy , Sleep Apnea Syndromes , Sleep Apnea, Obstructive , Sleep Initiation and Maintenance Disorders , Cognitive Behavioral Therapy/methods , Humans , Randomized Controlled Trials as Topic , Sleep , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/epidemiology , Sleep Apnea, Obstructive/therapy , Sleep Initiation and Maintenance Disorders/diagnosis , Sleep Initiation and Maintenance Disorders/epidemiology , Sleep Initiation and Maintenance Disorders/therapy , Treatment Outcome
3.
Sleep Med ; 87: 46-55, 2021 11.
Article in English | MEDLINE | ID: mdl-34509774

ABSTRACT

OBJECTIVE: To examine the individual and combined effects of daytime sleepiness and insomnia disorder (ID) on measures of cognitive functioning. DESIGN AND SETTING: This study was conducted at a medical center using a cross-sectional research design. PARTICIPANTS: 35 persons with ID (Mage = 40.6 years; 25 women) and 54 normal sleepers (NS; Mage = 31.5 years; 38 women). METHODS AND MEASURES: Participants underwent two nights of home-based polysomnography (PSG) followed by daytime testing with a four-trial Multiple Sleep Latency Test (MSLT). Before each MSLT nap, they completed a computer-administered battery of reaction time tasks. Measures of response latencies and response accuracy were tabulated and used as dependent measures. The ID and NS groups were each subdivided into "alert" (eg, MSLT mean latency > 8 min) and "sleepy" (eg, MSLT mean latency ≤ 8 min) subgroups to identify hyperaroused persons with ID and allow for their comparisons with the other participant subgroups. RESULTS: Multivariate analyses of variance showed a significant main effect for level of daytime sleepiness (F [1, 84] = 8.52, p = 0.0045) on simpler performance tasks and a significant main effect for presence vs. absence of ID (F [1,84] = 6.62, p = 0.012) on complex tasks. A lack of significant participant type x MSLT alertness level interactions in study analyses suggested those ID participants with presumed hyperaousal were not relatively more impaired than the other participant subgroups. CONCLUSIONS: Daytime performance deficits on simple tasks seem most dependent on individuals' levels of daytime sleepiness, whereas performance deficits on more complex tasks appears related to the presence of ID. Therefore, it seems best to use complex performance measures both to document cognitive deficits among those with ID and to determine if insomnia treatments reduce such impairments. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02290405.


Subject(s)
Disorders of Excessive Somnolence , Sleep Initiation and Maintenance Disorders , Adult , Cognition , Cross-Sectional Studies , Female , Humans , Male , Sleep Initiation and Maintenance Disorders/complications , Task Performance and Analysis
4.
Respirology ; 24(12): 1204-1211, 2019 12.
Article in English | MEDLINE | ID: mdl-31012225

ABSTRACT

BACKGROUND AND OBJECTIVE: Patients with chronic respiratory failure are increasingly managed with domiciliary non-invasive ventilation (NIV). There may be limited ability to provide NIV titration for these complex patients, and ventilatory requirements and upper airway support needs may change over time. Therefore, an automatically adjusting expiratory positive airway pressure (AutoEPAP) algorithm may offer advantages over manually adjusted EPAP for treating these patients. This study compared 4% oxygen desaturation index (ODI4%) values during the use of an AutoEPAP algorithm versus manual EPAP titration with the intelligent volume-assured pressure support (iVAPS) algorithm. METHODS: This prospective, single-blind, randomized, crossover study was conducted at six US sites. Patients with chronic respiratory failure (neuromuscular disease, chronic obstructive pulmonary disease, obesity hypoventilation and other aetiologies) and an apnoea-hypopnoea index of >5/h who were already established NIV users underwent a single night of NIV with the iVAPS manual EPAP and iVAPS AutoEPAP in the sleep laboratory in random order. RESULTS: A total of 38 patients constituted the study population. Mean ODI4% was statistically non-inferior with AutoEPAP versus manual EPAP (P < 0.0001). There was no difference in the effect on ODI4% across respiratory failure subgroups. Ventilation parameters and gas exchange were similar with either NIV mode, indicating equally effective treatment of respiratory failure. Sleep parameters were improved during AutoEPAP versus manual EPAP. CONCLUSION: A single night of NIV using the iVAPS with AutoEPAP algorithm was non-inferior to a single night of iVAPS with manual EPAP titration in patients with respiratory failure. CLINICAL TRIAL REGISTRATION: NCT02683772 at clinicaltrials.gov.


Subject(s)
Noninvasive Ventilation , Obesity Hypoventilation Syndrome/therapy , Positive-Pressure Respiration , Pulmonary Disease, Chronic Obstructive/therapy , Adult , Cross-Over Studies , Female , Humans , Male , Middle Aged , Neuromuscular Diseases/complications , Noninvasive Ventilation/adverse effects , Noninvasive Ventilation/methods , Obesity Hypoventilation Syndrome/diagnosis , Positive-Pressure Respiration/adverse effects , Positive-Pressure Respiration/methods , Pulmonary Disease, Chronic Obstructive/diagnosis , Single-Blind Method , Sleep/physiology , Treatment Outcome
5.
Sleep Breath ; 23(3): 943-951, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30689097

ABSTRACT

PURPOSE: The aim of this study was to describe the polysomnographic characteristics of adolescents with asthma who are at low risk for sleep-disordered breathing (SDB) based on the Pediatric Sleep Questionnaire (PSQ). METHODS: Overnight polysomnography was performed on 85 adolescents with asthma and a score < 0.33 on the PSQ. The Asthma Control Questionnaire was used to define "well-controlled" versus "inadequately controlled" asthma. RESULTS: Mean age of participants was 14.5 ± 1.6 years (range, 11 to 17 years), 63.5% were girls, 57.6% were Caucasians, and the mean body mass index percentile was 65.1 ± 26.5. Asthma was well-controlled in 51.7% of the adolescents and inadequately controlled in 15.3%. Mean sleep efficiency (SE) was 88.0 ± 11.1%, and 24.7% had SE < 85%. Mean wakefulness after sleep onset (WASO) was 40.9 ± 44.0 min, and the mean arousal index was 10.8 ± 5.6 per hour. The mean apnea/hypopnea index (AHI) was 2.3 ± 4.2, and 29.4% of participants had SDB (defined by an AHI ≥ 2). Compared with normative values, adolescents with asthma had more nocturnal awakenings and WASO, and less REM sleep. SDB risk was higher in boys [odds ratio = 4.6 (confidence interval 1.4-14.7), p = 0.01]. Asthma control did not impact sleep and respiratory parameters, with no differences found between youth with well-controlled and inadequately controlled asthma. CONCLUSIONS: Adolescents with asthma are at increased risk of sleep-disordered breathing and suffer from disturbances in sleep continuity with more arousals and sleep fragmentation. Study results highlight the importance of proper screening for sleep-disordered breathing in adolescents with asthma.


Subject(s)
Asthma/complications , Polysomnography/methods , Severity of Illness Index , Sleep Apnea Syndromes/complications , Sleep Apnea Syndromes/diagnosis , Adolescent , Arousal/physiology , Female , Humans , Male , Risk Factors , Sleep/physiology
6.
J Sleep Res ; 27(6): e12747, 2018 12.
Article in English | MEDLINE | ID: mdl-30069961

ABSTRACT

Given the recent evidence on the association between hyperarousal in insomnia disorder and neurocognitive deficits, we aimed to examine the effect of short sleep duration on neurocognitive reaction time tests in insomnia disorder sufferers. We recruited subjects with insomnia disorder (n = 35, mean age = 40.6 years) who scored ≥29 on a Hyperarousal Scale, and a group of controls (n = 54, mean age = 31.5 years) who had no sleep disorders and scored <26 on the Hyperarousal Scale. Participants completed two in-home polysomnograms and four daytime trials of neurocognitive tests, including simple reaction time, choice reaction time, big circle-little circle, rapid visual information processing, attention switching task, and spatial working memory tests. Total sleep time divided study cohorts into subgroups of short (total sleep time <6 hr) and normal (total sleep time ≥6 hr) sleepers. ANCOVA showed a significant interaction between participant type (insomnia disorder versus controls) and sleep duration (short versus normal) for spatial working memory-latency (p = 0.020) and spatial working memory-errors (p = 0.025). The short-sleeping insomnia disorder group had longer spatial working memory-latencies and more spatial working memory-errors than did normal-sleeping controls. Regardless of sleep duration, those with insomnia disorder had more attentional deficits with longer attention switching task-latency (p = 0.011) and more attention switching task-incorrect trials (p = 0.015) than the control group. Normal-sleepers only had longer attention switching task-latency than short-sleepers (p = 0.004). A phenotype of insomnia disorder with hyperarousal and short sleep duration is associated with daytime cognitive deficits in complex attentional and spatial working memory tasks.


Subject(s)
Cognition/physiology , Neurocognitive Disorders/epidemiology , Sleep Arousal Disorders/epidemiology , Sleep Initiation and Maintenance Disorders/epidemiology , Sleep/physiology , Adult , Cohort Studies , Cross-Sectional Studies , Female , Humans , Male , Memory, Short-Term/physiology , Mental Status and Dementia Tests , Middle Aged , Neurocognitive Disorders/diagnosis , Neurocognitive Disorders/psychology , Polysomnography/methods , Reaction Time/physiology , Sleep Arousal Disorders/diagnosis , Sleep Arousal Disorders/psychology , Sleep Initiation and Maintenance Disorders/diagnosis , Sleep Initiation and Maintenance Disorders/psychology , Time Factors
7.
Curr Opin Pulm Med ; 23(2): 124-128, 2017 03.
Article in English | MEDLINE | ID: mdl-27984243

ABSTRACT

PURPOSE OF REVIEW: Sleep related disorders are common and under-recognized in the chronic obstructive pulmonary disease (COPD) population. COPD symptoms can disrupt sleep. Similarly, sleep disorders can affect COPD. This review highlights the common sleep disorders seen in COPD patients, their impact, and potential management. RECENT FINDINGS: Treatment of sleep disorders may improve quality of life in COPD patients. Optimizing inhaler therapy improves sleep quality. Increased inflammatory markers are noted in patients with the overlap syndrome of COPD and obstructive sleep apnea versus COPD alone. There are potential benefits of noninvasive positive pressure ventilation therapy for overlap syndrome patients with hypercapnia. Nocturnal supplemental oxygen may be beneficial in certain COPD subtypes. Nonbenzodiazepine hypnotic therapy for insomnia has shown benefit without associated respiratory failure or worsening respiratory symptoms. Melatonin may provide mild hypnotic and antioxidant benefits. SUMMARY: This article discusses the impact of sleep disorders on COPD patients and the potential benefits of managing sleep disorders on respiratory disease control and quality of life.


Subject(s)
Pulmonary Disease, Chronic Obstructive/physiopathology , Sleep Wake Disorders/physiopathology , Humans , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/therapy , Quality of Life , Sleep Wake Disorders/complications , Sleep Wake Disorders/therapy
8.
Sleep Med Clin ; 11(3): 313-21, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27542877

ABSTRACT

Obstructive sleep apnea (OSA) is associated with numerous comorbid medical conditions. Symptoms of OSA may mimic those of comorbid conditions. The presence of OSA may worsen outcomes from the primary condition. Conversely, OSA treatment may benefit both sleep symptomatology and comorbid illness. Because of potential significant benefit, it is important to screen for sleep apnea symptoms, to have a low threshold to perform diagnostic testing, to treat OSA if present, and to closely monitor symptoms. OSA management does not necessarily replace, but rather, should be performed in conjunction with primary therapy for comorbid conditions.


Subject(s)
Cardiovascular Diseases/therapy , Comorbidity , Endocrine System Diseases/therapy , Lung Diseases/therapy , Mental Disorders/therapy , Sleep Apnea, Obstructive/therapy , Sleep Wake Disorders/therapy , Cardiovascular Diseases/epidemiology , Endocrine System Diseases/epidemiology , Humans , Lung Diseases/epidemiology , Mental Disorders/epidemiology , Sleep Apnea, Obstructive/epidemiology , Sleep Wake Disorders/epidemiology
9.
Sleep Med Clin ; 11(1): 115-26, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26972038

ABSTRACT

In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed.

10.
Crit Care Clin ; 31(3): 403-18, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26118912

ABSTRACT

In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed.


Subject(s)
Endocrine System/physiology , Sleep/physiology , Circadian Rhythm/physiology , Critical Care , Endocrine System Diseases/physiopathology , Humans
11.
Sleep ; 38(4): 597-605, 2015 Apr 01.
Article in English | MEDLINE | ID: mdl-25409101

ABSTRACT

STUDY OBJECTIVES: To compare a positive airway pressure (PAP) device's detection of respiratory events and airway status during device-detected apneas with events scored on simultaneous polysomnography (PSG). DESIGN: Prospective PSGs of patients with sleep apnea using a new-generation PAP device. SETTINGS: Four clinical and academic sleep centers. PATIENTS: Forty-five patients with obstructive sleep apnea (OSA) and complex sleep apnea (Comp SA) performed a PSG on PAP levels adjusted to induce respiratory events. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: PAP device data identifying the type of respiratory event and whether the airway during a device-detected apnea was open or obstructed were compared to time-synced, manually scored respiratory events on simultaneous PSG recording. Intraclass correlation coefficients between device-detected and PSG scored events were 0.854 for apnea-hypopnea index (AHI), 0.783 for apnea index, 0.252 for hypopnea index, and 0.098 for respiratory event-related arousals index. At a device AHI (AHIFlow) of 10 events/h, area under the receiver operating characteristic curve was 0.98, with sensitivity 0.92 and specificity 0.84. AHIFlow tended to overestimate AHI on PSG at values less than 10 events/h. The device detected that the airway was obstructed in 87.4% of manually scored obstructive apneas. Of the device-detected apneas with clear airway, a minority (15.8%) were manually scored as obstructive apneas. CONCLUSIONS: A device-detected apnea-hypopnea index (AHIFlow) < 10 events/h on a positive airway pressure device is strong evidence of good treatment efficacy. Device-detected airway status agrees closely with the presumed airway status during polysomnography scored events, but should not be equated with a specific type of respiratory event.


Subject(s)
Respiration , Respiratory System/physiopathology , Sleep Apnea Syndromes/diagnosis , Sleep Apnea Syndromes/physiopathology , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/physiopathology , Arousal , Female , Humans , Male , Middle Aged , Polysomnography , Prospective Studies , ROC Curve , Respiratory System/anatomy & histology , Sleep
12.
Clin Chest Med ; 35(3): 557-69, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25156771

ABSTRACT

Sleep respiration is regulated by circadian, endocrine, mechanical and chemical factors, and characterized by diminished ventilatory drive and changes in Pao2 and Paco2 thresholds. Hypoxemia and hypercapnia are more pronounced during rapid eye movement. Breathing is influenced by sleep stage and airway muscle tone. Patient factors include medical comorbidities and body habitus. Medications partially improve obstructive sleep apnea and stabilize periodic breathing at altitude. Potential adverse consequences of medications include precipitation or worsening of disorders. Risk factors for adverse medication effects include aging, medical disorders, and use of multiple medications that affect respiration.


Subject(s)
Antidepressive Agents/pharmacology , Hypnotics and Sedatives/pharmacology , Respiration/drug effects , Sleep/drug effects , Sleep/physiology , Acetazolamide/pharmacology , Altitude , Androgens/pharmacology , Anticonvulsants/pharmacology , Antipsychotic Agents/pharmacology , Benzodiazepines/pharmacology , Humans , Hypercapnia/physiopathology , Hypoxia/physiopathology , Phosphodiesterase Inhibitors/pharmacology , Sleep Apnea, Obstructive/physiopathology , Sleep, REM/physiology , Testosterone/pharmacology , Theophylline/pharmacology
13.
Clin Chest Med ; 31(2): 341-51, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20488292

ABSTRACT

Sleepiness is a commonly experienced symptom affecting up to one-fifth of the population chronically. Sleepiness contributes to systemic health effects, and has been shown to contribute to mood disorders and cardiovascular risks. Sleepiness also presents a significant public health risk: it has been associated with major catastrophes, motor vehicle accidents, and medical errors by health care workers. This article reviews the implications of sleepiness on public health, the evaluation of sleepiness, disorders that result in sleepiness, and the management of these disorders.


Subject(s)
Disorders of Excessive Somnolence/physiopathology , Affect , Algorithms , Chronotherapy , Disorders of Excessive Somnolence/etiology , Disorders of Excessive Somnolence/psychology , Humans , Polysomnography , Public Health , Sleep/drug effects , Sleep Disorders, Circadian Rhythm/physiopathology , Sleep Disorders, Circadian Rhythm/therapy
15.
Am J Pathol ; 163(2): 445-52, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12875966

ABSTRACT

Mice with homozygous deletion of the plasminogen activator inhibitor-1 gene (PAI-1(-/-)) are relatively protected from bleomycin-induced pulmonary fibrosis. At least part of the protective effect appears to occur during the latter stages of the pathological process when fibrotic tissue is being deposited. To investigate the effect of PAI-1 deficiency on fibrosis, we studied the accumulation of fibrotic tissue within subcutaneously implanted polyvinyl alcohol sponges. Similar to the effect of PAI-1 deficiency on bleomycin-induced pulmonary fibrosis, the accumulation of fibrotic tissue within implanted sponges occurred more slowly in PAI-1(-/-) compared to wild-type mice. Another striking difference observed in the PAI-1(-/-) mice was the rapid removal of a fibrin-rich matrix that formed within the sponges by 1 day after implantation in both wild-type and PAI-1(-/-) mice. The pattern of connective tissue invasion also differed: cells in wild-type mice infiltrated as individually penetrating cells whereas in PAI-1(-/-) mice they did so as a well-demarcated advancing front. Providing an alternative provisional matrix by impregnating sponges with a low concentration of collagen before implantation corrected the changes induced by PAI-1 deficiency. In conclusion, PAI-1 deficiency appears to affect fibrotic tissue formation in part by altering the provisional matrix that forms soon after tissue injury.


Subject(s)
Fibrosis/pathology , Lung/pathology , Plasminogen Activator Inhibitor 1/genetics , Animals , Collagen/metabolism , Extracellular Matrix/metabolism , Fibrin/metabolism , Fibrosis/metabolism , Foreign Bodies , Hydroxyproline/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Plasminogen Activator Inhibitor 1/metabolism , Polyvinyl Alcohol , Prostheses and Implants
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