A narrative review of risk factors and predictors for poor outcome and prolonged recovery after a mild traumatic brain injury.

Mild traumatic brain injuries (mTBI) are often caused by a blow to the head or a sudden jolt resulting in a wide range of physical, cognitive, and emotional temporary symptoms. Mild TBI diagnosis can be challenging and most commonly followed by post-concussion syndrome (PCS). When the symptoms are present for more than 3 months, prolonged post-concussive syndrome (PPCS) can be suspected. This review aims to identify and summarize the current status of the knowledge regarding the risk factors and predictors of the recovery from PCS and PPCS. A comprehensive search of the main scientific databases (PubMed, Web of Science, Embase, and Cochrane Library) was performed using keywords, such as: 'prolonged post-concussion syndrome', combined with 'risk factors', 'predictors', and 'outcomes'. Multiple studies reported more than one risk factor for PPCS development following mTBIs that were generally the results of sports-related concussions and car accidents. The most prevalent risk factor associated with PPCS was the female sex. Social factors/personality traits, anxiety, mental health disorders, or other health conditions from their past medical history, the occurrence of headache/migraines during TBI recovery, somatization, physical activity, and litigation were also reported to contribute to PPCS risk. An exhaustive approach is required to mitigate the risk of PPCS and to ensure optimal recovery after concussive events. However, larger prospective cohort studies evaluating patients that were examined and treated with standardized protocols could be needed to further validate these associations and mandate the highest risk factors for delayed recovery.

Predictive factors contributing to prolonged recovery in patients after Fontan operation.

BACKGROUND: Prolonged recovery is a severe issue in patients after Fontan operation. However, predictive factors related to this issue are not adequately evaluated. The present study aimed to investigate potential predictive factors which can predict Fontan postoperative recovery. METHODS: We retrospectively reviewed the perioperative medical records of patients with Fontan surgery between January 2015 and December 2018, and divided patients with > 75%ile cardiac intensive care unit stay into prolonged recovery group. The others were assigned to standard recovery group. Patients that died or underwent a Fontan takedown were excluded. Statistical analysis was performed to compare data difference of the two groups. RESULTS: 282/307 cases fulfilled the inclusion criteria. Seventy patients were considered in prolonged recovery and 212 patients were defined as standard recovery. Pre- and intra-operative data showed a higher incidence of heterotaxy syndrome, longer cardiopulmonary bypass and aortic cross-clamp time in the prolonged recovery group. Postoperative information analysis displayed that ventilation time, oxygen index after extubation, hemodynamic data, inotropic score (IS), drainage volume, volume resuscitation, pulmonary hypertension (PH) treatment, and surgical reintervention were significantly different between the two groups. Higher IS postoperatively, and PH treatment and higher fluid resuscitation within two days were independent predictive factors for prolonged recovery in our multivariate model. C-statistic model showed a high predictive ability in prolonged recovery by using the three factors. CONCLUSIONS: Ventilation time, higher IS in postoperative day, and PH treatment and higher fluid resuscitation within two days were independent risk factors and have a high predictability for Fontan prolonged recovery.

Systematic Review of Pre-injury Migraines as a Vulnerability Factor for Worse Outcome Following Sport-Related Concussion.

Background: Individuals with migraine disorders may be affected differently by concussions compared to individuals without migraine disorders. Prior studies on this topic have had mixed results. The purpose of this study was to systematically examine clinical outcomes following a sport-related concussion in athletes who have a pre-injury history of migraines. Methods: All studies published prior to 15 May 2021 that examined pre-injury migraines as a possible predictor of clinical recovery from concussion were included. The search included (i) sport/athlete-related terms, (ii) concussion-related terms, and (iii) diverse predictor/modifier terms. After removing duplicates, 5,118 abstracts were screened, 538 full-text articles were reviewed, and 27 articles were included for narrative synthesis without meta-analysis (n = 25 with unique samples). Risk of bias was assessed using the domain-based Quality In Prognosis Studies (QUIPS) tool. Results: Most studies did not find pre-injury migraines to be associated with concussion outcome, but several of these studies had small or very small sample sizes, as well as other methodological weaknesses. Risk of bias varied greatly across studies. Some of the larger, better-designed studies suggested pre-injury migraines may be a risk factor for worse concussion outcome. Most articles examined pre-injury migraines as an exploratory/secondary predictor of concussion outcome; very few were designed to examine migraine as the primary focus of the study. Migraine history was predominantly based on self-report and studies included minimal information about migraine (e.g., age of onset, frequency/severity, past treatment). Effect sizes were usually not reported or able to be calculated from reported study data. Conclusion: There is some evidence to suggest that pre-injury migraines may be a vulnerability factor for a worse outcome following concussion, with studies having the lowest risk of bias reporting a positive association. Future studies should focus on improving methodological quality when assessing the relationship between pre-injury migraines and concussion outcome and better characterizing pre-injury migraine status. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019128292, identifier: PROSPERO 2019 CRD42019128292.

Somatization in Adolescents With Persistent Symptoms After Concussion: A Retrospective Chart Review.

OBJECTIVE: After concussion, approximately 30% of adolescents experience symptoms that persist beyond 1 month postinjury. For some, these symptoms affect functioning, development, and quality of life. Somatization, where psychological distress contributes to physical symptoms, may contribute to persistent symptoms after concussion in some adolescents. Understanding how clinicians identify somatization in adolescents with persistent symptoms after concussion in practice is a critical next step in improving our understanding, identification, and subsequent treatment of somatization in this patient population. To address this, the investigators assessed and compared characteristics of adolescents with persistent symptoms after concussion with and without clinician-identified somatization. METHODS: Participants were adolescents (N=94) referred for persistent symptoms after concussion to a specialty youth concussion clinic between January 2016 and May 2018. A retrospective chart review extracted demographic and injury characteristics, symptoms after concussion, school attendance, premorbid experiences, mental health, and medical service use. Participants with physician-identified somatization were compared with those without physician-identified somatization on these measures. RESULTS: Adolescents with identified somatization had more severe and atypical neurological and psychiatric symptoms after concussion and more postinjury impairment in school attendance, were more likely to have a history of premorbid chronic pain or medically unexplained symptoms, and obtained more neuroimaging and health care after injury compared with those unaffected by somatization. They did not differ in mood or anxiety symptom self-reports. CONCLUSIONS: This study identified characteristic differences and similarities in adolescents with and without clinician-identified somatization after a prolonged concussion recovery. These findings have the potential to improve clinical identification of somatization in youths following a concussion and may aid in treatment among this demographic group.

Factors Associated With a Prolonged Time to Return to Play After a Concussion.

BACKGROUND: Prognosticating recovery times for individual athletes with a concussion remains a challenge for health care providers. Several preinjury and postinjury factors have been proposed to be predictive of prolonged return-to-play (RTP) times, but the data in this area are still sparse. PURPOSES: This study aimed to identify risk factors associated with prolonged recovery times and determine which are most predictive of prolonged recovery times in a head-to-head comparison. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: All concussions occurring between September 2017 and August 2020 at a single National Collegiate Athletic Association Division I institution were reviewed and included in this study. Preinjury modifiers including age, sex, sport, concussion history, and past medical problems were collected from the electronic medical records. Postinjury modifiers analyzed included initial and follow-up Sport Concussion Assessment Tool 5th Edition scores, vestibular evaluation findings, and eye tracking results. RESULTS: A total of 159 athletes and 187 concussion cases were included. Preinjury factors that were correlated with prolonged RTP times included a history of concussions (P = .015), a history of migraines (P = .013), and whether an athlete participated in an individual sport (P = .009). Postinjury factors correlated with prolonged RTP times included the total number (P = .020) and severity (P = .023) of symptoms as well as abnormal Vestibular Ocular Motor Screening findings (P = .002). Overall, 6 different symptoms (balance problems, difficulty concentrating, light sensitivity, drowsiness, fatigue/low energy, and difficulty remembering) were significantly correlated with prolonged RTP times. The study also found that the number and severity of symptoms were additive in a dose-dependent fashion. On multivariable analysis of all these factors, a history of concussions was found to be the most predictive of prolonged RTP times, while participation in an individual sport had the largest effect on recovery times. CONCLUSION: Several preinjury and postinjury risk factors were identified as being correlated with prolonged recovery times. Many of these risk factors were also found to be additive in nature. This information provides clinicians with a valuable tool in prognosticating and estimating recovery times for athletes. The study also revealed that athletes participating in individual sports had longer RTP times compared with athletes in team sports, which is a novel finding that requires further research.

Elevated bilirubin, alkaline phosphatase at onset, and drug metabolism are associated with prolonged recovery from DILI.

BACKGROUND & AIMS: Although most drug-induced liver injury (DILI) cases resolve after the offending medication is discontinued, time to recovery varies among patients, with 6 -12% developing a chronic disease. Herein, we investigated clinical factors and drug properties as potential risk determinants that influence the time course for DILI recovery and developed a model to predict its trajectory. METHODS: We applied an accelerated failure time model to 294 cases collected by the International Drug-Induced Liver Network Consortium (iDILIC). Factors included in the multivariate recovery score model were selected through univariate analysis. The model was externally validated using 257 cases from the Spanish DILI Registry and 191 cases from the LiverTox database. RESULTS: Higher serum bilirubin and alkaline phosphatase (ALP) at DILI onset, a longer time to onset, and non-significant drug metabolism were associated with a longer recovery and were included in the recovery score model. We defined high- and low-risk groups based on the scores assigned by the model. The estimated probability of recovery by 6 months was 0.46 (95% CI 0.26-0.61) for the high-risk group and 0.93 (95% CI 0.58-0.99) for the low-risk group in the iDILIC. Model performance was validated in both validation sets. The high- and low-risk cases identified by the model showed a significantly different time course for recovery, with a majority of low-risk cases recovering sooner. CONCLUSION: The trajectory of biochemical recovery from DILI is predicted by the extent of drug metabolism, serum bilirubin and ALP at DILI onset. The model can be used to compute an estimated DILI recovery and, when a significant delay is predicted, clinicians may consider additional investigations such as histologic evaluation or extended follow-up. LAY SUMMARY: In this study, we investigated whether drug properties and clinical factors are associated with the time it takes to recover from drug-induced liver injury (DILI). We found that total bilirubin, alkaline phosphatase level at DILI onset, time to onset, and extent of drug metabolism were consistently associated with recovery time. Using these factors, we built a model to predict the trajectory of recovery from DILI and validated this model in 2 independent cohorts. Our findings offer important insights into the factors influencing the trajectory of recovery from DILI. Additional investigations and longer follow-ups can be planned in those for whom a delayed recovery is predicted.

Clinical characteristics and risk factors for prolonged recovery after one-stage arterial switch operation for patients with transposition of the great arteries / 中国胸心血管外科临床杂志

@#Objective    To summarize the early clinical features and perioperative management strategies for patients with transposition of the great arteries (TGA) after one-stage arterial switch operation (ASO), and investigate the risk factors for prolonged recovery in ICU, with a focus on the age structure and deformity complexity. Methods    The clinical data of 231 consecutive TGA patients who underwent one-stage ASO were retrospectively analyzed. There were 165 males and 66 females, aged from 3 d to 10 years. The patients were sequenced by the length of ICU stay. The time at the 75th percentile was defined as the critical value for grouping. Patients with an ICU stay time over this point were allocated to a prolonged recovery group (n=54), while the rest were allocated to a normal recovery group (n=177). The perioperative clinical data were compared between the two groups, and the risk factors for prolonged recovery were evaluated. Results    About half (49.6%) of the patients received late operation. The mean ICU stay time was 23.9±15.6 d in the prolonged recovery group, and 4.9±2.3 d in the normal recovery group. Complication of aortic arch lesion, delayed chest closure and postoperative pulmonary infection were independent risk factors for prolonged recovery after ASO in ICU. However, late operation had no significant effect on the overall recovery. Conclusion    With strict surgery indications and excellent postoperative management, most patients can have satisfactory early-stage outcomes, but are confronted with  increased complications, which is associated with prolonged recovery. Complication of aortic arch lesion, delayed chest closure and postoperative pulmonary infection are independent factors for delayed recovery of ASO.

Repeat Concussion and Recovery Time in a Primary Care Pediatric Office.

The authors enrolled 95 patients in a primary care office who presented with a concussion. Of these patients, 63% were sport concussions. The authors matched 90 of these patients to children in the authors' practice presenting for sports physicals or regular check-ups in the following demographics: age, participating in a particular sport, having attention-deficit disorder/attention-deficit hyperactivity disorder, gender, and grade. The authors found the odds of recurrent concussions, in a primary care pediatric office, to be a ratio of 2.909 (95% confidence interval 1.228-7.287). Recovery time for repeat concussion versus an initial concussion was analyzed. Patients with a recurrent concussion after a year recovered an average of 12.0 days after injury versus 13.4 days for those with no previous concussion (NS). Patients with a recurrent concussion within a year recovered a mean of 6.27 (SD 1.29) days sooner than patients with no previous concussion (P < .0001). This unexpected finding is preliminary, and the authors encourage further research.

Genetic variation in SLC17A7 promoter associated with response to sport-related concussions.

OBJECTIVE: To determine the association of the single nucleotide polymorphism (SNP) rs74174284 within SLC17A7 promoter with concussion severity or duration. DESIGN: A between-subjects design was utilized. METHODS: Saliva samples and concussion severity and duration data were collected from 40 athletes diagnosed with a sport-related concussion by a physician, utilizing a standardized concussion assessment protocol. DNA was extracted, estimated and genotyped. RESULTS: An association was found between the dominant genetic model (CC vs GG + GC; p = 0.0179) and recovery, where those carrying the minor allele were 6.33-times more likely to experience prolonged recovery rates. Within the ImPACT assessment, those carrying the CC genotype (33.38 ± 10.15, p = 0.01) had worse motor speed scores upon initial assessment compared to both heterozygous (CG) and homozygous (GG) genotypes (41.59 ± 7.39). CONCLUSIONS: This study was the first to demonstrate an association between genetic polymorphism at rs7417284 SNP in the promoter region of the SLC17A7 gene and concussion severity and duration. Based upon these findings, rs74174284 is a potential predictive genetic marker for identifying athletes who are more susceptible for altered recovery times and worse motor speed ImPACT scores after sport-related concussion.

Relationship Between Thyroid Hormone Levels and Prolonged Recovery After Cardiac Surgery With Cardiopulmonary Bypass in Congenital Heart Disease Children Younger Than 1 Year of Age / 中国循环杂志

Objective: To explore the relationship between thyroid hormone levels and prolonged recovery after cardiac surgery with cardiopulmonary bypass (CPB) in congenital heart disease (CHD) children younger than 1 year of age. Methods: A total of 186 CHD children younger than 1 year treated in our hospital from 2014-01 to 2015-01 were retrospectively summarized. According to the pediatric intensive care unit (PICU) stay time, the patients were divided into 2 groups: Prolonged recovery group, the patients stated in PICU≥5 days,n=39 and Non-prolonged recovery group, the patients stayed in PICU0.05. Multivariable logistical regression analysis presented that low level of FT3 within 24 hours of operation was the independent risk factor for prolonged recovery (OR= 0.32, 95% CI 0.12-0.84,P=0.02); linear regression analysis indicated that post-operative reduction of thyroid hormone was related to low body weight of the patients (r=0.11,P<0.001). Conclusion: Lower body weight was usually having lower level of FT3 within 24 hours of operation, which was the independent predictor for prolonged recovery in CHD children younger than 1 year after cardiac surgery.

A Preliminary Formula to Predict Timing of Symptom Resolution for Collegiate Athletes Diagnosed With Sport Concussion.

CONTEXT: Symptom presentation and recovery after sport concussion (SC) are variable. Empirically based models documenting typical symptom duration would assist health care providers in managing return to play after SC. OBJECTIVE: To develop a prediction model for SC symptom duration. DESIGN: Cross-sectional study. SETTING: Two National Collegiate Athletic Association Division I university laboratories. PATIENTS OR OTHER PARTICIPANTS: Seventy-six (51 male and 25 female) concussed athletes with an average age of 19.5 ± 1.65 years who were evaluated within 24 hours of diagnosis. INTERVENTION(S): Participants completed the Revised Head Injury Scale (HIS-r), Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), and Sensory Organization Test within 24 hours of SC diagnosis. MAIN OUTCOME MEASURE(S): A stepwise multivariate regression incorporating ImPACT and Sensory Organization Test composites and HIS-r symptom severity-duration was used to predict the number of days athletes reported symptoms after SC. The resulting regression formula was cross-validated using the Stine cross-validation coefficient. RESULTS: The final formula consisted of the HIS-r's self-reported neck pain, drowsiness, tingling, and nervousness duration and ImPACT total symptom severity (R = 0.62, R(2) = 39%, R(2)(adj) = 34.2%, P < .001). Approximately 29% (R(2)(cv) = 29%) of the variance associated with total days symptomatic after SC was explained by our preliminary formula when cross-validated. The current formula correctly identified 76% of participants who recovered within 10 days of injury. CONCLUSIONS: Our results suggest that self-reported duration of 4 symptoms during the initial 24 hours after injury along with total symptom severity as measured by ImPACT accounted for a considerable amount of variance associated with days symptomatic after SC in collegiate athletes. Until the formula is cross-validated in a college-aged sample, caution is warranted in using it clinically.

Risk factors associated with prolonged recovery after the total cavopulmonary connection / 中华胸心血管外科杂志

Objective To study the risk factors of prolonged postoperative recovery after the total cavopulmonary connection(TCPC) in the current era.Methods Data on all patients admitted to the cardiac intensive care unit (CICU) after a TCPC between January 2013 and March 2014 were retrospectively analyzed.We excluded all patients who died and required TCPC takedown.The study cohort was further divided into a prolonged recovery group that included patients with 75％ ile for duration of mechanical ventilation or pleural drainage,and a standard recovery group which included all other patients.A multivariable logistic regression model was used to compare demographic,anatomic,and physiological variables between the prolonged and standard recovery groups.Then,the cohort was separated into a high volume resuscitation group and a low volume resuscitation based on the 75％ ile for volume resuscitation(ml/kg) administered on the first three days after the TCPC.Results Totally 118 TCPC operations were performed.Of the study population (n =118),the median age was 3.8 years (3.1 to 4.8 years) and median weight was 14.8 kg(13.3 to 17.1 kg).The most common diagnosis was double outlet of right ventricle (n =47,39.8％).The extracardiac conduit fenestrated TCPC was the most common surgery(n =79,66.9％).Within the study population,43 (39.8％) patients met criteria for prolonged recovery.Univariate risk factors for prolonged recovery included higher preoperative mPAP(P =0.022),atrioventricular valve regurgitation (P =0.000),longer total bypass time (P =0.044),higher postoperative central venous pressure (P =0.000),AST (P =0.001),ALT (P =0.010),NT-proBNP (P =0.000),SaO2 (P =0.012),I n-otropic score (P =0.001),higher incidence of arrhythmia (P =0.000),low cardiac output syndrome (P =0.000),need for peritoneal dialysis (P =0.000),and requirement for greater volume resuscitation during the 72 postoperative hours(75％ for the entire group,P =0.000).In a multivariable Logistic model,need for greater volume resuscitation (OR 10.860,95 ％ CI 2.681,43.987) and the higher postoperative central venous pressure (OR 1.446,95 ％ C I 1.113,1.879) were the only two independent risk factors for prolonged outcome after the TCPC.Conclusion The need for high volume expansion and higher central venous pressure were the risk factors of mediate prolonged recovery.