Can Red Blood Cell and Platelet Transfusions Have a Pathogenic Role in Bronchopulmonary Dysplasia?

OBJECTIVE: To evaluate whether transfusions in infants born preterm contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). STUDY DESIGN: We conducted a multihospital, retrospective study seeking associations between red blood cell or platelet transfusions and BPD. We tabulated all transfusions administered from January 2018 through December 2022 to infants born ≤29 weeks or <1000 g until 36 weeks postmenstrual age and compared those with BPD grade. We performed a sensitivity analysis to assess the possibility of a causal relationship. We then determined whether each transfusion was compliant with restrictive guidelines, and we estimated effects fewer transfusions might have on future BPD incidence. RESULTS: Eighty-four infants did not develop BPD and 595 did; 352 developed grade 1 (mild), 193 grade 2 (moderate), and 50 grade 3 (severe). Transfusions were given at <36 weeks to 7% of those who did not develop BPD, 46% who did, and 98% who developed severe BPD. For every transfusion the odds of developing BPD increased by a factor of 2.27 (95% CI, 1.59-3.68; P < .001). Sensitivity analyses suggested that transfusions might contribute to BPD. Fifty-seven percent of red blood cell transfusions and 68% of platelet transfusions were noncompliant with new restrictive guidelines. Modeling predicted that complying with restrictive guidelines could reduce the transfusion rate by 20%-30% and the moderate to severe BPD rate by ∼4%-6%. CONCLUSIONS: Transfusions were associated with BPD incidence and severity. Lowering transfusion rates to comply with current restrictive guidelines might result in a small but meaningful reduction in BPD rates.

Designing a Fall Prediction Model for Inpatient Rehabilitation Facilities Using Readily Available Data.

OBJECTIVE: To create a fall risk assessment tool for inpatient rehabilitation facilities (IRFs) using available data and compare its predictive accuracy with that of the Morse Fall Scale (MFS). DESIGN: We conducted a secondary analysis from a retrospective cohort study. Using a nomogram that displayed the contributions of QI codes associated with falls in a multivariable logistic regression model, we created a novel fall risk assessment, the Inpatient Rehabilitation Fall Scale (IRF Scale). To compare the predictive accuracy of the IRF Scale and MFS, we used receiver operator characteristic (ROC) curve analysis. SETTING: We included data from 4 IRFs owned and operated by Intermountain Health. PARTICIPANTS: Data came from the medical records of 1699 patients. All participants were over the age of 14 and were admitted and discharged from 1 of the 4 sites between January 1 and December 31, 2020. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): We assigned point values on the IRF Scale based on the adjusted associations of QI codes with falls. Using ROC curve analysis, we discovered an optimal cutoff score, sensitivity, specificity, and overall AUC of the IRF Scale and MFS. RESULTS: ROC curve analysis revealed the optimal IRF Scale cutoff score of 22.4 yielded a sensitivity of 0.74 and a specificity of 0.63. With an AUC of 0.72, the IRF Scale demonstrated acceptable accuracy at identifying patients who fell in our retrospective cohort. CONCLUSIONS: Because the IRF Scale uses readily available data, it minimizes staff assessment and outperforms the MFS at identifying patients who previously fell. Prospective research is needed to investigate if it can adequately identify in advance which patients will fall during their IRF stay.

Using Quality Indicator Codes to Identify Patients' Fall Risk in Inpatient Rehabilitation Facilities.

OBJECTIVE: To discover if quality indicator (QI) codes are associated with patient falls in inpatient rehabilitation facilities (IRFs). DESIGN: This retrospective cohort study explored differences between patients who fell and those who did not fall. We analyzed potential associations between QI codes and falls using univariable and multivariable logistic regression models. SETTING: We collected data from electronic medical records at 4 IRFs. PARTICIPANTS: In 2020, our 4 data collection sites admitted and discharged a total of 1742 patients older than 14 years . We only excluded patients (N=43) from statistical analysis if they were discharged before admission data had been assigned. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Using a data extraction report, we collected age, sex, race and ethnicity, diagnosis, falls, and QI codes for communication, self-care, and mobility performance. Staff documented communication codes on a 1-4 scale and self-care and mobility codes on a 1-6 scale, with higher codes representing greater independence. RESULTS: Ninety-seven patients (5.71%) fell in the 4 IRFs over a 12-month period. The group who fell had lower QI codes for communication, self-care, and mobility. When adjusting for bed mobility, transfer, and stair-climbing ability, low performance with understanding, walking 10 feet, and toileting were significantly associated with falls. Patients with admission QI codes below 4 for understanding had 78% higher odds of falling. If they were assigned admission QI codes below 3 for walking 10 feet or toileting, they had 2 times greater odds of falling. We did not find a significant association between falls and patients' diagnosis, age, sex, or race and ethnicity in our sample. CONCLUSIONS: Communication, self-care, and mobility QI codes appear to be significantly associated with falls. Future research should explore how to use these required codes to better identify patients likely to fall in IRFs.

Decision Accuracy and Safety of Transcutaneous Bilirubin Screening at Intermountain Healthcare.

OBJECTIVE: To quantify the risk that transcutaneous bilirubin (TcB) screening would fail to recommend phototherapy for a neonate who would have qualified for it if total serum bilirubin (TSB) screening were used. STUDY DESIGN: We conducted a quality improvement project where simultaneous TcB and TSB were obtained on neonates ≥35 weeks of gestation during birth hospitalizations in our hospital system. Using our Utah bilirubin management algorithm, we quantified the risk that TcB screening would fail to identify the need for a confirmatory TSB when TSB screening alone would have revealed that phototherapy was indicated. RESULTS: In 3 hospitals, we obtained 727 paired TcB/TSB measurements. Two instances utilized a blood gas radiometer for TSB, and 725 utilized the clinical laboratory-based TSB method. One of the 727 instances had a TcB indicating NO PHOTOTHERAPY, when the simultaneous TSB indicated PHOTOTHERAPY NEEDED. The TSB from that instance was 1 of the 2 from the blood gas radiometer. We estimate the risk of such an error occurring is 1.4 per 1000 TcB measurements (95% CI 0.03-7.6 per 1000). When only the laboratory TSB is used, we estimate the risk of such an error occurring to be 0 per 1000 TcB measurements (95% CI 0.0-5.1 per 1000). CONCLUSIONS: Using TcB for screening at the birth hospital can identify those qualifying for phototherapy, using the Utah guidelines, with 1 of 727 neonates with a blood gas bilirubin and none of 725 with a laboratory-based analysis misidentified as not needing phototherapy when by TSB they did.

Screening umbilical cord blood for congenital Iron deficiency.

OBJECTIVES: Small for gestational age infants (SGA), infants of diabetic mothers (IDM), and very low birth weight infants (VLBW) are at risk for congenital iron deficiency. We evaluated the iron status of SGA, IDM, and VLBW neonates at birth and sought mechanistic explanations in those with iron deficiency. METHODS: This was a prospective study. If congenital iron deficiency was present, maternal iron studies were obtained. When neonates were two weeks old, their iron status was reevaluated. RESULTS: Sixteen of 180 neonates screened were iron deficient at birth. The Body Mass Index of the 16 mothers was high. These mothers often had mild iron deficiency and measurable hepcidin levels. Two weeks after birth, neonates had improved iron measurements. CONCLUSIONS: Among SGA, IDM, and VLBW neonates, maternal obesity is a risk factor for congenital iron deficiency. We speculate that elevated hepcidin levels in obese pregnant women impede iron absorption and interfere with transplacental iron transfer.

Association of neonatal red blood cell transfusion with increase in serum bilirubin.

BACKGROUND: It is not clear whether red blood cell (RBC) transfusions typically increase a neonate's total serum bilirubin (TSB) level or if so by how much. STUDY DESIGN AND METHODS: In this retrospective analysis, from 2009 through 2012, we collected TSB measurements before and after transfusions, recording blood types of mothers, neonates, and blood donors and whether phototherapy was used before, during, or after transfusion. RESULTS: Of 7272 neonates admitted during this period, 658 (9%) received 2597 RBC transfusions. TSB levels were drawn before and after 431 transfusions, 255 of which did not have phototherapy at the time the transfusion was administered. The mean increase in TSB was 2.2 mg/dL (95% confidence interval, 1.9-2.5 mg/dL). Seven percent of all transfusions and 12% of transfusions to very-low-birthweight (VLBW) infants (<1500 g) were followed by a TSB increase of at least 5 mg/dL. Transfusions with "universal donor" blood (O-) resulted in a higher TSB increase (p < 0.0001), but the magnitude was clinically insignificant (0.3 mg/dL). Older blood (days since donor draw) did not generate significantly higher posttransfusion TSB levels (p = 0.092). A focused study of the 10 neonates with the highest TSB increases revealed that six were unexplained other than transfusion related. CONCLUSIONS: We describe an association between RBC transfusion and TSB elevation, but we recognize that this does not establish a cause-and-effect relationship. However, the observation that an increase of at least 5 mg/dL occurs after 12% of transfusions to VLBW neonates suggests to us that clinicians will want to evaluate jaundice, or measure bilirubin, on VLBW neonates after transfusion.

Sleep disordered breathing in patients receiving therapy with buprenorphine/naloxone.

Patients using chronic opioids are at risk for exceptionally complex and potentially lethal disorders of breathing during sleep, including central and obstructive apnoeas, hypopnoeas, ataxic breathing and nonapnoeic hypoxaemia. Buprenorphine, a partial µ-opioid agonist with limited respiratory toxicity, is widely used for the treatment of opioid dependency and chronic nonmalignant pain. However, its potential for causing sleep disordered breathing has not been studied. 70 consecutive patients admitted for therapy with buprenorphine/naloxone were routinely evaluated with sleep medicine consultation and attended polysomnography. The majority of patients were young (mean±sd age 31.8±12.3 years), nonobese (mean±sd body mass index 24.9±5.9 kg·m(-2)) and female (60%). Based upon the apnoea/hypopnoea index (AHI), at least mild sleep disordered breathing (AHI ≥5 events·h(-1)) was present in 63% of the group. Moderate (AHI ≥15- <30 events·h(-1)) and severe (AHI ≥30 events·h(-1)) sleep apnoea was present in 16% and 17%, respectively. Hypoxaemia, defined as an arterial oxygen saturation measured by pulse oximetry, of <90% for ≥10% of sleep time, was present in 27 (38.6%) patients. Despite the putative protective ceiling effect regarding ventilatory suppression observed during wakefulness, buprenorphine may induce significant alterations of breathing during sleep at routine therapeutic doses.

Interleukin receptor family member ST2 concentrations in patients following heart transplantation.

OBJECTIVE: To evaluate soluble (s) ST2 as a biomarker of rejection, allograft vasculopathy and mortality after orthotopic heart transplantation (OHT). METHODS: sST2 concentrations were measured in 241 patients following OHT. RESULTS: Elevated sST2 was associated with cellular rejection (CR) ≥ 1R, with highest rates of CR in the 4th sST2 quartile (p = 0.003). No significant association between sST2 and antibody-mediated rejection or allograft vasculopathy was found. sST2 ≥ 30 ng/mL independently predicted death over 7-year follow-up (HR = 2.01; 95% CI 1.15-3.51; p = 0.01). CONCLUSION: Concentrations of sST2 are associated with the presence of CR and predict long-term mortality following OHT.

Evidence of autoinflammation as a principal mechanism of myocardial injury in SARS-CoV-2 PCR-positive medical examiner cases.

BACKGROUND: Disease from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) remains the seventh leading cause of death in the United States. Many patients infected with this virus develop later cardiovascular complications including myocardial infarctions, stroke, arrhythmia, heart failure, and sudden cardiac death (20-28%). The purpose of this study is to understand the primary mechanism of myocardial injury in patients infected with SARS-CoV-2. METHODS: We investigated a consecutive cohort of 48 medical examiner cases who died with PCR-positive SARS-CoV-2 (COVpos) infection in 2020. We compared them to a consecutive cohort of 46 age- and sex-matched controls who were PCR-negative for SARS-CoV-2 (COVneg). Clinical information available at postmortem examination was reviewed on each patient. Formalin-fixed sections were examined using antibodies directed against CD42 (platelets), CD15 (myeloid cells), CD68 (monocytes), C4d, fibrin, CD34 (stem cell antigen), CD56 (natural killer cells), and myeloperoxidase (MPO) (neutrophils and neutrophil extracellular traps(NETs)). We used a Welch 2-sample T-test to determine significance. A cluster analysis of marker distribution was also done. RESULTS: We found a significant difference between COVpos and COVneg samples for CD42, CD15, CD68, C4d, fibrin, and MPO, all of which were significant at p < 0.001. The most prominent features were neutrophils (CD15, MPO) and MPO-positive debris suggestive of NETs. A similar distribution of platelets, monocytes, fibrin and C4d was seen in COVpos cases. Clinical features were similar in COVpos and COVneg cases for age, sex, and body mass index (BMI). CONCLUSION: These findings suggest an autoinflammatory process is likely involved in cardiac damage during SARS-CoV-2 infection. No information about clinical cardiac disease was available.

Excluding pregnancy-associated deep vein thrombosis with whole-leg ultrasound.

Background: Deep vein thrombosis (DVT) is common in pregnancy, yet data are limited on the best diagnostic strategies in pregnant patients suspected of DVT. Objectives: We conducted a prospective cohort study to evaluate the rate of symptomatic DVT in the 90 days after a negative whole-leg compression ultrasound (CUS) in pregnant women presenting with DVT symptoms. Methods: In this prospective cohort study, we enrolled pregnant patients suspected of DVT between 2011 and 2019 who were referred to the vascular imaging laboratory at a tertiary care center and had anticoagulation held after a negative whole-leg CUS. Primary outcome was objectively confirmed DVT or pulmonary embolism or death due to venous thromboembolism (VTE). Results: Whole-leg CUS yielded normal results in 186 patients (97.9%) and identified DVT in 4 (2.1%). The mean age was 30 and 164 were White. Among the 186 patients with a negative, initial whole-leg CUS who did not receive anticoagulation, there were 2 DVT events identified over the 90-day follow-up period, for an overall rate of 1.1% (95% CI: 0.2-3.4%). The study was terminated before full planned accrual for administrative reasons. Conclusion: The rate of symptomatic DVT is low in pregnant patients who have a single, negative whole-leg CUS and did not receive anticoagulation. Adequately powered studies should prospectively assess whole-leg CUS in a larger population alone and in combination with pre-test probability scores and/or D-dimer to determine its role in the evaluation of suspected DVT in pregnancy.

Variation in Outcomes and Number of Visits Following Care Guideline Implementation: Part 2 of an Analysis of 12 355 Patients After Total Knee Arthroplasty.

OBJECTIVE: To describe the variation in outcomes and number of visits before and after implementing a care guideline for total knee arthroplasty (TKA) rehabilitation. DESIGN: Nonrandomized intervention study. METHODS: We compared 2558 patients with TKA who received care that was not standardized (non-care guideline [NCG] group) to 9797 patients with TKA who received care according to the care guideline (CG). We fit 2 Bayesian hierarchical linear regression models using the Knee Outcome Survey - Activities of Daily Living (KOS-ADL) change score and number of physical therapy (PT) visits as the response variables, controlling for relevant predictor variables. We also compared the ratio of the standard deviations of the KOS-ADL change scores and the number of PT visits within and between clinics. RESULTS: The overall estimated mean improvement in KOS-ADL change score was 23.0 points (95% confidence interval [CI]: 20.3, 25.7) in the NCG group and 28.7 points (95% CI: 27.5, 29.7) in the CG group; the mean difference was 5.6 (2.7-8.6). Mean KOS-ADL change scores were higher in the CG group than the NCG group in every clinic, although only 8 clinics improved significantly. The number of PT visits did not change meaningfully (NCG: mean, 10.7 [95% CI: 9.9, 11.5]; CG: mean, 10.5 [95% CI: 9.9, 10.9]). Variation in KOS-ADL change score decreased by 4% within clinics (CG-NCG ratio: 0.96 [95% CI: 0.93, 0.99]) and 63% between clinics (CG-NCG ratio: 0.37 [95% CI: 0.21, 0.62]). Variation in number of visits decreased by 7% within clinics (CG-NCG ratio: 0.93 [95% CI: 0.90, 0.96]) and 19% between clinics (CG-NCG ratio: 0.81 [95% CI: 0.39, 1.49]). CONCLUSION: Implementing a care guideline for TKA rehabilitation may improve outcomes and reduce unwarranted variation in practice within clinics and especially between clinics within a large health care system. J Orthop Sports Phys Ther 2023;53(3):151-158. Epub: 12 December 2022. doi:10.2519/jospt.2022.11370.

Improved Outcomes Following a Care Guideline Implementation: Part 1 of an Analysis of 12 355 Patients After Total Knee Arthroplasty.

OBJECTIVE: To describe the application and examine the influence of a continuous quality improvement intervention, which had a goal of standardizing care to reduce the proportion of patients who do not have a meaningful improvement in patient-reported outcomes following total knee arthroplasty (TKA). DESIGN: Continuous quality improvement. METHODS: A physical therapy (PT) care guideline was initiated in 2013 for patients following TKA. The Knee Outcome Survey - Activities of Daily Living (KOS-ADL) was measured at every visit, and scores were extracted from a clinical outcomes database to calculate the proportion of patients who did not achieve a minimal clinically important difference. Based on logistic regression analysis, we compared the proportion of patients who did not progress on the KOS-ADL in a non-care guideline group (2008-2012) to a care guideline (CG) group (2014-2019). RESULTS: This study included 12 355 patients (aged 18-92 years) following TKA incurring at least 3 PT visits from 2008 to 2019. The percentage of patients who did not progress in the non-care guideline group was 25.8% and in the care guideline group 14.3% (P<0.001). The relationship between care guideline adherence and lack of progression on the KOS-ADL was statistically significant, X2 (df = 1) = 148.7, P<.001. CONCLUSION: The percentage of patients who did not achieve meaningful progress on the KOS-ADL declined significantly in the 6 years after implementing a TKA care guideline without an increase in the number of clinical visits. The standardized care guideline was associated with meaningful improvements for patients following TKA when applied in conjunction with PT access to outcome data, feedback through audits, performance goals, and financial incentives. J Orthop Sports Phys Ther 2023;53(3):143-150. Epub: 12 December 2022. doi:10.2519/jospt.2022.11369.

Donor Age, Sex, and Cause of Death and Their Relationship to Heart Transplant Recipient Cardiac Death.

BACKGROUND: Recent studies indicate that donor innate immune responses participate in initiating and accelerating innate responses and allorecognition in the recipient. These immune responses negatively affect recipient outcomes and predispose recipients to cardiovascular death (CV death). We hypothesized that a donor cause of death (COD) associated with higher levels of innate immune response would predispose recipients to more adverse outcomes post-transplant, including CV death. METHODS: We performed a single-institution retrospective analysis comparing donor characteristics and COD to recipient adverse cardiovascular outcomes. We analyzed the medical records of local adult donors (age 18-64) in a database of donors where adequate data was available. Donor age was available on 706 donors; donor sex was available on 730 donors. We linked donor characteristics (age and sex) and COD to recipient CV death. The data were analyzed using logistic regression, the log-rank test of differences, and Tukey contrast. RESULTS: Donor age, female sex, and COD of intracranial hemorrhage were significantly associated with a higher incidence of recipient CV death. CONCLUSIONS: In this single institution study, we found that recipients with hearts from donors over 40 years, donors who were female, or donors who died with a COD of intracranial hemorrhage had a higher frequency of CV death. Donor monitoring and potential treatment of innate immune activation may decrease subsequent recipient innate responses and allorecognition stimulated by donor-derived inflammatory signaling, which leads to adverse outcomes.

A blinded trial to investigate whether 'pressure-familiar' individuals can determine chamber pressure.

INTRODUCTION: We conducted a prospective study to determine whether divers or hyperbaric chamber attendants could discern chamber pressure--important to protecting blinding if they were to participate in blinded hyperbaric oxygen (HBO2) trials. METHODS: Experienced divers and chamber attendants were randomized by appointment group to one of four pressure changes. These pressure changes caused volume changes corresponding to starting compression from sea level or altitude, with final pressures of 1.5 atm abs (breathing 100% oxygen) or 1.2 atm abs (breathing air). Following the pressure excursions, participants estimated their depth in feet of sea water (fsw) and breathing gas. RESULTS: 42 volunteers participated: 10 females, 32 males, age 46 +/- 10 years (mean +/- 1 SD), dive experience 366 +/- 562 dives. Four were chamber attendants. When estimating the depth exposure, 19/42 (45%) selected I do not know. 3/23 (13%) were within 2 fsw of the actual depth (correlation between actual depth and estimate -0.0067) (p = 0.98). Two underestimated their depth. We found no indication of cluster randomization effect (p = 0.16). Participants could not discern breathing air or oxygen. CONCLUSIONS: The results suggest experienced divers cannot discriminate chamber pressures of 1.2 and 1.5 atm abs, and could be included in hyperbaric clinical trials using this dosing without compromising masking integrity.

D-dimer Thresholds to Exclude Pulmonary Embolism among COVID-19 Patients in the Emergency Department: Derivation with Independent Validation.

OBJECTIVE: To derive and validate a D-dimer cutoff for ruling out pulmonary embolism (PE) in COVID-19 patients presenting to the emergency department (ED). METHODS: A retrospective cohort study was performed in an integrated healthcare system including 22 adult ED's between March 1, 2020, and January 31, 2021. Results were validated among patients enrolled in the RECOVER Registry, representing data from 154 ED's from 26 US states. Consecutive ED patients with laboratory confirmed COVID-19, a D-dimer performed within 48 h of ED arrival, and with objectively confirmed PE were compared to those without PE. After identifying a D-dimer threshold at which the 95% confidence lower bound of the negative predictive value for PE was higher than 98% in the derivation cohort, it was validated using RECOVER registry data. RESULTS: Among 3978 patients with a D-dimer result, 3583 with confirmed COVID-19 infection were included in the derivation cohort. Overall, PE incidence was 4.1% and a D-dimer cutoff of <2 µ/mL (2000 ng/mL) was associated with a NPV of 98.5% (95% CI = 98.0%-98.9%). In the validation cohort of 13,091 patients with a D-dimer, 7748 had confirmed COVID-19 infection, and the PE incidence was 1.14%. A D-dimer cutoff of <2 µ/mL was associated with a NPV of 99.5% (95% CI = 99.3%-99.7%). CONCLUSION: A D-dimer cutoff of <2 µ/ml was associated with a high negative predictive value for PE among patients with COVID-19. However, the resultant sensitivity for PE result at that threshold without pre-test probability assessment would be considered clinically unsafe.

Red blood cell transfusion of preterm neonates with a Grade 1 intraventricular hemorrhage is associated with extension to a Grade 3 or 4 hemorrhage.

BACKGROUND: Some preterm infants with a Grade 1 intraventricular hemorrhage (IVH) are subsequently found to have a Grade 3 or 4 IVH, while in others the Grade 1 resolves without extending. STUDY DESIGN AND METHODS: We identified all neonates in our health system in the past 6 years with a Grade 1 IVH and compared those where the hemorrhage extended versus resolved. RESULTS: Grade 1 IVH was identified in 417 neonates; 24 subsequently became a Grade 3, and 22 a Grade 4. These 46 were born earlier, 25 ± 2 weeks versus 30 ± 3 weeks (p = 0.000), with lower birth weight, 811 ± 284 g versus 1432 ± 603 g (p = 0.000); lower 5-minute Apgar scores, 5 ± 2 versus 8 ± 2 (p = 0.000); and slightly lower cord pH, 7.24 ± 0.16 versus 7.28 ± 0.10 (p = 0.009). Older gestational age was the most significant contributor lowering the odds of IVH extension (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.92-0.98). Administering a red blood cell (RBC) transfusion up to and on the day the Grade 1 was detected was the most significant contributor increasing the odds (OR, 2.92; 95% CI, 2.19-3.90) of extension. In both groups (resolving vs. extending) criteria for ordering transfusions were similar as was the proportion of transfusions given out of compliance with guidelines. CONCLUSIONS: An association exists between RBC transfusion and extension of a Grade 1 IVH into a Grade 3 or 4. However, the explanation is unclear and could involve either the reasons transfusion are ordered or the transfusions themselves. Additional studies are needed to discover why neonates are more likely to have IVH extension if transfused.

Among very-low-birth-weight neonates is red blood cell transfusion an independent risk factor for subsequently developing a severe intraventricular hemorrhage?

BACKGROUND: A severe intraventricular hemorrhage (IVH) in a preterm neonate can result in life-long disabilities or death. Pathogenic mechanisms responsible for IVH are incompletely understood. We postulated that if the timing of a severe IVH could be approximated by serial ultrasound, potentially relevant antecedents could be identified. STUDY DESIGN AND METHODS: We retrospectively identified all very-low-birth-weight (VLBW) neonates in our health system, over a 5-year period, with an initial head ultrasound showing no hemorrhage but a subsequent ultrasound showing a Grade 3 or 4. Controls that did not develop an IVH were matched with cases using demographic features and degree of illness measures. RESULTS: Fifty-four cases were matched (1:2) with controls. No differences were found between cases and controls in initial pH, sepsis, ventilation, coagulation studies, or proportion with severe thrombocytopenia. However, during the period when the head ultrasound was normal, cases were more likely to have had a red blood cell (RBC) transfusion (p < 0.001). In 94% of the cases the sequence was 1) no IVH, 2) RBC transfusion, and 3) severe IVH. With the use of logistic regression, each subsequent RBC transfusion during the first week was determined to double the risk of a severe IVH (each transfusion increases relative risk, 2.02; 95% confidence interval, 1.54-3.33). Sensitivity analysis indicated a high likelihood that RBC transfusion, independent of hemoglobin level or other factors, increases the risk of developing a severe IVH. CONCLUSION: These findings suggest a new hypothesis. Namely, RBC transfusions given before the development of an IVH are an independent risk factor for developing a severe IVH.

Predicting Clinical Improvement for Patients With Low Back Pain: Keeping It Simple for Patients Seeking Physical Therapy Care.

OBJECTIVE: This study sought to develop and validate an original prediction formula that estimated the probability of success for patients with low back pain (LBP) to achieve a minimal clinically important difference (MCID) on the Modified Low Back Disability Questionnaire (MDQ). METHODS: Patients were 10 to 90 years old in this retrospective cohort study. Data were extracted from Intermountain Healthcare's registry, Rehabilitation Outcomes Management System: 62,858 patients admitted to physical therapy from 2002 to 2013 formed the training dataset, and 15,128 patients admitted 2015 to 2016 formed the verification dataset. Predicted probability to achieve MCID was compared with the actual percentage who succeeded. Two models were developed: 6-point improvement and 30% improvement. MDQ assessed disability, and numeric pain score assessed pain intensity. Predictive models used restricted cubic splines on age, initial pain, and disability scores for non-linear effects. Sex, symptom duration, and payer type were included as indicator variables. Predicted chance of success was compared with the actual percentage of patients that succeeded. Relative change in R-squared was calculated to assess variable importance in predicting success. Odds ratios for duration of injury and payer were calculated. RESULTS: A positive trend was observed in both models between predicted and actual success achieved. Both "verification" models appear accurate and closely approximate the "training dataset." Baseline MDQ score was the most important factor to predict a 6-point improvement. Payer type and injury duration were important factors to predict 30% improvement. Best odds to achieve an MCID was having a workers compensation insurance payer and seeking care within 14 days. CONCLUSION: The 2 models demonstrated an accurate visualization of the chance of patients achieving significant improvement compared with the usual representation of the average rate of improvement for all patients. IMPACT: Enhancing physical therapists' understanding of the probability of a patient achieving significant clinical improvement can enhance decision-making processes and help physical therapists manage a patient's care more effectively.

Post-discharge thrombosis and bleeding in medical patients: A novel risk score derived from ubiquitous biomarkers.

BACKGROUND: Some hospitalized medical patients experience venous thromboembolism (VTE) following discharge. Prophylaxis extended beyond hospital discharge (extended duration thromboprophylaxis [EDT]) may reduce this risk. However, EDT is costly and can cause bleeding, so selecting appropriate patients is essential. We formerly reported the performance of a mortality risk prediction score (Intermountain Risk Score [IMRS]) that was minimally predictive of 90-day hospital-associated venous thromboembolism (HA-VTE) and major bleeding (HA-MB). We used the components of the IMRS to calculate de novo risk scores to predict 90-day HA-VTE (HA-VTE IMRS) and major bleeding (HA-MB IMRS). METHODS: From 45 669 medical patients we randomly assigned 30 445 to derive the HA-VTE IMRS and the HA-MB IMRS. Backward stepwise regression and bootstrapping identified predictor covariates from the blood count and basic chemistry. These candidate variables were split into quintiles, and the referent quintile was that with the lowest event rate for HA-VTE and HA-MB; respectively. A clinically relevant rate of HA-VTE and HA-MB was used to inform outcome rates. Performance was assessed in the derivation set of 15 224 patients. RESULTS: The HA-VTE IMRS and HA-MB IMRS area under the receiver operating curve (AUC) in the derivation set were 0.646, and 0.691, respectively. In the validation set, the HA-VTE IMRS and HA-MB IMRS AUCs were 0.60 and 0.643. CONCLUSIONS: Risk scores derived from components of routine labs ubiquitous in clinical care identify patients that are at risk for 90-day postdischarge HA-VTE and major bleeding. This may identify a subset of patients with high HA-VTE risk and low HA-MB risk who may benefit from EDT.

Is "transfusion-associated necrotizing enterocolitis" an authentic pathogenic entity?

BACKGROUND: Necrotizing enterocolitis (NEC) sometimes occurs after a transfusion, but it is unclear whether this is a chance association or cause and effect. STUDY DESIGN AND METHODS: We compared features of neonates that developed surgical NEC within 48 hours after transfusion with others that developed NEC not preceded by transfusion. We assessed the blood used for transfusion and feeding practices among NEC cases and controls. RESULTS: Forty neonates developed surgical NEC after a transfusion and 72 developed NEC unrelated to a transfusion. Those with NEC after transfusion were born at earlier gestation (mean 27 weeks, 90% confidence interval [CI] 26-28 years vs. mean 30, 90% CI 29-31; p < 0.001) and were of lower birth weight (mean 981 g, 90% CI 835-1128 g vs. mean 1371 g, 90% CI 1245-1496; p < 0.001) and developed NEC later during their neonatal intensive care unit course (day of life: mean 23, 90% CI 20-27 vs. mean 16, 90% CI 13-19; p < 0.001). Transfusions were more prevalent among those that developed NEC (p < 0.001). The blood transfused to those that developed NEC was not older, but those who developed NEC had been fed larger volumes of milk in the 24 hours before and during transfusion (p = 0.04) and were more likely to have been fed a bovine product during that period (p = 0.004). CONCLUSION: Approximately one-third of surgical NEC cases in our system occurred after a transfusion. We speculate that a target area for reducing the prevalence of posttransfusion NEC involves feeding practices immediately before and during RBC transfusion.