External validation of a smartphone app model to predict the need for massive transfusion using five different definitions.

BACKGROUND: Previously, a model to predict massive transfusion protocol (MTP) (activation) was derived using a single-institution data set. The PRospective, Observational, Multicenter, Major Trauma Transfusion database was used to externally validate this model's ability to predict both MTP activation and massive transfusion (MT) administration using multiple MT definitions. METHODS: The app model was used to calculate the predicted probability of MTP activation or MT delivery. The five definitions of MT used were: (1) 10 units packed red blood cells (PRBCs) in 24 hours, (2) Resuscitation Intensity score ≥ 4, (3) critical administration threshold, (4) 4 units PRBCs in 4 hours; and (5) 6 units PRBCs in 6 hours. Receiver operating curves were plotted to compare the predicted probability of MT with observed outcomes. RESULTS: Of 1,245 patients in the data set, 297 (24%) met definition 1, 570 (47%) met definition 2, 364 (33%) met definition 3, 599 met definition 4 (49.1%), and 395 met definition 5 (32.4%). Regardless of the outcome (MTP activation or MT administration), the predictive ability of the app model was consistent: when predicting activation of the MTP, the area under the curve for the model was 0.694 and when predicting MT administration, the area under the curve ranged from 0.695 to 0.711. CONCLUSION: Regardless of the definition of MT used, the app model demonstrates moderate ability to predict the need for MT in an external, homogenous population. Importantly, the app allows the model to be iteratively recalibrated ("machine learning") and thus could improve its predictive capability as additional data are accrued. LEVEL OF EVIDENCE: Diagnostic test study/Prognostic study, level III.

Damage control resuscitation in patients with severe traumatic hemorrhage: a practice management guideline from the Eastern Association for the Surgery of Trauma

BACKGROUND: The resuscitation of severely injured bleeding patients has evolved into a multi-modal strategy termed damage control resuscitation (DCR). This guideline evaluates several aspects of DCR including the role of massive transfusion (MT) protocols, the optimal target ratio of plasma (PLAS) and platelets (PLT) to red blood cells (RBC) during DCR, and the role of recombinant activated factor VII (rVIIa) and tranexamic acid (TXA). METHODS: Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, a subcommittee of the Practice Management Guidelines (PMG) Section of EAST conducted a systematic review using MEDLINE and EMBASE. Articles in English from1985 through 2015 were considered in evaluating four PICO questions relevant to DCR. RESULT: A total of 37 studies were identified for analysis, of which 31 met criteria for quantitative meta-analysis. In these studies, mortality decreased with use of an MT/DCR protocol vs. no protocol (OR 0.61, 95% CI 0.43-0.87, p = 0.006) and with a high ratio of PLAS:RBC and PLT:RBC (relatively more PLAS and PLT) vs. a low ratio (OR 0.60, 95% CI 0.46-0.77, p < 0.0001; OR 0.44, 95% CI 0.28-0.71, p = 0.0003). Mortality and blood product use were no different with either rVIIa vs. no rVIIa or with TXA vs. no TXA. CONCLUSION: DCR can significantly improve outcomes in severely injured bleeding patients. After a review of the best available evidence, we recommend the use of a MT/DCR protocol in hospitals that manage such patients and recommend that the protocol target a high ratio of PLAS and PLT to RBC. This is best achieved by transfusing equal amounts of RBC, PLAS, and PLT during the early, empiric phase of resuscitation. We cannot recommend for or against the use of rVIIa based on the available evidence. Finally, we conditionally recommend the in-hospital use of TXA early in the management of severely injured bleeding patients.

Birth characteristics and childhood carcinomas.

BACKGROUND: Carcinomas in children are rare and have not been well studied. METHODS: We conducted a population-based case-control study and examined associations between birth characteristics and childhood carcinomas diagnosed from 28 days to 14 years during 1980-2004 using pooled data from five states (NY, WA, MN, TX, and CA) that linked their birth and cancer registries. The pooled data set contained 57,966 controls and 475 carcinoma cases, including 159 thyroid and 126 malignant melanoma cases. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: White compared with 'other' race was positively associated with melanoma (OR=3.22, 95% CI 1.33-8.33). Older maternal age increased the risk for melanoma (OR(per 5-year age increase)=1.20, 95% CI 1.00-1.44), whereas paternal age increased the risk for any carcinoma (OR=1.10(per 5-year age increase), 95% CI 1.01-1.20) and thyroid carcinoma (OR(per 5-year age increase)=1.16, 95% CI 1.01-1.33). Gestational age < 37 vs 37-42 weeks increased the risk for thyroid carcinoma (OR=1.87, 95% CI 1.07-3.27). Plurality, birth weight, and birth order were not significantly associated with childhood carcinomas. CONCLUSION: This exploratory study indicates that some birth characteristics including older parental age and low gestational age may be related to childhood carcinoma aetiology.

Parental educational attainment as an indicator of socioeconomic status and risk of childhood cancers.

BACKGROUND: Little has been reported on socioeconomic (SES) patterns of risk for most forms of childhood cancer. METHODS: Population-based case-control data from epidemiological studies of childhood cancer conducted in five US states were pooled and associations of maternal, paternal and household educational attainment with childhood cancers were analysed. Odds ratios (ORs) and 95% confidence intervals were estimated using logistic regression, controlling for confounders. RESULTS: Although there was no association with parental education for the majority of cancers evaluated, there was an indication of a positive association with lower education for Hodgkin's and Burkitt's lymphoma and Wilm's tumour, with the ORs ranging from 1.5 to >3.0 times that of more educated parents. A possible protective effect was seen for lower parental education and astrocytoma and hepatoblastoma, with ORs reduced by 30 to 40%. CONCLUSIONS: These study results should be viewed as exploratory because of the broad nature of the SES assessment, but they give some indication that childhood cancer studies might benefit from a more thorough assessment of SES.

Birth characteristics and the risk of childhood rhabdomyosarcoma based on histological subtype.

BACKGROUND: Little is known about risk factors for childhood rhabdomyosarcoma (RMS) and the histology-specific details are rare. METHODS: Case-control studies formed by linking cancer and birth registries of California, Minnesota, New York, Texas and Washington, which included 583 RMS cases (363 embryonal and 85 alveolar RMS) and 57 966 randomly selected control subjects, were analysed using logistic regression. The associations of RMS (overall, and based on embryonal or alveolar histology) with birth weight across five 500 g categories (from 2000 to 4500 g) were examined using normal birth weight (2500-3999 g) as a reference. Large (>90th percentile) and small (<10th percentile) size for gestational age were calculated based on birth weight distributions in controls and were similarly examined. RESULTS: High birth weight increased the risk of embryonal RMS and RMS overall. Each 500 g increase in birth weight increased the risk of embryonal RMS (odds ratio (OR)=1.27, 95% confidence interval (CI)=1.14-1.42) and RMS overall (OR=1.18, 95% CI=1.09-1.29). Large size for gestational age also significantly increased the risk of embryonal RMS (OR=1.42, 95% CI=1.03-1.96). CONCLUSIONS: These data suggest a positive association between accelerated in utero growth and embryonal RMS, but not alveolar RMS. These results warrant cautious interpretation owing to the small number of alveolar RMS cases.

Irritability and sociability in women with symptomatic premenstrual change.

Sociability and irritability are commonly cited symptoms of premenstrual syndrome but there has been little investigation of these cycle related changes using clearly defined test instruments. We examined the two symptoms using symptom specific subscales from the Multiscore Depression Inventory (Berndt, 1983). Clear and consistent cycle related changes in irritability and sociability were seen in 20 women with prospectively validated symptomatic premenstrual change but not in a control group of 8 women without symptomatic premenstrual change. The study suggests that these variables can be measured using specific brief scales.

Intermenstrual affect in women with symptomatic premenstrual change.

To determine whether women seeking treatment for symptomatic premenstrual change have ongoing psychological disturbance, we undertook a cross-sectional, comparative study across four groups of reproductive-age women. Subjects were 35 patients with symptomatic premenstrual change and no psychiatric history, 35 women without symptomatic premenstrual change, 35 patients with affective disorders, and 35 women from the community at large. All women except those in the community sample were tested in the intermenstrual phase (after menses but before the 12th cycle day). Psychological tests administered were Profile of Mood States, State-Trait Anxiety Inventory, Institute for Personality and Ability Testing (IPAT) Anxiety Scale, IPAT Depression Scale, General Health Questionnaire and the Family Inventory of Life Events (FILE). Demographic data and information concerning present and past stresses were also collected. Women with symptomatic premenstrual change were distinguishable from psychiatric patients on assessment of intermenstrual mood state. They were no different from women within the community at large or from non-symptomatic women. When symptomatic women reported on time periods, which include the premenstrual phase of the cycle, we found results at variance with those obtained in relation to current state mood. While not unlike the women from the community at large in longer term affective characteristics, they were consistently different from non-symptomatic women and sometimes indistinguishable from psychiatric patients. Women with symptomatic premenstrual change also reported higher levels of past external stresses than women taken from the community at large.

Fluid intake in women with premenstrual syndrome.

Fluid intake was measured at 3 phases of the menstrual cycle in twenty women with prospectively validated premenstrual syndrome and 8 women with prospectively validated absence of cyclic symptoms. There was no cycle related change in fluid intake in either group but fluid intake was significantly lower in women with PMS than in controls at all phases of the menstrual cycle. All subjects but one denied voluntary fluid restriction. The mechanism, therefore, appears subconscious and may be related to perceived increase in fluid retention.

"So mean and cranky, I could bite my mother": an ethnosemantic analysis of women's descriptions of premenstrual change.

Textual analysis was used to examine responses to an open ended question about women's experiences of premenstrual change. The question was the final item of the Premenstrual Assessment Form (PAF), a retrospective PMS questionnaire. Of the 336 women who answered the PAF, 261 provided a written narrative summary. We found a logical hierarchy of distinctions covering the presence or absence of changes, their timing, and attributive aspects, and a final cumulative distinction in which women provided information about the consequences of their premenstrual change. Although attribute aspects mirrored the PAF, distinctions in timing and in the cumulative effect of changes differed. The analysis suggests that questionnaires could be designed which more precisely reflect premenstrual change.

Assessment of premenstrual complaint using the Premenstrual Assessment Form: comparison of two populations.

The Premenstrual Assessment Form (PAF) provides frequencies of diagnoses for subjects meeting the criteria for typological classifications which are similar in New York and Edmonton, suggesting that the instrument is stable in assessing premenstrual complaint. However, the frequency with which an unselected population meet the criteria suggests that more strict criteria and/or a "severity index" would be appropriate. It seems likely that a modified form of the PAF could fulfil some of the intentions of its originators.

Frequency and severity of premenstrual symptoms in women taking birth control pills.

A retrospective study of a wide range of premenstrual symptomatology using the Premenstrual Assessment Form found little difference between women taking a low-dose birth control pill and non-pill-takers. These data are in keeping with older, but narrower, studies of women taking high-dose pills and raise questions about mechanisms of symptomatic and subclinical premenstrual changes.

Towards a definition of PMS.II: A factor analytic evaluation of premenstrual change in women with symptomatic premenstrual change.

We have examined the value of the Premenstrual Assessment Form (PAF) in 109 women with prospectively validated symptomatic premenstrual change. Results were compared with those of non-complaining women previously published (J Psychosom Res 1990; 34: 439-446.), there was considerable overlap in categorical and numerical scales so that selection of homogeneous populations of complainers could not be achieved. However, fewer than 7% of complainers had a total PAF numerical score in the normal range (defined as 2 SD above the mean total score of controls). Factor analysis of numerical scores in women with symptomatic premenstrual change suggested three factors similar to but not identical with those of non-complaining women. These were physiological depression, anxiety-volatility and increased well-being. While the negative syndromes are compatible with clinical experience, prospective investigation will be required to assess their homogeneity.

Premenstrual anxiety and depression: comparison of objective psychological tests with a retrospective questionnaire.

Increased anxiety and depression are among the most frequently reported psychological problems in women seeking help for severe symptomatic premenstrual change, but there has been little objective evaluation of these symptoms. We therefore examined the results of objective psychological testing in 40 women with no apparent psychiatric or psychological disorder who had reported moderate to extreme increased anxiety and depression on a retrospective assessment form. Scores on the State-Trait Anxiety Inventory and Institute of Personality and Ability Testing (IPAT) Depression Scale increased from the low symptom intermenstrual phase of the cycle (days 5-10) to the premenstrual phase (within the last 6 days of the cycle), suggesting that retrospective complaints of increased premenstrual anxiety and depression can be confirmed on objective psychological assessment. However, it was observed that the distribution of intermenstrual IPAT depression scores was bimodal. Cyclic changes varied among the tests depending upon the IPAT depression score. The study suggests that 2 populations may exist in this screened sample; one population appears to have "pure PMS" and the second groups manifests a premenstrual exacerbation of subclinical depression.

Towards a definition of PMS: a factor analytic evaluation of premenstrual change in non-complaining women.

Symptomatic premenstrual change remains enigmatic and much disputed. To establish baselines in a non-complaining population, we administered the Premenstrual Assessment Form (PAF) to 133 volunteers not seeking or using treatment for premenstrual symptoms. The PAF, a 95-item self report questionnaire, provides categorical, bipolar and quantitative data on a wide range of premenstrual symptoms. Only 27 women (20.3%) failed to meet criteria for at least one of the negative PAF syndromes suggesting that the criteria are lax for clinical investigative purposes. Most common syndromes were minor and major depressive syndromes (87, 65%) with atypical and hostile subtypes most common, general physical discomfort syndrome (82, 61.7%) and fluid retention syndrome (71, 53.4%). Factor analysis was used with the quantitative data to group symptoms. The analysis suggested three factors: a physiological depression (depression with physical change), an anxiety-volatility, and an increased well-being unrelated to other changes. The clearer delineation of premenstrual changes in non-complaining women will define the control group in research with premenstrually symptomatic complainers.