Spartanburg Regional Healthcare System

IMPORTANCE: To integrate the patient perspective into adverse event reporting, the National Cancer Institute developed a patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). OBJECTIVE: To assess the construct validity, test-retest reliability, and responsiveness of PRO-CTCAE items. DESIGN, SETTING, AND PARTICIPANTS: A total of 975 adults with cancer undergoing outpatient chemotherapy and/or radiation therapy enrolled in this questionnaire-based study between January 2011 and February 2012. Eligible participants could read English and had no clinically significant cognitive impairment. They completed PRO-CTCAE items on tablet computers in clinic waiting rooms at 9 US cancer centers and community oncology practices at 2 visits 1 to 6 weeks apart. A subset completed PRO-CTCAE items during an additional visit 1 business day after the first visit. MAIN OUTCOMES AND MEASURES: Primary comparators were clinician-reported Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30). RESULTS: A total of 940 of 975 (96.4%) and 852 of 940 (90.6%) participants completed PRO-CTCAE items at visits 1 and 2, respectively. At least 1 symptom was reported by 938 of 940 (99.8%) participants. Participants' median age was 59 years; 57.3% were female, 32.4% had a high school education or less, and 17.1% had an ECOG PS of 2 to 4. All PRO-CTCAE items had at least 1 correlation in the expected direction with a QLQ-C30 scale (111 of 124, P<.05 for all). Stronger correlations were seen between PRO-CTCAE items and conceptually related QLQ-C30 domains. Scores for 94 of 124 PRO-CTCAE items were higher in the ECOG PS 2 to 4 vs 0 to 1 group (58 of 124, P<.05 for all). Overall, 119 of 124 items met at least 1 construct validity criterion. Test-retest reliability was 0.7 or greater for 36 of 49 prespecified items (median [range] intraclass correlation coefficient, 0.76 [0.53-.96]). Correlations between PRO-CTCAE item changes and corresponding QLQ-C30 scale changes were statistically significant for 27 prespecified items (median [range] r=0.43 [0.10-.56]; all P≤.006). CONCLUSIONS AND RELEVANCE: Evidence demonstrates favorable validity, reliability, and responsiveness of PRO-CTCAE in a large, heterogeneous US sample of patients undergoing cancer treatment. Studies evaluating other measurement properties of PRO-CTCAE are under way to inform further development of PRO-CTCAE and its inclusion in cancer trials.

Colorectal cancer (CRC) is a highly heterogeneous disease, for which prognosis has been relegated to clinicopathologic staging for decades. There is a need to stratify subpopulations of CRC on a molecular basis to better predict outcome and assign therapies. Here we report targeted exome-sequencing of 1,321 cancer-related genes on 468 tumour specimens, which identified a subset of 17 genes that best classify CRC, with APC playing a central role in predicting overall survival. APC may assume 0, 1 or 2 truncating mutations, each with a striking differential impact on survival. Tumours lacking any APC mutation carry a worse prognosis than single APC mutation tumours; however, two APC mutation tumours with mutant KRAS and TP53 confer the poorest survival among all the subgroups examined. Our study demonstrates a prognostic role for APC and suggests that sequencing of APC may have clinical utility in the routine staging and potential therapeutic assignment for CRC.

BACKGROUND: Chemotherapy-induced damage of hematopoietic stem and progenitor cells (HSPC) causes multi-lineage myelosuppression. Trilaciclib is an intravenous CDK4/6 inhibitor in development to proactively preserve HSPC and immune system function during chemotherapy (myelopreservation). Preclinically, trilaciclib transiently maintains HSPC in G1 arrest and protects them from chemotherapy damage, leading to faster hematopoietic recovery and enhanced antitumor immunity. PATIENTS AND METHODS: This was a phase Ib (open-label, dose-finding) and phase II (randomized, double-blind placebo-controlled) study of the safety, efficacy and PK of trilaciclib in combination with etoposide/carboplatin (E/P) therapy for treatment-naive extensive-stage small-cell lung cancer patients. Patients received trilaciclib or placebo before E/P on days 1-3 of each cycle. Select end points were prespecified to assess the effect of trilaciclib on myelosuppression and antitumor efficacy. RESULTS: A total of 122 patients were enrolled, with 19 patients in part 1 and 75 patients in part 2 receiving study drug. Improvements were seen with trilaciclib in neutrophil, RBC (red blood cell) and lymphocyte measures. Safety on trilaciclib+E/P was improved with fewer ≥G3 adverse events (AEs) in trilaciclib (50%) versus placebo (83.8%), primarily due to less hematological toxicity. No trilaciclib-related ≥G3 AEs occurred. Antitumor efficacy assessment for trilaciclib versus placebo, respectively, showed: ORR (66.7% versus 56.8%, P = 0.3831); median PFS [6.2 versus 5.0 m; hazard ratio (HR) 0.71; P = 0.1695]; and OS (10.9 versus 10.6 m; HR 0.87; P = 0.6107). CONCLUSION: Trilaciclib demonstrated an improvement in the patient's tolerability of chemotherapy as shown by myelopreservation across multiple hematopoietic lineages resulting in fewer supportive care interventions and dose reductions, improved safety profile, and no detriment to antitumor efficacy. These data demonstrate strong proof-of-concept for trilaciclib's myelopreservation benefits. CLINICAL TRAIL NUMBER: NCT02499770.

Pharmacologic management of acute pain should be tailored for each patient, including a review of treatment expectations and a plan for the time course of prescriptions. Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are first-line treatment options for most patients with acute mild to moderate pain. Topical NSAIDs are recommended for non-low back, musculoskeletal injuries. Acetaminophen is well tolerated; however, lower doses should be used in patients with advanced hepatic disease, malnutrition, or severe alcohol use disorder. Nonselective NSAIDs are effective but should be used with caution in patients with a history of gastrointestinal bleeding, cardiovascular disease, or chronic renal disease. Selective cyclooxygenase-2 NSAIDs are a more expensive treatment alternative and are used to avoid the gastrointestinal adverse effects of nonselective NSAIDs. Adjunctive medications may be added as appropriate for specific conditions if the recommended dose and schedule of first-line agents are inadequate (e.g., muscle relaxants may be useful for acute low back pain). For severe or refractory acute pain, treatment can be briefly escalated with the use of medications that work on opioid and monoamine receptors (e.g., tramadol, tapentadol) or with the use of acetaminophen/opioid or NSAID/opioid combinations. The opioid epidemic has increased physician and community awareness of the harms of opioid medications; however, severe acute pain may necessitate short-term use of opioids with attention to minimizing risk, including in patients on medication-assisted therapy for opioid use disorder.

Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonergic activity in the nervous system. It is characterized by mental status changes, autonomic instability, and neuromuscular hyperactivity. Most reported cases of serotonin syndrome are in patients using multiple serotonergic drugs or who have had considerable exposure to a single serotonin-augmenting drug. Diagnosis is made using the Hunter Serotonin Toxicity Criteria, which require the presence of one of the following classical features or groups of features: spontaneous clonus; inducible clonus with agitation or diaphoresis; ocular clonus with agitation or diaphoresis; tremor and hyperreflexia; or hypertonia, temperature above 100.4 degrees F (38 degrees C), and ocular or inducible clonus. Most cases of serotonin syndrome are mild and may be treated by withdrawal of the offending agent and supportive care. Benzodiazepines may be used to treat agitation and tremor. Cyproheptadine may be used as an antidote. Patients with moderate or severe cases of serotonin syndrome require hospitalization. Critically ill patients may require neuromuscular paralysis, sedation, and intubation. If serotonin syndrome is recognized and complications are managed appropriately, the prognosis is favorable.

Despite decades of theory and empirical research on employee burnout, its temporal and developmental aspects are still not fully understood. This lack of understanding is problematic because burnout is a dynamic phenomenon and burnout interventions may be improved by a greater understanding of who is likely to experience changes in burnout and when these changes occur. In this article, we advance existing burnout theory by articulating how the 3 burnout dimensions should differ in their pattern of change over time as a result of career transition type: organizational newcomers, internal job changers (e.g., promotions or lateral moves), and organizational insiders (i.e., job incumbents). We tested our model in a broad sample of 2,089 health care employees, with 5 measurement points over 2 years. Using random coefficient modeling, we found that burnout was relatively stable for organizational insiders but slightly dynamic for organizational newcomers and internal job changers. We also found that the dimensions of emotional exhaustion and depersonalization were more sensitive to career transition type than reduced personal accomplishment. Finding some differences among different types of employees as well as the dimensions of burnout may begin to explain longstanding inconsistencies between theory and research regarding the dynamics of burnout, offering directions for future research that address both dynamism and stability.

OBJECTIVE: The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients. BACKGROUND: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality. METHODS: We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications. RESULTS: A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P <0.05). After controlling for center, age, sex, MOI, and injury severity score, we found no differences in the rates of acute kidney injury, deep vein thrombosis/pulmonary embolism or pulmonary complications. WB patients were 9% less likely to experience bleeding complications and were 48% less likely to die than BCT patients ( P <0.0001). CONCLUSIONS: Compared with BCT, the use of WB was associated with a 48% reduction in mortality in trauma patients. Our study supports the use of WB use in the resuscitation of trauma patients.

BACKGROUND: Dendritic cells (DCs) enhance the quality of anti-tumor immune response in patients with cancer. Thus, we posit that DC-based immunotherapy, in conjunction with toll-like receptor (TLR)-3 agonist poly-ICLC, is a promising approach for harnessing immunity against metastatic or locally advanced unresectable pancreatic cancer (PC). METHODS: peptide-pulsed DC vaccines every 2 weeks (Day 0, 14, 28, and 42). Concurrently, patients received intramuscular administration of Poly-ICLC at 30 μg/Kg on vaccination days (i.e., day 0, 14, 28, and 42), as well as on days 3, 17, 21, 31, 37, and 45. Our key objective was to assess safety and feasibility. The effect of DC vaccination on immune response was measured at each DC injection time point by enumerating the phenotype and function of patient T cells. RESULTS: Twelve patients underwent apheresis: nine patients with metastatic disease, and three patients with locally advanced unresectable disease. Vaccines were successfully manufactured from all individuals. We found that this treatment was well-tolerated, with the most common symptoms being fatigue and/or self-limiting flu-like symptoms. Among the eight patients who underwent imaging on day 56, four patients experienced stable disease while four patients had disease progression. The median overall survival was 7.7 months. One patient survived for 28 months post leukapheresis. MHC class I -tetramer analysis before and after vaccination revealed effective generation of antigen-specific T cells in three patients with stable disease. CONCLUSION: Vaccination with peptide-pulsed DCs in combination with poly-ICLC is safe and induces a measurable tumor specific T cell population in patients with advanced PC. TRIAL REGISTRATION: NCT01410968 ; Name of registry: clinicaltrials.gov; Date of registration: 08/04/2011).

Three patients with bacteremic pneumonia caused by multidrug-resistant Streptococcus pneumoniae were treated unsuccessfully with azithromycin. One S. pneumoniae isolate carried a mef determinant for an efflux pump; a second isolate had an erm determinant. All 3 patients were successfully treated with levofloxacin, an antipneumococcal fluoroquinolone.

BACKGROUND: PRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. METHODS: Participants (n = 112; median age 56.5; 24 % high school or less) receiving treatment for cancer at seven US sites completed 28 PRO-CTCAE items (scoring range 0-4) by three modes (order randomized) at a single study visit. Subjects completed one page (approx. 15 items) of the EORTC QLQ-C30 between each mode as a distractor. Item scores by mode were compared using intraclass correlation coefficients (ICC); differences in scores within the 3-mode crossover design were evaluated with mixed-effects models. Difficulties with each mode experienced by participants were also assessed. RESULTS: 103 (92 %) completed questionnaires by all three modes. The median ICC comparing tablet vs IVRS was 0.78 (range 0.55-0.90); tablet vs paper: 0.81 (0.62-0.96); IVRS vs paper: 0.78 (0.60-0.91); 89 % of ICCs were ≥0.70. Item-level mean differences by mode were small (medians [ranges] for tablet vs. IVRS = -0.04 [-0.16-0.22]; tablet vs paper = -0.02 [-0.11-0.14]; IVRS vs paper = 0.02 [-0.07-0.19]), and 57/81 (70 %) items had bootstrapped 95 % CI around the effect sizes within +/-0.20. The median time to complete the questionnaire by tablet was 3.4 min; IVRS: 5.8; paper: 4.0. The proportion of participants by mode who reported "no problems" responding to the questionnaire was 86 % tablet, 72 % IVRS, and 98 % paper. CONCLUSIONS: Mode equivalence of items was moderate to high, and comparable to test-retest reliability (median ICC = 0.80). Each mode was acceptable to a majority of respondents. Although the study was powered to detect moderate or larger discrepancies between modes, the observed ICCs and very small mean differences between modes provide evidence to support study designs that are responsive to patient or investigator preference for mode of administration, and justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration. TRIAL REGISTRATION: NCT Clinicaltrials.gov identifier: NCT02158637.

PURPOSE: The purpose of this guideline is to provide a list of critical performance tests in order to assist the Qualified Medical Physicist (QMP) in establishing and maintaining a safe and effective quality assurance (QA) program. The performance tests on a linear accelerator (linac) should be selected to fit the clinical patterns of use of the accelerator and care should be given to perform tests which are relevant to detecting errors related to the specific use of the accelerator. METHODS: A risk assessment was performed on tests from current task group reports on linac QA to highlight those tests that are most effective at maintaining safety and quality for the patient. Recommendations are made on the acquisition of reference or baseline data, the establishment of machine isocenter on a routine basis, basing performance tests on clinical use of the linac, working with vendors to establish QA tests and performing tests after maintenance. RESULTS: The recommended tests proposed in this guideline were chosen based on the results from the risk analysis and the consensus of the guideline's committee. The tests are grouped together by class of test (e.g., dosimetry, mechanical, etc.) and clinical parameter tested. Implementation notes are included for each test so that the QMP can understand the overall goal of each test. CONCLUSION: This guideline will assist the QMP in developing a comprehensive QA program for linacs in the external beam radiation therapy setting. The committee sought to prioritize tests by their implication on quality and patient safety. The QMP is ultimately responsible for implementing appropriate tests. In the spirit of the report from American Association of Physicists in Medicine Task Group 100, individual institutions are encouraged to analyze the risks involved in their own clinical practice and determine which performance tests are relevant in their own radiotherapy clinics.

Viruses are a common cause of central nervous system (CNS) infections with many host, agent, and environmental factors influencing the expression of viral diseases. Viruses can be responsible for CNS disease through a variety of mechanisms including direct infection and replication within the CNS resulting in encephalitis, infection limited to the meninges, or immune-related processes such as acute disseminated encephalomyelitis. Common pathogens including herpes simplex virus, varicella zoster, and enterovirus are responsible for the greatest number of cases in immunocompetent hosts. Other herpes viruses (eg, cytomegalovirus, John Cunningham virus) are more common in immunocompromised hosts. Arboviruses such as Japanese encephalitis virus and Zika virus are important pathogens globally, but the prevalence varies significantly by geographic region and often season. Early diagnosis from radiographic evidence and molecular (eg, rapid) diagnostics is important for targeted therapy. Antivirals may be used effectively against some pathogens, although several viruses have no effective treatment. This article provides a review of epidemiology, diagnostics, and management of common viral pathogens in CNS disease.

The Wilderness Medical Society convened an expert panel in 2011 to develop a set of evidence-based guidelines for the recognition, prevention, and treatment of heat illness. We present a review of the classifications, pathophysiology, and evidence-based guidelines for planning and preventive measures, as well as best practice recommendations for both field- and hospital-based therapeutic management of heat illness. These recommendations are graded based on the quality of supporting evidence and balance the benefits and risks or burdens for each modality. This is an updated version of the original Wilderness Medical Society Practice Guidelines for the Treatment and Prevention of Heat-Related Illness published in 2013.

As one of the earliest developed antimicrobial classes, sulfonamides remain important therapeutic options for the empiric and definitive treatment of various infectious diseases. In the general population, approximately 3–8% of patients are reported to experience a sulfonamide allergy. Sulfonamide allergies can result in various physical manifestations; however, rash is reported as the most frequently observed. In patients with human immunodeficiency virus (HIV), dermatologic reactions to sulfonamide antimicrobial agents occur 10 to 20 times more frequently compared to immunocompetent patients. This article describes the incidence, manifestations, and risk factors associated with sulfonamide allergies. The potential for cross-reactivity of allergies to sulfonamide antimicrobials with nonantimicrobial sulfonamide medications is also reviewed. Data suggest that substitutions at the N1 and N4 positions are the primary determinants of drug allergy instead of the common sulfonamide moiety. For patients with an indication for a sulfonamide antimicrobial with a listed allergy, it is important for healthcare practitioners to adequately assess the allergic reaction to determine appropriate management. Rechallenge and desensitization strategies may be appropriate for patients with delayed maculopapular eruptions, while alternative treatment options may be prudent for more severe reactions. Available data suggests a low risk of cross-allergenicity between sulfonamide antimicrobial and nonantimicrobial agents.

One half of the world's population has Helicobacter pylori infection, with an estimated prevalence of 30 percent in North America. Although it is unclear whether eradication of H. pylori improves symptoms in patients with nonulcer dyspepsia, there is strong evidence that eradication of this bacteria improves healing and reduces the risk of recurrence or rebleeding in patients with duodenal or gastric ulcer. A "test-and-treat" strategy is recommended for most patients with undifferentiated dyspepsia. With this approach, patients undergo a noninvasive test for H. pylori infection and, if positive, are treated with eradication therapy. This strategy reduces the need for antisecretory medications as well as the number of endoscopies. The urea breath test or stool antigen test is recommended. Until recently, the recommended duration of therapy for H. pylori eradication was 10 to 14 days. Shorter courses of treatment (i.e., one to five days) have demonstrated eradication rates of 89 to 95 percent with the potential for greater patient compliance. A one-day treatment course consists of bismuth subsalicylate, amoxicillin, and metronidazole, all given four times with a one-time dose of lansoprazole. In children with documented H. pylori infection, however, all regimens should continue to be prescribed for seven to 14 days until short-course treatment is studied and its effectiveness has been established in this population.

p27(Kip1) was first discovered as a key regulator of cell proliferation. The canonical function of p27(Kip1) is inhibition of cyclin-dependent kinase (CDK) activity. In addition to its initial identification as a CDK inhibitor, p27(Kip1) has also emerged as an intrinsically unstructured, multifunctional protein with numerous non-canonical, CDK-independent functions that exert influence on key processes such as cell cycle regulation, cytoskeletal dynamics and cellular plasticity, cell migration, and stem-cell proliferation and differentiation. Many of these non-canonical functions, depending on the cell-specific contexts such as oncogenic activation of signaling pathways, have the ability to turn pro-oncogenic in nature and even contribute to tumor-aggressiveness and metastasis. This review discusses the various non-canonical, CDK-independent mechanisms by which p27(Kip1) functions either as a tumor-suppressor or tumor-promoter.

AIM: To describe the findings from a qualitative study exploring acute care nurses' experiences with patient falls. BACKGROUND: Patient falls continue to be a problem in acute care settings for nurses at the point of care. Despite the growing body of knowledge related to risk factors and interventions for fall prevention, minimal attention has been given to nurses' perspectives of patient falls. DESIGN: A qualitative descriptive design was used. METHOD: Focus group discussions were conducted with nurses working on a cross-section of inpatient acute care settings. Audio-taped sessions were transcribed and analysed thematically. RESULTS: Nurses described their experience of falls as 'knowing the patient as safe', an ongoing affirmation that the patient was free from harm. In this focused, narrowly defined and highly specific knowing, nurses employed the key strategies of assessment, monitoring and communicating. Variable conditions influenced whether these strategies were effective in giving nurses the knowledge they needed to keep the patient safe. When strategies failed to provide nurses with knowledge of their patients as safe and patients fell, this created considerable stress for nurses and prompted them to use a range of coping strategies. CONCLUSION: Knowing the patient as safe has the potential to resolve the tension between patient safety and independence. The critical, often taken for granted, activities used by nurses in this knowing must be expanded to include the meaning falls have for patients and attend to factors beyond nurses control such as environmental redesign and staffing. RELEVANCE TO CLINICAL PRACTICE: Nurses play an important role in fall prevention through knowing the patient as safe but must be supported through the use of a multi-faceted approach extending from the individual nurse to the institutional level.

A number of antidepressants have emerged in the U.S. market in the past two decades. Selective serotonin reuptake inhibitors have become the drugs of choice in the treatment of depression, and they are also effective in the treatment of obsessive-compulsive disorder, panic disorder, and social phobia. New indications for selective serotonin reuptake inhibitors include post-traumatic stress disorder, premenstrual dysphoric disorder, and generalized anxiety disorder. Extended-release venlafaxine has recently been approved by the U.S. Food and Drug Administration for the treatment of generalized anxiety disorder. Mirtazapine, which is unrelated to the selective serotonin reuptake inhibitors, is unique in its action--stimulating the release of norepinephrine and serotonin. The choice of antidepressant drug depends on the agent's pharmacologic profile, secondary actions, and tolerability. Sexual dysfunction related to the use of antidepressants may be addressed by reducing the dosage, switching to another agent, or adding another drug to overcome the sexual side effects. Augmentation with lithium or triiodothyronine may be useful in patients who are partially or totally resistant to antidepressant treatment. Finally, tapering antidepressant medication may help to avoid discontinuation syndrome or antidepressant withdrawal.

The incidence of allergy and autoimmune disease in the US and other industrialized nations is increasing, and gluten-related disorders are no exception. The US has documented a profound rise in celiac disease that cannot be fully explained by improved serological techniques or better recognition by physicians. Non-celiac gluten sensitivity, a condition only recently recognized by the medical community, has become a commonly diagnosed entity. Proteins, including gluten are increasingly being identified as a source of wheat allergy. Although the gluten free diet represents a safe and effective treatment for these conditions, there is still much to be learned about the development of gluten-related disorders and the apparent increase in incidence within the US. In this article, we present a review of current knowledge on the epidemiology of gluten-related disorders within a global context, with a focus on diagnostic trends and the evaluation of potential risk factors.

OBJECTIVE: To determine whether the method used to expand the uterine incision for caesarean delivery affects the incidence of intra-operative haemorrhage. DESIGN: A prospective randomised study of women undergoing a low segment transverse caesarean delivery. Participants were assigned to have their uterine incision either sharply or bluntly expanded. PARTICIPANTS: Between June 1998 and June 2000, 470 women drew assignments to the sharp expansion group and 475 to the blunt group. RESULTS: The maternal demographics of age, race, nulliparity, and body mass index as well as pre-operative haematocrit were similar between groups. Compared with the blunt group, the estimated blood loss (886 versus 843mL, P = 0.001), change in the mean haematocrit (6.1% versus 5.5%, P = 0.003), incidence of postpartum haemorrhage (13% versus 9%; relative risk = 1.23, 95% CI 1.03, 1.46) and need for a transfusion (2% versus 0.4%; relative risk = 1.65, 95% CI 1.25, 2.21) were significantly greater in the sharp group. CONCLUSION: In caesarean delivery, sharply expanding the uterine incision significantly increases intra-operative blood loss and the need for subsequent transfusion.