Adult Cancer Pain, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.

In recent years, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain have undergone substantial revisions focusing on the appropriate and safe prescription of opioid analgesics, optimization of nonopioid analgesics and adjuvant medications, and integration of nonpharmacologic methods of cancer pain management. This selection highlights some of these changes, covering topics on management of adult cancer pain including pharmacologic interventions, nonpharmacologic interventions, and treatment of specific cancer pain syndromes. The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional aspects of this topic, including pathophysiologic classification of cancer pain syndromes, comprehensive pain assessment, management of pain crisis, ongoing care for cancer pain, pain in cancer survivors, and specialty consultations.

Mannose receptor (MR) and Toll-like receptor 2 (TLR2) influence phagosome maturation during Leishmania infection.

Leishmania enter macrophages through receptor-mediated phagocytosis and survive the harsh environment of a phagolysosome. Here, we investigated the interaction between mannose receptor (MR), Toll-like receptor 2 (TLR2), and Leishmania, and the subsequent impact on phagosome maturation. Leishmania parasites are able to delay phagosome maturation, not reaching full maturation until 5 hours post-engulfment. Here, maturation of Leishmania major- and Leishmania donovani-containing phagosomes proceeded as expected in the WT macrophages becoming LAMP1 positive by 6 hours. Interestingly, MR-/- macrophages become LAMP1 positive by ~2 hours and ~4 hours post-infection Leishmania-containing phagosomes lost LAMP1 expression and gained the early marker EEA1. LAMP1 expression was again observed by 6 hours. Leishmania LPG was essential for the delay in both WT and MR-/- macrophages but was not essential for the early maturation (2 hours) observed in MR-/- macrophages. Serum opsonization of Leishmania prior to infection induced identical phagosome maturation patterns in WT and MR-/- macrophages. In the absence of MyD88 or TLR2 on macrophages, Leishmania phagosomes matured significantly faster, becoming LAMP1 positive by ~1-2 hours. These studies add to the knowledge that phagosome maturation is influenced by multiple receptor-ligand interactions and signalling pathways.

Characterization of microRNA expression profiles in Leishmania-infected human phagocytes.

Leishmania are intracellular protozoa that influence host immune responses eliciting parasite species-specific pathologies. MicroRNAs (miRNAs) are short single-stranded ribonucleic acids that complement gene transcripts to block protein translation and have been shown to regulate immune system molecular mechanisms. Human monocyte-derived dendritic cells (DC) and macrophages (MP) were infected in vitro with Leishmania major or Leishmania donovani parasites. Small RNAs were isolated from total RNA and sequenced to identify mature miRNAs associated with leishmanial infections. Normalized sequence read count profiles revealed a global downregulation in miRNA expression among host cells following infection. Most identified miRNAs were expressed at higher levels in L. donovani-infected cells relative to L. major-infected cells. Pathway enrichments using in silico-predicted gene targets of differentially expressed miRNAs showed evidence of potentially universal MAP kinase signalling pathway effects. Whereas JAK-STAT and TGF-ß signalling pathways were more highly enriched using targets of miRNAs upregulated in L. donovani-infected cells, these data provide evidence in support of a selective influence on host cell miRNA expression and regulation in response to differential Leishmania infections.

The characterization of the Phlebotomus papatasi transcriptome.

As important vectors of human disease, phlebotomine sand flies are of global significance to human health, transmitting several emerging and re-emerging infectious diseases. The most devastating of the sand fly transmitted infections are the leishmaniases, causing significant mortality and morbidity in both the Old and New World. Here we present the first global transcriptome analysis of the Old World vector of cutaneous leishmaniasis, Phlebotomus papatasi (Scopoli) and compare this transcriptome to that of the New World vector of visceral leishmaniasis, Lutzomyia longipalpis. A normalized cDNA library was constructed using pooled mRNA from Phlebotomus papatasi larvae, pupae, adult males and females fed sugar, blood, or blood infected with Leishmania major. A total of 47 615 generated sequences was cleaned and assembled into 17 120 unique transcripts. Of the assembled sequences, 50% (8837 sequences) were classified using Gene Ontology (GO) terms. This collection of transcripts is comprehensive, as demonstrated by the high number of different GO categories. An in-depth analysis revealed 245 sequences with putative homology to proteins involved in blood and sugar digestion, immune response and peritrophic matrix formation. Twelve of the novel genes, including one trypsin, two peptidoglycan recognition proteins (PGRP) and nine chymotrypsins, have a higher expression level during larval stages. Two novel chymotrypsins and one novel PGRP are abundantly expressed upon blood feeding. This study will greatly improve the available genomic resources for P. papatasi and will provide essential information for annotation of the full genome.

Leishmania major inhibits IL-12 in macrophages by signalling through CR3 (CD11b/CD18) and down-regulation of ETS-mediated transcription.

Leishmania major is an aetiological agent of cutaneous leishmaniasis. The parasite primarily infects immune sentinel cells, specifically macrophages and dendritic cells, in the mammalian host. Infection is receptor mediated and is known to involve parasite binding to cell surface protein complement receptor 3 (CR3, Mac-1, CD11b/CD18). Engagement of CR3 by various ligands inhibits production of interleukin-12 (IL-12), the cytokine that drives antileishmanial T helper 1-type immune responses. Likewise, L. major infection inhibits IL-12 production and activation of host macrophages. Our data indicate that in the absence of CR3, L. major-infected bone marrow-derived macrophages produce more IL-12 and nitric oxide compared with WT cells upon lipopolysaccharide (LPS) stimulation. We therefore investigated multiple signalling pathways by which L. major may inhibit IL-12 transcription through CR3 ligation. We demonstrate that L. major infection does not elicit significant NFκB p65, MAPK, IRF-1 or IRF-8 activation in WT or CD11b-deficient macrophages. Furthermore, infection neither inhibits LPS-induced MAPK or NFκB activation nor blocks IFN-γ-activated IRF-1 and IRF-8. ETS-mediated transcription, however, is inhibited by L. major infection independently of CR3. Our data indicate that L. major-mediated inhibition of IL-12 occurs through CR3 engagement; however, the mechanism of inhibition is independent of NFκB, MAPK, IRF and ETS.

Prevalence and predictors of cancer specific distress in men with a family history of prostate cancer.

OBJECTIVE: To examine prevalence and predictors of cancer-specific distress in undiagnosed men with and without a family history of prostate cancer, and to examine the contribution of perceptions of an affected relative's cancer experience on the distress of unaffected male relatives. METHODS: Men with a first degree relative with prostate cancer (n = 207) and men without a family history (n = 239) from Australia completed a Computer Assisted Telephone Interview. Participants completed the Prostate Cancer Anxiety Subscale of the Memorial Anxiety Scale for Prostate Cancer, measures of perceived risk, and socio-demographic information. Men with a family history provided details about their family history (number of relatives diagnosed with and dead from prostate cancer, relationship to affected relative, months since diagnosis) and reported their perceptions of their affected relative's prostate cancer experience including perceptions of threat related to the relative's diagnosis and perceived treatment phase and prognosis. RESULTS: Cancer-specific distress was low for all men and there was no significant difference in the distress experienced by men with and without a family history. Regression analyses showed that for all men, cancer-specific distress increased with urinary symptoms and decreased in those with higher education and in older participants. For men with a family history, having a relative who died from prostate cancer and perceiving greater threat from a relative's diagnosis was associated with greater cancer-specific distress. CONCLUSIONS: Interventions would benefit from examining appraisals of familial risk and examining prospective assessments of distress in the unaffected male relatives of men with prostate cancer over the course of the cancer trajectory.

Indoleamine 2,3-dioxygenase (IDO) induced by Leishmania infection of human dendritic cells.

Dendritic cells (DC) play a pivotal role in regulating immunity, establishing immunologically privileged tissue microenvironments and maintaining homoeostasis. It is becoming increasingly clear that one key mechanism that mediates many DC functions is production of the immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO). For pathogens that cause chronic infection, exploitation of host DCs is a solution to establish and persist within a host. Leishmania parasites cause a range of clinical manifestations, all involving chronic infection, and are proficient at avoiding immune responses. We demonstrate here that infection of human myeloid-derived DC with L. major and L. donovani induces IDO expression using a mechanism that involves autocrine or paracrine stimulation with a DC-secreted factor. Leishmania-induced IDO suppresses allogeneic and tetanus toxoid-specific lymphocyte proliferation, an inhibition that is reversed with the IDO inhibitor, 1-methyl tryptophan (1-MT). Furthermore, IDO expression by human DC does not require live Leishmania infection, as parasite lysates also up-regulate IDO mRNA production. Our data suggest that one mechanism Leishmania parasites utilize to circumvent immune clearance may be to promote the induction of IDO among host DC within the infection microenvironment.

Identifying content to improve risk assessment communications within the Risk Profile: Literature reviews and focus groups with expert and non-expert stakeholders.

OBJECTIVE: To improve consumer decision making, the results of risk assessments on food, feed, consumer products or chemicals need to be communicated not only to experts but also to non-expert audiences. The present study draws on evidence from literature reviews and focus groups with diverse stakeholders to identify content to integrate into an existing risk assessment communication (Risk Profile). METHODS: A combination of rapid literature reviews and focus groups with experts (risk assessors (n = 15), risk managers (n = 8)), and non-experts (general public (n = 18)) were used to identify content and strategies for including information about risk assessment results in the "Risk Profile" from the German Federal Institute for Risk Assessment. Feedback from initial focus groups was used to develop communication prototypes that informed subsequent feedback rounds in an iterative process. A final prototype was validated in usability tests with experts. RESULTS: Focus group feedback and suggestions from risk assessors were largely in line with findings from the literature. Risk managers and lay persons offered similar suggestions on how to improve the existing communication of risk assessment results (e.g., including more explanatory detail, reporting probabilities for individual health impairments, and specifying risks for subgroups in additional sections). Risk managers found information about quality of evidence important to communicate, whereas people from the general public found this information less relevant. Participants from lower educational backgrounds had difficulties understanding the purpose of risk assessments. User tests found that the final prototype was appropriate and feasible to implement by risk assessors. CONCLUSION: An iterative and evidence-based process was used to develop content to improve the communication of risk assessments to the general public while being feasible to use by risk assessors. Remaining challenges include how to communicate dose-response relationships and standardise quality of evidence ratings across disciplines.

Cancer pain management in ambulatory care: can we link assessment and action to outcomes?

PURPOSE: Good cancer pain control requires appropriate assessment and treatment. The purpose of this study was to examine the relationships among physician, nurse practitioner, and nurse knowledge, documentation of assessment, treatment, and pain reduction in cancer patients seen in ambulatory settings. METHOD: The study method included an assessment of pain knowledge of providers (physicians, nurse practitioners, and nurses) who worked in cancer clinics and a retrospective review of patients' records treated for cancer-related pain in their clinics. Fifty-eight providers from eight cancer clinics completed the knowledge questionnaire; 56 patient records were reviewed for assessment, treatment, and outcome data. Pain relief, the outcome, was obtained from documentation at the next clinic visit. RESULTS: Of the 54 patient records that documented pain relief at the next clinic visit, 61.9% reported no relief. Chi square analysis revealed clinics with a higher level of pain knowledge documented a greater number of elements of an ideal pain assessment (p = 0.03) but was unrelated to treatment and pain relief reported. Assessment and treatment were unrelated to reported pain relief at the next clinic visit. CONCLUSION: These data suggest that providers' pain knowledge is related to pain assessment but not treatment or outcome. In addition, these data showed no relationship between assessment, treatment prescribed, and pain relief in these ambulatory settings.

Cannabidiol: Knowledge, Beliefs, and Experiences of Patients With Cancer.

BACKGROUND: Cannabidiol (CBD) is purported to work for a variety of therapeutic indications. Interest in CBD products has significantly increased as patients with cancer seek ways to improve symptom control and quality of life. OBJECTIVES: The purpose of this study was to explore patients' knowledge of and experience with CBD. METHODS: A panel of oncology nurse practitioners, an oncologist, and oncology pharmacy specialists developed a survey to capture information about patient knowledge and use of CBD. The initial survey was pilot tested and further refined, resulting in the final item survey. The final survey was administered to 100 participants undergoing or having completed cancer treatment and being followed in a supportive oncology care clinic at a large academic medical center. FINDINGS: Most patients learned about CBD through a family member or friend. The majority of patients had never tried CBD. The most common reported indications were pain, anxiety, and nausea. Of those who had not tried CBD, the most common reasons included lack of knowledge about CBD and providers not recommending CBD.

Predictors of change in unmet supportive care needs in cancer.

OBJECTIVE: Patient Reported Outcome (PRO) assessments can assist health professionals to tailor their health practices to the individual needs of patients and improve patient care over time. The present study assessed prospective predictors of unmet supportive care needs in cancer patients over a six-month period. METHODS: Participants were recruited from a regional cancer treatment centre in Australia and completed the Supportive Care Needs Survey (SCNS) at recruitment (n=439; 61.4% response rate) and six months follow-up (n=396). Hierarchical logistic regression was used to identify predictors of change in unmet needs across each supportive care domain. Predictor variables were socio-demographic, treatment and psychosocial factors including depression, anxiety, social support, and patient satisfaction. RESULTS: Unmet needs were reported by approximately two-thirds of patients at baseline and half of patients at six months follow-up. Having unmet needs at baseline was the strongest predictor of unmet needs at six months. Longer time since diagnosis was a consistent predictor of greater unmet needs, associated with change in physical/daily living, psychological and health system and information unmet needs over time. By contrast, a complex relationship was found in that patient satisfaction, psychosocial and treatment characteristics predicted higher needs in some domains and lower needs in others. CONCLUSIONS: Unmet supportive care needs persist over time and psychological needs may emerge later in the illness continuum. Interventions to meet the needs of longer term cancer survivors are needed and should closely articulate with reported supportive care needs.

A review of prostate-specific antigen screening prevalence and risk perceptions for first-degree relatives of men with prostate cancer.

First-degree relatives of men with prostate cancer have a higher risk of being diagnosed with prostate cancer than men without a family history. The present review examines the prevalence and predictors of testing in first-degree relatives, perceptions of risk, prostate cancer knowledge and psychological consequences of screening. Medline, PsycInfo and Cinahl databases were searched for articles examining risk perceptions or screening practices of first-degree relatives of men with prostate cancer for the period of 1990 to August 2007. Eighteen studies were eligible for inclusion. First-degree relatives participated in prostate-specific antigen (PSA) testing more and perceived their risk of prostate cancer to be higher than men without a family history. Family history factors (e.g. being an unaffected son rather than an unaffected brother) were consistent predictors of PSA testing. Studies were characterized by sampling biases and a lack of longitudinal assessments. Prospective, longitudinal assessments with well-validated and comprehensive measures are needed to identify factors that cue the uptake of screening and from this develop an evidence base for decision support. Men with a family history may benefit from targeted communication about the risks and benefits of prostate cancer testing that responds to the implications of their heightened risk.

Attenuation of ischaemic injury in the equine jejunum by administration of systemic lidocaine.

REASONS FOR PERFORMING STUDY: Absorption of endotoxin across ischaemic-injured mucosa is a major cause of mortality after colic surgery. Recent studies have shown that flunixin meglumine retards mucosal repair. Systemic lidocaine has been used to treat post operative ileus, but it also has novel anti-inflammatory effects that could improve mucosal recovery after ischaemic injury. HYPOTHESIS: Systemic lidocaine ameliorates the deleterious negative effects of flunixin meglumine on recovery of mucosal barrier function. METHODS: Horses were treated i.v. immediately before anaesthesia with either 0.9% saline 1 ml/50 kg bwt, flunixin meglumine 1 mg/kg bwt every 12 h or lidocaine 1.3 mg/kg bwt loading dose followed by 0.05 mg/kg bwt/min constant rate infusion, or both flunixin meglumine and lidocaine, with 6 horses allocated randomly to each group. Two sections of jejunum were subjected to 2 h of ischaemia by temporary occlusion of the local blood supply, via a midline celiotomy. Horses were monitored with a behavioural pain score and were subjected to euthanasia 18 h after reversal of ischaemia. Ischaemic-injured and control jejunum was mounted in Ussing chambers for measurement of transepithelial electrical resistance (TER) and permeability to lipopolysaccharide (LPS). RESULTS: In ischaemic-injured jejunum TER was significantly higher in horses treated with saline, lidocaine or lidocaine and flunixin meglumine combined, compared to horses treated with flunixin meglumine. In ischaemic-injured jejunum LPS permeability was significantly increased in horses treated with flunixin meglumine alone. Behavioural pain scores did not increase significantly after surgery in horses treated with flunixin meglumine. CONCLUSIONS: Treatment with systemic lidocaine ameliorated the inhibitory effects of flunixin meglumine on recovery of the mucosal barrier from ischaemic injury, when the 2 treatments were combined. The mechanism of lidocaine in improving mucosal repair has not yet been elucidated.

Tables for the selection of correct blood pressure cuff size based on self-reported height and weight and estimating equations for mid-arm circumference: data from the US National Health and Nutrition Examination Survey.

The purpose of this study was to develop practical prediction equations for estimating adult mid-arm circumference (AC) using self-reported height and weight data from NHANES III 1988-1994 and NHANES 1999-2000. Both surveys used a complex sample design to obtain nationally representative data for the US civilian noninstitutionalized population. The analytic sample consisted of 4801 men and 4854 women in NHANES III and 1960 men and 2180 women from NHANES 1999-2000. Self-reported weight, height, and age data from NHANES III were used for model building, and similar data from NHANES 1999-2000 were used for validation. An all-possible regressions procedure by gender was used to derive the mid-AC prediction equations. The final prediction equations for adult mid-AC are (for self-reported weight in pounds and height in inches) for men: AC (cm) = 32.52145 + 0.10975 x (wt)-0.26057 x (ht)-0.03028 x (age), R2 = 0.76; and for women: AC (cm) = 30.22126 + 0.13534 x (wt)-0.34121 x (ht) + 0.09014 x (age)-0.00082565 x (age2), R2 = 0.81. Based on these equations, tables were created to predict mid-AC using self-reported height and weight. Clinicians can refer to our prediction equations and reference tables to determine mid-AC and proper BP cuff sizes.

Inhibition of host cell signal transduction by Leishmania: observations relevant to the selective impairment of IL-12 responses.

Leishmania parasites are able to delay the onset of cell-mediated immunity by selectively impairing the ability of infected macrophages to produce interleukin (IL)-12. Leishmania infection arrests the JAK/STAT-mediated signal transduction involved in activation of the IL-12 p40 promoter; the phosphorylation defects may be initiated by ligation of the phagocyte receptors used by these organisms to gain entry into the host cell.

Overexpression of the XPA repair gene increases resistance to ultraviolet radiation in human cells by selective repair of DNA damage.

Overexpression of XPA genes, both wild type and a missense mutant, which code for a damage-specific, DNA-binding protein, increased the survival of repair-deficient and -competent human cells to levels above that of normal cells that did not overexpress XPA. The first 3 h after cells were damaged were most critical to achieving this increased survival. The dose at which 37% of the irradiated population survives could be restored to about one-half that of normal cells, with no detectable genome-wide repair of pyrimidine dimers or (6-4) photoproducts, suggesting that intermediate levels of XPA gene expression can direct repair to restricted critical regions of the genome. Current views of repair implicate transcriptionally active genes as a major component of such critical regions. Consistent with this interpretation, the repair of a transfected, actively expressed luciferase gene was higher than that of genomic DNA at intermediate and higher levels of XPA expression. High levels of XPA expression resulted in increased repair at early times after irradiation and extensive repair of (6-4) photoproducts but little, if any, pyrimidine dimer repair in the whole genome. At the highest level of expression, some clonal cell lines acquired resistance to radiation that corresponded to a dose at which 37% of the irradiated population survives that was about 1.5 to 2 times that of normal cells. The XPA gene product, therefore, can influence levels of DNA repair and radiation sensitivity quantitatively by contributing to selective repair at certain sites in the genome.

Increased ultraviolet sensitivity and chromosomal instability related to P53 function in the xeroderma pigmentosum variant.

The xeroderma pigmentosum (XP) variant (XPV) is a form of XP that has normal excision repair but shows defective DNA replication after UV irradiation. In developing various transformed fibroblast cell lines from these patients, we have found that there are significant phenotypic changes in transformed cells that seem to correlate with inactivation of p53. After transformation with SV40, XPV cell lines are only slightly UV sensitive, like their primary counterparts, but their sensitization with caffeine and the induction of sister chromatid exchanges (SCEs) by UV irradiation are greatly enhanced. After transformation by HPV16 E7, which targets the retinoblastoma cell cycle regulatory gene, there is no change in the UV sensitivity of XPV cells; but, when transformed by HPV16 E6 or E6 and E7 combined, there is a large increase in UV sensitivity and in the induction of SCEs. These changes are not associated with any detectable changes in the reactivation of an externally irradiated luciferase expression vector, the excision of cyclobutane pyrimidine dimers from bulk DNA, or unscheduled DNA synthesis and, therefore, do not involve excision repair. We suggest that if SCEs represent homologous recombination between sister chromatids, then in the absence of p53 function, the DNA chain arrest typical of UV-damaged XPV cells initiates strand exchange during recovery. In untransformed cells with normal p53, the preferred mode of recovery would then be replication bypass. The symptoms of elevated solar carcinogenesis in XPV patients may, therefore, be associated with increased genomic instability in cells of the skin in which p53 is inactivated by UV-induced mutations.

US demographic trends in mid-arm circumference and recommended blood pressure cuffs: 1988-2002.

Mid-arm circumference (AC) measurement is a prerequisite for the selection of properly sized blood pressure (BP) cuffs and accurate BP readings. This study examined trends in the frequency distribution of mid-AC and corresponding recommended BP cuff sizes using National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES 1999-2002 data. Both surveys used a complex sample design to obtain nationally representative samples of the civilian noninstitutionalized US population. The sample consisted of 7453 men and 8372 women from NHANES III and 4295 men and 4838 women from NHANES 1999-2002. Mean mid-AC (cm) and associated American Heart Association-defined cuff sizes were assessed. Variables were analysed by gender, age, race/ethnicity, and by hypertension or diabetic co-morbidity. Mid-AC increased significantly between surveys for all age groups; the greatest increase in mid-AC occurred in the 20-39 year age group. Data from NHANES 1992-2002 show that among nonHispanic white and nonHispanic black men aged 20-59 years, the mean mid-AC was >34 cm. Among NHB women aged 40 years and above, the mean mid-AC was greater than or equal to 34 cm. In all, 42% of all men and 26% of all women aged 40-59 years required large BP cuffs. In all, 39% of individuals classified as hypertensive and 47% of self-reported diabetics required a BP cuff greater than the standard adult size. In conclusion, mean mid-AC has increased across many demographic subgroups in the US with implications for the accuracy of BP measurement in clinical practice.

Urinary mercury concentrations associated with dental restorations in adult women aged 16-49 years: United States, 1999-2000.

BACKGROUND: Mercury amalgam dental restorations have been used by dentists since the mid 19th century and issues on safety continue to be periodically debated within the scientific and public health communities. Previous studies have reported a positive association between urine mercury levels and the number of dental amalgams, but this relation has never been described in a nationally representative sample in the United States. AIMS AND METHODS: Using household interview, dietary interview, dental examination, and laboratory data from the 1999-2000 National Health and Nutrition Examination Survey (NHANES), the association between mercury concentrations and dental restorations was examined in US women of reproductive age. RESULTS: In women of childbearing age, approximately 13% of all posterior dental surfaces were restored with amalgams and the average urinary mercury level in women was low (1.34 microg/l). It is estimated that an increase of 1.8 microg/l in the log transformed values for mercury in urine would occur for each 10 dental surfaces restored with amalgam. CONCLUSIONS: Although the findings do not address the important issues of adverse health effects at low thresholds of mercury exposure, they do provide important reference data that should contribute significantly to the ongoing scientific and public health policy debate on the use of dental amalgams in the USA.

A controlled study on batted ball speed and available pitcher reaction time in slowpitch softball.

OBJECTIVES: To investigate safety risks in slowpitch softball by conducting laboratory and experimental studies on the performance of high tech softball bats with polyurethane softballs. To compare the results with the recommended safety standards. METHODS: ASTM standard compression testing of seven softball models was conducted. Using these seven softball models, bat/ball impact testing was performed using seven adult male softball players and six high tech softball bat models to determine mean batted ball speeds. Over 500 bat/ball impact measurements were recorded and analysed. Available pitcher reaction time was calculated from the mean batted ball speed measurements. RESULTS: According to the United States Specialty Sports Association and the Amateur Softball Association, the maximum initial batted ball speed should be 137.2 km/h, which corresponds to a minimum pitcher reaction time of 0.420 second. These experiments produced mean batted ball speeds of 134.0-159.7 km/h, which correspond to available pitcher reaction times of 0.409-0.361 second. CONCLUSION: The use of high tech softball bats with polyurethane softballs can result in batted ball speeds that exceed the recommended safety limits, which correspond to decreased available pitcher reaction times.