Cell cycle status in AML blast cells from peripheral blood, bone marrow aspirates and trephines and implications for biological studies and treatment.

Using immunohistochemistry and flow cytometry to define phases of the cell cycle, this study shows that a high proportion of acute myeloid leukaemia (AML) blasts obtained from trephine biopsies are cycling, whereas >95% of peripheral blood-derived blasts are arrested in G1 . Results obtained from bone marrow aspirates are more similar to those from blood rather than from trephine biopsies. These differences were confirmed by gene expression profiling in a patient with high count AML. This has implications for cell cycle and other biological studies using aspirates rather than trephine biopsies and for the use of cell mobilising agents before chemotherapy.

Management of refractory pain in hospitalized adolescents with sickle cell disease: changing from intravenous opioids to continuous infusion epidural analgesia.

BACKGROUND: Prolonged hospitalizations for sickle cell disease painful episodes are not uncommon, as analgesic options are often suboptimal. OBSERVATIONS: Seven patients (15.4 ± 3.7 y, 6 females) were treated with epidural analgesia for refractory pain. The median duration of epidural catheter placement was 4 days (interquartile range, 3 to 6 d). Mean pain scores changed from 6.8 ± 2.7 to 4.8 ± 2.2, whereas mean daily parenteral opioid requirements changed from 79.7 ± 100.4 to 13.0 ± 13.1 mg of morphine equivalents. CONCLUSION: Continuous epidural analgesia is an alternative to continuing intravenous opioids in sickle cell disease patients with refractory pain, and may reduce opioid-related side effects and facilitate transition to oral analgesics.

Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic pain syndromes.

PURPOSE: We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes. MATERIALS AND METHODS: We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events during study treatment and rate of response to therapy as assessed by the patient global response assessment. Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. RESULTS: There were 23 (49%) men and 24 (51%) women randomized during a 6-month period. Of the patients 24 (51%) were randomized to global therapeutic massage, 23 (49%) to myofascial physical therapy and 44 (94%) completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group (p = 0.03). CONCLUSIONS: We judged the feasibility of conducting a full-scale trial of physical therapy methods and the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study.

Juror Decision-Making in a Child Trafficking Case: The Impact of Defendant and Victim Gender, Defendant Age, and Defendant Status.

There has been an increase in human trafficking in Canada from 2018 to 2019, which suggests a rising trend in human trafficking, and as such, the number of court cases are likely increasing. Because of this, the current study sought to examine how a defendant and victim's gender, and defendant social status and age impacted mock jurors' decision-making in a child trafficking case. Participants (N = 584) read a mock trial transcript depicting a child trafficking case. They were then asked to render a verdict, answer questions relating to perceptions of the victim and defendant and rate their level of agreements on statements concerning sex and human trafficking. Although there was no effect on dichotomous verdict, mock jurors attributed higher guilt ratings to the male trafficker. Moreover, participants reported more favorable perceptions of the victim when the trafficker was female, and the victim was male compared to female. Participants also reported more favorable perceptions of the victim when the trafficker was of high social status and younger compared to older. Additionally, when mock jurors were well-informed about trafficking victim blaming did not occur. The results of the current study provide some insight into juror perceptions of child sex trafficking cases.

Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic pain syndromes.

PURPOSE: We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes. MATERIALS AND METHODS: We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events during study treatment and rate of response to therapy as assessed by the patient global response assessment. Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. RESULTS: There were 23 (49%) men and 24 (51%) women randomized during a 6-month period. Of the patients 24 (51%) were randomized to global therapeutic massage, 23 (49%) to myofascial physical therapy and 44 (94%) completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group (p = 0.03). CONCLUSIONS: We judged the feasibility of conducting a full-scale trial of physical therapy methods and the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study.

Polycyclic Indoline Derivatives by Dearomatizing Anionic Cyclization of Indole and Tryptamine-Derived Ureas.

The base-promoted dearomatizing cyclization of anionic indole-containing urea derivatives provided tri- or tetracyclic indoline-containing scaffolds from lithiated urea intermediates. 3-Substituted indoles, including tryptamine derivatives, generally underwent the reaction in high yield and with excellent diastereoselectivity. In situ IR spectroscopy suggests a deprotonation-carbolithiation-reprotonation mechanism.

Regular in-situ simulation training of paediatric Medical Emergency Team leads to sustained improvements in hospital response to deteriorating patients, improved outcomes in intensive care and financial savings.

AIM OF THE STUDY: The introduction of a paediatric Medical Emergency Team (pMET) was accompanied by weekly in-situ simulation team training. Key ward staff participated in team training, focusing on recognition of the deteriorating child, teamwork and early involvement of senior staff. Following an earlier study [1], this investigation aimed to evaluate the long-term impact of ongoing regular team training on hospital response to deteriorating ward patients, patient outcome and financial implications. METHODS: Prospective cohort study of all deteriorating in-patients in a tertiary paediatric hospital requiring admission to paediatric intensive care (PICU) the year before, 1year after and 3 years after the introduction of pMET and team training. RESULTS: Deteriorating patients were recognised more promptly (before/1year after/3years after pMET; median time 4/1.5/0.5h, p<0.001), more often reviewed by consultants (45%/76%/81%, p<0.001) and more rapidly escalated to PICU (median time 10.5/5/3.5h, p=0.02). There was a significant reduction in associated PICU admissions (56/51/32, p=0.02) and PICU bed days (527/336/193, p<0.001). The total annual cost of training (£74,250) was more than offset by savings from reduced PICU bed days (£801,600 per annum). Introduction of pMET coincided with significantly reduced hospital mortality (p<0.001). CONCLUSION: These results indicate that lessons learnt by ward staff during team training led to sustained improvements in the hospital response to critically deteriorating in-patients, significantly improved patient outcomes and substantial savings. Integration of regular in-situ simulation training of medical emergency teams, including key ward staff, in routine clinical care has potential application in all acute specialties.

Newborn bloodspot results: predictive value of screen positive test for thalassaemia major.

AIM: There are limited published data on the performance of the percentage of haemoglobin A (Hb A) as a screening test for beta thalassaemia major in the newborn period. This paper aims to analyse data derived from a national newborn bloodspot screening programme for sickle cell disease on the performance of haemoglobin A (Hb A) as a screening test for beta thalassaemia major in the newborn period. METHODS: Newborn bloodspot sickle cell screening data from 2,288,008 babies were analysed. Data reported to the NHS Sickle Cell and Thalassaemia Screening Programme in England for the period 2005 to 2012 were also reviewed to identify any missed cases (4,599,849 babies). RESULTS: Within the cohort of 2,288,008 births, 170 babies were identified as screen positive for beta thalassaemia major using a cut-point of 1.5% HbA. There were 51 identified through look-back methods and 119 prospectively identified from 4 screening laboratories. Among 119 babies with prospective data, 7 were lost to follow up and 15 were false positive results. Using a cut-off value of 1.5% Hb A as a percentage of the total haemoglobin as a screening test for beta thalassaemia major in the newborn provides an estimated sensitivity of 99% (from the look back arm of the study) with a positive predictive value of 87% (from the prospective arm of the study). Excluding infants born before 32 weeks gestation, the positive predictive value rose to 95%. CONCLUSION: A haemoglobin A value of less than 1.5% is a reliable screening test for beta thalassaemia major in the newborn period.