Leiomyoma is a benign tumor of smooth muscle origin most common in areas of the body with abundant smooth muscle including the gynecologic, genitourinary, and gastrointestinal system. Leiomyoma ...outside of these locations is believed to arise from vascular smooth muscle and arrector pili muscles. Leiomyoma of an extremity is a rare diagnosis, especially when present in a digit of the hand due to the paucity of smooth muscle in this location. We report three cases of leiomyoma of a digit of the hand.
•Leiomyoma is a rare but important differential diagnosis for benign masses found in the digit.•Leiomyoma can be found in association with the neurovascular bundle, tendon sheath, or confined to soft tissue.•Leiomyoma can show variable staining patterns for smooth muscle markers.
Aim
We report on two Phase 1, open‐label, single‐arm studies assessing the effect of osimertinib on simvastatin (CYP3A substrate) and rosuvastatin (breast cancer resistance protein substrate BCRP ...substrate) exposure in patients with advanced epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancer who have progressed after treatment with an EGFR tyrosine kinase inhibitor, to determine, upon coadministration, whether osimertinib could affect the exposure of these agents.
Methods
Fifty‐two patients in the CYP3A study (pharmacokinetic PK analysis, n = 49), and 44 patients in the BCRP study were dosed (PK analysis, n = 44). In the CYP3A study, patients received single doses of simvastatin 40 mg on Days 1 and 31, and osimertinib 80 mg once daily on Days 3–32. In the BCRP study, single doses of rosuvastatin 20 mg were given on Days 1 and 32, and osimertinib 80 mg once daily on Days 4–34.
Results
Geometric least squares mean (GLSM) ratios (90% confidence intervals) of simvastatin plus osimertinib for area under the plasma concentration–time curves from zero to infinity (AUC) were 91% (77–108): entirely contained within the predefined no relevant effect limits, and Cmax of 77% (63, 94) which was not contained within the limits. GLSM ratios of rosuvastatin plus osimertinib for AUC were 135% (115–157) and Cmax were 172 (146, 203): outside the no relevant effect limits.
Conclusions
Osimertinib is unlikely to have any clinically relevant interaction with CYP3A substrates and has a weak inhibitory effect on BCRP. No new safety concerns were identified in either study.
Pre-operative chemoradiotherapy (CRT) for MRI-defined, locally advanced rectal cancer is primarily intended to reduce local recurrence rates by downstaging tumours, enabling an improved likelihood of ...curative resection. However, in a subset of patients complete tumour regression occurs implying that no viable tumour is present within the surgical specimen. This raises the possibility that surgery may have been avoided. It is also recognised that response to CRT is a key determinant of prognosis. Recent radiological advances enable this response to be assessed pre-operatively using the MRI tumour regression grade (mrTRG). Potentially, this allows modification of the baseline MRI-derived treatment strategy. Hence, in a 'good' mrTRG responder, with little or no evidence of tumour, surgery may be deferred. Conversely, a 'poor response' identifies an adverse prognostic group which may benefit from additional pre-operative therapy.
TRIGGER is a multicentre, open, interventional, randomised control feasibility study with an embedded phase III design. Patients with MRI-defined, locally advanced rectal adenocarcinoma deemed to require CRT will be eligible for recruitment. During CRT, patients will be randomised (1:2) between conventional management, according to baseline MRI, versus mrTRG-directed management. The primary endpoint of the feasibility phase is to assess the rate of patient recruitment and randomisation. Secondary endpoints include the rate of unit recruitment, acute drug toxicity, reproducibility of mrTRG reporting, surgical morbidity, pathological circumferential resection margin involvement, pathology regression grade, residual tumour cell density and surgical/specimen quality rates. The phase III trial will focus on long-term safety, regrowth rates, oncological survival analysis, quality of life and health economics analysis.
The TRIGGER trial aims to determine whether patients with locally advanced rectal cancer can be recruited and subsequently randomised into a control trial that offers MRI-directed patient management according to radiological response to CRT (mrTRG). The feasibility study will inform a phase III trial design investigating stratified treatment of good and poor responders according to 3-year disease-free survival, colostomy-free survival as well as an increase in cases managed without a major resection.
ClinicalTrials.gov, ID: NCT02704520 . Registered on 5 February 2016.
PURPOSEThe implementation and quality assessment of a pharmacy services call center (PSCC) for outpatient pharmacies and specialty pharmacy services within an academic health system are described.
...SUMMARYProlonged wait times in outpatient pharmacies or hold times on the phone affect the ability of pharmacies to capture and retain prescriptions. To support outpatient pharmacy operations and improve quality, a PSCC was developed to centralize handling of all outpatient and specialty pharmacy calls. The purpose of the PSCC was to improve the quality of pharmacy telephone services by (1) decreasing the call abandonment rate, (2) improving the speed of answer, (3) increasing first-call resolution, (4) centralizing all specialty pharmacy and prior authorization calls, (5) increasing labor efficiency and pharmacy capacities, (6) implementing a quality evaluation program, and (7) improving workplace satisfaction and retention of outpatient pharmacy staff. The PSCC centralized pharmacy calls from 9 pharmacy locations, 2 outpatient clinics, and a specialty pharmacy. Since implementation, the PSCC has achieved and maintained program goals, including improved abandonment rate, speed of answer, and first-call resolution. A centralized 24-7 support line for specialty pharmacy patients was also successfully established. A quality calibration program was implemented to ensure service quality and excellent patient experience. Additional ongoing evaluations measure the impact of the PSCC on improving workplace satisfaction and retention of outpatient pharmacy staff.
CONCLUSIONThe design and implementation of the PSCC have significantly improved the health system’s patient experiences, efficiency, and quality.
Plagued by geographic isolation, poverty, and acute shortages of health professionals and hospital beds, the South was dubbed by Surgeon General Thomas Parran "the nation's number one health ...problem." The improvement of southern, rural, and black health would become a top priority of the U.S. Public Health Service during the Roosevelt and Truman administrations.
Karen Kruse Thomas details how NAACP lawsuits pushed southern states to equalize public services and facilities for blacks just as wartime shortages of health personnel and high rates of draft rejections generated broad support for health reform. Southern Democrats leveraged their power in Congress and used the war effort to call for federal aid to uplift the South. The language of regional uplift, Thomas contends, allowed southern liberals to aid blacks while remaining silent on race. Reformers embraced, at least initially, the notion of "deluxe Jim Crow"-support for health care that maintained segregation. Thomas argues that this strategy was, in certain respects, a success, building much-needed hospitals and training more black doctors.
By the 1950s, deluxe Jim Crow policy had helped to weaken the legal basis for segregation. Thomas traces this transformation at the national level and in North Carolina, where "deluxe Jim Crow reached its fullest potential." This dual focus allows her to examine the shifting alliances-between blacks and liberal whites, southerners and northerners, activists and doctors-that drove policy.Deluxe Jim Crowprovides insight into a variety of historical debates, including the racial dimensions of state building, the nature of white southern liberalism, and the role of black professionals during the long civil rights movement.
The first known university food pantry started at Michigan State University in 1993. Since then, campus food pantries are more widespread, although little is known about them. The current study ...examined how college pantries best serve students and foster their success. Twenty‐eight food pantry directors and staff from across sixteen Michigan college campuses engaged in concept mapping, a technique used to examine the interrelationships among concepts understood by stakeholders. Analyses identified six concepts, examined importance of each concept as assigned by participants, and evaluated variation among institutions. Implications for findings and future research directions are discussed.
ObjectiveTo understand poststroke fatigue from the perspective of stroke survivors and caregivers expressed in an online discussion forum.DesignThe search terms ‘tiredness’, ‘fatigue’, ‘tired’, ...‘weary’ and ‘weariness’ were used to identify relevant posts. Thematic analysis performed by two independent researchers who coded all forum posts and identified pertinent themes. Posts were coded in relation to two research questions: (1) how is poststroke fatigue described? and (2) what coping strategies are suggested to target poststroke fatigue? Each theme was then summarised by a lead quotation in forum users’ own words.SettingUK-based web forum hosted by Stroke Association, TalkStroke. Archives from 2004 to 2011 were accessed.Participants65 stroke survivors and caregivers (mean age 54 years, 61% female) contributed to 89 relevant posts that included a relevant search term. This included 38 stroke survivors, 23 individuals with family or carer role and 4 others unidentified.ResultsSix themes were generated: (1) medicalisation of poststroke fatigue: ‘a classic poststroke symptom’, (2) a tiredness unique to stroke: ‘a legacy of stroke’, (3) normalisation and acceptance of poststroke fatigue: ‘part and parcel of stroke’, (4) fighting the fatigue: ‘an unwelcome guest’, (5) survivors’ and caregivers’ biological explanations: ‘the brain healing’ and (6) coping mechanisms: ‘pace yourself’. Forum users also repeatedly commented that poststroke fatigue was ‘not understood by the profession’.ConclusionThis is the first study to employ data from an online forum to characterise poststroke fatigue. Our data are considered naturalistic owing to the absence of a researcher guiding the discussion and thus generates useful insights for healthcare professionals. Findings suggest a requirement for consistent understanding and explanation to be provided by healthcare professionals. The beliefs outlined here highlight the gap between clinical and community knowledge. Further research to translate understanding of patient and carer perspective into improved management of poststroke fatigue is required.
Environmental particulate matter (PM) pollutants adversely affect human health, but the molecular basis is poorly understood. The ion channel transient receptor potential vanilloid-1 (TRPV1) has been ...implicated as a sensor for environmental PM and a mediator of adverse events in the respiratory tract. The objectives of this study were to determine whether TRPV1 can distinguish chemically and physically unique PM that represents important sources of air pollution; to elucidate the molecular basis of TRPV1 activation by PM; and to ascertain the contributions of TRPV1 to human lung cell and mouse lung tissue responses exposed to an insoluble PM agonist, coal fly ash (CFA1). The major findings of this study are that TRPV1 is activated by some, but not all of the prototype PM materials evaluated, with rank-ordered responses of CFA1 > diesel exhaust PM > crystalline silica; TRP melastatin-8 is also robustly activated by CFA1, whereas other TRP channels expressed by airway sensory neurons and lung epithelial cells that may also be activated by CFA1, including TRPs ankyrin 1 (A1), canonical 4α (C4α), M2, V2, V3, and V4, were either slightly (TRPA1) or not activated by CFA1; activation of TRPV1 by CFA1 occurs via cell surface interactions between the solid components of CFA1 and specific amino acid residues of TRPV1 that are localized in the putative pore-loop region; and activation of TRPV1 by CFA1 is not exclusive in mouse lungs but represents a pathway by which CFA1 affects the expression of selected genes in lung epithelial cells and airway tissue.
Interferon-β (IFN-β) has been identified as the signature cytokine induced via the Toll-like receptor (TLR) 4, “MyD88-independent” signaling pathway in macrophages stimulated by Gram-negative ...bacterial lipopolysaccharide (LPS). In this study, we analyzed the responses of macrophages derived from wild-type (IFN-β+/+) mice or mice with a targeted mutation in IFN-β (IFN-β-/-) to the prototype TLR4 agonist, Escherichia coli LPS. A comparison of basal and LPS-induced gene expression (by reverse transcription-PCR, real-time PCR, and Affymetrix microarray analyses) resulted in the identification of four distinct patterns of gene expression affected by IFN-β deficiency. Analysis of a subset of each group of differentially regulated genes by computer-assisted promoter analysis revealed putative IFN-responsive elements in all genes examined. LPS-induced activation of intracellular signaling molecules, STAT1 Tyr-701, STAT1 Ser-727, and Akt, but not p38, JNK, and ERK MAPK proteins, was significantly diminished in IFN-β-/-versus IFN-β+/+ macrophages. “Priming” of IFN-β-/- macrophages with exogenous recombinant IFN-β significantly increased levels of LPS-induced gene expression for induction of monocyte chemotactic protein 5, inducible nitric-oxide synthase, IP-10, and IL-12 p40 mRNA, whereas no increase or relatively small increases were observed for IL-1β, IL-6, monocyte chemotactic protein 1, and MyD88 mRNA. Finally, IFN-β-/- mice challenged in vivo with LPS exhibited increased survival when compared with wild-type IFN-β+/+ controls, indicating that IFN-β contributes to LPS-induced lethality; however, not to the extent that one observes in mice with more complete pathway deficiencies (e.g. TLR4-/- or TRIF-/- mice). Collectively, these findings reveal unanticipated regulatory roles for IFN-β in response to LPS in vitro and in vivo.
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