Outcome and feasibility of radiotherapy bridging in large B-cell lymphoma patients receiving CD19 CAR T in the UK.

Radiotherapy (RT) has potential synergistic effects with chimeric antigen receptor (CAR) T but is not widely used as bridging therapy due to logistical challenges and lack of standardised protocols. We analysed RT bridging in a multicentre national cohort of large B-cell lymphoma patients approved for 3L axicabtagene ciloleucel or tisagenlecleucel across 12 UK centres. Of 763 approved patients, 722 were leukapheresed, 717 had data available on bridging therapy. 169/717 (24%) received RT bridging, 129 as single modality and 40 as combined modality treatment (CMT). Of 169 patients, 65.7% had advanced stage, 36.9% bulky disease, 86.5% elevated LDH, 41.7% international prognostic index (IPI) ≥3 and 15.2% double/triple hit at the time of approval. Use of RT bridging varied from 11% to 32% between centres and increased over time. Vein-to-vein time and infusion rate did not differ between bridging modalities. RT-bridged patients had favourable outcomes with 1-year progression-free survival (PFS) of 56% for single modality and 47% for CMT (1-year PFS 43% for systemic bridging). This is the largest cohort of LBCL patients receiving RT bridging prior to CAR T reported to date. Our results show that RT bridging can be safely and effectively used even in advanced stage and high-risk disease, with low dropout rates and excellent outcomes.

Management of lateral abdominal hernias.

PURPOSE: Lateral abdominal wall hernias are rare defects but, due to their location, repair is difficult, and recurrence is common. Few studies exist to support a standard protocol for repair of these lateral hernias. We hypothesized that anchoring our repair to fixed bony structures would reduce recurrence rates. METHODS: A retrospective review of all patients who underwent lateral hernia repair at our institution was performed. RESULTS: Eight cases (seven flank and one thoracoabdominal) were reviewed. The median defect size was 105 cm2 (range 36-625 cm2). The median operative time was 185 min (range 133-282 min). There were no major complications. One patient who was repaired without mesh attachment to bony landmarks developed a recurrence at ten months and subsequently underwent reoperation. Patients with mesh secured to bony landmarks were recurrence free at a median follow-up of 171 days. CONCLUSIONS: Lateral hernias present a greater challenge due to their anatomic location. An open technique with mesh fixation to bony structures is a promising solution to this complex problem.

Piscine reovirus, but not Jaundice Syndrome, was transmissible to Chinook Salmon, Oncorhynchus tshawytscha (Walbaum), Sockeye Salmon, Oncorhynchus nerka (Walbaum), and Atlantic Salmon, Salmo salar L.

A Jaundice Syndrome occurs sporadically among sea-pen-farmed Chinook Salmon in British Columbia, the westernmost province of Canada. Affected salmon are easily identified by a distinctive yellow discolouration of the abdominal and periorbital regions. Through traditional diagnostics, no bacterial or viral agents were cultured from tissues of jaundiced Chinook Salmon; however, piscine reovirus (PRV) was identified via RT-rPCR in all 10 affected fish sampled. By histopathology, Jaundice Syndrome is an acute to peracute systemic disease, and the time from first clinical signs to death is likely <48 h; renal tubular epithelial cell necrosis is the most consistent lesion. In an infectivity trial, Chinook Salmon, Sockeye Salmon and Atlantic Salmon, intraperitoneally inoculated with a PRV-positive organ homogenate from jaundiced Chinook Salmon, developed no gross or microscopic evidence of jaundice despite persistence of PRV for the 5-month holding period. The results from this study demonstrate that the Jaundice Syndrome was not transmissible by injection of material from infected fish and that PRV was not the sole aetiological factor for the condition. Additionally, these findings showed the Pacific coast strain of PRV, while transmissible, was of low pathogenicity for Atlantic Salmon, Chinook Salmon and Sockeye Salmon.

A multi-method approach to assessing deadlines and workload variation among newspaper workers.

OBJECTIVES: Working under frequent deadlines was previously found to be associated with upper limb work-related musculoskeletal disorders (WMSDs) in newspaper workers. Further investigation was required so that concrete recommendations for change could be offered to the workplace parties (labour and management of a large metropolitan newspaper). STUDY DESIGN: The assessment was based on three methods. A questionnaire was used to clarify time-related aspects of work on deadlines for a larger group of workers. Experience sampling was used to document temporal variation in various aspects of physical and psychological demands over work shifts and deadline cycles. Focus groups were also conducted. RESULTS: Differences were found between the "High" and "Low" deadline groups: Those working with frequent deadlines more frequently were required: to work together with others, to perform tasks on a specific schedule and specific order, to work at a fast paced, to perceive their work as hectic and "hard". Experience sampling showed differential trends in workload across daily, weekly, and no deadline days. The lack of breaks for extended periods of time leading up to a deadline was noticeable. The focus groups were useful in highlighting issues not addressed by the other two methods and to understand the feasibility of various possible interventions. CONCLUSIONS: The integration of results from all methods lead to recommendations for issues upon which to focus prevention related activities where deadlines are present: delays in work flow from others, interruptions from technology related problems, excessive work, insufficient staff/insufficient time, extra/unexpected work, compromising of work quality for speed, and lack of time for breaks.

Practice management skills for the nurse practitioner.

The faculties of three schools of nursing involved in a collaborative family nurse practitioner (FNP) program designed a study to address issues involved in preparing the nurse practitioner for the challenges of practice management in the clinical environment. The purposes of the study were to (1) identify business concepts necessary to successfully manage a primary care practice; (2) determine which of these concepts should be incorporated into an FNP curriculum; and (3) clarify information to be taught regarding each identified concept. Fifty-four business concepts related to primary care were identified from a literature review. A survey was then developed to assess the extent to which the identified concepts were necessary for an FNP to effectively manage a practice. Seven experts and five FNP faculty responded to the survey. The Content Validity Index (CVI) defined by Lynn (1986) was applied and 20 concepts necessary for an FNP to effectively manage a practice were identified. A focus group that included nurse practitioners (both faculty and nonfaculty) from the three collaborative sites connected by interactive telecommunications determined that all 20 of the identified concepts should be included in an FNP curriculum. Additionally, the focus group clarified relevant information to be taught regarding each identified concept.

Upper limb work-related musculoskeletal disorders among newspaper employees: cross-sectional survey results.

At a metropolitan newspaper office in Canada with extensive video display terminal (VDT) use, researchers carried out a survey (n = 1,007, 84% response) to establish baseline prevalence of work-related musculoskeletal disorders (WMSDs) and to identify demographic, postural, task, and psychosocial factors associated with WMSD symptoms. One-fifth of the respondents reported moderate or worse upper limb pain recurring at least monthly or lasting more than a week over the previous year. Logistic regression showed that employees who faced frequent deadlines and high psychological demands (fast work pace and conflicting demands), had low skill discretion and social support, spent more time keyboarding, or who had their screen in a non-optimal position were more likely to report moderate to severe symptoms. Women reported significantly higher levels of symptoms than men.

Prevalence of signs and symptoms of craniomandibular disorders and orofacial parafunction in 4-6-year-old African-American and Caucasian children.

Children, 4-6 years old, 153 Caucasian and 50 African-American, from a pre-school and kindergarten programme in a low income industrial area, who participated in a voluntary oral health examination, were questioned and examined for signs and symptoms of craniomandibular disorders (CMD) and of oral parafunctions. Most of the CMD signs and symptoms were mild. Eight per cent had recurrent (at least 1-2 times per week) TMJ pain, and 5% had recurrent neck pain, African-American children more often than Caucasian children (P < 0.05). Seventeen per cent had recurrent headache. Three per cent had recurrent earache. Pain or tiredness in the jaws during chewing was reported by 25% of the children, more often by African-American than by Caucasian children (P < 0.001) and more often by girls than by boys (P < 0.05). Pain at jaw opening occurred in 10% of the children, more often in the African-American than in the Caucasian group (P < 0.001). Thirteen per cent of the children had problems in opening the mouth. Deviation during opening was observed in 17% and reduced opening in 2%. Reduced lateral movements, locking or luxation were not observed in any child. Palpation pain was found in the lateral TMJ area in 16%, in the posterior TMJ area in 25%, in the temporalis and masseter areas in 10%, and pain for all regions was found more often in the African-American than in the Caucasian children (P < 0.01). Thirty-four per cent of the African-American, and 15% of the Caucasian children admitted to having ear noises (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Association between CMD signs and symptoms, oral parafunctions, race and sex, in 4-6-year-old African-American and Caucasian children.

The associations between oral parafunctions, signs and symptoms of craniomandibular disorders (CMD), race, and sex were analysed in recordings from 203 4-6-year-old African-American and Caucasian children. Significant correlations were found between bruxism, nail biting, thumb sucking and most of the CMD signs and symptoms. There were also significant associations between most of the signs and symptoms and race, while significant association with sex was found only regarding headache, TMJ sounds and chewing pain. Significant associations were found between most CMD signs and TMJ sounds supporting the view that joint sound recordings have diagnostic value. There were also significant associations between the pain variables recorded by questionnaire and those recorded by palpation, which indicates that reliable data can be obtained by interviewing children as young as five. The results of this study support the concept that oral parafunctions have a significant role in the aetiology of CMD. The results also show that race and sex need to be considered when analysing the possible aetiological role of oral parafunctions in CMD. Longitudinal studies, beginning with low age groups are needed to better determine the role of childhood oral parafunctions in CMD aetiology.

Resident and parental perceptions of adolescent problems and family communications in a low socioeconomic population.

This cross-sectional survey of a low socioeconomic patient group was designed to determine the prevalence and severity of parentally perceived behavioral problems in adolescents as well as to investigate the correlation between such problems and single parenting, family communications, and medical care delivered. The sample population consisted of 79 parents and 121 teenagers selected from a family practice center. The medical record and telephone interview were the sources of information. Results include a parental perception of a high prevalence of problems with school grades (48 percent), school attendance (38 percent), and household problems (chores and sibling rivalry). Of low prevalence but high severity were perceived problems related to suicidal ideation, running away, sexual activity, and gang membership. Single-parent homes had a threefold higher incidence of behavioral problems, a greater degree of communication, and a lower use of community resources than two-parent families. None of the approximately 400 perceived behavioral problems listed by parents was found in the family physicians' master problem list. The results indicate the need for physician education of low socioeconomic and single-parent patients with regard to communication and coping style. In addition, it appears that training programs should provide more education in the care of adolescents.

Fatty acid composition of prepared infant formulas.

The fatty acid composition of eight American, eight European, and four Japanese prepared infant formulas were determined and compared with fat sources listed on labels. Unsaturated fatty acids ranged from 20 to 83 per cent of the total. Generally, the fatty acid composition was consistent with the types of ingredients used; those with corn or soy oil had the highest levels of unsaturated fat, and those with milk fat the lowest; formulas of mixed composition fell in between. The formulas were compared with values for the fatty acid composition of human milk in the literature.

Rapid detection of ampicillin-resistant Haemophilus influenzae and their susceptibility to sixteen antibiotics.

Ampicillin-resistant and -susceptible strains of Haemophilus influenzae were tested for susceptibility to 16 antibiotics. Chloramphenicol and a new cephalosporin, cefamandole, were most active with minimal inhibitory concentrations (MICs) for all bacteria tested between 0.5 to 2.0 mug/ml. All but two organisms were susceptible to tetracycline. Ampicillin-resistant strains of H. influenzae were less susceptible (MIC, 4 to 32 mug/ml) to carbenicillin and ticarcillin than ampicillin-susceptible organisms (MIC, 0.25 to 1.0 mug/ml). A rapid assay for beta-lactamase, utilizing a chromogenic cephalosporin substrate, detected enzyme production in all 17 ampicillin-resistant strains of H. influenzae.

Viral protein synthesis in bacteriophage phi 29-infected Bacillus subtilis.

Twenty-three (14)C-labeled phage phi29-specific proteins in lysates of UV-irradiated Bacillus subtilis have been resolved by sodium dodecyl sulfate polyacrylamide gel electrophoresis and identified by autoradiography. Included in this group of proteins are the six major structural proteins of the virion. Analysis of the temporal sequence of viral protein synthesis indicates that three groups of proteins can be identified by time of appearance, beginning at 2 to 4, 4 to 6, or 8 to 10 min after infection, respectively. These proteins account for approximately 90% of the coding capacity of the phi29 genome.

Transcription during the development of bacteriophage phi 29: production of host- and phi 29-specific ribonucleic acid.

The synthesis of ribonucleic acid (RNA) during development of the virulent Bacillus subtilis bacteriophage phi29 has been analyzed. Transcription of host deoxyribonucleic acid (DNA) continues at the preinfection rate throughout the latent period of viral growth. RNA-DNA hybridization was used to show that host messenger RNA synthesis continues late into the phage lytic cycle. Amino acid-labeling experiments show that this RNA is continuously used to produce protein. Ribosomal RNA production is not inhibited by phage infection. Small quantities of phage-specific RNA first appear between min 6 and 9 after infection. This RNA is made exclusively from one of the phi29 DNA strands. At 12 min postinfection, when phage DNA replication commences, large quantities of viral RNA start to be synthesized. This RNA appears to be transcribed from both strands of phi29 DNA. Studies with rifamycin and rifamycin-resistant host strains showed that the production of all phage phi29-specific RNA requires those components of the host RNA polymerase which are sensitive to this antibiotic. Thus, phage phi29 does not stop transcription of host DNA and may produce only one element for regulation of transcription of its own DNA. These findings may reflect the limited amount of genetic information carried by this phage.