The 'goodness-of-fit' of fit models: creating a multidimensional survey for person-organisation and person-group fit in health care.

BACKGROUND: Person-environment fit, which examines the individual's perceptions of if, and in what way, he or she is compatible with aspects of the work context, offers a promising conceptual model for understanding employees and their interactions in health care environments. There are numerous potential ways an individual feels they "fit" with their environment. The construct was first noted almost thirty years ago, yet still remains elusive. Feelings of fit with one's environment are typically measured by surveys, but current surveys encompass only a subset of the different components of fit, which may limit the conclusions drawn. Further, these surveys have rarely been conducted in a focused way in health care settings. METHOD: This article describes the development of a multidimensional survey tool to measure fit in relation to the person's work group (termed person-group (P-G) fit) and their organisation (person-organisation (P-O) fit). The participants were mental health care employees, volunteers, and university interns (n = 213 for P-O fit; n = 194 for P-G fit). Confirmatory Factor Analyses (CFAs) were conducted using LISREL. RESULTS: Valid and reliable sub-scales were found. CONCLUSION: This advanced multidimensional survey tool can be used to measure P-O and P-G fit, and illuminates new information about the theoretical structure of the fit construct.

The Quality of Care for Australian Children with Autism Spectrum Disorders.

Knowledge about the quality of care delivered to children with autism spectrum disorders (ASD) in relation to that recommended by clinical practice guidelines (CPGs) is limited. ASD care quality indicators were developed from CPGs and validated by experts, then used to assess the quality of care delivered by general practitioners (GPs) and pediatricians in Australia. Data were retrospectively collected from the medical records of 228 children (≤ 15 years) with ASD for 2012-2013. Overall quality of care was high, but with considerable variation among indicators, and between GPs and pediatricians-e.g., GPs were less likely to complete the assessment care bundle (61%; 95% CI 21-92). Findings highlight potential areas for improvement in the need for standardized criteria for diagnosis.

Physician attitudes about non-medical switching to biosimilars: results from an online physician survey in the United States.

OBJECTIVE: This study was designed to understand the level of familiarity of US rheumatologists, gastroenterologists and dermatologists with biosimilar therapies, their experience with non-medical switching (switching medications for reasons unrelated to patient health) of patients between biologics and their attitudes towards switching from a biologic to a biosimilar. METHODS: A total of 297 US physicians who currently prescribe biologics for their patients completed a 15-minute online survey. Rheumatologists, dermatologists and gastroenterologists were included. RESULTS: The majority of physicians (84%) did not want stable patients undergoing a non-medical switch to a biosimilar. While 60% of physicians believed non-medical switching to biosimilars may have a positive impact on healthcare system costs, multiple negative impacts were also expected. A majority of physicians anticipated a negative impact on patient mental health (59%), treatment efficacy (57%), patient safety (53%) and physician office management (60%). CONCLUSIONS: The majority of physicians had concerns regarding non-medical switching to biosimilars and the impact such switching would have on patient care and physician practice.

Patient attitudes about non-medical switching to biosimilars: results from an online patient survey in the United States.

OBJECTIVE: To evaluate patient attitudes regarding non-medical switching (NMS) to biosimilars among patients with autoimmune disease currently receiving a biologic. METHODS: An online survey was conducted among patients meeting the following criteria: ≥18 years of age; residing in the US; diagnosis of rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis or psoriatic arthritis; currently taking a biologic; and consenting to participate. Patients answered questions about their attitudes and experiences related to NMS. Descriptive statistics were used to summarize responses. RESULTS: A total of 1696 patients completed the 20-min survey. Eighty-five per cent of patients were concerned that biosimilars wouldn't treat their disease as well; 85% didn't want to switch to a biosimilar if their current biologic was helping their disease; and 83% were concerned that switching may cause more side-effects. Twenty per cent of patients had previously received notification about a potential NMS to another biologic (that was not a biosimilar) from their insurance company. Of these, 79% took at least one action to avoid the NMS and 45% ultimately switched. Of these patients (n = 150), 67% indicated that their previous biologic worked well for them and 70% didn't want to switch to another biologic. Most patients who switched (67%) did so to avoid paying a higher cost. More than half (56%) went without therapy for administrative reasons during the period of transition from the old biologic to the other treatment. CONCLUSIONS: Patients reported multiple concerns about NMS that might impact treatment outcomes, and many of the patients who non-medically switched in this survey missed treatments. Future studies should be conducted on patient expectations and experiences with NMS to understand the impact on healthcare delivery, treatment persistency, and patient outcomes. The patient perspective and experience should be considered by decision-makers when developing coverage policies for biosimilar medications and associated communication strategies.

Managers' perceptions of the effects of a national mandatory accreditation program in Danish hospitals. A cross-sectional survey.

OBJECTIVE: This study aimed to examine and compare middle and senior hospital managers' perceptions of the effects of a mandatory accreditation program in Denmark, the Danish Healthcare Quality Program (Den Danske Kvalitetsmodel [DDKM]) after it was terminated in 2015. DESIGN: A cross-sectional online questionnaire survey. SETTING: All 26 somatic and psychiatric public hospitals in Denmark. PARTICIPANTS: All senior and middle managers. METHODS: A questionnaire with open and closed response (five-point Likert scale) questions. Quantitative data were analyzed descriptively and through ordered logistic regression by management level. Qualitative data were subjected to a software-assisted content analysis. RESULTS: The response rate was 49% (533/1059). In both the qualitative and quantitative data sets, participants perceived the DDKM as having: led to an increased focus on registration, documentation and additional and unnecessary procedures. While the DDKM was perceived as increasing a focus on quality, the time required for accreditation was at the expense of patient care. There were significant differences by management level, with middle managers having more negative perceptions of the DDKM related to time spent on documentation and registration. CONCLUSION: While the DDKM had some perceived benefits for quality improvement, it was ultimately considered time-consuming and outdated or having served its purpose. Including managers, particularly middle managers, in refinements to the new quality improvement model could capitalize on the benefits while redressing the problems with the terminated accreditation program.

Factors Associated with Pre-Event Hydration Status and Drinking Behavior of Middle-Aged Cyclists.

OBJECTIVES: Water is an essential nutrient for thermoregulation, metabolism, cognition, and overall physiological homeostatic function. However, aging adults display a blunted thirst mechanism and subsequently have an increased risk for dehydration or hyponatremia. Fluid consumption behaviors are modifiable and the importance of practicing adequate drinking behaviors for aging adults is amplified during exercise. Identification of aging adult's hydration beliefs and how they attain hydration advice could provide valuable information into ways to promote better drinking habits to reduce fluid imbalances. Thus, this investigation evaluated the knowledge, beliefs and behaviors of middle-aged cyclists (MA) that were associated with hydration status and drinking behavior, before and during a 164-km mass-participation event (ambient temperature, 33.3±2.8ºC(mean±SD)). DESIGN: This cross-sectional field study retrospectively grouped participants by their second urine specific gravity (Usg) measurement of the event morning prior to a mass participation cycling event. Usg was assessed via handheld refractometer. SETTING: The Hotter N' Hell Hundred 164-km cycling event in Wichita Falls, Texas during the month of August. PARTICIPANTS: 36 male recreational cyclists (age, 53±9 y(mean±SD)). MEASUREMENTS: Participants were grouped according their urine specific gravity as either slightly hyperhydrated (SH; n=12, Usg≤1.014), euhydrated (EUH; n=12, Usg, 1.015-1.020), or slightly dehydrated (SD; n=12, Usg≥1.021). Exercise histories and questionnaires were recorded 24-48 h prior to the cycling event. RESULTS: Regardless of pre-event hydration status, all groups experienced a similar body mass loss during the 164-km event and finished with statistically similar exercise times; also, drinking behavior within all groups was influenced by multiple factors. The primary factors associated with MA cyclist drinking behavior were trial and error/personal history and thirst; further, the majority of cyclists (≥65%) in SH, EUH, and SD believed that dehydration affects performance negatively. The least important factors included rehydration recommendations from scientific and sports medicine organizations, plus information from sports drink manufacturers. CONCLUSION: Considering the complexity of the present findings and the physiological changes that accompany aging such as delayed thirst perception, we recommend that MA cyclists formulate an individualized drinking plan that is based on observations during exercise.

Increased chromosome translocations and aneuploidy in peripheral blood lymphocytes of patients having revision arthroplasty of the hip.

The long-term biological effects of wear debris are unknown. We have investigated whether there is any evidence of cumulative mutagenic damage in peripheral blood lymphocytes of patients undergoing revision arthroplasty of predominantly metal-on-plastic total hip replacements compared with those at primary arthroplasty. There was a threefold increase in aneuploidy and a twofold increase in chromosomal translocations which could not be explained by the confounding variables of smoking, gender, age and diagnostic radiographs. In the patients with TiVaAl prostheses there was a fivefold increase in aneuploidy but no increase in chromosomal translocations. By contrast, in patients with cobalt-chrome prostheses there was a 2.5-fold increase in aneuploidy and a 3.5-fold increase in chromosomal translocations. In six patients with stainless-steel prostheses there was no increase in either aneuploidy or chromosomal translocations. Our results suggest that future epidemiological studies of the putative long-term risks of joint replacement should take into account the type of alloy used in the prosthesis.

Genetic analysis of the connexin-26 M34T variant: identification of genotype M34T/M34T segregating with mild-moderate non-syndromic sensorineural hearing loss.

Mutations in the human gap junction beta-2 gene (GJB2) that encodes connexin-26 have been shown to cause non-syndromic sensorineural hearing loss (NSSNHL) at the DFNB1 locus on 13q11. Functional and genetic data regarding the disease causing potential of one particular GJB2 sequence variant, 101 T-->C (M34T), have proven contradictory. In this study, we found the prevalence of the M34T allele in a cohort of white sib pairs and sporadic cases with NSSNHL from the United Kingdom and Ireland to be 3.179% of chromosomes screened. Significantly, we identified the first M34T/M34T genotype cosegregating in a single family with mid to high frequency NSSNHL. Screening a control population of 630 subjects we identified 25 M34T heterozygotes; however, no M34T homozygotes were detected. Surprisingly, the majority of M34T alleles (88%) were in cis with a 10 bp deletion in the 5' non-coding sequence. This non-coding deletion was also homozygous in the homozygous M34T subjects. Microsatellite analysis of flanking loci in M34T heterozygotes and controls does not define an extensive ancestral haplotype but preliminary data suggest two common alleles in subjects with the M34T allele. In summary, we provide data that support M34T acting as a recessive GJB2 allele associated with mild-moderate prelingual hearing impairment.

A comparison of fluorescent SSCP and denaturing HPLC for high throughput mutation scanning.

We examined 67 different mutations in 16 different amplicons in a comparison of mutation detection by fluorescent single strand conformation polymorphism (F-SSCP) and by denaturing HPLC (DHPLC). F-SSCP was used to analyze fluorescent amplicons with internal size standards and automated fragment analysis (GeneScan, PE Applied Biosystems, Foster City, CA). In DHPLC, unlabelled amplicons were analyzed by reverse phase HPLC with fragment detection by absorbance at 260nm. Both methods had high sensitivity (95-100%) and specificity (100%). Overall, F-SSCP with external temperature control was the more sensitive method, but DHPLC was particularly useful for the rapid analysis of novel fragments.

Chromatographic and hyphenated methods for elemental speciation analysis in environmental media.

This review discusses chromatographic techniques that permit the analysis of speciated metals in the environment using conventional detectors, such as UV, and element-specific detectors, such as flame atomic absorption spectrometry, electrothermal atomic absorption spectrometry and inductively coupled plasma mass spectrometry. The importance of determining precise elemental forms in hazardous waste-contaminated soil, water and biota in terms of toxicity is outlined. Previous reviews on this subject are described and recent research on this subject is discussed. Most of the work cited has been performed in the 1990s and a table summarizing the chromatographic method and the detector system used, including brief comments on the work, is included to enable quick reference.

Do milk-borne cytokines and hormones influence neonatal immune cell function?

Cytokines, growth factors and various hormones collectively control the proliferation, survival, differentiation and function of immune cells. A wide array of these compounds is present in maternal milk and ingested by neonates during a period of rapid maturation of gut-associated and peripheral lymphoid tissues. The functional consequences of most milk immunomodulatory constituents in neonates are unknown. However, there is evidence that milk prolactin acts as a developmental regulator of the neonatal immune system, supporting the premise that milk constituents with immunomodulatory activity may serve as neonatal immunodevelopment agents.

Terminal beta-linked tyvelose creates unique epitopes in Trichinella spiralis glycan antigens.

Indirect evidence that the immunodominant N-glycans of the parasite, Trichinella spiralis are capped by novel beta-linked 3,6-dideoxy-D-arabinohexopyranosyl residues (tyvelose, Tyv) was obtained from immunochemical assays employing monoclonal antibodies and synthetic oligosaccharides. Three of four previously characterized monoclonal antibodies generated from the lymphocytes of T.spiralis infected rats bind BSA glycoconjugates bearing the synthetic epitope beta-D-Tyvp(1-->3)-beta-D-GalNAcp but not to the corresponding alpha-D-Tyvp(1-->3)-beta-D-GalNAcp-BSA glycoconjugate. Monosaccharide and disaccharide glycoside inhibition data mirrors the results of the direct binding experiments. The branched tetrasaccharide beta-D-Tyv(1-->3)-beta-D-GalNAcp(1-->4)[alpha-L-Fucp(1 -->3)] beta-D-GalNAcp is the most active synthetic oligosaccharide inhibitor for all four monoclonal antibodies studied, while the corresponding alpha-D-Tyv containing tetrasaccharide and the core trisaccharide beta-D-GalNAcp(1-->4)[alpha-L-Fucp(1-->3)]beta-D-GlcNAcp+ ++ are inactive. The exceptional inhibitory activity of the disaccharide beta-D-Tyvp(1-->3)-beta-D-GalNAcp with one mAb (18H) compared to that of the branched tetrasaccharide beta-D-Tyvp(1-->3)-beta-D-GalNAcp(1-->4)[alpha-L-Fucp( 1-->3)]-beta-D-GlcNAcp is indicative of the presence of linear, nonfucosylated glycan epitopes (beta-D-Tyvp(1-->3)-beta-D-GalNAcp(1-->4) beta-D-GlcNAcp) that lack a fucose residue in one arm of the antigenic, tetra-antennary N-glycan. This observation supports earlier FAB-mass spectrometry evidence for the existence of tetra-antennary, core fucosylated glycans that lack a fucose residue on one of their antennae.

Digestive enzymes in human milk: stability at suboptimal storage temperatures.

BACKGROUND: Women who return to work outside of the home while still breastfeeding must often store the expressed milk at less than optimal temperatures. Human milk provides digestive enzymes (amylase and lipase) that compensate in the newborn for immature pancreatic function. METHODS: We have assessed the stability of amylase and bile salt-dependent lipase after storage for 1-24 h at 15, 25, and 38 degrees C. RESULTS: Both enzymes were stable at 15 and 25 degrees C for 24 h, whereas at 38 degrees C there was a 15 and 20% decrease in lipase and amylase activity, respectively. The stability of milk lipoprotein lipase was also tested. This very labile enzyme was more stable in milk than previously reported for blood and tissues, i.e., 20 and 50% decrease in activity after storage at 15 or 25 degrees C for 24 h, respectively. A two-unit drop in milk pH by 24 h of storage would not affect the activity of digestive enzymes, which are stable at pH > 3.5. CONCLUSIONS: We conclude that milk provides the same compensatory digestive activity after short-term storage, even at relatively high temperature, as when fed fresh to the infant.

Milk-borne prolactin and neonatal development.

Milk is primarily regarded as a food furnishing essential nutrients for infant growth and development, but milk can also serve as a vehicle for mother to neonate transfer of molecules that regulate development. A wide array of biologically active compounds such as hormones, cytokines and enzymes are present in milk, especially early milk. The premise that prolactin (PRL) in milk is an important and possibly essential developmental factor for the newborn is explored. Both PRL and structurally modified isoforms are abundant in early milk and gradually diminish with the progression of lactation. Milk PRL is absorbed and biologically active in the neonate. Assays of PRL variants, experimental paradigms to test them as developmental regulators and the body of evidence supporting the hypothesis that milk PRL regulates differentiation and maturation of neonatal neuroendocrine, reproductive, and immune systems is presented.

Breastfeeding and the working mother: effect of time and temperature of short-term storage on proteolysis, lipolysis, and bacterial growth in milk.

BACKGROUND: Women who breastfeed have to store expressed milk while at work for later feeding to their infants; however, storage conditions are often not optimal. OBJECTIVE: Top assess microbial growth and stability of milk protein and lipid at 15 degrees C to 38 degrees C for up to 24 hours. METHODS: Sixteen healthy women who breastfed exclusively, either at home (n=11) or who expressed milk for their infants (n=5), were studied during early (1 month) or late (5 to 6 months) lactation. Expressed milk was stored at 15 degrees C, 25 degrees C, and 38 degrees C for 1 to 24 hours for quantitation of pH, proteolysis, and lipolysis; bacterial growth was quantified at 0, 4, 8, and 24 hours of storage. RESULTS: Milk pH decreased 2 units by 24 hours of storage at all temperatures tested. Proteolysis was minimal during milk storage at 15 degrees C or at 25 degrees C for 24 hours and was apparent only after 24 hours of storage at 38 degrees C. Lipolysis was rapid, starting in the first hours of storage and progressing to 8% at 24 hours. Thus, while the greatest increment in proteolysis products was a 40% increase above baseline after 24 hours of storage at 38 degrees C, free fatty acid concentration at this storage time was 440% to 710% higher than in freshly expressed milk. Bacterial growth was restricted mainly to nonpathogens, was minimal at 15 degrees C throughout the 24 hours of storage, was low at 25 degrees C for the first 4 to 8 hours, and was considerably higher at 38 degrees C even during the relatively short period of 4 hours. CONCLUSIONS: Storage of human milk is safe at 15 degrees C for 24 hours, whereas at 25 degrees C it is safe for 4 hours. Milk should not be stored at 38 degrees C. Minimal proteolysis during storage suggests that milk proteins probably maintain their structure and function during short-term storage, while the marked lipolysis might slow bacterial growth during this time.

Automated genotyping in diagnosis.

At present automated genotyping in diagnosis involves the detection, digitrzation, and analysis of labeled DNA using computer software. This chapter describes the use of the Applied Biosystems (Foster City, CA) 373 DNA Sequencer and Genescan 672 software for sizing fluorescently labeled PCR products in a diagnostic molecular genetics laboratory. The Applied Biosystems Genotyper software is not covered since this is not used at present in this laboratory. An outline of the steps involved in automated genotyping, from polymerase chain reaction (PCR) to archiving data, is shown in Fig. 1. Fig. 1. Overview of the procedure. Labeled PCR products are produced by either incorporation of fluorescent dNTPs or labeled primers. A polyacrylamide gel is cast, scanned, and prerun, and the Genescan collection and analysis files are set up. The PCR products are mixed with a size standard, denatured, and loaded onto the prerun gel. After electrophoresrs the collected data is transferred to another Macintosh for analysis. A results file is generated and the PCR products are scored and checked. The results file is then archived.

Bioactive and immunoreactive prolactin variants in human milk.

Human milk from mothers of term (T) and preterm (PT) infants was collected during early (days 2-7), mature (2-16 weeks), or late (> 16 weeks) lactation. PRL-like bioactivity (B) was measured by Nb2 cell proliferation, and PRL immunoreactivity (I) was determined by RIA. PRL activity is reported in PRL equivalents (1 PRL equivalent = 1 ng NIDDK reference material). Milk from early lactation contained significantly greater PRL-like B compared to I (T:B, 132.5 +/- 13.0; I, 83.43 +/- 12; PT:B, 195.8 +/- 56; I, 74.45 +/- 13.7). PRL-like B and I declined as lactation progressed (T mature: B, 41.74 +/- 8.9; I, 27.19 +/- 5.5; T late: B, 17.84 +/- 5.5; I, 27.33 +/- 1.8; PT mature: B, 59.85 +/- 16; I, 45.16 +/- 4.3). Milk PRL B to I ratios were consistently greater than serum B to I ratios during early lactation (milk: T, 1.4 +/- 0.3; PT, 3.6 +/- 1.3; serum: T, 1.0 +/- 0.2; PT, 0.58 +/- 0.12). During early lactation, high PRL-like B was widely distributed among several (n = 4-6) bioactive forms differing in molecular mass [8 to > 66 kilodaltons (kDa)] in T milk, but the majority of B in PT milk was detected in two or three forms. During mature and late lactation, lower PRL-like B was associated with two or three peaks (20 to > 66 kDa). A large fraction of PRL-like B (67%-84%) was associated with the phosphorylated (P-) fraction of human milk. Four immunoreactive forms (24, 30, 32, and 40 kDa) of P-PRL were identified by immunoblot analyses. Alkaline phosphatase treatment converted the 40-kDa immunoreactive P-PRL to 24-kDa PRL, increased the B of the P-fraction by 2-fold, but did not change total PRL I detected. PRL in the Concanavalin-A-retained fraction accounted for 59-69% of PRL in milk based on RIA results. No PRL-like B was detected in the Concanavalin-A-retained fraction of human milk; however, treatment of the glycosylated fraction of milk with peptide-N-glycosidase F increased thymidine incorporation by Nb2 cells 1.67-fold compared to that in controls. The results of this study show that human milk contains considerably greater PRL-like activity than previous reports based on RIA detection. The appearance and regulation of multiple bioactive PRL variants in milk throughout the course of lactation may serve as a mechanism by which milk PRL influences neonatal development.

Novel tyvelose-containing tri- and tetra-antennary N-glycans in the immunodominant antigens of the intracellular parasite Trichinella spiralis.

The larval stage of the intestinal nematode, Trichinella spiralis, secretes and displays on its cuticle a number of antigenically cross-reactive glycoproteins. These so-called TSL-1 antigens induce a powerful antibody response in parasitized animals. In rats, anti-TSL-1 antibodies mediate a protective immunity that expels invading larvae from the intestine. The vast majority of anti-TSL-1 antibodies are specific for glycans. Although the biological functions of TSL-1 antigens are not known, the powerful effect of glycan-specific antibodies on the intestinal survival of T. spiralis suggests that they play an important role in parasite establishment. Little is known about the structures of the glycans present on the TSL-1 glycoproteins. Recent studies have suggested, however, that the antigens contain very unusual glycans (Wisnewski, N., McNeil, M., Grieve, R.B. and Wassom, D.L., Mol. Biochem. Parasitol., 61, 25-36, 1993). Sugar and linkage analysis of the combined secreted products unexpectedly showed that a major terminal sugar is tyvelose (3,6-dideoxy-D-arabino-hexose; Tyv) which has previously been found only in certain gram-negative bacterial lipopolysaccharides. In this paper, we report the first rigorous structural study of oligosaccharides released from TSL-1 antigens by peptide N-glycosidase F digestion. Using strategies based on fast atom bombardment mass spectrometry (FAB-MS), we have discovered a novel family of tri- and tetra-antennary N-glycans whose antennae are comprised of the tyvelose-capped structure: Tyv1,3GalNAc beta 1,4(Fuc alpha 1,3)GlcNAc beta 1-. Thus a major population of TSL-1 glycans contains clusters of hydrophobic terminal structures which are likely to be highly immunogenic.

Glycans as targets for monoclonal antibodies that protect rats against Trichinella spiralis.

We have investigated the role of glycans on Trichinella spiralis antigens in recognition by rat monoclonal antibodies (mAbs) which protect rat pups against challenge with the parasite. In pups born to infected dams or pups passively immunized with mAbs, antibodies eliminate a challenge dose from the intestine within hours ('rapid expulsion'). Because such dramatic protection can be afforded by mAbs, we have sought to characterize the parasite antigens they target. In this report we show that protective antibodies were unable to bind excretory/secretory (ES) antigens deglycosylated with trifluoromethanesulphonic acid (TFMS). In addition, oligosaccharides isolated from glycoproteins by alkaline hydrolysis or peptide: N glycosidase F (PNGase F) digestion were bound by protective, but not non-protective, mAbs. Glycans affinity purified with protective mAb 9D bound to all but one protective mAb. These antibodies have been shown previously to bind to the surfaces of intact larvae, indicating that the glycan is exposed on the parasite surface. Candidate glycans that may be involved in binding protective mAbs have unusual tri- and tetra-antennary structures with terminal tyvelose moieties (Reason et al., Glycobiology, 4, 000-000, 1994). Coating of the larval surface with such glycans may serve to protect the parasite and its secreted products from enzymatic attack as the parasite travels to and resides in its epithelial niche.