Problematic substance use: an assessment of workplace implications in midwifery.

BACKGROUND: Problematic substance use (PSU) poses occupational, personal and professional risks. As an occupational group, midwives have been under-represented in research on PSU. AIMS: The aim of this study was to assess self-reported occurrences of PSU, help-seeking behaviours and barriers, and perceptions of impairment in UK-based midwives. METHODS: Self-selecting registered midwives were anonymously surveyed using the Tobacco, Alcohol, Prescription Medications, and Substance Use/Misuse (TAPS) tool, the Perceptions of Nursing Impairment Inventory (PNII) and open-ended/closed questions. Quantitative data were used to explore PSU, help-seeking and attitudes to impairment. Qualitative responses were used to provide richer understandings. RESULTS: From 623 completed surveys, 28% (n = 176) self-reported PSU in response to work-related stress and anxiety, bullying, traumatic clinical incidents and maintenance of overall functioning. PSU was related to alcohol and a range of restricted drugs. While 11% of those affected indicated they had sought help, 27% felt they should seek help but did not. Reported barriers to help-seeking included fear of repercussions, shame, stigma, practicalities and a perceived lack of support either available or required. Perceptions of impairment were predominantly compassionate with a minority of stigmatizing attitudes displayed. CONCLUSIONS: Overall, 10% of the sample reported they had attended work under the influence of alcohol, and 6% under the influence of drugs other than tobacco or those as prescribed to them. Furthermore, 37% indicated concern about a colleague's substance use. As stigmatizing attitudes and punitive actions can dissuade help-seeking, changed perceptions and policies which favour alternatives to discipline are suggested to reduce the risk overall.

A longitudinal, observational study of the features of transitional healthcare associated with better outcomes for young people with long-term conditions.

BACKGROUND: Most evidence about what works in transitional care comes from small studies in single clinical specialties. We tested the hypothesis that exposures to nine recommended features of transitional healthcare were associated with better outcomes for young people with long-term conditions during transition from child-centred to adult-oriented health services. METHODS: This is a longitudinal, observational cohort study in UK secondary care including 374 young people, aged 14-18.9 years at recruitment, with type 1 diabetes (n = 150), cerebral palsy (n = 106) or autism spectrum disorder with an associated mental health problem (n = 118). All were pre-transfer and without significant learning disability. We approached all young people attending five paediatric diabetes centres, all young people with autism spectrum disorder attending four mental health centres, and randomly selected young people from two population-based cerebral palsy registers. Participants received four home research visits, 1 year apart and 274 participants (73%) completed follow-up. Outcome measures were Warwick Edinburgh Mental Wellbeing Scale, Mind the Gap Scale (satisfaction with services), Rotterdam Transition Profile (Participation) and Autonomy in Appointments. RESULTS: Exposure to recommended features was 61% for 'coordinated team', 53% for 'age-banded clinic', 48% for 'holistic life-skills training', 42% for 'promotion of health self-efficacy', 40% for 'meeting the adult team before transfer', 34% for 'appropriate parent involvement' and less than 30% for 'written transition plan', 'key worker' and 'transition manager for clinical team'. Three features were strongly associated with improved outcomes. (1) 'Appropriate parent involvement', example association with Wellbeing (b = 4.5, 95% CI 2.0-7.0, p = 0.001); (2) 'Promotion of health self-efficacy', example association with Satisfaction with Services (b = - 0.5, 95% CI - 0.9 to - 0.2, p = 0.006); (3) 'Meeting the adult team before transfer', example associations with Participation (arranging services and aids) (odds ratio 5.2, 95% CI 2.1-12.8, p < 0.001) and with Autonomy in Appointments (average 1.7 points higher, 95% CI 0.8-2.6, p < 0.001). There was slightly less recruitment of participants from areas with greater socioeconomic deprivation, though not with respect to family composition. CONCLUSIONS: Three features of transitional care were associated with improved outcomes. Results are likely to be generalisable because participants had three very different conditions, attending services at many UK sites. Results are relevant for clinicians as well as for commissioners and managers of health services. The challenge of introducing these three features across child and adult healthcare services, and the effects of doing so, should be assessed.

Tenofovir disoproxil fumarate in pregnancy and prevention of mother-to-child transmission of HIV-1: is it time to move on from zidovudine?

OBJECTIVES: Zidovudine (ZDV) has been the cornerstone of antiretroviral (ARV) therapy for pregnant women infected with HIV-1 in the prevention of mother-to-child transmission (MTCT) and remains the only licensed ARV for use in pregnancy. We explored the current and future roles of tenofovir disoproxil fumarate (TDF) in the prevention of MTCT of HIV-1. METHODS: We reviewed the published literature by conducting database searches of in vitro, animal and clinical studies, reported in journals and at conferences, using the search terms Tenofovir/gs4331/viread, pregnant/pregnancy, lactate, lactation, natal, reproduce/reproduction, placenta/placental, malformation, and teratogenicity/teratogenic. RESULTS: In a macaque model, perinatal exposure to very high dose tenofovir resulted in bone toxicity in some offspring. However, perinatal use of TDF, both single dose and as part of highly active antiretroviral therapy in women, has been well tolerated in the short term by mothers and their infants. Further, the addition of single-dose TDF to single-dose nevirapine (SD-NVP) during delivery following maternal ZDV use during pregnancy significantly reduces the frequency of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance. CONCLUSIONS: The addition of TDF to SD-NVP reduces NNRTI resistance. The role of TDF in this setting and during pregnancy for reducing rates of MTCT requires investigation. While short-term toxicity data are encouraging, long-term follow-up of exposed mothers and infants is required.

Conceptual structure and social functions of behavior explanations: beyond person--situation attributions.

The traditional approach to studying behavior explanations involves treating them as either person causes or situation causes and assessing them by using rating scales. An analysis of people's free-response behavior explanations reveals, however, that the conceptual distinctions people use in their explanations are more complex and sophisticated than the person-situation dichotomy suggests. The authors, therefore, introduce a model of the conceptual structure of folk behavior explanations (the network of concepts and assumptions on which explanations are based) and test it in 4 studies. The modes and features of behavior explanations within this conceptual structure also have specific social functions. In 2 additional studies, the authors demonstrate that people alter distinct features of their explanations when pursuing particular impression-management goals and that listeners make inferences about explainers' goals on the basis of these features.

Present and future of osteoporosis therapy.

In the 50-year "modern" history of osteoporosis, there have been about 17 antifracture studies with sufficient attention to design to allow inference regarding efficacy. Antivertebral fracture efficacy has been reported with etidronate, estrogen patch, calcitonin, and 1,25-dihydroxyvitamin D. Two studies using fluoride were positive, and two were negative. Hip fractures have been neglected. One study showed efficacy of hip protectors, one showed efficacy of vitamin D and calcium in nursing home dwellers. The source of most hip fractures is the community. One community based antihip fracture efficacy study using annual injections of vitamin D was positive. There have been no antivertebral or antihip fracture studies in men, or in corticosteroid-related osteoporosis in men or women. Lack of independently repeated demonstration of efficacy, small fracture numbers, and data pooling in some of these (the best) studies leave great uncertainty. Estrogen and bisphosphonates appear to be the best options at this time. New data suggest that calcium supplementation is likely to reduce the rate of bone loss and perhaps reduce fracture rates. The challenge is to maintain and restore the constituents of bone mineral density (BMD), that is: to promote periosteal and endosteal bone formation; reduce endosteal bone resorption and cortical porosity; and increase trabecular thickness, number, and connectivity. There are many opportunities, for instance, intermittent parathyroid hormone (PTH) increases bone strength and, with estrogen, may increase connectivity. The anabolic effects of PTH may be partly mediated by IGF-1. IGF-1 increases periosteal, endosteal, and trabecular bone formation, cortical and trabecular width, and trabecular and endocortical connectivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Purification and characterization from tobacco (Nicotiana tabacum) leaves of six small, wound-inducible, proteinase isoinhibitors of the potato inhibitor II family.

Six small molecular mass, wound-inducible trypsin and chymotrypsin inhibitor proteins from tobacco (Nicotiana tabacum) leaves were isolated to homogeneity. The isoinhibitors, cumulatively called tobacco trypsin inhibitor (TTI), have molecular masses of approximately 5500 to 5800 D, calculated from gel filtration analysis and amino acid content. The amino acid sequence of the entire 53 residues of one isoinhibitor, TTI-1, and the sequence of 36 amino acid residues from the N terminus of a second isoinhibitor, TTI-5, were determined. The two isoinhibitors differ only at residue 11, which is threonine in TTI-1 and lysine in TTI-5. The isoinhibitors are members of the potato inhibitor II family and show considerable identity with the small molecular mass members of this family, which include the eggplant inhibitor, two small molecular mass trypsin and chymotrypsin inhibitors from potatoes, and an inhibitor from pistils of the ornamental plant Nicotiana alata. Antibodies produced against the isoinhibitors in rabbits were used in radial immunoassays to quantify both the systemic wound inducibility of TTI in tobacco leaves and its constitutive levels in flowers.

Oligouronide signaling of proteinase inhibitor genes in plants: structure-activity relationships of Di- and trigalacturonic acids and their derivatives.

Polygalacturonic acid (DPave approximately 20), alpha-1,4-di- and trigalacturonic acids, delta 4,5-alpha-1,4-di- and delta 4,5-alpha-trigalacturonic acids, and several chemically modified derivatives of these oligomers were prepared. Their proteinase inhibitor-inducing activities were determined by supplying solutions of the compounds to young, excised tomato plants through their cut stems. Digalacturonic acid, on a molar basis, was the most active oligomer (ED50 approximately 1.5 micrograms/plant), being about three times more active than the parent oligogalacturonic acid (ED50 approximately 5.5 micrograms/plant). The specific inducing activity of trigalacturonic acid was about half that of digalacturonic acid. Both delta 4,5-di- and delta 4,5-trigalacturonic acids were about half as active as di- and trigalacturonic acids, respectively. Reduction of the hemiacetal (carbonyl) group of the di- and trigalacturonic acids with sodium borohydride completely destroyed proteinase inhibitor inducing activities, indicating that the inducing activity of both acids depends upon an intact hemiacetal at the reducing termini. Reduction of the double bonds of delta 4,5-di- and delta 4,5-trigalacturonic acids by catalytic hydrogenation with H2 (palladium catalyst) produced derivatives with specific inducing activities of approximately one-half that of the parent compounds. Thus, while the reducing termini of oligogalacturonides require an intact hemiacetal for proteinase inhibitor inducing activities, the nonreducing termini of the small oligouronides do not require a C4 hydroxyl nor a C5 proton to be active inducers.

Structure, expression, and antisense inhibition of the systemin precursor gene.

A gene that encodes systemin, a mobile 18-amino acid polypeptide inducer of proteinase inhibitor synthesis in tomato and potato leaves, has been isolated from tomato, Lycopersicon esculentum. Induction of proteinase inhibitors in plants is a response to insect or pathogen attacks. The gene has 10 introns and 11 exons, ten of which are organized as five homologous pairs with an unrelated sequence in the eleventh, encoding systemin. Systemin is proteolytically processed from a 200-amino acid precursor protein, prosystemin. Prosystemin messenger RNA was found in all organs of the plant except the roots and was systemically wound-inducible in leaves. Tomato plants transformed with an antisense prosystemin complementary DNA exhibited greatly suppressed systemic wound induction of proteinase Inhibitor I and II synthesis in leaves.

Isolation and characterization of the proteinase inhibitor-inducing factor from tomato leaves. Identity and activity of poly- and oligogalacturonide fragments.

Mild acid hydrolysis of a small (Mr = 6 kDa) pectic polysaccharide isolated from tomato leaves, an inducer of the synthesis and accumulation of two proteinase inhibitors in excised tomato plants, yielded a alpha-D-polygalacturonic acid polymer with degree of polymerization = 20 that retained proteinase inhibitor-inducing activity. Enzymic and acid hydrolysis of this polygalacturonan yielded a series of alpha-1,4-D-galacturonic acid oligomers with degrees of polymerization from 2 to 6 which were purified to homogeneity and assayed for proteinase inhibitor-inducing activity in young excised tomato plants. All of the oligomers exhibited activity. The hexagalacturonide possessed the highest activity and the trimer the lowest. The evidence supports a possible role for plant cell wall fragments as systemic messengers that regulate the expression of proteinase inhibitor genes in plant leaves in response to pest attacks.

Heat inhibition of in vitro lipolysis and 14C ibuprofen protein binding in plasma from heparinized uraemic subjects.

Protein binding determination in post heparin plasma samples is complicated by the continued post heparin lipase activity, in vitro, during the binding analysis. The decomposition of lipoproteins and accumulation of nonesterified fatty acids (NEFA) results in artifically elevated free fractions of many drugs. This artefact is particularly accentuated in haemodialysis patients who are frequently hypertriglyceridaemic and receive large doses of heparin. Rapid heat treatment (60 degrees for 15 min) of plasma from heparinized uraemic subjects is shown to inhibit the in vitro lipolysis occurring during 2 hours of equilibrium dialysis at 37 degrees (ED). Mean NEFA concentrations in heat treated plasma after ED (means = 400 +/- 141 mumol/L) were not different (p greater than 0.05, n = 9) from the baseline values in fresh plasma (means 351 +/- 117 mumol/L) but were considerably less (p less than 0.005) than NEFA levels in untreated plasma after ED (means = 1025 +/- 523 mumol/L). The degree of in vitro lipolysis inhibition (92 +/- 6.6%) was very much greater than using the chemical inhibitors phenyl methyl sulphonyl fluoride, EDTA, Triton X100 or protamine sulphate. Heat treatment at 60 degrees for 15 min increased the percentage of free 14C ibuprofen in 3.5% isolated human serum albumin from 0.34% to 0.62%. Reduced binding as a result of heat treatment was not observed however in whole plasma. The percentage free ibuprofen in heat treated, whole plasma from both heparinized and non heparinized subjects (means = 1.22 +/- 0.19; n = 29) was not different (p greater than 0.05) from the percentage free determined in plasma from a non heparinized group (means = 1.16 +/- 0.23; n = 15). In contrast the % free ibuprofen in untreated plasma from heparinized subjects was markedly higher (means = 1.56 +/- 0.41; n = 24; p less than 0.05). There was a strong correlation between % free ibuprofen and plasma NEFA concentration (r = 0.8; p less than 0.005; n = 68). The heat treatment of plasma for 15 min at 60 degrees is proposed as an effective means of controlling heparin induced lipolysis in vitro and may be valuable in overcoming the post heparin binding artefact.