The FAST-M complex intervention for the detection and management of maternal sepsis in low-resource settings: a multi-site evaluation.

OBJECTIVE: To evaluate whether the implementation of the FAST-M complex intervention was feasible and improved the recognition and management of maternal sepsis in a low-resource setting. DESIGN: A before-and-after design. SETTING: Fifteen government healthcare facilities in Malawi. POPULATION: Women suspected of having maternal sepsis. METHODS: The FAST-M complex intervention consisted of the following components: the FAST-M maternal sepsis treatment bundle and the FAST-M implementation programme. Performance of selected process outcomes was compared between a 2-month baseline phase and 6-month intervention phase with compliance used as a proxy measure of feasibility. MAIN OUTCOME RESULT: Compliance with vital sign recording and use of the FAST-M maternal sepsis bundle. RESULTS: Following implementation of the FAST-M intervention, women were more likely to have a complete set of vital signs taken on admission to the wards (0/163 [0%] versus 169/252 [67.1%], P < 0.001). Recognition of suspected maternal sepsis improved with more cases identified following the intervention (12/106 [11.3%] versus 107/166 [64.5%], P < 0.001). Sepsis management improved, with women more likely to receive all components of the FAST-M treatment bundle within 1 hour of recognition (0/12 [0%] versus 21/107 [19.6%], P = 0.091). In particular, women were more likely to receive antibiotics (3/12 [25.0%] versus 72/107 [67.3%], P = 0.004) within 1 hour of recognition of suspected sepsis. CONCLUSION: Implementation of the FAST-M complex intervention was feasible and led to the improved recognition and management of suspected maternal sepsis in a low-resource setting such as Malawi. TWEETABLE ABSTRACT: Implementation of a sepsis care bundle for low-resources improved recognition & management of maternal sepsis.

Efficacy and cultural appropriateness of psychosocial interventions for paediatric burn patients and caregivers: a systematic review.

BACKGROUND: Paediatric burns are highly painful and traumatising injuries that are overrepresented among Aboriginal and Torres Strait Islander people. Paediatric burn patients' pain remains poorly managed by pharmacological interventions, leading to increased anxiety, distress, and trauma in patients and their caregivers. Non-pharmacological psychosocial interventions have been suggested as effective in reducing pain and psychological morbidities among paediatric burn patients and their caregivers; however, their degree of effectiveness and appropriateness for Aboriginal and Torres Strait Islander people is unclear. METHODS: A non-date restricted systematic review was conducted through four databases. Studies published in English assessing psychosocial interventions on paediatric burn patients' physical pain along with theirs and/or their caregiver's anxiety, distress, or trauma symptoms were identified and included in this review. Included studies were assessed for their ability to reduce one of the outcomes of interests and for their reflection of Aboriginal and Torres Strait Islander peoples' perspectives of health. RESULTS: Of the 3178 identified references, 17 were eligible. These include distraction based techniques (n = 8), hypnosis/familiar imagery (n = 2), therapeutic approaches (n = 4), and patient preparation/procedural control (n = 3). Distraction techniques incorporating procedural preparation reduced pain, while discharge preparation and increased 'patient control' reduced patient and caregiver anxiety; and internet based Cognitive Behaviour Therapy reduced short-term but not long-term post-traumatic stress symptoms. No interventions reflected Aboriginal and Torres Strait Islander peoples' perspectives of health; and few targeted caregivers or focused on reducing their symptoms. CONCLUSIONS: The development and assessment of psychosocial interventions to appropriately meet the needs of Aboriginal and Torres Strait Islander paediatric burn patients is required.

The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM trial.

OBJECTIVES: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. DESIGN: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial. SETTING: Forty-eight UK NHS early pregnancy units. POPULATION: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. METHODS: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. MAIN OUTCOME MEASURES: Cost per additional live birth at ≥34 weeks of gestation. RESULTS: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673). CONCLUSIONS: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s). TWEETABLE ABSTRACT: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage.

Development of the FAST-M maternal sepsis bundle for use in low-resource settings: a modified Delphi process.

OBJECTIVE: To develop a sepsis care bundle for the initial management of maternal sepsis in low resource settings. DESIGN: Modified Delphi process. SETTING: Participants from 34 countries. POPULATION: Healthcare practitioners working in low resource settings (n = 143; 34 countries), members of an expert panel (n = 11) and consultation with the World Health Organization Global Maternal and Neonatal Sepsis Initiative technical working group. METHODS: We reviewed the literature to identify all potential interventions and practices around the initial management of sepsis that could be bundled together. A modified Delphi process, using an online questionnaire and in-person meetings, was then undertaken to gain consensus on bundle items. Participants ranked potential bundle items in terms of perceived importance and feasibility, considering their use in both hospitals and health centres. Findings from the healthcare practitioners were then triangulated with those of the experts. MAIN OUTCOME MEASURE: Consensus on bundle items. RESULTS: Consensus was reached after three consultation rounds, with the same items deemed most important and feasible by both the healthcare practitioners and expert panel. Final bundle items selected were: (1) Fluids, (2) Antibiotics, (3) Source identification and control, (4) Transfer (to appropriate higher-level care) and (5) Monitoring (of both mother and neonate as appropriate). The bundle was given the acronym 'FAST-M'. CONCLUSION: A clinically relevant maternal sepsis bundle for low resource settings has been developed by international consensus. TWEETABLE ABSTRACT: A maternal sepsis bundle for low resource settings has been developed by international consensus.

Sulfide resorption during crustal ascent and degassing of oceanic plateau basalts.

Mantle plume-related magmas typically have higher chalcophile and siderophile element (CSE) contents than mid-ocean ridge basalts (MORB). These differences are often attributed to sulfide-under-saturation of plume-related melts. However, because of eruption-related degassing of sulfur (S) and the compositional, pressure, temperature and redox effects on S-solubility, understanding the magmatic behavior of S is challenging. Using CSE data for oceanic plateau basalts (OPB), which rarely degas S, we show that many OPB are sulfide-saturated. Differences in the timing of sulfide-saturation between individual OPB suites can be explained by pressure effects on sulfur solubility associated with ascent through over-thickened crust. Importantly, where S-degassing does occur, OPB have higher CSE contents than S-undegassed melts at similar stages of differentiation. This can be explained by resorption of earlier-formed sulfides, which might play an important role in enriching degassed melts in sulfide-compatible CSE and potentially contributes to anomalous enrichments of CSE in the crust.

Predictors of beef calf temperament at weaning and its impact on temperament at breeding and reproductive performance.

Two experiments were conducted to determine (i) factors influencing calf temperament at weaning, (ii) association between heifer-calf temperament at weaning and temperament at breeding and (iii) effect of heifer-calf temperament on pregnancy rate per artificial insemination (P/AI). In experiment 1, beef cows and their calves (n = 285) from three farms were used. Sire docility estimated progeny difference (EPD) score, birth type (normal or assisted), calf gender, calf behaviour (during 1st 4 weeks) and calf health status (until weaning) were recorded. Cows and calves were assigned a temperament score (0-calm; 1-excitable), and all cows were given a body condition score (BCS, 1-9; 1-emaciated; 9-obese) at weaning. Calf's illness (p < .05), low sire docility EPD score (p < .05), altered gait (p < .05), altered resting behaviour (p < .01), reduced/no play behaviour (p < .05) and cow excitable temperament (p < .001) increased calf excitable temperament at weaning. In experiment 2, replacement heifer-calves (n = 758) from 12 farms were assigned a temperament score at weaning and later at breeding. Blood from 40 calves at weaning and 31 heifers at initiation of synchronization (same animals) was collected by coccygeal venipuncture for determination of circulating cortisol and substance P concentrations. Heifers were assigned a BCS and reproductive tract score (RTS, 1-5; 1-immature, acyclic; 5-mature, cyclic), synchronized for fixed time AI, observed for oestrus and were artificially inseminated. Cortisol concentrations were increased in excitable heifer-calves compared to calm heifer-calves at weaning (p < .05), and substance P was increased in excitable compared to calm females both at weaning and breeding (p < .05). Low sire EPD docility score (p < .01), heifer-calf excitable temperament at weaning increased excitable temperament at breeding (p < .01). Controlling for BCS categories (p < .01), oestrous expression (p < .0001) and temperament at breeding by oestrous expression (p < .05), the calf's excitable temperament at weaning (p < .001) reduced P/AI (Calm, 62.7 (244/389) vs. Excitable, 53.4% (197/369); p < .01). In conclusion, selection of docile cows and sires with greater docility EPD score should be given consideration to reduce calf excitement. Temperament in beef female can be detected earlier in their life and could be used as a tool in the selection process and to improve their performances.

Health professional's perspectives of the barriers and enablers to cancer care for Indigenous Australians.

To investigate health professionals' perspectives about factors that impede or facilitate cancer care for Indigenous people. Semi-structured interviews with 22 health professionals involved in Indigenous cancer care. Data were interpreted using an inductive thematic analysis approach. Participants presented their perspectives on a number of barriers and enablers to Indigenous cancer care. Barriers were related to challenges with communication, the health system and coordination of care, issues around individual and community priorities and views of cancer treatment and health professional judgement. Enablers to cancer care were related to the importance of trust and rapport as well as health care system and support factors. The findings highlighted the need for recording of Indigenous status in medical records and a coordinated approach to the provision of evidence-based and culturally appropriate cancer care. This could go some way to improving Indigenous patient's engagement with tertiary cancer care services.

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Outbreak of Escherichia coli O157 in a nursery: lessons for prevention.

OBJECTIVES: To identify risk factors for transmission of verocytotoxin producing Escherichia coli O157 (VTECO157) and means of prevention. STUDY DESIGN: Outbreak investigation: retrospective cohort study. SETTING: A nursery (child care centre) in North Wales. SUBJECTS: Children attending (n = 104). METHODS: Faeces were examined using sorbitol MacConkey agar (SMAC), with cefixime, tellurite, and rhamnose; enrichment in modified tryptone soya broth; and immunomagnetic separation. Symptoms and exposure data were obtained from questionnaires to parents/guardians and children's toiletting and feeding records kept at the nursery. MAIN OUTCOME MEASURE: A "case" was defined as a child with verocytotoxin producing E coli O157 isolated from faeces, or a history of haemolytic uraemic syndrome (HUS) and antibodies to E coli O157 lipopolysaccharide, during the period 10 August to 30 September 1995. RESULTS: The attack rate was 31 in 104. Two children developed HUS. There were higher attack rates among girls and friends who played together. Cases were more likely to attend the nursery more frequently. The mean number of recorded bowel motions/child/half day was 0.51 in cases and 0.21 in well children. Child to staff ratios were high preceding and during the outbreak. CONCLUSIONS: A sick child is the most plausible source of infection with subsequent person to person transmission. The record of children's toiletting discriminated between cases and well children and might have allowed earlier detection of the outbreak. This simple record could be considered by other child care facilities as a means of giving early warning of problems with infectious intestinal diseases.

Adolescents' reported usage of selected foods in relation to their perceptions and social norms for those foods.

This paper reports a study of factors associated with the consumption of 22 diverse foods among 2082 students aged 12-15 years in Tasmania, Australia. Students provided data by completing a printed questionnaire. Multiple linear regression was used to assess how well self-reported usual (past) frequency of consumption of a food could be estimated from their perceptions of the qualities of the food (their liking for it, its healthfulness) and their descriptive social norms for the food (its usage by parents and its usage by friends). For all foods, multiple R was significant (p < 0.0001), with values ranging from 0.28-0.64 (median for the 22 foods being 0.49). Standardized regression coefficients for liking and parental usage were highly significant (p < 0.0001) for all foods. However, consistently lower coefficients were found for friends' usage (11 with p < 0.01, but only three with p < 0.0001) and healthfulness (five with p < 0.01, but only one with p < 0.0001). The absolute and relative magnitudes of the regression coefficients varied substantially between the foods. Liking was a stronger predictor than parental usage for 11 of the foods, and parental usage out-ranked liking for the remaining 11. Regression coefficients for friends' usage and healthfulness were smaller than those for liking and parental usage for all foods studied.

TNF-alpha is a principal cytokine involved in the recruitment of NK cells to liver parenchyma.

Isolated murine splenic NK cells and the cultured murine endothelioma cell line, eEND2, were used to study the effects of cytokines on NK cell/endothelial cell adhesion. Treatment of eEND2 cells with TNF-alpha induced a marked increase (four- to sevenfold) in adherence of NK cells, as compared with control cultures of endothelioma cells or eEND2 cells treated with IL-1 alpha or IL-6. TNF-alpha induction of NK cell adherence to eEND2 was dose dependent with rapid kinetics, reaching a maximum at concentrations between 10 and 1000 U/ml after a 2-h incubation. TNF-alpha treatment of L929 fibroblasts or CL-2 hepatoma cells did not result in increased NK cell adhesion. The concentration range of TNF-alpha that was found to maximally augment NK cell adhesion to eEND2 also induced NK cell chemokinetic activity. The relevance of these in vitro results was subsequently analyzed in vivo. Initial studies confirmed that a single dose of polyinosinic-polycytidylic acid and poly-L-lysine stabilized in carboxymethyl cellulose (poly-ICLC), augmented hepatic NK activity and resulted in a 2.2-fold increase in the number of liver-associated NK cells. Concomitant treatment of mice with a TNF-alpha neutralizing antisera eliminated both the hepatic influx of NK cells and the increase in poly-ICLC-induced liver NK activity. These results suggest that TNF-alpha is a principal cytokine involved in the in vivo recruitment and localization of parenchymal NK cells after treatment with a biological response modifier, and that this regulation seems to occur via alterations in NK cell/endothelial cell interactions.

Time-course of medial and intimal thickening in pig venous arterial grafts: relationship to endothelial injury and cholesterol accumulation.

With use of an established model of pig saphenous vein grafts in the carotid artery, the time-course of the following changes was related: (1) medial and intimal size by morphometry of transverse sections, (2) cell number by deoxyribonucleic acid concentration, (3) cell density by deoxyribonucleic acid concentration per milligram wet weight and by counting nuclei in transverse sections, (4) endothelial morphology by scanning electron microscopy, and (5) cholesterol concentration. In the first week after grafting, medial and intimal thickening occurred associated with an increase in cell number. Between 1 and 4 weeks after grafting, further rapid medial and intimal thickening occurred with no further increase in cell number but with a reduction in cell density, which suggested that cell migration, hypertrophy, and the laying down of extracellular matrix were responsible. Between 4 and 39 weeks after grafting, a slower increase in medial and intimal size occurred, associated with a parallel increase in cell number and no further change in cell density. The endothelium of grafts showed only localized abnormalities, including loss of cells and leukocyte adhesion, either 1 or 4 weeks after grafting. Cholesterol concentration was slightly elevated 1 week after grafting but returned to values similar to those in vein by 4 weeks after grafting. Distention to 600 mm Hg during surgical preparation of vein for grafting resulted in lower graft patency after either 1 or 4 weeks and caused significant medial and endothelial injury. Distention did not, however, affect changes in medial or intimal size, deoxyribonucleic acid, or cholesterol concentration caused by grafting. We conclude that three processes contribute to medial and intimal thickening, namely: (1) an initial phase of rapid smooth muscle cell proliferation, (2) smooth muscle cell migration, hypertrophy, and synthesis of extracellular matrix, and (3) a late phase of slower smooth muscle cell proliferation. The incomplete late suppression of smooth muscle cell proliferation occurs despite regeneration of a morphologically intact endothelium and in the absence of progressive cholesterol accumulation.

Cancer therapy: reimbursement of new therapeutic technologies.

New drugs and technologies for cancer treatment are being developed at a rate that has created a reimbursement crisis. This article discusses third-party concerns about this problem and describes generic criteria that have proven to be useful in assessing any new technology. It is equally important to discontinue funding of ineffective and obsolete therapies as it is to devise a strategy for identifying and encouraging the development of new therapy that will be both clinically useful and cost-effective. Examples are provided to show that these are not necessarily mutually exclusive goals. Off-label application of standard therapy as well as the funding of new cancer therapy are considered. High-dose chemotherapy with autologous stem-cell support for treatment of a variety of neoplasms has become a major reimbursement challenge. Other technologies such as autolymphocyte therapy and use of colony-stimulating factors are considered in detail. Finally, a process for deciding how to fund new cancer therapy is described.

Distention promotes platelet and leukocyte adhesion and reduces short-term patency in pig arteriovenous bypass grafts.

A pig model of autologous saphenous vein to common carotid artery bypass grafting was developed. An end-to-end anastomotic technique led to lower middle graft and distal turbulence. Saphenous veins were surgically prepared with or without distention at 600 mm Hg, implanted into the arterial circulation, and removed 2 hours later. Medial integrity was then assessed by adenosine triphosphate/adenosine diphosphate concentration ratio, and endothelial integrity, leukocyte and platelet adhesion by scanning electron microscopy. In grafts made with undistended vein adenosine triphosphate/adenosine diphosphate concentration ratio was not significantly lower (3.0 +/- 0.1, n = 32) than in freshly isolated vein (3.3 +/- 0.1, n = 26), endothelial cover was 98% +/- 1%, n = 6, and there was little platelet or leukocyte adhesion. In distended grafts adenosine triphosphate/adenosine diphosphate concentration ratio was reduced to 2.2 +/- 0.2 (n = 7, p less than 0.005), endothelial cover was reduced to 38% +/- 14% (n = 6, p less than 0.001), and there was extensive platelet and leukocyte adhesion to exposed subendothelium. In separate experiments graft patency measured at 1 to 5 weeks was significantly greater (96%, n = 25) when undistended vein was used than when distended vein was used (64%, n = 25, p less than 0.005). The data show that distention leads to medial and endothelial damage and that this is associated with increased platelet and leukocyte adhesion and with reduced early patency.

The prevalence of antibiotic resistance in Haemophilus influenzae in Ireland.

From January to April 1988, 36 clinical microbiology laboratories in Northern Ireland and Eire took part in a survey to determine the prevalence of antibiotic resistance in Haemophilus influenzae. All isolates were collected and despatched to a coordinating laboratory where identification was confirmed and antibiotic sensitivity tests repeated. One thousand seven hundred and ninety strains were available for analysis. Of these, 10.9% were resistant to ampicillin (10.2% being beta-lactamase producers), 0.4% to amoxycillin-clavulanate, 2.1% to cefaclor, 3.7% to chloramphenicol, 2.6% to erythromycin, 4.1% to tetracycline, 2.6% to sulphonamide and 5.1% to trimethoprim. One hundred and nine strains (6.3%) were resistant to two or more of the antibiotics tested and 31 (1.7%) exhibited combined resistance to ampicillin, chloramphenicol and tetracycline. The prevalence of resistance to ampicillin and chloramphenicol was higher than had been previously recorded in largescale studies conducted on the British mainland.

The effects of triiodothyronine on cultured neonatal rat cardiac myocytes.

The purpose of this study was to determine whether thyroid hormone could directly affect the phenotypic expression of two isozymic systems [lactate dehydrogenase (LDH) and myosin] and the energy transducing potential of cultured neonatal heart cells. In addition we determined if these biochemical systems developed in culture as they normally do during in vivo post-natal development. Cells were maintained for 14 days in culture medium containing 10% horse serum and Earle's salts. Experimental cultures were supplemented with 10 nmol/l 3,3',5-triiodo-L-thyronine (T3). Hearts used to study in vivo development were excised from rats at the ages of 2 and 14 days post-natal to correspond with the time of isolating and harvesting the cultured heart cells, respectively. Adult hearts were used to represent the final developmental stage. Cultured cardiomyocytes without T3 administered to the culture medium showed no change in the isozymic profiles (myosin and LDH) or in metabolic potential during the 2 week culture period. The T3 treated cultures showed a complete shift to the V1 myosin isozyme. The glycolytic and aerobic metabolic potential [i.e., phosphofructokinase (PFK) and citrate synthase (CS) activities] and the LDH isozyme distribution were unaltered by T3 treatment. During in vivo development a shift toward the V1 myosin and H-LDH isozymes along with an increase in aerobic metabolism occurred in the rat heart. These findings indicate that the development of these selected biochemical systems in cultured cardiac myocytes does not result from an intrinsic myogenetic program and thus must be regulated in vivo by epigenetic factor(s). These results show that T3 has the potential to be the prime determinant of the phenotypic expression of the myosin isoforms, but does not have the potential to be the sole determinant for the expression of the LDH isozymes or the glycolytic (PFK) and aerobic (CS) capacities of cardiac muscle cells.

Compensatory adaptation of the heart to chronic rate overload: increase in calcium transport ATPase activity of myocardial sarcoplasmic reticulum.

This study was undertaken to test the hypothesis that a compensatory response of the heart to a chronic and continuous, metabolic and heart rate overload was an increase in the calcium sequestering activity of the myocardial sarcoplasmic reticulum. Calcium sequestering activity was estimated by determination of the calcium-dependent ATPase (Ca2+-ATPase) activity of isolated microsomes. Chronic rate overload was modelled by comparing: dysthyroid and control rats; control swine and swine with implanted cardiac pacemakers set at 180 beats/min; and different species of mammals with widely different heart rates. The myocardial sarcoplasmic reticulum Ca2+-ATPase pump activity was significantly increased by 39% for hyperthyroid rats compared to control rats and by 87% for control rats compared to thyroidectomized rats; by 63% for paced swine compared to control swine; and by 43% for rats compared to guinea pigs, by 140% for guinea pigs compared to dogs and by 120% for dogs compared to cows. These data indicate that calcium sequestering activity of myocardial sarcoplasmic reticulum increases in equivalent proportion to the chronotropic demand and that heart rate is a hemodynamic correlate of the sarcoplasmic reticulum Ca2+-ATPase activity.