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.

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.

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.

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.

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.

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.

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.

The effect of administration rate on cisplatin-induced emesis.

In an attempt to determine the influence of administration time on cisplatin-induced emesis, 20 adults previously untreated with cisplatin were enrolled into this double-blind study. Twenty patients were randomly assigned to receive high-dose cisplatin (greater than 100 mg/m2) either by a one-hour infusion or by an eight-hour infusion. All patients received antiemetic therapy with metoclopramide 2 mg/kg intravenously one-half hour before cisplatin administration, and 1 1/2, 3 1/2, 5 1/2, and 8 1/2 hours after cisplatin administration. Patients in the eight-hour infusion group experienced significantly fewer emesis episodes than did patients in the one-hour infusion group. The median of emesis episodes in the eight-hour group was one (range, 0 to 2) and in the one-hour group was three (range, 0 to 8). In patients receiving high-dose cisplatin plus metoclopramide, increasing the administration time from one hour to eight hours resulted in a small but significant decrease in emesis episodes. The cisplatin infusion rate should be considered as a variable in cisplatin-antiemetic trials.

Preparation of human saphenous vein for coronary artery bypass grafting impairs its capacity to produce prostacyclin.

Prostacyclin production was measured from freshly isolated human saphenous vein and from vein subjected to routine surgical preparation for coronary bypass grafting. Surgical preparation had no effect on spontaneous prostacyclin production but significantly reduced stimulated rates from 16.9(1.1) to 7.1(0.5) pg.min-1 per mg wet weight (n = 27). Stimulated prostacyclin production was not reduced by storage of vein for 2 h at 23 degrees C in blood or saline nor by distension, but it was reduced to 5.0(0.6) pg.min-1 per mg (n = 10) by de-endothelialisation. Reduced prostacyclin production, which might in itself contribute to vein graft occlusion, provides a quantitative biochemical estimate of endothelial integrity.

A surgical preparative technique for coronary bypass grafts of human saphenous vein which preserves medial and endothelial functional integrity.

Measurements of adenosine triphosphate concentration and adenosine triphosphate/diphosphate ratio provided quantitative markers for medial integrity and stimulated (vortex-mixing) prostacyclin production for endothelial function. Freshly isolated vein had an adenosine triphosphate concentration of 470 +/- 60 nmol X gm-1 wet weight and an adenosine triphosphate/diphosphate ratio of 2.50 +/- 0.13; it produced prostacyclin at a rate of 9.3 +/- 1.0 pg X min-1 X mg-1 wet weight. Vein subjected to dissection, proximal anastomosis, and distention with the patient's own arterial pressure had an adenosine triphosphate concentration of 490 +/- 70 nmol X gm-1 wet weight and an adenosine triphosphate/diphosphate ratio of 2.29 +/- 0.13; it produced prostacyclin at a rate of 10.4 +/- 2.2 pg X min-1 X mg-1 wet weight. All values were indistinguishable from those in freshly isolated vein. In vein subjected to dissection, distention at less than 300 mm Hg with patient's heparinized blood, and distal anastomosis, adenosine triphosphate concentration, adenosine triphosphate/diphosphate ratio, and prostacyclin production (5.5 +/- 0.6 pg X min-1 X mg-1 wet weight) were all significantly (p less than 0.001) reduced. These results demonstrated that surgical preparation by first proximal anastomosis preserved both medial and endothelial function.

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.

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.

Effect of exercise on plasma pyruvate kinase and creatine kinase activity.

Plasma pyruvate kinase (PK) and creatine kinase (CK) were measured in healthy subjects engaging in (a) mild exercise, 30 min on an exercise cycle maintaining a pulse rate of 150/min, (b) moderate exercise, squeezing a ball until exhaustion with a sphygmomanometer cuff inflated above systolic pressure around the arm (max. 2 min) and (c) severe exercise, completing a marathon race. Mild exercise resulted in no change in enzyme levels over 24 h. Moderate exercise produced a small increase in PK but no change in CK. PK activity rose from 35.3 +/- 10 U/l pre-exercise to 41.3 +/- 13 U/l 15 min post-exercise (n = 8, p less than 0.025). Severe exercise (completing a marathon race) resulted in a 3-fold increase in PK from 26 (4-87) U/l pre-race to 69 (21-156) U/l immediately post-race, and also, as expected, an increase in CK from 60 (15-164) U/l to 257 (72-1535) U/l (results are means and ranges, n = 69, p less than 0.001 for both enzymes). Runners showed parallel increases in PK and CK (p less than 0.05 by Spearman rank correlation). The mean post-race activity of CK-MB was less than 5% of total CK but 18 runners had values greater than 6% (mean 4.8, range 1-18). We conclude that PK, like CK, is increased following exercise due to liberation of muscle enzyme. However, only severe exercise is likely to lead to a substantial increase in plasma PK activity and therefore prejudice its clinical usefulness as a diagnostic test.

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.