Falling perinatal mortality in twins in the UK: organisational success or chance?

In June 2018, Mothers and Babies Reducing Risks through Audits and Confidential Enquiries across the UK (MBRRACE-UK) published a Perinatal Surveillance report of an audit between 2013-2016. This noted that the stillbirth rate for twins nearly halved between 2014-2016; whereas the stillbirth rate for singletons remained static. There was a statistically significant reduction in the rate of stillbirth in twins over this period from 11.07 (95% CI, 9.78-12.47) to 6.16 (95% CI, 5.20-7.24) per 1000 total births. This commentary discusses these observations, the effects of twin chorionicity, and the potential obstetric and neonatal interventions, as well as public health improvements, that may have influenced these findings.

Canadian survey on pandemic flu preparations.

BACKGROUND: The management of pandemic influenza creates public health challenges.An ethical framework, 'Stand on Guard for Thee: ethical considerations in pandemic influenza preparedness' that served as a template for the World Health Organization's global consultation on pandemic planning, was transformed into a survey administered to a random sample of 500 Canadians to obtain opinions on key ethical issues in pandemic preparedness planning. METHODS: All framework authors and additional investigators created items that were pilot-tested with volunteers of both sexes and all socioeconomic strata. Surveys were telephone administered with random sampling achieved via random digit dialing (RDD). Eligible participants were adults, 18 years or older, with per province stratification equaling provincial percent of national population. Descriptive results were tabulated and logistic regression analyses were used to assess whether demographic factors were significantly associated with outcomes. RESULTS: 5464 calls identified 559 eligible participants of whom 88.5% completed surveys. Over 90% of subjects agreed the most important goal of pandemic influenza preparations was saving lives, with 41% endorsing saving lives solely in Canada and 50% endorsing saving lives globally as the highest priority. Older age (OR = 8.51, p < 0.05) and current employment (OR = 9.48, p < 0.05) were associated with an endorsement of saving lives globally as highest priority. About 90% of respondents supported the obligation of health care workers to report to work and face influenza pandemic risks excepting those with a serious health condition that increased risks. Over 84% supported the government's provision of disability insurance and death benefits for health care workers facing elevated risk. Strong majorities favored stocking adequate protective antiviral dosages for all Canadians (92%) and, if effective, influenza vaccinations (95%). Over 70% agreed Canada should provide international assistance to poorer countries for pandemic preparation, even if resources for Canadians were reduced. While 92% of this group, believed provision should be 7 to 10% of all resources generated, 43% believed the provision should be greater than 10%. CONCLUSIONS: Results suggest trust in public health officials to make difficult decisions, providing emphasis on reciprocity and respect for individual rights.

Clinical ethicists' perspectives on organisational ethics in healthcare organisations.

BACKGROUND: Demand for organisational ethics capacity is growing in health organisations, particularly among managers. The role of clinical ethicists in, and perspective on, organisational ethics has not been well described or documented in the literature. OBJECTIVE: To describe clinical ethicists' perspectives on organisational ethics issues in their hospitals, their institutional role in relation to organisational ethics, and their perceived effectiveness in helping to address organisational ethics issues. DESIGN AND SETTING: Qualitative case study involving semi-structured interviews with 18 clinical ethicists across 13 health organisations in Toronto, Canada. RESULTS: From the clinical ethicists' perspective, the most pressing organisational ethics issues in their organisations are: resource allocation, staff moral distress linked to the organisation's moral climate, conflicts of interest, and clinical issues with a significant organisational dimension. Clinical ethicists were consulted in particular on issues related to staff moral distress and clinical issues with an organisational dimension. Some ethicists described being increasingly consulted on resource allocation, conflicts of interest, and other corporate decisions. Many clinical ethicists felt they lacked sufficient knowledge and understanding of organisational decision-making processes, training in organisational ethics, and access to organisational ethics tools to deal effectively with the increasing demand for organisational ethics support. CONCLUSION: Growing demand for organisational ethics expertise in healthcare institutions is reshaping the role of clinical ethicists. Effectiveness in organisational ethics entails a re-evaluation of clinical ethics training to include capacity building in organisational ethics and organisational decision-making processes as a complement to traditional clinical ethics education.

Recent studies on the molecular biology and biochemistry of CO2 fixation in phototrophic bacteria.

Rhodobacter sphaeroides was found to contain two clusters of chromosomally encoded CO2 fixation structural genes. Recent studies indicate that genes within each cluster are cotranscribed, suggesting that there is a single long transcript for each cluster. All of the genes have been sequenced, homologies noted, specific mutations obtained, and interesting upstream regulatory sequences found. Site-directed mutagenesis studies of the Anacystis rbcS has begun to provide information relative to RubisCO structure and function. In addition, RubisCO-negative strains of photosynthetic bacteria have been constructed to screen for altered RubisCO sequences.

Increased nitrotyrosine in the diabetic placenta: evidence for oxidative stress.

OBJECTIVE: To evaluate the presence of nitrotyrosine (NT) residues in placental villous tissue of diabetic pregnancies as an index of vascular damage linked to oxidative stress. RESEARCH DESIGN AND METHODS: Villous tissue was collected and flash frozen after delivery from 10 class C and D IDDM patients (37.9+/-3.2 weeks) and 10 normotensive pregnant individuals (37.5+/-3.8 weeks). Serial sections of tissue were immunostained with specific antibodies to NT, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and manganese superoxide dismutase (MnSOD). Sections were scored for intensity of immunostaining (0-3) by three observers blinded to the identity of tissue. RESULTS: All tissues demonstrated immunostaining for eNOS in both syncytiotrophoblast and stem villous vascular endothelium with no apparent differences between groups. Immunostaining for iNOS was seen in the villous stroma, but again was not different between the two groups. Significantly more intense NT staining was apparent in vascular endothelium and villous stroma (both P < 0.02) of diabetic placentas. The endothelium of large villous vessels of diabetic tissues also showed more intense immunostaining for MnSOD (P < 0.01). CONCLUSIONS: In these diabetic pregnancies, we were unable to show increased eNOS, unlike previous findings in preeclamptic pregnancies. The presence of NT may indicate vascular damage in the diabetic placenta due to peroxynitrite action formed from increased synthesis/interaction of nitric oxide and superoxide. The apparently paradoxical increase in MnSOD expression may be an adaptive response to increased superoxide generation.

Isolation of the Rhodopseudomonas sphaeroides form I ribulose 1,5-bisphosphate carboxylase/oxygenase large and small subunit genes and expression of the active hexadecameric enzyme in Escherichia coli.

A library of cloned Rhodopseudomonas sphaeroides DNA was screened by colony hybridization for form I ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBPC/O) sequences using heterologous RuBPC/O probes. A recombinant plasmid was identified that hybridized to both the Anacystis nidulans and the R. sphaeroides form II RuBPC/O genes. Subcloning of a hybridizing 4-kb SmaI fragment allowed expression of active enzyme in Escherichia coli that was identical to form I RuBPC/O based on polyacrylamide gel electrophoresis and Western immunoblot analysis.

Identification of epitopes and affinity purification of thyroid stimulating auto-antibodies using synthetic human TSH receptor peptides.

We prepared a series of overlapping peptides (29 in total, 20 amino acids each) containing the sequence of the entire extracellular domain of the human TSH receptor. Three peptides (181-200, 376-394, and EC3 (629-639)) bound IgG from patients with Graves' disease in an enzyme linked immunoassay. Peptide 181-200 bound IgG from 9 of 10, EC3 from 8 of 10, and 376-394 from 6 of 10 patients respectively, compared to 0 of 9 controls. We affinity purified TSHr auto-antibodies from four Graves' patients using the three above noted peptides bound to epoxy-activated sepharose. Thyroid stimulating activity was enriched in the bound fraction from at least two of the three peptide affinity columns in each of the four patients, although the pattern of affinity enrichment differed between patients. One patient was found to possess a combination of stimulatory and inhibitory TSHr antibodies and, after affinity purification, the anti-376-394 and anti-EC3 fractions were enriched in stimulatory activity, suggesting that those regions of the receptor were epitopes for stimulatory antibodies. However, affinity purification against peptide 181-200 produced an IgG preparation that was not stimulatory, but was a potent thyroid inhibitor. Thus, we have not only partially purified TSHr auto-antibodies, but also successfully separated stimulatory and inhibitory antibodies from a single patient using combination TSHr peptide affinity.

A case of recurrent typhoid fever in the United States: importance of the grandmother connection and the use of large restriction fragment pattern analysis of genomic DNA for strain comparison.

An 8-year old girl was infected for a second time with Salmonella typhi by contact with her grandmother, a known typhoid carrier. The S. typhi from both patient and grandmother had closely related genomic pulsed field gel electrophoresis patterns that differed from epidemiologically unrelated strains. The girl responded well to a 14-day course of oral trimethoprimsulfamethoxazole. The grandmother was treated successfully with a 28-day regimen of oral ciprofloxacin. Typhoid fever remains an endemic disease in the United States, largely because of recognized chronic stool carriers. Most of these carriers had typhoid in the preantibiotic era and remain potential sources of disease when they provide meals for others, not uncommonly grandchildren. The importance of this "grandmother" connection to endemic typhoid fever is reviewed, as is the potential use of pulsed field gel electrophoresis pattern analysis for comparison of strains of S. typhi.

Circulating cell adhesion molecule concentrations in diabetic women during pregnancy.

OBJECTIVE: To determine whether circulating concentrations of defined cell adhesion molecules, which are thought to reflect endothelial expression, are increased in insulin-dependent diabetic women during pregnancy. METHODS: Pregnant diabetic women demonstrating good glycemic control and without major complications before pregnancy were studied at 8-12 (n = 15), 18 (n = 15), 28 (n = 16), 32 (n = 16), and 36 (n = 16) weeks' gestation. A subgroup of ten diabetic women was sampled longitudinally through all five gestational ages. The diabetic women were compared with healthy nondiabetic women sampled cross sectionally at 12 (n = 20), 28 (n = 19), and 36 (n = 19) weeks' gestation. Nonpregnant diabetic (n = 22) and nonpregnant nondiabetic women (n = 28) also were studied. Plasma concentrations of the cell adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular endothelial cell adhesion molecule-1 (VCAM-1) were measured by enzyme-linked immunosorbent assay. RESULTS: Significantly higher median (range) concentrations of E-selectin (63.0 [20.2-107.0] ng/mL) and ICAM-1 (281.5 [171.6-778.4] ng/mL) but not VCAM-1 (459.7 [301.0-909.7] ng/mL) were found in nonpregnant diabetic women compared with nonpregnant nondiabetic women (43.5 [18.1-93.2], 243.6 [174.4-329.2], and 476.0 [253.8-929.4] ng/mL, respectively). During pregnancy these significant differences between diabetic and control groups were lost. The median (range) concentration of E-selectin (50.0 [21.2-96.3] ng/mL) was significantly lower in pregnant compared with nonpregnant diabetic women. The plasma concentrations of E-selectin and ICAM-1 did not change significantly with gestation in either diabetic or nondiabetic pregnant groups. Vascular endothelial cell adhesion molecule-1 concentration changed significantly with gestation in the diabetic pregnant group only. CONCLUSION: Circulating concentrations of defined vascular cell adhesion molecules are not increased abnormally in diabetic women with good glycemic control during otherwise uncomplicated pregnancy.

Uniform designation for genes of the Calvin-Benson-Bassham reductive pentose phosphate pathway of bacteria.

Structural and regulatory genes encoding enzymes and proteins of the reductive pentose phosphate pathway have been isolated from a number of bacteria recently. In the phototroph Rhodobacter sphaeroides, and in two chemoautotrophic bacteria, Alcaligenes eutrophus and Xanthobacter flavus, these genes have been found in distinct operons. However, in these three organisms and in other bacteria where certain of these genes have been discovered, a uniform nomenclature to designate these genes has been lacking. This report represents an effort to provide uniformity to the designation of these genes from all bacteria.

A single-blind, placebo-controlled study of glycosaminoglycan-peptide complex ('Rumalon') in patients with osteoarthritis of the hip or knee.

A randomized, single-blind, placebo-controlled trial was carried out in 62 patients (30 with osteoarthritis of the hip, 32 with osteoarthritis of the knee) to examine the efficacy of glycosaminoglycan-peptide complex in the treatment of osteoarthritis. Patients received 8-week courses of trial medication, each consisting of intramuscular injections of 3 x 2 ml ampoules per week, alternating with 8-week periods free of trial medication, in addition to conventional drug therapy and physiotherapy, as required. After 2-years' treatment, glycosaminoglycan-peptide-treated patients showed significant improvements, as compared with placebo, in relation to night pain, pain during the day, joint mobility and walking ability. Similar results were seen with both osteoarthritis of the hip and knee. In osteoarthritis of the knee it was also possible to assess joint swelling and this also showed a significant improvement. There were no significant changes in range of joint movement except for a significant decrease in active flexion in the patients with osteoarthritis of the knee treated with placebo. In contrast with many anti-osteoarthritic drugs, glycosaminoglycan-peptide complex was very well tolerated. These results suggest that glycosaminoglycan-peptide complex may be a valuable alternative form of long-term therapy for patients with osteoarthritis.

Effect of ketorolac and low-molecular-weight heparin individually and in combination on haemostasis.

Low-molecular-weight heparins, when used in surgical patients for thromboprophylaxis, may be used concurrently with ketorolac, a non-steroidal anti-inflammatory drug that is used for analgesia. Because these two agents can influence the haemostatic system, it is important to identify any such effect. The haemostatic interaction between dalteparin and ketorolac was assessed in a double-blind, placebo-controlled, randomized, crossover study of healthy male volunteers each given all four combinations of ketorolac/placebo and dalteparin/placebo. The effect of ketorolac and dalteparin on haemostasis was assessed by measuring in-vitro platelet aggregation, anti-factor-Xa, activated partial thromboplastin times and skin bleeding time. The results were analysed for evidence of an interaction between ketorolac and dalteparin. Ketorolac inhibited platelet aggregation in whole blood and platelet-rich plasma. The administration of dalteparin led to a significant increase in levels of anti-factor-Xa and a significant prolongation in the activated partial thromboplastin time, although it remained within the range of the normal population. There was no evidence of any interaction between ketorolac and dalteparin with regard to platelet aggregation, anti-factor-Xa activity or activated partial thromboplastin time. The administration of ketorolac significantly prolonged the skin bleeding time. There was a significant interaction between ketorolac and dalteparin to prolong the bleeding time, although dalteparin alone had no effect on bleeding time. There was an interaction between ketorolac and dalteparin, which affected bleeding times. Such an interaction raises the possibility of haemorrhagic complications developing perioperatively when these agents are used concomitantly. Further studies are required to examine the clinical importance of this interaction.

Marital relationships, evaluations of spouse and self, and anxiety.

Questionaire data were gathered from 164 married couples to test hypotheses that husbands' and wives' anxiety levels will be low to the extent that: (a)they share decision-making power, share household role responsibilities, and express high maritial solidarity; and (b) they hold positive evaluations of one another, perceive positive reactions from one another, and show positive self-evaluations. The first hypothesis was supported only for solidarity. The second hypothesis received strong support for husbands and wives. For wives, solidarity was the strongest predictor of anxiety, while self-evaluation was the most important factor for husbands.