Socio-economic disadvantage and utilisation of labour epidural analgesia in Scotland: a population-based study†.

Socio-economic deprivation is associated with adverse maternal and childhood outcomes. Epidural analgesia, the gold standard for labour analgesia, may improve maternal well-being. We assessed the association of socio-economic status with utilisation of epidural analgesia and whether this differed when epidural analgesia was advisable for maternal safety. This was a population-based study of NHS data for all women in labour in Scotland between 1 January 2007 and 23 October 2020, excluding elective caesarean sections. Socio-economic status deciles were defined using the Scottish Index of Multiple Deprivation. Medical conditions for which epidural analgesia is advisable for maternal safety (medical indications) and contraindications were defined according to national guidelines. Of 593,230 patients in labour, 131,521 (22.2%) received epidural analgesia. Those from the most deprived areas were 16% less likely to receive epidural analgesia than the most affluent (relative risk 0.84 [95%CI 0.82-0.85]), with the inter-decile mean change in receiving epidural analgesia estimated at -2% ([95%CI -2.2% to -1.7%]). Among the 21,219 deliveries with a documented medical indication for epidural analgesia, the socio-economic gradient persisted (relative risk 0.79 [95%CI 0.75-0.84], inter-decile mean change in receiving epidural analgesia -2.5% [95%CI -3.1% to -2.0%]). Women in the most deprived areas with a medical indication for epidural analgesia were still less likely (absolute risk 0.23 [95%CI 0.22-0.24]) to receive epidural analgesia than women from the most advantaged decile without a medical indication (absolute risk 0.25 [95%CI 0.24-0.25]). Socio-economic deprivation is associated with lower utilisation of epidural analgesia, even when epidural analgesia is advisable for maternal safety. Ensuring equitable access to an intervention that alleviates pain and potentially reduces adverse outcomes is crucial.

Comparison of ultra-low, low and high concentration local anaesthetic for labour epidural analgesia: a systematic review and network meta-analysis.

Lumbar epidural is the gold standard for labour analgesia. Low concentrations of local anaesthetic are recommended. This network meta-analysis investigated whether further reducing the concentration of local anaesthetic can improve maternal and neonatal outcomes without compromising analgesia. We conducted a systematic search of relevant databases for randomised controlled trials comparing high (>0.1%), low (>0.08% to ≤0.1%) or ultra-low (≤0.08%) concentration local anaesthetic (bupivacaine or equivalent) for labour epidural. Outcomes included mode of delivery, duration of labour and maternal/neonatal outcomes. Bayesian network meta-analysis with random-effects modelling was used to calculate odds ratios or weighted mean differences and 95% credible intervals. A total of 32 studies met inclusion criteria (3665 women). The total dose of local anaesthetic received increased as the concentration increased; ultra-low compared with low (weighted mean difference -14.96 mg, 95% credible interval [-28.38 to -1.00]) and low compared with high groups (weighted mean difference -14.99 [-28.79 to -2.04]), though there was no difference in the number of rescue top-ups administered between the groups. Compared with high concentration, ultra-low concentration local anaesthetic was associated with increased likelihood of spontaneous vaginal delivery (OR 1.46 [1.18 to 1.86]), reduced motor block (Bromage score >0; OR 0.32 [0.18 to 0.54]) and reduced duration of second stage of labour (weighted mean difference -13.02 min [-21.54 to -4.77]). Compared with low, ultra-low concentration local anaesthetic had similar estimates for duration of second stage of labour (weighted mean difference -1.92 min [-14.35 to 10.20]); spontaneous vaginal delivery (OR 1.07 [0.75 to 1.56]; assisted vaginal delivery (OR 1.35 [0.75 to 2.26]); caesarean section (OR 0.76 [0.49 to 1.22]); pain (scale 1-100, weighted mean difference -5.44 [-16.75 to 5.93]); and maternal satisfaction. Although a lower risk of an Apgar score < 7 at 1 min (OR 0.43 [0.15 to 0.79]) was reported for ultra-low compared with low concentration, this was not sustained at 5 min (OR 0.12 [0.00 to 2.10]). Ultra-low concentration local anaesthetic for labour epidural achieves similar or better maternal and neonatal outcomes as low and high concentration, but with reduced local anaesthetic consumption.

A comparison of clinical practice guidelines for proximal femoral fracture.

Clinical practice guidelines are designed to assist clinical decision-making by summarising evidence and forming recommendations. The number of available guidelines is vast and they vary in relevance and quality. We reviewed guidelines relevant to the management of a patient with a fractured neck of femur and explored similarities and conflicts between recommendations. As guidelines are often produced in response to an area of clinical uncertainty, recommendations differ. This can result in a situation where the management of a particular clinical problem will depend upon which guideline is followed. We explore the reasons for such differences.

Neuraxial analgesia in labour and the foetus.

Providing pain relief during labour is a fundamental human right and can benefit both mother and foetus. Epidural analgesia remains the 'gold standard', providing excellent pain relief, as well as the facility to convert to anaesthesia should operative intervention be required. While maternal well-being remains the primary focus, epidural analgesia may also have implications for the foetus. Data from meta-analyses finds that epidural compared with systemic opioids in labour is associated with reduced neonatal respiratory depression. Clinically relevant neonatal outcomes such as Apgar score <7 at 5 min, neonatal resuscitation and need for admission to a neonatal unit are reassuring, with the benefits of epidural analgesia for both mother and neonate outweighing any potential risks. Recent concerns regarding an association of epidural with the development of autism spectrum disorder in childhood appear to be unfounded, with several large observational studies refuting this association. This review discusses the evidence relating to maternal neuraxial analgesia in labour, implications for the foetus in utero, and childhood outcomes both in the immediate peripartum period and longer term.

Diagnostic terminology in Placenta Accreta Spectrum: a scoping review.

BACKGROUND: Anaesthetic management strategies for Placenta Accreta Spectrum (PAS) remain diverse, and literature interpretation is complicated by a range of terminology. The International Federation for Gynaecology and Obstetrics (FIGO) published guidance in 2018 to improve PAS diagnosis and management by standardising definitions. We mapped the range, clarity and consistency of terminology in literature pertaining to both PAS and anaesthesia, and determined whether this changed followed FIGO guidance. METHODS: A literature search of four medical databases was performed. Papers included had PAS (or any 'synonym') in the title, and mode of anaesthesia in the title or abstract. Narrative reviews, and papers not containing original data, were excluded. Diagnostic terms, and evidence supporting their use, were described. RESULTS: Among 680 abstracts identified, 62 papers were included. Thirty distinct terms were used to describe PAS and subtypes. Terminology was clearly defined 46% of the time and used consistently within a paper 47% of the time. Nine papers (15%) provided no diagnostic evidence to support the terminology used. In 14 (23%) papers published after FIGO guidelines, 14 terms were used to describe PAS. Two papers (14%) specified the diagnostic criteria used. Six (43%) confirmed diagnoses using pathology. Four (29%) were consistent in use of terminology throughout the paper. CONCLUSIONS: Despite international consensus criteria for reporting PAS, the language pertaining to PAS and anaesthesia remains heterogeneous, inconsistent and variably defined. Reporting of PAS should adhere to FIGO criteria to allow unambiguous interpretation of work, and generation of evidence that is transferrable into clinical practice.

Evaluation of M43B Lumbar puncture simulator-II as a training tool for identification of the epidural space and lumbar puncture.

The identification of the epidural space, insertion of an epidural catheter and lumbar puncture are advanced technical skills that can be challenging to teach to novice anaesthetists. The M43B Lumbar puncture simulator-II (Limbs & Things Ltd., Sussex Street, Bristol, UK) is a teaching aid designed for epidural and spinal insertion. The aim of this study was to determine if experienced anaesthetists thought this simulator may be a useful tool for training novice anaesthetists in these procedures. Experienced anaesthetists performed an epidural insertion followed by a lumbar puncture procedure on the simulator model. Various aspects of both epidural and lumbar puncture insertions were scored by the anaesthetists for likeness to a real patient using a Likert scale (0--strongly disagree; 1--disagree; 2--neither agree nor disagree; 3--agree; 4--strongly agree). The simulator was found to be life-like for most aspects of epidural insertion. Median (IQR [range]) scores were: iliac crests 3.0 (3.0-3.2 [3-4]); spinous processes 3.0 (3.0-3.2 [2-4]); skin puncture 3.0 (3.0-3.0 [1-4]); subcutaneous tissues 3.0 (2.7-3.0 [1-4]); and loss of resistance 3.0 (3.0-4.0 [3-4]). The scores for supraspinous ligament 2.0 (1.0-3.0 [0-3]), interspinous ligament 2.5 (1.7-3.0 [0-3]) and ligamentum flavum 2.0 (1.0-3.0 [0-4]) were borderline for life-likeness. The volunteers found threading of the epidural catheter difficult and rated it unlike a real patient (score 1.0 (0.2-2.0 [0-3])). During lumbar puncture, dural puncture scored 3.0 (3.0-4.0 [2-4]) and intrathecal injection scored 2.5 (1.0-3.0 [1-4]). However, the overall impression was that the simulator could be a useful tool for training of both epidurals (score 3.0 (3.0-4.0 [3-4])) and spinals (score 3.0 (3.0-3.5 [2-4])).

Suppression of natural killer and lymphocyte functions associated with carcinogen-induced premalignant hyperplastic nodules in rat liver.

The effects of chemical carcinogenesis to produce premalignant hyperplastic nodules in rat liver on concomitant immune function were studied. Induction of hyperplastic nodules in Fischer rats was accomplished using a combined regimen of diethylnitrosamine, 2-acetylaminofluorene, and partial hepatectomy. Hyperplastic nodules were detected in carcinogen-treated rats from 5 to 23 weeks as confirmed by gross pathology, histopathology, and significantly elevated liver gamma-glutamyltransferase activity. Suppression of natural killer activity of either peritoneal or peripheral blood lymphoid, but not splenic, cells for YAC-1 target cells occurred during 5 to 20 weeks in carcinogen-treated rats. Spleen and blood lymphocyte mitogenic responses to concanavalin A and pokeweed mitogen were also suppressed at most intervals from 8 through 20 weeks. Control groups given individual carcinogen or partial hepatectomy alone or in dual combination were not suppressed in their immune function and failed to develop hyperplastic foci or changes in liver gamma-glutamyltransferase. Our findings indicate that immunosuppression of natural killer and lymphocyte mitogenic functions occurs for a protracted period concurrently with the development of the premalignant hyperplastic state in rat liver. The data suggest a potential role for immune competency during the onset of malignant neoplasia.

Effect of age, breed and dietary omega-6 (n-6): omega-3 (n-3) fatty acid ratio on immune function, eicosanoid production, and lipid peroxidation in young and aged dogs.

The focus of this study was to examine the influence of age and diet on various parameters of immune function in young and old Fox Terriers and Labrador Retrievers. Eighteen young and old dogs were utilized for this study. Young and old dogs were fed a basal diet containing an (n-6):(n-3) ratio of 25:1 for sixty days (Phase I). Half of the dogs were then switched to a diet with an (n-6):(n-3) ratio of 5:1, and all were maintained on their respective diets for an additional sixty days (Phase II). Results from these studies revealed an age-associated decline in several immune parameters measured. Both these breeds demonstrated a reduction in sheep red blood cell titers, as well as in their ability to respond to different mitogens. Interestingly, this decline was greater in Fox Terriers, suggesting a decrease in cellular proliferative capacity in lymphocytes isolated from the larger breed. Neither cytokine production or DTH response was affected by age. Diet and breed interactions resulted in a significant increase in T- and B-cell mitogen responsiveness. In contrast, supplementation with n-3 fatty acids did not affect IL-1, IL-6 or TNF-alpha production. Supplementation with n-3 fatty acids resulted in increased PGE3 production from peritoneal macrophages but had no effect on PGE2 production from peripheral blood mononuclear cells or peritoneal macrophages. The n-3 fatty acid supplementation did not influence alpha-tocopherol status although older dogs had significantly lower serum alpha-tocopherol concentrations. Oxidative status of these dogs was assessed by serum levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Feeding an n-3-enriched diet did not affect 4-HNE levels but significantly decreased MDA levels in old dogs. In summary, this study indicates that feeding a diet containing an (n-6):(n-3) fatty acid ratio of 5:1 had a positive, rather than a negative, effect on the immune response of young or geriatric dogs.

Efficacy of antibiotics in low-velocity gunshot fractures.

We have investigated the efficacy of intravenous antibiotic therapy as a prophylactic measure to prevent infection following low-velocity gunshot fractures. Ninety-six consecutive patients were randomized prospectively to either an antibiotic group (Group I) or a nonantibiotic group (Group II) and were followed in a special gunshot wound clinic. Only patients with fractures that could be treated by closed techniques and did not require internal fixation were included. Sixty-seven patients (73 fractures) were followed radiographically. At follow-up, 36 fractures in Group 1 and 37 fractures in Group II comprised the study group. A total of two infections, one in each group, was documented. No significant infection prophylaxis was demonstrated by the use of intravenous antibiotics in these injuries.

Adamantinoma. A case report with aspiration cytology and differential diagnostic and immunohistochemical considerations.

Fine needle aspiration biopsy of bone lesions is routinely used in the metastatic workup of patients with radiographically suspicious areas. However, caution must be used when interpreting smears from aspirates performed on primary bone neoplasms. These tumors are often heterogeneous, and problems with sampling may be encountered. We report a case of a 25-year-old male who presented with a 3-cm lytic lesion in the tibia. A diagnosis of benign fibroosseous lesion was based on the clinical presentation, radiographic appearance and presence of numerous sheets and single cytologically bland spindle cells. Subsequent curettage of the specimen revealed an adamantinoma with a prominent fibrous component. Most of these rare, locally aggressive neoplasms are located in the tibia. They are characterized histologically as having a fibrous background with islands of basaloid, spindle or squamoid cells. Furthermore, a differentiated, regressing variant with an osteofibrous dysplasia-like appearance also exists. Smears consisting primarily of spindle cells or fibrous tissue may lead to an erroneous diagnosis of a fibrohistiocytic neoplasm, fibrous dysplasia, fibrous cortical defect or ossifying fibroma. Pertinent cytomorphologic features should aid in establishing the correct diagnosis of adamantinoma.

The introduction of a surgical safety checklist in a tertiary referral obstetric centre.

BACKGROUND Surgery-related adverse events remain a significant and often under-reported problem. In a recent study, the introduction of a perioperative checklist by the WHO reduced deaths and complications by 46% and 36% respectively. The authors wished to evaluate the introduction of a surgical safety checklist in a busy obstetric tertiary referral centre by assessing staff attitudes, checklist compliance and effects upon patients. METHODS A questionnaire-based assessment was performed on staff working in obstetric theatres before and after the introduction of the surgical safety checklist. Checklist compliance was assessed at 3 months and 1 year. Patients were asked questions relating to the performance of the surgical safety checklist in order to evaluate any anxiety caused. RESULTS Non-medical staff were significantly more likely than medical staff to feel familiar with other team members both before (p<0.001) and after (p=0.03) the introduction of the checklist. 69.6% of all staff felt that interprofessional communication had improved following the introduction of the checklist. Compliance with pre- and postoperative checks was 61.2% and 67.6%, respectively, improving to 79.7% and 84.7% after 1 year. Although the majority of patients were aware of the checks being performed, this did not provoke anxiety. CONCLUSION Following consultation with staff and patients, the authors managed to institute and sustain the performance of a surgical safety checklist for elective cases in obstetric theatres. While significant progress has been made, the authors recognise that further work is required in order to further evaluate and optimise this process.

Production of migration inhibitory factor by Listeria-immune mouse T lymphocytes, but not B lymphocytes.

Antigens and B cell mitogens have been reported to induce migration inhibition factor (MIF) production by mouse B cells. Immune resistance to the intracellular bacterium, Listeria monocytogenes is thought to involve T cells, but not B cells. Since Listeria-derived components are B cell, but not T cell mitogens, it was important to determine whether these materials could stimulate secretion of the lymphokine, MIF by T cells, B cells, or both. Thus populations of whole, unfractionated spleen cells, obtained from normal and Listeria-immune BDF1 mice, were cultured with or without 100 micrograms/ml of Listeria intracellular product (LIP). The culture supernatants obtained 24 h later were assayed for MIF activity using the in vitro macrophage migration inhibition assay. Data obtained show that immune T lymphocytes release MIF in response to specific Listeria antigens, but that spleen B cells from immune and normal mice, obtained as immune, nylon-wool-adherent cells treated with anti-T-cell serum plus complement, are not capable of releasing MIF. This suggests that release of lymphokines by Listeria-immune or normal B cells stimulated with Listeria-derived antigens and mitogens is unlikely to contribute to resistance against Listeria in vivo.

Modulation of natural killer activity in mice following infection with Listeria monocytogenes.

Mice that received a sublethal, intraperitoneal dose of viable Listeria monocytogenes, virulent strain 10403, exhibited a systemic increase in natural killer (NK) activity. The kinetics of the response differed with respect to the various effector cell populations analyzed. Resident peritoneal cells and peripheral blood leukocytes demonstrated high NK activity on Days 3, 7, and 10. Peak spleen and bone marrow NK activity was observed on Day 3, returning to normal levels by Day 7. In contrast, peritoneal exudate cells, elicited with proteose peptone, expressed enhanced NK activity for 60 days following infection with viable Listeria. Augmented NK activity was detected with all cell types as early as 12 hr after infection. The intraperitoneal injection of nonviable antigenic preparations derived from L. monocytogenes, strain 10403, resulted in the enhancement of peritoneal and splenic NK activity. In contrast, mice that received an intraperitoneal injection of avirulent Listeria, strain 19113, failed to express enhanced levels of NK activity. The genetic trait of anti-listerial resistance which is associated with non-H-2 linked genes was of no importance with respect to enhanced NK activity. Listeria-resistant C57BL/6J and Listeria-susceptible DBA/2J mice both produced systemic augmentation of NK activity following infection. NK activity was not abrogated by macrophage depletion or by treatment with anti-Thy 1.2 serum plus complement. These results confirm the potent immunostimulatory capacity of virulent Listeria for NK activity and provide further insight into the kinetics of this response in various lymphoid compartments. The protracted augmentation of NK activity of elicited peritoneal exudate cells as compared to nonelicited peritoneal cells in Listeria-primed mice suggests that the influx of inflammatory cells may provide NK-enriched and/or accessory populations for immunopotentiation of NK activity in inflammatory sites.

In vivo administration of anti-asialo-GM1 antibody enhances splenic clearance of Listeria monocytogenes.

Resistance of mice to infection by Listeria monocytogenes involves a biphasic response. The first phase consists of the first 48 h after infection, during which there is multiplication of Listeria in the liver and spleen of infected mice. In these nonimmune mice, macrophages and polymorphonuclear leukocytes are the effector cells involved in controlling multiplication. In the second phase, cell-mediated immunity develops, beginning on day 2, during which multiplication of Listeria is prevented by macrophages possessing increased microbicidal activity that is mediated through the action of lymphokines released by immunologically committed T lymphocytes. The purpose of the present study was to define a role for natural killer (NK) cells in natural resistance to Listeria during the first 48 h after infection, prior to the development of specific immunity. Splenic NK cell activity was enhanced following a sublethal intravenous injection of viable Listeria as early as 24 h after injection and remained elevated throughout the nonimmune phase of infection. Interestingly, treatment of mice with anti-asialo-GM1 significantly enhanced the ability of mice to clear Listeria from the spleen relative to infected controls possessing intact NK cell populations. This was evidenced by 23-fold fewer bacteria obtained from the spleens of anti-asialo-GM1-treated mice. In addition, Percoll-enriched NK cell populations obtained from 48-hour Listeria-infected mice do not exhibit in vitro listericidal activity. These observations suggest a regulatory role of NK cells in resistance against Listeria and preclude a role for NK cells in direct cytolysis. Perhaps these cells modulate the immune response to Listeria by down-regulating the activity of the immune cells crucial to listerial resistance.

Analysis of the kinetics of natural killer cell activity in mice during an active infection with Pseudomonas aeruginosa.

The present study was designed to determine the effect of Pseudomonas aeruginosa (PA) infection on the activity of natural killer (NK) cells in mice. Following a sublethal injection of the bacterium, increased NK cell activity is evident as early as 24 h and peaks within 72 h, returning to normal levels by 168 h. Interestingly, the route by which PA was administered was very important with respect to increased NK activity. For example, the greatest augmentation of activity was seen in the peritoneal cavity when mice were injected intraperitoneally and in the spleen when injected intravenously. Peripheral blood leukocytes expressed the greatest augmentation in animals which received an intravenous injection of viable PA. In addition, a nonviable preparation of PA was used and found to significantly augment NK cell activity in a dose-dependent manner. To determine whether the presence of the organism is required for augmentation of NK activity, the rate at which PA is cleared from the animals was evaluated. Regardless of the route of injection, PA is effectively cleared within 24 h, thus eliminating the possibility that viable PA is required for augmentation of NK activity. This augmentation is proximal to the route of injection with little systemic effect seen. The data presented in this report illustrate that both viable and nonviable preparations of PA produce a significant increase in NK cell activity. This augmentation may suggest a role for these cells as effectors in natural resistance to infectious disease.

Kinetics and maintenance of acquired resistance in mice to Listeria monocytogenes.

In the mouse system, acquired resistance to Listeria monocytogenes can only be demonstrated after immunization with viable microorganisms. A successful state of immunity cannot be elicited with formalin-killed organisms or bacterial cell-derived products. Viable, serologically cross-reactive organisms (not mouse pathogenic) do not induce a state of immunity as measured by acquired resistance. The duration of immunity, once established, is dose independent, and the absolute interval of its existence is not extended by secondary challenge with large numbers of viable organisms. The decline of immunity in actively immunized animals is not altered by antigenic challenge with formalin-killed cells or cell products. This indicates that the cellular requirements for the development of host resistance are similar for induction as well as maintenance. In vitro measurements of cellular immunity by migration inhibition indicate that formalin-killed organisms as well as cell products were recognized by actively sensitized lymphocytes obtained from immune animals.

Heat-labile B-cell mitogen obtained from Listeria monocytogenes.

A water-soluble extract of Listeria monocytogenes strain 10403 acts as a mitogen on cultured mouse spleen lymphocytes. This mitogen induced a response six to nine times that of controls, as measured by [3H]thymidine incorporation. The mitogen extract was derived from washed bacterial cells which were mechanically disrupted with a French press. The extract was centrifuged at 105,000 X g and filtered through a 0.22-micrometer filter. Similar levels of lymphocyte stimulation were observed in lymphocyte cultures prepared from spleens of nude mice, indicating the effect of this mitogen on B-cells. The mitogenic property of this extract was destroyed by heating to 56 degrees C. This heat treatment does not destroy the antigens in the extract, which stimulate spleen cell cultures obtained from specifically immune mice. Similarly prepared extracts from Staphylococcus epidermidis and Salmonella typhimurium did not show similar levels of mitogenic activity. The mitogenic property of the L. monocytogenes extract was present in two strains of Listeria tested and was not associated with mouse virulence.