A retrospective cohort study evaluating pregnancy outcomes in women with MIDD.

AIMS: The most common pathogenic mitochondrial mutation associated with mitochondrial disease is m.3243A>G. Increased obstetric complications, such as spontaneous abortion, gestational diabetes (GDM), preterm delivery, and preeclampsia, have been reported in women carrying this mutation. We aimed to determine the fetal and maternal outcomes in pregnant women with mitochondrial disease. METHODS: We retrospectively studied the obstetric and perinatal outcomes in 88 pregnancies of 26 women with genetically confirmed mitochondrial disease (m.3243A>G in the MTTL1 gene (n = 25); m.12258C>A in the MT-TS2 gene (n = 1)). Outcomes included pregnancy related complications, mode of delivery, gestational age at delivery and birthweight. RESULTS: Mean heteroplasmy rate was 18%. The miscarriage rate was higher than background at 25%. 21 pregnancies (24%) were complicated by GDM; 9 pregnancies (13.6%) had a preterm delivery and 2 of them (3%) an extreme premature delivery < 32 weeks. One woman had preeclampsia and one had a postpartum hemorrhage. The caesarean section (CS) rate was 20%. For every unit increase in maternal heteroplasmy levels there was a 26% increased risk of undergoing an assisted operative vaginal delivery (OR 1.26, 95% CI 1.04-1.53, P = 0.002, Bonferroni corrected P = 0.005) and an 18% increased risk of undergoing a CS (OR 1.18, 95% CI 1.01-1.39, P = 0.01, Bonferroni corrected P = 0.03) compared to a spontaneous vaginal delivery. There was a statistical significant correlation between maternal and offspring heteroplasmy levels. Spearman correlation rho = 0.96, 95% CI 0.78-0.99, P = 0.0002. CONCLUSION: Women with mitochondrial disease appear to have more frequent obstetric complications including miscarriage and GDM. Pre-pregnancy diagnosis of m.3243A>G will enable the counseling of women and increase awareness of possible obstetric complications.

Severe maternal morbidity trends over 20 years in a tertiary referral stand-alone maternity unit.

OBJECTIVE: Severe maternal morbidity (SMM) is a better indicator of quality of care than maternal mortality, which is a rare event. Risk factors such as advanced maternal age, caesarean section (CS) and obesity are increasing. The aim of this study was to examine the rate and trends in SMM at our hospital over a 20-year period. STUDY DESIGN: Retrospective review was performed of cases of SMM from January 1st 2000 to December 31st 2019. Yearly rates for SMM and Major Obstetric Haemorrhage (MOH) were calculated (per 1000 maternities) and linear regression analysis was used to model the trends over time. Average SMM and MOH rates were also calculated for the periods 2000-2009 and 2010-2019 and compared using a chi-square test. The patient demographics of the SMM group were compared to the background population delivered at our hospital using a chi-square test. RESULTS: 702 women with SMM were identified out of 162,462 maternities over the study period yielding an incidence of 4.3 per 1000 maternities. When the two time periods (2000-2009 and 2010-2019) are compared, the rate of SMM increased 2.4 vs 6.2 (p < 0.001), largely due to an increase in MOH 1.72 vs 3.86 (p < 0.001) and pulmonary embolus (PE) also increased 0.2 vs 0.5 (p = 0.012). Intensive-care unit (ICU) transfer rates more than doubled 0.19 vs 0.44 (p = 0.006). Eclampsia rates decreased 0.3 vs 0.1 (p = 0.047) but the rate of peripartum hysterectomy 0.39 vs 0.38 (p = 0.495), uterine rupture 0.16 vs 0.14 (p = 0.867), cardiac arrest (0.04 vs 0.04) and cerebrovascular accidents (CVA) (0.04 vs 0.04) remained unchanged. Maternal age > 40 years 9.7% vs 5% (p = 0.005), previous CS 25.7% vs 14.4%; p < 0.001 and multiple pregnancy 8 vs 3.6% (p = 0.002) were more prevalent in the SMM cohort compared to the hospital population. CONCLUSIONS: Overall, rates of SMM have increased threefold and transfer for ICU care has doubled over 20 years in our unit. The main driver is MOH. The rate of eclampsia has decreased and peripartum hysterectomy, uterine rupture, CVA and cardiac arrest remain unchanged. Advanced maternal age, previous caesarean delivery and multiple pregnancy were more prevalent in the SMM cohort compared to the background population.

Prospective comparison of prostatic aspirate culture and cystocentesis urine culture for detection of bacterial infection in dogs with prostatic neoplasia.

OBJECTIVE: The purpose of this study was to determine whether prostatic aspirate culture is a superior method to detect infection compared to culture of urine collected by cystocentesis in dogs with prostatic neoplasia. MATERIALS AND METHODS: A prospective study was conducted and dogs with suspected or confirmed prostatic neoplasia were enrolled. Urinalysis was done and culture and antimicrobial susceptibility testing was performed on paired urine and prostatic aspirate samples collected at a single timepoint. RESULTS: Ten dogs with prostatic neoplasia were enrolled. All dogs had one or more clinical sign consistent with lower urinary tract disease. One dog (10%) had a positive urine culture, but negative prostatic aspirate culture, one dog (10%) had a positive prostatic aspirate culture, but negative urine culture, and one dog (10%) had both positive urine and prostatic aspirate cultures. Using prostatic aspirate culture as the reference standard, urine culture had a sensitivity for detecting infection of 87.5% (95% confidence interval 52.9 to 99.4) and specificity of 50% (92.6 to 97.4) in this population of dogs. CLINICAL SIGNIFICANCE: Positive cultures were uncommon with both culture collection methods. Study results did not identify prostatic aspirate culture to be a more sensitive method of detecting prostatic infection than urine culture collected by cystocentesis in these dogs with prostatic neoplasia.

A generic curriculum development model for the biomedical physics component of the educational and training programmes of the non-physics healthcare professions.

The objective of the study was the construction of a generic curriculum development model for the use of biomedical physics (BMP) educators teaching the non-physics healthcare professions (HCP) in Europe. A comprehensive, qualitative cross-sectional Europe-wide survey of the curricula delivered by BMP in Faculties of Medicine and Health Sciences (FMHS) was carried out. Curricular content was collected from faculty web-sites, curricular documents and textbooks. The survey data was supplemented with semi-structured interviews and direct observation during onsite visits. The number of faculties studied was 118 from 67 universities spread all over Europe, whilst the number of onsite visits/interviews was 15 (geographically distributed as follows: Eastern Europe 6, North Western Europe 5, and South Western Europe 4). EU legislation, recommendations by European national medical councils, educational benchmark statements by higher education quality assurance agencies, research journals concerning HCP education and other documents relevant to standards in clinical practice and undergraduate education were also analyzed. Best practices and BMP learning outcomes were elicited from the curricular materials, interviews and documentation and these were subsequently used to construct the curriculum development model. A structured, comprehensive BMP learning outcomes inventory was designed in the format required by the European Qualifications Framework (EQF). The structures of the inventory and curriculum development model make them ideally suited for use by BMP involved in European curriculum development initiatives for the HCP.

Antibiotics and antimicrobial resistance: Evaluation of the knowledge, attitude, and perception among students and faculty within US dental schools.

PURPOSE: This study examined knowledge, attitudes, perceptions, and awareness regarding antibiotic use among students and academic faculty in US dental schools. METHODS: Two questionnaires, 1 for third-year/fourth-year dental students and the other for academic deans/department chairs were administered electronically. Questions on demographics, antibiotic knowledge, educational formats, and the role of dentistry in antibiotic stewardship were included. Knowledge about antibiotics and antibiotics stewardship was compared between third-year and fourth-year students and between students and academic faculty using t-test and chi-squared test at 0.05 significance level. RESULTS: A total of 18 responses on the academic dean and department chair survey and 172 responses on the dental student survey were collected. Overall, 71% of students reported that they could benefit from more education regarding antibiotics. Both faculty and students agreed that dentistry should play an important role in reducing antimicrobial resistance, but most dental students were "not at all familiar" with the term antimicrobial stewardship and several (32%) were unsure if clinical guidelines were present at their schools. CONCLUSION: Improvements to the dental educational curriculum regarding the responsible use of antibiotics, along with the implementation of stewardship programs within dentistry are strongly encouraged.

Contrasting Regional Carbon Cycle Responses to Seasonal Climate Anomalies Across the East-West Divide of Temperate North America.

Across temperate North America, interannual variability (IAV) in gross primary production (GPP) and net ecosystem exchange (NEE) and their relationship with environmental drivers are poorly understood. Here, we examine IAV in GPP and NEE and their relationship to environmental drivers using two state-of-the-science flux products: NEE constrained by surface and space-based atmospheric CO2 measurements over 2010-2015 and satellite up-scaled GPP from FluxSat over 2001-2017. We show that the arid western half of temperate North America provides a larger contribution to IAV in GPP (104% of east) and NEE (127% of east) than the eastern half, in spite of smaller magnitude of annual mean GPP and NEE. This occurs because anomalies in western ecosystems are temporally coherent across the growing season leading to an amplification of GPP and NEE. In contrast, IAV in GPP and NEE in eastern ecosystems is dominated by seasonal compensation effects, associated with opposite responses to temperature anomalies in spring and summer. Terrestrial biosphere models in the MsTMIP ensemble generally capture these differences between eastern and western temperate North America, although there is considerable spread between models.

Advancements in AAV-mediated Gene Therapy for Pompe Disease.

Pompe disease (glycogen storage disease type II) is caused by mutations in acid α-glucosidase (GAA) resulting in lysosomal pathology and impairment of the muscular and cardio-pulmonary systems. Enzyme replacement therapy (ERT), the only approved therapy for Pompe disease, improves muscle function by reducing glycogen accumulation but this approach entails several limitations including a short drug half-life and an antibody response that results in reduced efficacy. To address these limitations, new treatments such as gene therapy are under development to increase the intrinsic ability of the affected cells to produce GAA. Key components to gene therapy strategies include the choice of vector, promoter, and the route of administration. The efficacy of gene therapy depends on the ability of the vector to drive gene expression in the target tissue and also on the recipient's immune tolerance to the transgene protein. In this review, we discuss the preclinical and clinical studies that are paving the way for the development of a gene therapy strategy for patients with early and late onset Pompe disease as well as some of the challenges for advancing gene therapy.

How Much Greater is Obstetric Intervention in Women with Medical Disorders in Pregnancy When Compared to the General Population?

Introduction The purpose of this study was to compare obstetric and neonatal outcomes between women attending a specialised maternal medicine service and the general obstetric population. Methods Women attending from January 2011 to December 2016 were identified from the clinic database. Medical diagnosis, demographics, obstetric and neonatal outcomes were compared with data from hospital annual report 2014. Results 1873 women were compared with 8632 women who delivered at the hospital in 2014. Delivery before 34 weeks [82 (4.5%) vs 189 (2.2%)], induction of labour [761 (40.6%) vs 2664 (30.9%)] and delivery by Caesarean Section (CS) [664 (35%) vs 2479 (29%)] were higher p<0.001; but elective CS [334 (18%) vs 1425 (17%), p=0.18] did not differ between the two groups. Neonatal outcomes were similar. Conclusion Premature delivery, induction of labour and CS rates are higher in women with medical disorders in pregnancy. Encouragingly, 77% of women attempting vaginal birth in this group were successful.

Analgesia, anaesthesia and obstetric outcome in women with inherited bleeding disorders.

OBJECTIVE: Vertebral canal haematoma (VCH) complicates 1 in 168,000 obstetric epidurals (Ruppen et al., 2006). This risk is increased in women with inherited bleeding disorders (IBD). The impact of a contraindication to regional anaesthesia on pain management and obstetric outcome in these women is unknown. The purpose of this study was to determine anaesthetic use and obstetric outcomes in a cohort of women with IBD. STUDY DESIGN: 97 women with IBD that delivered 130 babies at the CWIUH from Jan 2011 to Dec 2016 were identified from a maternal medicine database. Multidisciplinary planning of peripartum care was communicated to labour ward staff using a simple checklist. The primary bleeding disorders were: Von Willebrands disease (VWD) Type 1 27 (27.8%); VWD Type 2A 3 (3.8%); Low VWF 3 (3.8%); Bleeding disorder of unknown aetiology (BDUA) 19 (19.6%); deficiency of Factors VII, VIII, IX, X, and XI 13 (13.4%); Carriers of Factor VIII, IX, X, XIII deficiency 17 (17.5%); 5 had combined deficiencies (5.2%) and there was one platelet function defect. 9 had a family history of a bleeding disorder (9.3%). Haemostatic support, analgesia, mode of delivery and maternal and fetal outcomes were compared between pregnancies where regional anaesthesia was permitted and those that were not using the Chi-squared test. RESULTS: When pregnancies where regional anaesthesia was not recommended (49) were compared with pregnancies where regional anaesthesia was considered safe (81), the women were more likely to see an anaesthetist before labour 46 (94%) vs 46 (61%): p < 0.001; to require prophylactic haemostatic support for delivery 30 (61%) vs 1 (1%): p < 0.001; to use a remifentanil infusion 15 (31%) vs 0: p < 0.001, and have general anaesthesia for Caesarean Section (CS) 10 (20%) vs 1(1%): p < 0.001. Vaginal birth 35 (71%) vs 53(65%): p = 0.4 and CS rates 14 (29%) vs 26 (32%) p = 0.28 were similar. Postpartum haemorrhage (PPH) was more common 11 (24%) vs 9(12%) vs p = 0.07 but not statistically so. There were no cases of neonatal bleeding or VCH. CONCLUSION: Contraindication to neuraxial blockade in labouring women with IBD does not influence mode of delivery. This information is reassuring to these women who may be anxious about delivery without regional anaesthesia.

Enterococcus infections in foals.

Enterococci have been increasing in prevalence in foal sepsis over the past three decades. There are no published studies in the peer-reviewed literature documenting common sites of infection, antimicrobial susceptibility, or outcome specifically associated with enterococcal infections in foals. Our objectives were to evaluate the sites of origin, antimicrobial susceptibility, and survival outcome to discharge in foals with enterococcal infections compared with foals with sepsis of another bacterial etiology. Seventy-five foals 0-30 days of age with cultures positive for Enterococcus and 170 control foals 0-30 days of age with cultures positive for other bacteria were included. Enterococcus was 2.67 times (95% confidence interval [CI], 1.49-4.80; P = 0.0012) more likely to be isolated from the lower urogenital tract of foals than were other bacteria. Enterococci were less likely to be isolated from blood cultures than other bacteria, with an odds ratio (OR) of 0.17 (95% CI 0.09-0.35; P < 0.0001). For Enterococcus isolates, 48% (n = 29/61) had a multiple antimicrobial resistance (MAR) index of ≥30% and 46% (n = 28/61) had a multiple drug resistance (MDR) index of ≥30%. Foals with enterococcal infections were less likely to survive to discharge (49.9% vs. 63.5%; P = 0.03). Enterococcus is commonly isolated from the lower urogenital tract of foals, is often multidrug resistant, and foals with enterococcal infections were less likely to survive. Multidrug resistance is common among enterococcal isolates, and therefore antimicrobial susceptibility testing of cultured isolates is warranted.

Randomized trial of polychromatic blue-enriched light for circadian phase shifting, melatonin suppression, and alerting responses.

Wavelength comparisons have indicated that circadian phase-shifting and enhancement of subjective and EEG-correlates of alertness have a higher sensitivity to short wavelength visible light. The aim of the current study was to test whether polychromatic light enriched in the blue portion of the spectrum (17,000 K) has increased efficacy for melatonin suppression, circadian phase-shifting, and alertness as compared to an equal photon density exposure to a standard white polychromatic light (4000 K). Twenty healthy participants were studied in a time-free environment for 7 days. The protocol included two baseline days followed by a 26-h constant routine (CR1) to assess initial circadian phase. Following CR1, participants were exposed to a full-field fluorescent light (1 × 1014 photons/cm2/s, 4000 K or 17,000 K, n = 10/condition) for 6.5 h during the biological night. Following an 8 h recovery sleep, a second 30-h CR was performed. Melatonin suppression was assessed from the difference during the light exposure and the corresponding clock time 24 h earlier during CR1. Phase-shifts were calculated from the clock time difference in dim light melatonin onset time (DLMO) between CR1 and CR2. Blue-enriched light caused significantly greater suppression of melatonin than standard light ((mean ±â€¯SD) 70.9 ±â€¯19.6% and 42.8 ±â€¯29.1%, respectively, p < 0.05). There was no significant difference in the magnitude of phase delay shifts. Blue-enriched light significantly improved subjective alertness (p < 0.05) but no differences were found for objective alertness. These data contribute to the optimization of the short wavelength-enriched spectra and intensities needed for circadian, neuroendocrine and neurobehavioral regulation.

Is Maximal Dosage for Local Anesthetics Taught Consistently Across U.S. Dental Schools? A National Survey.

Administration of safe and effective local anesthesia is a cornerstone of dental practice, but there is some discrepancy in recommendations for maximum doses, with the Council on Dental Therapeutics and American Academy of Pediatric Dentistry's guidelines differing from the guidelines of manufacturers and contemporary textbooks. The aim of this study was to determine the level of uniformity across U.S. dental schools in teaching maximal safe doses for commonly used local anesthetics. Faculty members primarily responsible for teaching local anesthesia to dental students at all 62 U.S. dental schools that had graduated classes were invited to participate in a survey in March 2017. The survey included questions about maximum doses taught, awareness of the existence of two differing guidelines, and whether one or both guidelines were commonly taught to students. A total of 37 responses were received, for a response rate of 60%. The respondents included oral and maxillofacial surgeons, general dentists, dental anesthesiologists, and periodontists. Of the respondents, 22% reported being unaware of the existence of more than one standard, and there was inconsistency in teaching practices. A majority (73%) reported teaching the higher maximum dose (7 mg/kg) for lidocaine, while a similar but smaller majority (60%) reported teaching the lower dose threshold (4.4 mg/kg) for mepivacaine. This study found no standard recommended maximum dose of lidocaine or mepivacaine being taught in U.S dental schools. Students should be made aware that there is more than one standard, and teaching should emphasize sound medical and pharmacologic principles. There is also a need to ensure that questions on dental licensing examinations are consistent regarding maximum safe doses for local anesthesia.

Inequalities in Implementation and Different Outcomes During the Growth of Laparoscopic Colorectal Cancer Surgery in England: A National Population-Based Study from 2002 to 2012.

AIM: Laparoscopic colorectal cancer surgery has developed from unproven technique to mainstay of treatment. This study examined the application and relative outcomes of laparoscopic and open colorectal cancer surgery over time, as laparoscopic uptake and experience have grown. METHODS: Adults undergoing elective laparoscopic and open colorectal cancer surgery in the English NHS during 2002-2012 were included. Age, sex, Charlson Comorbidity Index and Index of Multiple Deprivation were compared over time. Post-operative 30-day mortality, length of stay, failure to rescue reoperation and the associated mortality rate were examined. RESULTS: Laparoscopy rates rose from 1.1 to 50.8%. Patients undergoing laparoscopic surgery had lower comorbidity by 0.24 points (95% confidence intervals (CI) 0.20-0.27) and lower socioeconomic deprivation by 0.16 deciles (95% CI 0.12-0.20) than those having open procedures. Overall mortality fell by 48.0% from 2002-2003 to 2011-2002 and was 37.8% lower after laparoscopic surgery. Length of stay and mortality after surgical re-intervention also fell. However, re-intervention rates were higher after laparoscopic procedures by 7.8% (95% CI 0.9-15.2%). CONCLUSIONS: There was clear and persistent inequality in the application of laparoscopic colorectal cancer surgery during this study. Further work must explore and remedy inequalities to maximise patient benefit. Higher re-intervention rates after laparoscopy are unexplained and differ from randomized controlled trials. This may reflect differences in surgeons and practice between research and usual care settings and should be further investigated.

Use of quantitative real-time PCR to determine viability of Streptococcus equi subspecies equi in respiratory secretions from horses with strangles.

BACKGROUND: In recent years, molecular approaches have been able to characterise the viability of equine upper respiratory tract pathogens using absolute molecular quantitation as well as detection of transcripts for virulence genes. OBJECTIVES: The objective of this study was to investigate molecular surrogates for S. equi subspecies equi (S. equi) viability in biological samples from horses with strangles. STUDY DESIGN: Retrospective cross-sectional study. METHODS: S. equi culture-positive and culture-negative upper airway secretions were assessed by qPCR at the genomic (gDNA) and complimentary DNA (cDNA) level for various target genes (SeM, SEQ2190, eqbE and szpSe). Absolute quantitation was performed using standard curves, and the results were expressed as number of S. equi target genes per µl of gDNA or cDNA. Additionally, the presence or absence of S. equi gene expression for the various target genes was assessed and compared with the culture results. RESULTS: While all 21 culture-positive samples tested S. equiqPCR positive, up to 43.7 and 18.9% of 64 culture-negative samples tested qPCR positive at the gDNA and cDNA level, respectively. Significant differences in absolute quantitation for S. equi at the gDNA level were found between culture-positive and culture-negative samples. When absolute quantitation of S. equi target genes at the gDNA level was assessed with the presence or absence of transcripts, there was a significantly higher S. equi target gene number in samples with expression of transcripts compared with samples with no expression of transcripts. MAIN LIMITATIONS: The lack of standardisation of samples collected in the field and the delay from sample collection to samples processing may have negatively affected the cultivability of S. equi and mRNA quality. CONCLUSIONS: Molecular viability for S. equi can be investigated by determining absolute quantitation and/or by detecting mRNA for specific target genes. However, veterinarians have to be cautioned that any qPCR-positive result for S. equi needs to be taken seriously and trigger biosecurity protocols aimed at reducing spread.

Evaluation of the Live Biotherapeutic Product, Asymptomatic Bacteriuria Escherichia coli 2-12, in Healthy Dogs and Dogs with Clinical Recurrent UTI.

BACKGROUND: Antimicrobial resistance is an emerging problem. HYPOTHESIS/OBJECTIVE: To investigate the safety and efficacy of a live biotherapeutic product, ASB E. coli 2-12 for UTI treatment. ANIMALS: Six healthy research dogs; nine client-owned dogs with recurrent UTI. METHODS: Prospective noncontrolled clinical trial. For safety data, research dogs were sedated, a urinary catheter was inserted into the bladder; 1010 CFU/mL of ASB E. coli 2-12 was instilled. Urine was cultured on days 1, 3, and 8 post-instillation and dogs were observed for lower urinary tract signs (LUTS). For client-owned dogs, ASB E. coli 2-12 was instilled similarly and urine cultures analyzed on days 1, 7, and 14 days postinstillation. RESULTS: No LUTS were noted in any of the 6 research dogs after ASB E. coli 2-12 infusion. Pulse field gel electrophoresis (PFGE) studies confirmed the bacterial strains isolated matched that ASB E. coli 2-12 strain. Four of the nine client-owned dogs had complete or nearly complete clinical cures by day 14. Of these four dogs, 3 also had microbiologic cures at day 14; one of these dogs had subclinical bacteriuria (in addition to ASB E. coli 2-12). Three of these four dogs had ASB E. coli 2-12 isolated from their urine at day 14. With the exception of mild, temporary, self-limiting, hyporexia in two dogs on the day of biotherapeutic administration, there were no major adverse effects. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest ASB E. coli 2-12 is safe and should be investigated in a larger controlled study evaluating clinical UTI in dogs.