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Ectopic pregnancy is a common gynaecological emergency accounting for a significant proportion of early pregnancy mortality. The chemotherapeutic methotrexate, through targeting rapidly diving cells, is a widely used non-invasive treatment option that has allowed many to avoid invasive surgery. Failure of methotrexate treatment necessitates emergency surgical management, at times to manage haemorrhage related to tubal rupture. As such, careful characterisation, and selection of those suitable for methotrexate treatment is essential. This chapter discusses the use of methotrexate for managing tubal ectopic pregnancy, including eligibility, factors associated with treatment success, and necessary patient counselling. Lastly, we explore the recent advances in knowledge and current landscape of novel therapeutics with potential to improve medical treatment of tubal ectopic pregnancy.
Urinary tract infections (UTI) are common and women with typical symptoms may be treated empirically without culture. We evaluated the utility of urine culture in men presenting with typical symptoms of uncomplicated UTI. Most pathogens isolated retained susceptibility to first-line antimicrobials suggesting urine cultures may be unnecessary in this population.
Ambulatory antibiotic stewardship has traditionally focused on acute respiratory infections with few studies evaluating metrics for other commonly encountered ambulatory conditions, including urinary tract infections (UTI). We describe the development and validation of an electronically captured appropriate antibiotic use metric for ambulatory UTIs using coding data.
Background: Frontotemporal dementia (FTD) often presents with varying neuropsychiatric symptoms (NPS), which may differ based on genetic mutations. We hypothesized distinct NPS trajectories in FTD progression among carriers of chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), and microtubule-associated protein tau (MAPT) mutations. Methods: We analyzed 1662 participants from ALLFTD, including 342 C9orf72, 148 GRN, 168 MAPT mutation carriers, and 1004 noncarriers. We categorized participants into four stages based on CDR plus NACC FTLD global scores: 1) Presymptomatic (consistent CDR=0), 2) Early conversion (CDR increasing from 0 to 0.5), 3) Advanced conversion (CDR increasing from 0.5 to ≥1.0), and 4) Symptomatic (CDR>1.0). The Neuropsychiatric Inventory-Questionnaire (NPI-Q) assessed NPS changes, analyzed using a mixed-effects model, accounting for age and baseline scores. Results: Our results indicated similar NPS trajectories in the presymptomatic stage for all groups. Notably, during early conversion, C9orf72 and GRN carriers exhibited significantly higher NPI-Q score increases than MAPT carriers, primarily in psychosis and hyperactivity domains. In later stages, increases in NPS were similar across groups. Conclusions: This study suggests familial FTD progression, particularly in TDP-43 pathology, may involve more severe NPS like psychosis or hyperactivity, differing from tau pathology or sporadic FTD. Further research is needed to explore these distinct trajectories.
OBJECTIVES/GOALS: Social isolation/loneliness is a public health crisis and one that is unlikely to be solved through pharmacology. Nonpharmacological approaches, such as dance, are needed. The objective of this study is to investigate the physiological correlates of dance-induced improvements in social connection. METHODS/STUDY POPULATION: Participants were randomly assigned to participate for 4 weeks (2 times per week, 90-minute sessions) in either 1) improvisational dance training (experimental group; n=7); or a 2) dance movie watching experience (control group; n=7). Before and after the intervention, using mobile brain-body imaging techniques, participants and their instructor had their brain (via electroencephalography) and body physiology (via photoplethysmography) recorded during a series of verbal and nonverbal interactive experiences. Participants were also video recorded via 4 surrounding cameras for later motion capture analysis. Neuropsychological assessments were also conducted before and after the intervention. RESULTS/ANTICIPATED RESULTS: We found that dance significantly increased social skills including empathy, interpersonal skills, emotional regulation, mindfulness, and attention. Additionally, we found that dance significantly increased interbrain synchrony during nonverbal experiences including theta (4-8 Hz), beta (12-35 Hz), and gamma (35-45 Hz) frequencies in the occipital lobe. Increases in interbrain synchrony were also positively correlated with increases in empathy. Additionally, intercardiac synchrony between the participant and instructor showed a significant correlation at post-intervention only. Future investigations will focus on the relationship between interbrain, intercardiac, and movement synchrony. DISCUSSION/SIGNIFICANCE: Our findings support the idea that dance increases interpersonal synchrony at the level of the brain, heart, and behavior. Understanding the neural and somatic mechanisms of social behaviors will help promote understanding and development of interventions for the critical problem of social isolation and loneliness.
The depth distribution of illite/smectite (I/S) compositions was investigated for a well drilled to a depth of 3462 m on Barbados Island, the only subaerial exposure of the Barbados accretionary complex. The classical pattern of increasing percentage of illite interlayers in the mixed-layer clay with increasing burial depth was not observed. Rather, the data describe an irregular, zig-zag trend with depth. This trend is probably the result of reverse faulting in the section. I/S data were also used to infer several kilometers of uplift and subsequent erosion of the section. This study shows that irregular patterns of clay diagenesis with depth can be anticipated for sequences that have undergone complicated tectonism and deformation. Combined with other geologic information, these patterns can help to determine the tectonic history of the sedimentary sequence.
Our institution sought to evaluate our antimicrobial stewardship empiric treatment recommendations for Salmonella. Results from 36 isolates demonstrated reduced susceptibilities to fluoroquinolones with 1 isolate susceptible only to ceftriaxone. Analysis supports the current recommendation of empiric ceftriaxone therapy for severe infection and updated recommendation for sulfamethoxazole-trimethoprim in non-severe infections.
Background: Patient registries are an effective tool in tracking the natural history of rare diseases as well as post-marketing surveillance of novel therapies. The Canadian Neuromuscular Disease Registry (CNDR) is a pan-neuromuscular disease registry that prospectively collects Spinal Muscular Atrophy (SMA)-specific data in 28 clinics across Canada. The objective of this study is to describe real-world data from the CNDR-SMA patient population. Methods: We report cross-sectional data from Canadian SMA patients. Patients were included in analysis if they were active (alive and with follow-up within 24 months). Results: Of 171 SMA patients included in analyses, 37% currently use non-invasive ventilation, 2% invasive ventilation, and 61% no ventilation support. Feeding tubes are used by 27% of patients. and 28% of patients have a history of scoliosis surgery. Of the 171 patients, 137 have had disease-modifying therapy: 96 on nusinersen, 22 on risdiplam, and 19 on onasemnogene abeparvovec (OA). Median (min,max) years of age at therapy initiation was 7 (0,54), 20.5 (5,53), and 1 (0,6), respectively. At therapy initiation, functional status was 32% non-sitters, 38% sitters, and 30% walkers. Conclusions: The CNDR captures a comprehensive SMA dataset that prospectively evaluates real-world data, supporting post-marketing surveillance of novel therapies in Canada.
No established guidelines exist regarding the role of oral antibiotic therapy (OAT) to treat bloodstream infections (BSIs), and practices may vary depending on clinician specialty and experience.
Objective:
To assess practice patterns regarding oral antibiotic use for treatment of bacteremia in infectious diseases clinicians (IDCs, including physicians and pharmacists and trainees in these groups) and non–infectious diseases clinicians (NIDCs).
Design:
Open-access survey.
Participants:
Clinicians caring for hospitalized patients receiving antibiotics.
Methods:
An open-access, web-based survey was distributed to clinicians at a Midwestern academic medical center using e-mail and to clinicians outside the medical center using social media. Respondents answered questions regarding confidence prescribing OAT for BSI in different scenarios. We used χ2 analysis for categorical data evaluated association between responses and demographic groups.
Results:
Of 282 survey responses, 82.6% of respondents were physicians, 17.4% pharmacists, and IDCs represented 69.2% of all respondents. IDCs were more likely to select routine use of OAT for BSI due to gram-negative anaerobes (84.6% vs 59.8%; P < .0001), Klebsiella spp (84.5% vs 69.0%; P < .009), Proteus spp (83.6% vs 71.3%; P < .027), and other Enterobacterales (79.5% vs 60.9%; P < .004). Our survey results revealed significant differences in selected treatment of Staphylococcus aureus syndromes. Fewer IDCs than NIDCs selected OAT to complete treatment for methicillin-resistant S. aureus (MRSA) BSI due to gluteal abscess (11.9% vs 25.6%; P = .012) and methicillin-susceptible S. aureus (MSSA) BSI due to septic arthritis (13.9% vs 20.9%; P = .219).
Conclusions:
Practice variation and discordance with evidence for the use of OAT for BSIs exists among IDCs versus NIDCs, highlighting opportunities for education in both clinician groups.
Although one of the fastest-growing populations in the USA, Latinx individuals remain underrepresented in research. In this study, we aimed to identify how Latina/Latinx participants of the Environment, Leiomyomas, Latinas, and Adiposity Study (ELLAS) learned about the research study and what motivated them to participate.
Materials and Methods:
Using a standardized survey tool, bilingual staff interviewed participants and asked them, 1) how they heard about ELLAS and 2) to identify and rank their top three reasons for participating in ELLAS.
Results:
“Word of mouth” through a friend or relative was the most common method of learning about ELLAS (49.0%), followed by a “community outreach event” (29.3%). The three most common reasons for participating in ELLAS were “to learn more about women’s health” (83.3%), “to receive a free health assessment” (79.4%), and “to contribute to scientific knowledge” (59.5%). Correlation between demographic and socioeconomic characteristics and participant responses indicated that there are different reasons for participation based on these factors.
Conclusions:
Community engagement and word of mouth are vital to the successful recruitment of Latina/Latinx participants to research studies. Latinx participants are most motivated to participate by health benefits and health education, as well as altruistic aspects of research studies. Therefore, establishing mutually beneficial relationships within Latinx communities and appealing to motivations for research participation with close attention to the demographics of participants can both expand and allow for targeted recruitment efforts for this underrepresented group in research studies.
ABSTRACT IMPACT: Our work provides guidance on whether dietary fat intake influences serum cholesterol levels in response to ketogenic diet therapy in adults with epilepsy. OBJECTIVES/GOALS: The modified Atkins diet (MAD) is used in the management of drug-resistant epilepsy in adults. Some patients on MAD show an increase in serum levels of total cholesterol and low-density lipoprotein (LDL) cholesterol. We explored whether dietary fat composition predicts short-term elevations in serum lipid levels in diet-naive adults who begin MAD. METHODS/STUDY POPULATION: Participants self-reported their diet intake with 3-day food records at baseline, 1 month and 2 months. Food records were analyzed using Nutrition Data System for Research software. Fasting serum levels of total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides were also collected and LDL level calculated at baseline, 1 month, and 2 months. RESULTS/ANTICIPATED RESULTS: 38 patients submitted complete food records at each study visit (baseline, 1 month, and 2 month). Compared to baseline diet intake, there was a significant reduction in daily carbohydrate intake at 1 and 2 months (p<0.001) and a significant increase in daily fat intake at 1 and 2 months (p<0.001). There was also a significant increase in daily saturated fatty acid (SFA) intake at 1 and 2 months (p<0.001), daily mono-unsaturated fatty acid (MUFA) intake at 1 and 2 months (p<0.001), and daily cholesterol intake at 1 month (p<0.05) and 2 months (p<0.001), but no change in daily poly-unsaturated fatty acid (PUFA) intake over time. Compared to baseline, there was a significant increase in serum LDL at 1 month (p<0.001) and 2 months (p<0.01) and an increase in serum TC at 1 month (p<0.01) but not 2 months. DISCUSSION/SIGNIFICANCE OF FINDINGS: Despite a significant increase in total fat, saturated fat and mono-unsaturated fat intake as well as an increase in total cholesterol and LDL levels following MAD initiation, dietary fat composition appears to minimally predict serum lipid values in the short term.
OBJECTIVES/GOALS: The modified Atkins diet (MAD) is used in the management of drug-resistant epilepsy in adults. Some patients on MAD show an increase in serum levels of total cholesterol and low-density lipoprotein (LDL) cholesterol. We explored whether dietary fat composition predicts short-term elevations in serum lipid levels in diet-naïve adults who begin MAD. METHODS/STUDY POPULATION: Participants self-reported their diet intake with 3-day food records at baseline, 1 month and 2 months. Food records were analyzed using Nutrition Data System for Research software. Fasting serum levels of total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides were also collected and LDL level calculated at baseline, 1 month, and 2 months. RESULTS/ANTICIPATED RESULTS: 38 patients submitted complete food records at each study visit (baseline, 1 month, and 2 month). Compared to baseline diet intake, there was a significant reduction in daily carbohydrate intake at 1 and 2 months months (p<0.001). There was also a significant increase in daily saturated fatty acid (SFA) intake at 1 and 2 months (p<0.001), daily mono-unsaturated fatty acid (MUFA) intake at 1 and 2 months (p<0.001), and daily cholesterol intake at 1 month (p<0.05) and 2 months (p<0.001), but no change in daily poly-unsaturated fatty acid (PUFA) intake over time. Compared to baseline, there was a significant increase in serum LDL at 1 month (p<0.001) and 2 months (p<0.01) and an increase in serum TC at 1 month (p<0.01) but not 2 months. DISCUSSION/SIGNIFICANCE OF IMPACT : Despite a significant increase in total fat, saturated fat and mono-unsaturated fat intake as well as an increase in total cholesterol and LDL levels following MAD initiation, dietary fat composition appears to minimally predict serum lipid values in the short term. CONFLICT OF INTEREST DESCRIPTION: Tanya McDonald has received speaking honoraria from Nutricia North America. Bobbie Henry-Barron receives grants from Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1 TR 001079 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research, Nutricia and Vitaflo. Diane Vizthum receives grants from the Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1 TR 001079 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Mackenzie C. Cervenka has received grant support from Nutricia North America, Vitaflo, Army Research Laboratory, The William and Ella Owens Medical Research Foundation and BrightFocus Foundation. She receives speaking honoraria from LivaNova, Epigenix, Nutricia North America and the Glut1 Deficiency Foundation and performs consulting with Nutricia North America and Sage Therapeutics and receives Royalties from Demos Health.
To utilise a community-based participatory approach in the design and implementation of an intervention targeting diet-related health problems on Navajo Nation.
Design:
A dual strategy approach of community needs/assets assessment and engagement of cross-sectorial partners in programme design with systematic cyclical feedback for programme modifications.
Setting:
Navajo Nation, USA.
Participants:
Navajo families with individuals meeting criteria for programme enrolment. Participant enrolment increased with iterative cycles.
Results:
The Navajo Fruit and Vegetable Prescription (FVRx) Programme.
Conclusions:
A broad, community-driven and culturally relevant programme design has resulted in a programme able to maintain core programmatic principles, while also allowing for flexible adaptation to changing needs.
Public awareness of ‘red flag’ symptoms for head and neck cancer is low. There is a lack of evidence regarding patient concerns and expectations in consultations for cancer assessment.
Method
This prospective questionnaire study examined the symptoms, concerns and expectations of 250 consecutive patients attending an ‘urgent suspicion of cancer’ clinic at a tertiary referral centre.
Results
The patients’ most frequent responses regarding their concerns were ‘no concerns’ (n = 72, 29 per cent); ‘all symptoms’ were a cause for concern (n = 65, 26 per cent) and ‘neck lump’ was a symptom causing concern (n = 37, 17 per cent). The expectations of patients attending clinic were that they would find out what was wrong with them, followed by having no expectations at all. Overall patient knowledge of red flag symptoms was lacking and their expectations were low.
Conclusion
Patients with non-cancer symptoms are frequently referred with suspected cancer. Patients with red flag symptoms are not aware of their significance and they have low expectations of healthcare.
The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.
Methods:
The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.
Results:
The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.
Conclusion:
Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.
Basic symptoms, defined as subjectively perceived disturbances in thought, perception and other essential mental processes, have been established as a predictor of psychotic disorders. However, the relationship between basic symptoms and family history of a transdiagnostic range of severe mental illness, including major depressive disorder, bipolar disorder and schizophrenia, has not been examined.
Aims
We sought to test whether non-severe mood disorders and severe mood and psychotic disorders in parents is associated with increased basic symptoms in their biological offspring.
Method
We measured basic symptoms using the Schizophrenia Proneness Instrument – Child and Youth Version in 332 youth aged 8–26 years, including 93 offspring of control parents, 92 offspring of a parent with non-severe mood disorders, and 147 offspring of a parent with severe mood and psychotic disorders. We tested the relationships between parent mental illness and offspring basic symptoms in mixed-effects linear regression models.
Results
Offspring of a parent with severe mood and psychotic disorders (B = 0.69, 95% CI 0.22–1.16, P = 0.004) or illness with psychotic features (B = 0.68, 95% CI 0.09–1.27, P = 0.023) had significantly higher basic symptom scores than control offspring. Offspring of a parent with non-severe mood disorders reported intermediate levels of basic symptoms, that did not significantly differ from control offspring.
Conclusions
Basic symptoms during childhood are a marker of familial risk of psychopathology that is related to severity and is not specific to psychotic illness.
Children of parents with mood and psychotic disorders are at elevated risk for a range of behavioral and emotional problems. However, as the usual reporter of psychopathology in children is the parent, reports of early problems in children of parents with mood and psychotic disorders may be biased by the parents' own experience of mental illness and their mental state.
Methods
Independent observers rated psychopathology using the Test Observation Form in 378 children and youth between the ages of 4 and 24 (mean = 11.01, s.d. = 4.40) who had a parent with major depressive disorder, bipolar disorder, schizophrenia, or no history of mood and psychotic disorders.
Results
Observed attentional problems were elevated in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia (effect sizes ranging between 0.31 and 0.56). Oppositional behavior and language/thought problems showed variable degrees of elevation (effect sizes 0.17 to 0.57) across the three high-risk groups, with the greatest difficulties observed in offspring of parents with bipolar disorder. Observed anxiety was increased in offspring of parents with major depressive disorder and bipolar disorder (effect sizes 0.19 and 0.25 respectively) but not in offspring of parents with schizophrenia.
Conclusions
Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.
The aim of this study was to test the hypothesis of an improved growth, dietary nutrient availability and overall health of broiler chickens reared on recycled litter when fed a standardised combination of essential oils (EO; carvacrol, cinnamaldehyde and capsicum oleoresin). To assess the effect of dietary treatments, feed intake, weight gain, feed efficiency, availability of dietary nutrients and energy, villus morphometry, excreta sialic acid concentration, hepatic antioxidants and serum amyloid A (SAA) when fed to broiler chickens were evaluated. Counts of Eimeria spp. oocysts were also determined in excreta samples. Four experimental diets were offered, including two basal control diets based on either wheat or maize that contained 215 g CP/kg and 12.13 MJ/kg metabolisable energy and another two diets using the basal control diets supplemented with the EO combination at 100 mg/kg diet. Each diet was fed to eight floor pens, containing two birds each, following randomisation. Birds fed the EO-supplemented diets had an improved (P<0.05) feed conversion ratio (FCR). Birds fed maize-based diet had an improved daily weight gain and FCR (P<0.05) compared with wheat-fed birds. Wheat-based diet tended (P=0.056) to have greater N-corrected apparent metabolisable energy and had greater fat retention coefficient (P<0.05) compared with maize-based diets. No differences (P>0.05) were observed in villus morphometry, sialic acid secretion, number of oocysts and SAA. Feeding the EO improved (P<0.05) the retention of dietary Ca and Na. Compared with maize, feeding wheat-based diets improved the retention coefficients for Ca, P and Na (P<0.05). Feeding dietary EO improved (P<0.05) the concentrations of the hepatic antioxidants, including carotene, coenzyme Q10 and total vitamin E. The hepatic concentration of carotene of the maize-fed birds was 55.6% greater (P<0.05) compared with the wheat-fed birds. These results demonstrated that the addition of a standardised combination of EO in wheat- and maize-based diets provided benefits in terms of feed efficiency, mineral retention and antioxidant status of the birds when reared on recycled litter.
Bentonite is one of the more safety-critical components of the engineered barrier system in the disposal concepts developed for many types of radioactive waste. It is used due to its favourable properties (including plasticity, swelling capacity, colloid filtration, low hydraulic conductivity, high retardation of key radionuclides) and its stability in relevant geological environments. However, bentonite is unstable under alkaline conditions and this has driven interest in low-alkali cements (leachate pH of 10–11). To build a robust safety case, it is important to have supporting natural analogue data to confirm understanding of the likely long-term performance of bentonite. In Cyprus, the presence of natural bentonite in close proximity to natural alkaline groundwaters permits the zones of potential bentonite/alkaline water reaction to be studied as an analogy of the potential reaction zones in the repository. Here, the results indicate minimal volumetric reaction of bentonite, with production of a palygorskite secondary phase.