Implementing genetic testing in diabetes: Knowledge, perceptions of healthcare professionals, and barriers in a developing country.

INTRODUCTION: Maturity-Onset Diabetes of the Young (MODY) is an unusual type of diabetes often missed in clinical practice, especially in Africa. Treatment decisions for MODY depend on a precise diagnosis, only made by genetic testing. We aimed to determine MODY knowledge among Nigerian healthcare professionals (HCPs), their perceptions, and barriers to the implementation of genetic testing in diabetes patients. METHODS: A cross-sectional survey was conducted among doctors and nurses in three levels of public and private healthcare institutions in Ibadan, Nigeria, from December 2018 to June 2019. In all, 70% and 30% of a total 415 participants were recruited from public and private centers, respectively. HCPs were recruited in a 60:40% ratio, respectively. A 51-item instrument was used to assess MODY knowledge, perceptions of HCPs, and barriers to the implementation of genetic testing in diabetes patients. RESULTS: In the survey, 43.4% self-rated their current MODY knowledge to be at least moderate. About 68%, 73% and 86%, respectively, correctly answered 3 of 5 questions on basic genetics' knowledge. However, only 1 of 7 MODY-specific questions was answered correctly by 72.7% of the respondents. The mean basic genetics and MODY-specific knowledge scores were 2.6/5 (SD=1.0) and 1.8/9 (SD=1.3), respectively. Multiple linear regression showed higher mean scores among those aged 30-49 years, those with degrees and fellowships (except PhD), and general practitioners; 360 (80.0%) perceived that genetic testing plays a central role in diabetes care. Barriers to genetic testing were lack of access to testing facilities, guidance on the use of and updates/educational materials on genetic testing (82.7%, 62.1% and 50.3%, respectively). CONCLUSIONS: The level of MODY awareness and knowledge among Nigerian HCPs is unacceptably low with a lack of access to genetic testing facilities. These can hinder the implementation of precision diabetes medicine. Increased awareness, provision of decision support aids, and genetic testing facilities are urgently needed.

The diagnostic accuracy of the ID NOW COVID-19 point of care test in acute hospital admissions.

BACKGROUND: Prompt identification of patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on admission to hospital is crucial to ensuring initiation of appropriate treatment, optimising infection control and maintaining patient flow. The Abbott ID NOW™ COVID-19 assay (ID NOW) is a point-of-care, isothermal nucleic acid amplification test, capable of producing a result within minutes, potentially placing it as an invaluable tool in helping to control the coronavirus-disease 2019 (COVID-19) pandemic. OBJECTIVES: To evaluate the diagnostic accuracy of ID NOW in acute hospital admissions. STUDY DESIGN: A prospective approach to data collection was undertaken in consecutive patients with ID NOW and Hologic Aptima™ SARS-CoV-2 transcription-mediated amplification assay (Aptima TMA) results, across three hospitals in the south-west of England between 1st March and 30th September 2021. A nasal swab was taken for ID NOW and a combined nose and throat swab for Aptima TMA. Measures of diagnostic accuracy were calculated for ID NOW against Aptima TMA. This study was conducted during a period of alpha and delta strain predominance. RESULTS: 19,698 ID NOW assays were performed, of which 12,821 had an Aptima TMA assay performed within 24 hours. ID NOW had sensitivity of 85.2 % (95 % CI, 82.2-87.9) and specificity of 99.6 % (95 % CI, 99.4-99.7) compared with the reference assay. The overall PPV was 91.0 % (95 % CI, 88.5-93.0) and the overall NPV was 99.3 % (95 % CI, 99.1-99.4). CONCLUSIONS: ID NOW offers a valid diagnostic tool to detect SARS-CoV-2, performing comparably to a reference laboratory-based assay which takes longer to provide results.

Androgenicity in Young Women and Development of Metabolic Syndrome Before Menopause: The CARDIA and CARDIA Women's Studies.

Context: There are no reported data from prospective long-term studies on the relation of androgen levels in young women with development of metabolic syndrome (MetS) before menopause. Objective: We investigated associations of androgens and SHBG with incident MetS during 23 years of follow-up. Methods: We included 366 White and 375 Black women ages 20 to 32 years participating in the CARDIA study and CARDIA Women's study, free of MetS at baseline examination (1987-1988), and premenopausal 23 years later. Androgens and SHBG were categorized into quartiles. MetS was defined according to the American Heart Association/National Heart, Lung, and Blood Institute 2009 Joint Scientific Statement. Cox proportional hazards models were used. Results: By year 23, 30% of women developed MetS. Adjusting for baseline age, race, and education, hazard ratios (95% CI) of developing MetS were 1.46 (1.02-2.10) and 2.22 (1.53-3.21) for women in the highest vs lowest total testosterone (T) and free T quartile, respectively. The hazards of developing MetS were 47%, 59%, and 53% lower for women with SHBG in the second, third, and fourth quartiles (vs lowest quartile), respectively. Associations were attenuated for total T with further adjustments for smoking, physical activity, menstrual status, oral contraceptive/hormone (OCHM) use, insulin level, oligomenorrhea, and age at menarche, but remained statistically significant for free T and SHBG. Associations were similar for both Blacks and Whites, and OCHM nonusers, but not for OCHM users. Conclusion: High androgenicity in young premenopausal women is associated with higher risk of future MetS, suggesting that early assessment of androgens may contribute to prevention.

Identifying the public health needs of a UK probation cohort: a cross-sectional analysis.

BACKGROUND: The health needs of those under probation are likely high, but they have received very little public health attention. Limited evidence exists on the public health needs and interventions to support this cohort. METHODS: Surveys were completed by 257 people on probation as part of a local health needs assessment. Results were compared with the general population responses from the National Survey for Wales (2021-22). RESULTS: People on probation were 4.2 times more likely to self-report not-good general health (fair, bad or very bad) than the general population (adjusted Odds Ratio [aOR] 4.2, 95% Confidence Intervals [CI] 3.2-5.4). The odds of having a mental health condition were over eight times higher than the general population (aOR 8.8, 95% CI 6.8-11.4). Prevalence of smoking (52%), drug use (60%), attention-deficit hyperactivity disorder (21%), autism (4%) and dyslexia (15%) were all higher than the general population. General Practitioner usage and hospital stays were higher, but dentist or optician usage lower than the general population (P < 0.05). Emergency departments were accessed by 35%, with 9% frequenting them three or more times. CONCLUSIONS: People on probation have poorer self-reported health, higher prevalence of unhealthy behaviours and higher accessing of reactive health services than the general population.

Pseudomonas guariconensis Necrotizing Fasciitis, United Kingdom.

We describe a case of necrotizing fasciitis in the United Kingdom in which Pseudomonas guariconensis was isolated from multiple blood culture and tissue samples. The organism carried a Verona integron-encoded metallo-ß-lactamase gene and evidence of decreased susceptibility to ß-lactam antimicrobial agents. Clinicians should use caution when treating infection caused by this rare pathogen.

Connections between cross-tissue and intra-tissue biomarkers of aging biology in older adults.

Background: Saliva measures are generally more accessible than blood, especially in vulnerable populations. However, connections between aging biology biomarkers in different body tissues remain unknown. Methods: The present study included individuals (N = 2406) who consented for saliva and blood draw in the Health and Retirement Telomere length study in 2008 and the Venous blood study in 2016 who had complete data for both tissues. We assessed biological aging based on telomere length in saliva and DNA methylation and physiology measures in blood. DNA methylation clocks combine information from CpGs to produce the aging measures representative of epigenetic aging in humans. We analyzed DNA methylation clocks proposed by Horvath (353 CpG sites), Hannum (71 CpG sites), Levine or PhenoAge, (513 CpG sites), GrimAge, (epigenetic surrogate markers for select plasma proteins), Horvath skin and blood (391 CpG sites), Lin (99 CpG sites), Weidner (3 CpG sites), and VidalBralo (8 CpG sites). Physiology measures (referred to as phenotypic age) included albumin, creatinine, glucose, [log] C-reactive protein, lymphocyte percent, mean cell volume, red blood cell distribution width, alkaline phosphatase, and white blood cell count. The phenotypic age algorithm is based on parametrization of Gompertz proportional hazard models. Average telomere length was assayed using quantitative PCR (qPCR) by comparing the telomere sequence copy number in each patient's sample (T) to a single-copy gene copy number (S). The resulting T/S ratio was proportional to telomere length, mean. Within individual, relationships between aging biology measures in blood and saliva and variations according to sex were assessed. Results: Saliva-based telomere length showed inverse associations with both physiology-based and DNA methylation-based aging biology biomarkers in blood. Longer saliva-based telomere length was associated with 1 to 4 years slower biological aging based on blood-based biomarkers with the highest magnitude being Weidner (ß = - 3.97, P = 0.005), GrimAge (ß = - 3.33, P < 0.001), and Lin (ß = - 3.45, P = 0.008) biomarkers of DNA methylation. Conclusions: There are strong connections between aging biology biomarkers in saliva and blood in older adults. Changes in telomere length vary with changes in DNA methylation and physiology biomarkers of aging biology. We observed variations in the relationship between each body system represented by physiology biomarkers and biological aging, particularly at the DNA methylation level. These observations provide novel opportunities for integration of both blood-based and saliva-based biomarkers in clinical care of vulnerable and clinically difficult to reach populations where either or both tissues would be accessible for clinical monitoring purposes.

The Natural History of Antibiotic-Treated Lower Limb Cellulitis: Analysis of Data Extracted From a Multicenter Clinical Trial.

Background: Although cellulitis is a relatively common skin infection, there remains uncertainty about management, particularly the length and route of antimicrobials required. Further information on the symptomatology and biomarker changes associated with cellulitis over time would guide clinicians and patients as to the expected natural history. Methods: We extracted data from a randomized clinical trial (NCT01876628) of clindamycin as adjunctive therapy in cellulitis to illustrate the evolution of local parameters (pain, swelling, local erythema, and warmth) and the resolution of biomarkers over time. Results: Data from 247 individuals with mild to moderate unilateral lower limb cellulitis, who attended at least 1 face-to-face interview following recruitment, were used to examine response dynamics. Although there was a local improvement in swelling, warmth, erythema, and pain by day 5 compared with baseline, some individuals still had evidence of local inflammation at 10 days. Most biomarkers demonstrated a return to normal by day 3, although the initial fall in albumin only returned to baseline by day 10. Conclusions: Although there was initial resolution, a significant number of individuals still had local symptoms persisting to day 10 and beyond. Clinicians can use these data to reassure themselves and their patients that ongoing local symptoms and signs after completion of antibiotic treatment do not indicate treatment failure or warrant extension of the initial antibiotic treatment or a change in antibiotic class or mode of administration.

Detection, survival, and persistence of Staphylococcus capitis NRCS-A in neonatal units in England.

BACKGROUND: The multidrug-resistant Staphylococcus capitis clone, NRCS-A, is increasingly associated with late-onset sepsis in low birthweight newborns in neonatal intensive care units (NICUs) in England and globally. Understanding where this bacterium survives and persists within the NICU environment is key to developing and implementing effective control measures. AIM: To investigate the potential for S. capitis to colonize surfaces within NICUs. METHODS: Surface swabs were collected from four NICUs with and without known NRCS-A colonizations/infections present at the time of sampling. Samples were cultured and S. capitis isolates analysed via whole-genome sequencing. Survival of NRCS-A on plastic surfaces was assessed over time and compared to that of non-NRCS-A isolates. The bactericidal activity of commonly used chemical disinfectants against S. capitis was assessed. FINDINGS: Of 173 surfaces sampled, 40 (21.1%) harboured S. capitis with 30 isolates (75%) being NRCS-A. Whereas S. capitis was recovered from surfaces across the NICU, the NRCS-A clone was rarely recovered from outside the immediate neonatal bedspace. Incubators and other bedside equipment were contaminated with NRCS-A regardless of clinical case detection. In the absence of cleaning, S. capitis was able to survive for three days with minimal losses in viability (<0.5 log10 reduction). Sodium troclosene and a QAC-based detergent/disinfectant reduced S. capitis to below detectable levels. CONCLUSION: S. capitis NRCS-A can be readily recovered from the NICU environment, even in units with no recent reported clinical cases of S. capitis infection, highlighting a need for appropriate national guidance on cleaning within the neonatal care environment.

Parapneumonic effusions related to Streptococcus pneumoniae: serotype and disease severity trends from 2006 to 2018 in Bristol, UK.

RATIONALE: Streptococcus pneumoniae epidemiology is changing in response to vaccination and some data suggest that empyema incidence is increasing. However, differences exist between the UK and US studies. We describe trends in the clinical phenotype of adult pneumococcal pleural infection, including simple parapneumonic effusions (SPE) in the pneumococcal conjugate vaccination (PCV) era. OBJECTIVES: To determine whether there were differences in pneumococcal disease presentation and severity associated with pleural infection. METHODS: A retrospective cohort study, all adults ≥16 years admitted to three large UK hospitals, 2006-2018 with pneumococcal disease. 2477 invasive pneumococcal cases were identified: 459 SPE and 100 pleural infection cases. Medical records were reviewed for each clinical episode. Serotype data were obtained from the UK Health Security Agency national reference laboratory. RESULTS: Incidence increased over time, including non-PCV-serotype disease. PCV7-serotype disease declined following paediatric PCV7 introduction, but the effect of PCV13 was less apparent as disease caused by the additional six serotypes plateaued with serotypes 1 and 3 causing such parapneumonic effusions from 2011 onwards.Patients with pleural infection had a median survival 468 days (95% CI 340 to 590) vs 286 days (95% CI 274 to 335) in those with SPE. Pleural infection associated with frank pus had lower 90-day mortality than pleural infection without pus (0% vs 29%, p<0.0001). 90-day mortality could be predicted by baseline increased RAPID (Renal, Age, Purulence, Infection source, and Dietary factors) score (HR 15.01, 95% CI 1.24 to 40.06, p=0.049). CONCLUSIONS: Pneumococcal infection continues to cause severe disease despite the introduction of PCVs. The predominance of serotype 1 and 3 in this adult UK cohort is in keeping with previous studies in paediatric and non-UK studies. Rising non-PCV serotype disease and limited impact of PCV13 on cases caused by serotypes 1 and 3 offset the reductions in adult pneumococcal parapneumonic effusion disease burden observed following the introduction of the childhood PCV7 programme.

Self-configuring nnU-Net for automatic delineation of the organs at risk and target in high-dose rate cervical brachytherapy, a low/middle-income country's experience.

BACKGROUND: The high-dose rate (HDR) brachytherapy treatment planning workflow for cervical cancer is a labor-intensive, time-consuming, and expertise-driven process. These issues are amplified in low/middle-income countries with large deficits in experienced healthcare professionals. Automation has the ability to substantially reduce bottlenecks in the planning process but often require a high level of expertise to develop. PURPOSE: To implement the out of the box self-configuring nnU-Net package for the auto-segmentation of the organs at risk (OARs) and high-risk CTV (HR CTV) for Ring-Tandem (R-T) HDR cervical brachytherapy treatment planning. METHODS: The computed tomography (CT) scans of 100 previously treated patients were used to train and test three different nnU-Net configurations (2D, 3DFR, and 3DCasc). The performance of the models was evaluated by calculating the Sørensen-dice similarity coefficient, Hausdorff distance (HD), 95th percentile Hausdorff distance, mean surface distance (MSD), and precision score for 20 test patients. The dosimetric accuracy between the manual and predicted contours was assessed by looking at the various dose volume histogram (DVH) parameters and volume differences. Three different radiation oncologists (ROs) scored the predicted bladder, rectum, and HR CTV contours generated by the best performing model. The manual contouring, prediction, and editing times were recorded. RESULTS: The mean DSC, HD, HD95, MSD and precision scores for our best performing model (3DFR) were 0.92/7.5 mm/3.0 mm/ 0.8 mm/0.91 for the bladder, 0.84/13.8 mm/5.3 mm/1.4 mm/0.84 for the rectum, and 0.81/8.5 mm/6.0 mm/2.2 mm/0.80 for the HR CTV. Mean dose differences (D2cc/90% ) and volume differences were 0.08 Gy/1.3 cm3 for the bladder, 0.02 Gy/0.7 cm3 for the rectum, and 0.33 Gy/1.5 cm3 for the HR CTV. On average, 65% of the generated contours were clinically acceptable, 33% requiring minor edits, 2% required major edits, and no contours were rejected. Average manual contouring time was 14.0 min, while the average prediction and editing times were 1.6 and 2.1 min, respectively. CONCLUSION: Our best performing model (3DFR) provided fast accurate auto generated OARs and HR CTV contours with a large clinical acceptance rate.

UK consensus definitions for necrotising otitis externa: a Delphi study.

OBJECTIVE: To establish consensus definitions for necrotising otitis externa (NOE) to facilitate the diagnosis and exclusion of NOE in clinical practice and expedite future high-quality study of this neglected condition. DESIGN: The work comprised of a systematic review of the literature, five iterative rounds of consultation via a Delphi process and open discussion within the collaborative. An expert panel analysed the results to produce the final outputs which were shared with and endorsed by national specialty bodies. SETTING: Secondary care in the UK. PARTICIPANTS: UK clinical specialists practising in infection, ear nose and throat (ENT) surgery or radiology. MAIN OUTCOME MEASURES: Definitions and statements meeting the following criteria were accepted: (a) minimum of 70% of respondents in agreement or strong agreement with a definition/statement AND (b) <15% of respondents in disagreement or strong disagreement with a definition/statement. RESULTS: Seventy-four UK clinicians specialising in ENT, Infection and Radiology with a special interest in NOE took part in the work which was undertaken between 2019 and 2021. The minimum response rate for a Round was 76%. Consensus criteria for all proposed case definitions, outcome definitions and consensus statements were met in the fifth round. CONCLUSIONS: This work distills the clinical opinion of a large group of multidisciplinary specialists from across the UK to create practical definitions and statements to support clinical practice and research for NOE. This is the first step in an iterative process. Further work will seek to validate and test these definitions and inform their evolution.

Hypertensive Disorders in Pregnancy at the John F. Kennedy Maternity Center (JFKMC), Liberia: Burden, Sub-Types, and Maternofetal Outcome.

Background: Hypertensive disorders in pregnancy (HDP) are a leading cause of maternal and fetal death, especially in a resource-constrained setting. There is no study from Liberia on the disorder. This pilot study aimed to determine the burden, sub-types, and maternal-fetal outcomes of hypertensive disorders in pregnancy at the John F. Kennedy Maternity Center (JFKMC), Liberia. Methods: From January 1 to December 31, 2020, the medical records of 130 pregnant and post-partum patients admitted with Hypertensive disorders in pregnancy (HDP) in a census method of sampling were retrieved, while 83.1% (108) were suitable for analysis in an institutional cross-sectional retrospective study in the department of obstetrics and gynecology at the John F. Kennedy Maternity Center, Liberia. The extracted information was analyzed using SPSS version 26. Results were presented in frequencies and percentages. The statistical association between categorical variables was subjected to the Chi-square test. The level of significance was set at a P-value of < 0.05. Results: There was an institutional prevalence of 3.0% of HDP. The maternal fatality rate was 12.3%, while the perinatal fatality rate was 14.3%. There was a significant association between HELLP syndrome and Severe pre-eclampsia with maternal death, P< 0.001. Prematurity, first minutes Apgar score <5, NICU admission, and low birth weight were associated with perinatal deaths (P <0.001). Conclusion: HDP was an important contributor to maternal and perinatal deaths at the JFKMC, Liberia. Continuous support by the government and development partners for the provision of critical life-saving medical equipment at the JFKMC is recommended.

Preventive Nail Care Among Diabetic Patients: A Quality Improvement Initiative.

PURPOSE: The purpose of this quality improvement initiative was to increase adherence to follow-up appointments in patients with diabetes mellitus for prevention of diabetic foot ulcers. PARTICIPANTS AND SETTING: The sample comprised 33 adults with diabetes mellitus being cared for at an outpatient wound care clinic affiliated with a large metropolitan hospital in the state of Mississippi, located in the Southern United States. APPROACH: This quality improvement approach used the Plan-Do-Study-Act method. Educational flyers and verbal instruction were provided to enhance adherence to preventive nail care and follow-up appointments. The goal for this quality improvement initiative was to increase adherence with preventive nail care and follow-up care. OUTCOMES: Participants were provided with educational flyers and verbal instruction that emphasized the importance of follow-up clinic appointments, which promoted increased attendance at follow-up appointments. The proportion of patients who did not attend follow-up appointments fell from 9.2% prior to the intervention to 5.8% after its introduction. IMPLICATIONS FOR PRACTICE: This quality improvement initiative positively impacted practice at a local wound care clinic in Mississippi resulting in a clinically relevant reduction in no-show follow-up visits when compared to the previous year.

Impact of material properties in determining quaternary ammonium compound adsorption and wipe product efficacy against biofilms.

BACKGROUND: Disinfectant wipes containing quaternary ammonium compounds (QACs) are widely used within health care. Viscose remains a popular material for these products, although limited information is available concerning its impact on performance against biofilms when compared with alternatives. AIM: To identify disinfectant wipe materials and surface properties which optimize product performance against biofilms. METHODS: Biofilm eradication performance of two commercial viscose-QAC wipes was determined against Staphylococcus aureus and Acinetobacter baumannii dry surface biofilms (DSBs) using an ASTM E2967-based procedure. Additionally, five materials were impregnated with a commercial liquid formulation containing didecyldimethylammonium chloride (DDAC). Following 24 h of storage, eradication performance and DDAC content of extracted liquid were determined and compared with material properties, including zeta potential, hydrophobicity and surface area. FINDINGS: Under stringent test conditions, eradication of DSBs by commercial products was no greater than equivalent materials impregnated with water. Extract from one viscose-based product contained 89% less DDAC than the impregnation solution, indicating extensive adsorption. Of the other tested materials, viscose performed worst; nearly 70% of DDAC had depleted from material extracts within 24 h. In contrast, DDAC depletion from polypropylene extracts was only 25%, and DSB eradication was >100 times greater than viscose. Biofilm eradication performance against both species correlated with the DDAC content of extracts, which, in turn, correlated with zeta potential and hydrophobicity. CONCLUSION: Biofilm eradication performance of QAC-based wipes was significantly greater when selecting thermoplastic substrates over viscose. However, these materials are non-sustainably sourced and non-biodegradable. This study highlights a need to develop new wipe products that are more effective against biofilms.

An epidemiological investigation of COVID-19 outbreaks in a group of care homes in Wales, UK: a retrospective cohort study.

BACKGROUND: This study describes the epidemiology of COVID-19 outbreaks in four care homes in terms of spread, severity, presentation and interventions. METHODS: Participants were 100 residents and 102 staff from four co-located care homes in Wales. Data were collected from the homes and Public Health Wales, including demographics, presentations, test status and results, hospital admissions and deaths. Genomic sequencing of confirmed case samples was completed, where possible. Epi-curves, crude attack rates, a Kaplan-Meier survival curve and adjusted hazard ratios were calculated using R. RESULTS: About 14 confirmed and 43 possible resident cases, 23 confirmed and 47 possible staff cases occurred. Crude attack rates of possible and confirmed cases were 57% (residents) and 69% (staff). Genomic sequencing for 10 confirmed case PCR samples identified at least 5 different UK lineages of COVID-19.42 (42%) residents died, 23 (55%) with COVID-19 or suspected COVID-19 recorded on the death certificate. The hazard ratio for death amongst resident possible and confirmed cases compared to null cases, adjusting for age and sex, was 13.26 (95% CI 5.61-31.34). CONCLUSIONS: There were extensive outbreaks of COVID-19 in these homes with high crude attack rates and deaths. Universal testing and early isolation of residents are recommended.

The burden of surgical complications from unsafe abortion treated at the John F. Kennedy Maternity Center (JFKMC), Monrovia, Liberia.

Background: The burden of surgical complications from unsafe abortion affects both health facilities and patients in most developing countries. This study aimed to determine the nature of surgical complications from unsafe abortion treated at the JFKMC, Liberia, and the estimated cost burden on facility and patient. Method: This was a retrospective study of the medical records of patients who had exploratory laparotomy for complications of induced abortion and presented at the JFKMC from June 15, 2018, to December 15, 2019. Results: The medical records of 44 out of the 49 patients who had exploratory laparotomy for unsafe abortion were captured and analyzed. Surgical complications from unsafe abortion accounted for 17.8% out of the 276 gynaecological surgeries at the JFKMC, Liberia. The case fatality was 22.4%. The mean age of subjects was 29.00 ±6.06 years. About 1/3 of the subjects were in their teens, over 4/5 were single, and half were students. Almost 60.0% of the subjects terminated their pregnancies in private health facilities. Ten subjects had a hysterectomy for necrotic/septic uterus. The mean cost of managing a patient with surgical complications from unsafe abortion at the JFKMC was $331.50, in contrast with $22.00, for spontaneous or induced abortion with mild complications treated as a day case. Conclusion: This study showed a cost burden on the facility, and patients as a result of surgical complications from induced abortion. A shift in current practice by health facilities in Liberia to medical management of abortion and MVA, training of health personnel on the use of MVA, and a less restrictive abortion law with effective contraceptive services are recommended.

Limited phylogenetic overlap between fluoroquinolone-resistant Escherichia coli isolated on dairy farms and those causing bacteriuria in humans living in the same geographical region.

BACKGROUND: Our primary aim was to test whether cattle-associated fluoroquinolone-resistant (FQ-R) Escherichia coli found on dairy farms are closely phylogenetically related to those causing bacteriuria in humans living in the same 50 × 50 km geographical region suggestive of farm-human sharing. Another aim was to identify risk factors for the presence of FQ-R E. coli on dairy farms. METHODS: FQ-R E. coli were isolated during 2017-18 from 42 dairy farms and from community urine samples. Forty-two cattle and 489 human urinary isolates were subjected to WGS, allowing phylogenetic comparisons. Risk factors were identified using a Bayesian regularization approach. RESULTS: Of 489 FQ-R human isolates, 255 were also third-generation-cephalosporin-resistant, with strong genetic linkage between aac(6')Ib-cr and blaCTX-M-15. We identified possible farm-human sharing for pairs of ST744 and ST162 isolates, but minimal core genome SNP distances were larger between farm-human pairs of ST744 and ST162 isolates (71 and 63 SNPs, respectively) than between pairs of isolates from different farms (7 and 3 SNPs, respectively). Total farm fluoroquinolone use showed a positive association with the odds of isolating FQ-R E. coli, while total dry cow therapy use showed a negative association. CONCLUSIONS: This work suggests that FQ-R E. coli found on dairy farms have a limited impact on community bacteriuria within the local human population. Reducing fluoroquinolone use may reduce the on-farm prevalence of FQ-R E. coli and this reduction may be greater when dry cow therapy is targeted to the ecology of resistant E. coli on the farm.

Streptococcus Pneumoniae septic arthritis in adults in Bristol and Bath, United Kingdom, 2006-2018: a 13-year retrospective observational cohort study.

Few studies on adult pneumococcal septic arthritis are sufficiently large enough to assess both epidemiological trends following routine pneumococcal immunization and clinical disease. With major shifts in serotypes causing invasive pneumococcal disease (IPD), we wanted to determine the clinical phenotype of adult septic arthritis caused by Streptococcus pneumoniae. We conducted a retrospective cohort study of pneumococcal infections in Bristol and Bath, UK, 2006-2018. We defined pneumococcal septic arthritis as adults with clinically-confirmed septic arthritis, with pneumococcus isolated from sterile-site culture or urinary antigen test positivity. Clinical records were reviewed for each patient in the cohort. Septic arthritis accounted for 1.7% of all IPD cases. 45 cases of adult pneumococcal septic arthritis occurred, with disease typically affecting older adults and those with underlying comorbidity. 67% patients had another focus of infection during their illness. 66% patients required increased care on discharge and 43% had reduced range of movement. In-hospital case fatality rate was 6.7%. One-year patient mortality was 31%. Currently most cases of adult pneumococcal septic arthritis are due to non-PCV13 serotypes which are associated with more severe disease. Non-PCV-13 serotypes had higher prevalence of concomitant pneumococcal infection at another site (73.7% versus 36.6%), increased intensive care or high-dependency unit requirement (32.4% versus 0%), and increased inpatient and 1-year case fatality rate (8.8% versus 0%, and 32.4% versus 27.4% respectively) compared to PCV-13 serotypes. Pneumococcal septic arthritis remains a small proportion of IPD. However, there is significant associated morbidity and mortality, and pneumococcal septic arthritis requires monitoring in coming years.

Trade-Offs between Antibacterial Resistance and Fitness Cost in the Production of Metallo-ß-Lactamases by Enteric Bacteria Manifest as Sporadic Emergence of Carbapenem Resistance in a Clinical Setting.

Meropenem is a clinically important antibacterial reserved for treatment of multiresistant infections. In meropenem-resistant bacteria of the family Enterobacterales, NDM-1 is considerably more common than IMP-1, despite both metallo-ß-lactamases (MBLs) hydrolyzing meropenem with almost identical kinetics. We show that blaNDM-1 consistently confers meropenem resistance in wild-type Enterobacterales, but blaIMP-1 does not. The reason is higher blaNDM-1 expression because of its stronger promoter. However, the cost of meropenem resistance is reduced fitness of blaNDM-1-positive Enterobacterales. In parallel, from a clinical case, we identified multiple Enterobacter spp. isolates carrying a plasmid-encoded blaNDM-1 having a modified promoter region. This modification lowered MBL production to a level associated with zero fitness cost, but, consequently, the isolates were not meropenem resistant. However, we identified a Klebsiella pneumoniae isolate from this same clinical case carrying the same blaNDM-1 plasmid. This isolate was meropenem resistant despite low-level NDM-1 production because of a ramR mutation reducing envelope permeability. Overall, therefore, we show how the resistance/fitness trade-off for MBL carriage can be resolved. The result is sporadic emergence of meropenem resistance in a clinical setting.