Frequency and yield of blood cultures for observation patients with skin and soft tissue infections.

OBJECTIVES: 1) To measure frequency and yield of blood cultures obtained for observation status adult patients with skin and soft tissue infection (SSTI), 2) describe how often blood cultures were performed according to Infectious Diseases Society of America (IDSA) SSTI guideline indications, 3) identify proportion of patients meeting Center for Medicare Services (CMS) sepsis criteria. DESIGN: Retrospective cohort. SETTING: Tertiary academic center. PATIENTS: Consecutive adult observation status patients hospitalized with SSTI between July 2017 and July 2018. METHODS: We measured the proportion and results of blood cultures obtained among the study cohort and proportion of obtained cultures that satisfied IDSA indications. RESULTS: We identified 132 observation status patients with SSTI during the study period; 67 (50.8%) had blood cultures drawn. Only 14 (10.6%) patients met IDSA indications for culture; 51 (38.%) met Center for Medicare Services definition for sepsis. We identified two (3.0%) cases of bacteremia and two (3.0%) cases of skin bacteria contamination. In multivariable analysis, only temperature > 38 °C (OR 3.84, 95%CI 1.09-13.60) and white race (OR 2.71, 95%CI 1.21-6.20) were associated with blood culture obtainment; neither meeting IDSA SSTI guideline indications nor meeting CMS sepsis criteria was associated with culture. CONCLUSIONS: Among observation status patients with SSTI, over half had blood cultures drawn, though 10% satisfied guideline indications for culture. The proportion of cultures with bacterial growth was low and yielded as many skin contaminants as cases of bacteremia. Our study highlights the need for further quality improvement efforts to reduce unnecessary blood cultures in routine SSTI cases.

GPR21 Inhibition Increases Glucose-Uptake in HepG2 Cells.

GPR21 is a constitutively active, orphan, G-protein-coupled receptor, with in vivo studies suggesting its involvement in the modulation of insulin sensitivity. However, its precise contribution is not fully understood. As the liver is both a major target of insulin signalling and critically involved in glucose metabolism, the aim of this study was to examine the role of GPR21 in the regulation of glucose uptake and production in human hepatocytes. In particular, HepG2 cells, which express GPR21, were adopted as cellular models. Compared with untreated cells, a significant increase in glucose uptake was measured in cells treated with siRNA to downregulate GPR21 expression or with the GPR21-inverse agonist, GRA2. Consistently, a significantly higher membrane translocation of GLUT-2 was measured under these conditions. These effects were accompanied by an increased ratio of phAKT(Ser473)/tot-AKT and phGSK-3ß(Ser9)/tot-GSK-3ß, thus indicating a marked activation of the insulin signalling pathway. Moreover, a significant reduction in ERK activation was observed with GPR21 inhibition. Collectively, these results indicate that GPR21 mediates the negative effects on glucose uptake by the liver cells. In addition, they suggest that the pharmacological inhibition of GPR21 could be a novel strategy to improve glucose homeostasis and counteract hepatic insulin resistance.

Tuberculosis, human rights, and law reform: Addressing the lack of progress in the global tuberculosis response.

Mathew Kavanagh and co-authors discuss law reform in the global tuberculosis response.

Trabecular micro-bypass stent implantation with cataract extraction in pigmentary glaucoma.

IMPORTANCE: Use of the trabecular micro-bypass stent with cataract surgery is well established to be safe and effective in primary open-angle glaucoma. This is the first study to exclusively evaluate use of the device in pigmentary glaucoma. BACKGROUND: This study aimed to investigate the safety and efficacy of a trabecular micro-bypass stent in combination with cataract surgery in pigmentary glaucoma. DESIGN: Retrospective, consecutive case series. PARTICIPANTS: Twenty-four eyes of 12 patients with pigmentary glaucoma implanted with one trabecular micro-bypass stent with concomitant cataract surgery. METHODS: Baseline data was collected and compared to the following postoperative time points: 1 day, 1 week, 1 month out to 36 months (M36) after the procedure. MAIN OUTCOME MEASURES: These included intraocular pressure (IOP), number of glaucoma medications and need for additional surgery. RESULTS: At M36 there was a 25% reduction in IOP to 14.68 ± 3.0 (P < .01) from 19.50 ± 6.7 mmHg at baseline. The mean number of glaucoma medications was 0.75 ± 1.0 prior to the surgery and 0.59 ± 0.6 (P > .05) at 36 M. At the 36 M time-point, 95% of eyes had IOP ≤ 18 mmHg and 68% of eyes were ≤ 15 mmHg. No eyes underwent a secondary glaucoma procedure. CONCLUSIONS AND RELEVANCE: The insertion of a single trabecular micro-bypass stent in combination with cataract surgery effectively provides a sustained reduction in IOP up to 3 years after surgery in patients with pigmentary glaucoma. The safety profile is favourable with low rate of IOP spikes and no patients requiring additional surgery.

Pediatric Hospitalization Trends at Children's and General Hospitals, 2000-2019.

This study examines whether pediatric inpatient care has been redistributed from general hospitals into children's hospitals.

Synthesis of pyrazolopyrimidinones using a "one-pot" approach under microwave irradiation.

A simple one-pot method for the microwave-assisted synthesis of substituted pyrazolo[1,5-a]pyrimidinones, a core scaffold in many bioactive and pharmaceutically relevant compounds, has been established. A variety of substituents was tolerated at the 2 and 5 positions, including functionalized aryls, heterocycles, and alkyl groups.

Healthcare Utilization and Spending for Constipation in Children With Versus Without Complex Chronic Conditions.

OBJECTIVES: The aim of the study was to examine the prevalence of diagnosis and treatment for constipation among children receiving Medicaid and to compare healthcare utilization and spending for constipation among children based on number of complex chronic conditions (CCCs). METHODS: Retrospective cohort study of 4.9 million children ages 1 to 17 years enrolled in Medicaid from 2009 to 2011 in 10 states in the Truven Marketscan Database. Constipation was identified using International Classification of Disease, 9th revision codes for constipation (564.0x), intestinal impaction (560.3x), or encopresis (307.7). Outpatient and inpatient utilization and spending for constipation were assessed. CCC status was identified using validated methodology. RESULTS: A total of 267,188 children (5.4%) were diagnosed with constipation. Total constipation spending was $79.5 million. Outpatient constipation spending was $66.8 million (84.1%) during 406,814 visits, mean spending $120/visit. Among children with constipation, 1363 (0.5%) received inpatient treatment, accounting for $12.2 million (15.4%) of constipation spending, mean spending $7815/hospitalization. Of children hospitalized for constipation, 552 (40.5%) did not have an outpatient visit for constipation before admission. Approximately 6.8% of children in the study had ≥1 CCC; these children accounted for 33.5% of total constipation spending, 70.3% of inpatient constipation spending, and 19.8% of emergency department constipation spending. Constipation prevalence was 11.0% for children with 1 CCC, 16.6% with 2 CCCs, and 27.1% with ≥3 CCCs. CONCLUSIONS: Although the majority of pediatric constipation treatment occurs in the outpatient setting, inpatient care accounts for a sizable percentage of spending. Children with CCCs have a higher prevalence of constipation and account for a disproportionate amount of constipation healthcare utilization and spending.

Synthesis, antibacterial and anti-MRSA activity, in vivo toxicity and a structure-activity relationship study of a quinoline thiourea.

We report the synthesis, antibacterial evaluation of a series of thiourea-containing compounds. 1-(3,5-Bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)-((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)thiourea 5, was the most active against a range of Gram-positive and Gram-negative bacteria, and exhibited bacteriostatic activity against methicillin resistant Staphylococcus aureus (MRSA) comparable to that of the well-known antibacterial agent vancomycin. Quinoline thiourea 5 was subjected to a detailed structure-activity relationship study, with 5 and its derivatives evaluated for their bacteriostatic activity against both Gram-negative and Gram-positive bacteria. A number of structural features important for the overall activity of quinoline thiourea 5 have been identified. A selection of compounds, including 5, was also evaluated for their in vivo toxicity using the larvae of the Greater wax moth, Galleria mellonella. Compound 5, and a number of derivatives, were found to be non-toxic to the larvae of Galleria mellonella. A new class of antibiotic can result from the further development of this family of compounds.

Who needs inpatient detox? Development and implementation of a hospitalist protocol for the evaluation of patients for alcohol detoxification.

BACKGROUND: Clinicians caring for patients seeking alcohol detoxification face many challenges, including lack of evidence-based guidelines for treatment and high recidivism rates. OBJECTIVES: To develop a standardized protocol for determining which alcohol dependent patients seeking detoxification need inpatient versus outpatient treatment, and to study the protocol's implementation. DESIGN: Review of best evidence by ad hoc task force and subsequent creation of standardized protocol. Prospective observational evaluation of initial protocol implementation. PARTICIPANTS: Patients presenting for alcohol detoxification. INTERVENTION: Development and implementation of a protocol for evaluation and treatment of patients requesting alcohol detoxification. MAIN MEASURES: Number of admissions per month with primary alcohol related diagnosis (DRG), 30-day readmission rate, and length of stay, all measured before and after protocol implementation. RESULTS: We identified one randomized clinical trial and three cohort studies to inform the choice of inpatient versus outpatient detoxification, along with one prior protocol in this population, and combined that data with clinical experience to create an institutional protocol. After implementation, the average number of alcohol related admissions was 15.9 per month, compared with 18.9 per month before implementation (p = 0.037). There was no difference in readmission rate or length of stay. CONCLUSIONS: Creation and utilization of a protocol led to standardization of care for patients requesting detoxification from alcohol. Initial evaluation of protocol implementation showed a decrease in number of admissions.

The continuous flow synthesis of azos.

Azo compounds find use in many areas of science, displaying crucial properties for important applications as photoconductive organic pigments, fluorescent quenchers, paints, cosmetics, inks, and in the large and valuable dye industry. Due to the unstable intermediates, and the exothermic and fast reactions used in their synthesis, high value azo compounds are excellent candidates for continuous flow manufacturing. This comprehensive review covers the progress made to date on developing continuous flow systems for azo synthesis and reflects on the main challenges still to be addressed, including scale up, conversion, product purity, and environmental impact. The further development of integrated continuous flow processes has the potential to help tackle these challenges and deliver improved methods for azo compound generation.

Pilot study of peripheral internal jugular venous catheters on a hospitalist-run medicine procedure service.

Providers caring for hospitalized patients with difficult intravenous access (DIVA) frequently use central venous catheters (CVCs). One potential alternative is a peripheral internal jugular (PIJ) catheter, which is less traumatic to place and has fewer lumens than a CVC. We describe the results of 2 years' experience from a pilot project of a medicine procedure service placing PIJ catheters in hospitalized patients with DIVA. We successfully placed 34/35 (97%) PIJ catheters in 32 patients with zero complications. Median duration of use was 2.5 days (range 0-53 days, IQR 1-5). Catheter failure rate within 7 days was 32.4%, though it varied across catheter types: 9.5% in 8-10 cm midline catheters versus 69.2% (p < .001) in 6 cm angiocatheter wire introducers or shorter peripheral intravenous catheters. Our results suggest that PIJ catheters may be an option to reduce the mechanical and infectious risks associated with CVCs in some hospitalized patients with DIVA.

Participation and co-production for learning and development of identities: wherever I go, I meet myself.

BACKGROUND: Contemporary society is characterised by constant change with an ever-increasing feature of interconnection, having clear implications for healthcare professional learning and role identity. It is proposed that active participation and coproduction for learning can provide options to understand contemporary challenges and opportunities in the development of personal and professional identity. AIMS: This research aimed to explore the value of learning and development of identity through participation in co-produced practical workshop activity involving service users and students across a Year 1 (level 4) undergraduate BSc(Hons) Physiotherapy module. Co-production was also reflected within the research project design and operationalisation. MATERIALS & METHODS: Following delivery of the workshops, data were collected and analysed from a series of individual semi-structured interviews (n = 11) and a focus group. RESULTS: Six emergent themes were identified. A central theme of identity and self-worth was deconstructed within five interdependent sub-themes; real and safe, person-centred, backstage learning, good to talk and staging of curriculum. CONCLUSION: A process of open dialogue within co-produced workshop design and delivery would appear to enhance learning and a contextual appreciation of a broader 'whole' for all participants. Future research is aimed at building on this project, to explore co-produced learning opportunities across levels and settings that provide further insight into personal and professional identity development.

P53 loss of heterozygosity (LOH) in formalin-fixed paraffin-embedded leiomyosarcoma (LMS): a novel report.

BACKGROUND: The occurrence of p53 loss of heterozygosity (LOH) is a common genetic event in malignancy. LOH occurs when a heterozygous locus loses one of its two parental alleles, becoming homozygous at that locus, by either copy number loss (CNL-LOH) or by becoming copy number neutral (CNN-LOH). A role for CNL-LOH (cnLOH) has been postulated in cancer aetiology. Loss of heterozygosity (LOH) results in irreversible genetic loss. AIMS: LOH was determined in DNA extracted from formalin-fixed paraffin-embedded (FFPE) leiomyosarcoma (LMS) specimens in a retrospective study from 30 patients, to assess the prognostic significance of LOH. The findings were analysed and their validity assessed. LOH was an adverse prognostic factor in LMS. Prospective uniform standardisation of formalin-fixation techniques is required. METHODS: DNA was extracted from 169 formalin-fixed paraffin blocks of 30 patients with LMS, following extensive tissue microdissection. Genomic DNA was amplified using the polymerase chain reaction (PCR) technique. Fluorescence-based microsatellite PCR was used to detect and quantitate heterozygosity loss. RESULTS: LOH was detected at gene locus 17p13 in 16 LMS (Four grade 2 and 12 grade 3 LMS). LOH was not detected in 14 LMS cases (one grade 1, five grade 2 and eight grade 3 LMS). LOH was associated with shorter patient survival. CONCLUSIONS: The results reported herein endorse the value of utilizing FFPE DNA in identifying LOH as a prognostic factor in LMS. The results have implications for tumour biobanking and precision medicine in patients with sarcomas.

Phlebotomy-free days in children hospitalized with common infections and their association with clinical outcomes.

BACKGROUND: Phlebotomy for hospitalized children has consequences (e.g., pain, iatrogenic anemia), and unnecessary testing is a modifiable source of waste in healthcare. Days without blood draws or phlebotomy-free days (PFDs) has the potential to serve as a hospital quality measure. OBJECTIVE: To describe: (1) the frequency of PFDs in children hospitalized with common infections and (2) the association of PFDs with clinical outcomes. DESIGN, SETTINGS AND PARTICIPANTS: We performed a cross-sectional study of children hospitalized 2018-2019 with common infections at 38 hospitals using the Pediatric Health Information System database. We included infectious All Patients Refined Diagnosis Related Groups with a median length of stay (LOS) >2 days. We excluded patients with medical complexity, interhospital transfers, those receiving intensive care, and in-hospital mortality. MAIN OUTCOME AND MEASURES: We defined PFDs as hospital days (midnight to midnight) without laboratory blood testing and measured the proportion of PFDs divided by total hospital LOS (PFD ratio) for each condition and hospital. Higher PFD ratios signify more days without phlebotomy. Hospitals were grouped into low, moderate, and high average PFD ratios. Adjusted outcomes (LOS, costs, and readmissions) were compared across groups. RESULTS: We identified 126,135 encounters. Bronchiolitis (0.78) and pneumonia (0.54) had the highest PFD ratios (most PFDs), while osteoarticular infections (0.28) and gastroenteritis (0.30) had the lowest PFD ratios. There were no differences in adjusted clinical outcomes across PFD ratio groups. Among children hospitalized with common infections, PFD ratios varied across conditions and hospitals, with no association with outcomes. Our data suggest overuse of phlebotomy and opportunities to improve the care of hospitalized children.

Outcomes associated with initial narrow-spectrum versus broad-spectrum antibiotics in children hospitalized with urinary tract infections.

OBJECTIVE: The aim of this study is to describe the proportion of children hospitalized with urinary tract infections (UTIs) who receive initial narrow- versus broad-spectrum antibiotics across children's hospitals and explore whether the use of initial narrow-spectrum antibiotics is associated with different outcomes. DESIGN, SETTING AND PARTICIPANTS: We performed a retrospective cohort analysis of children aged 2 months to 17 years hospitalized with UTI (inclusive of pyelonephritis) using the Pediatric Health Information System (PHIS) database. MAIN OUTCOME AND MEASURES: We analyzed the proportions of children initially receiving narrow- versus broad-spectrum antibiotics; additionally, we compiled antibiogram data for common uropathogenic organisms from participating hospitals to compare with the observed antibiotic susceptibility patterns. We examined the association of antibiotic type with adjusted outcomes including length of stay (LOS), costs, and 7- and 30-day emergency department (ED) revisits and hospital readmissions. RESULTS: We identified 10,740 hospitalizations for UTI across 39 hospitals. Approximately 5% of encounters demonstrated initial narrow-spectrum antibiotics, with hospital-level narrow-spectrum use ranging from <1% to 25%. Approximately 80% of hospital antibiograms demonstrated >80% Escherichia coli susceptibility to cefazolin. In adjusted models, those who received initial narrow-spectrum antibiotics had shorter LOS (narrow-spectrum: 33.1 (95% confidence interval [CI]: 30.8-35.4) h versus broad-spectrum: 46.1 (95% CI: 44.1-48.2) h) and reduced costs [narrow-spectrum: $4570 ($3751-5568) versus broad-spectrum: $5699 ($5005-$6491)]. There were no differences in ED revisits or hospital readmissions. In summary, children's hospitals have low rates of narrow-spectrum antibiotic use for UTIs despite many reporting high rates of cefazolin-susceptible E. coli. These findings, coupled with the observed decreased LOS and costs among those receiving narrow-spectrum antibiotics, highlight potential antibiotic stewardship opportunities.

Changing patterns of routine laboratory testing over time at children's hospitals.

BACKGROUND: Research into low-value routine testing at children's hospitals has not consistently evaluated changing patterns of testing over time. OBJECTIVES: To identify changes in routine laboratory testing rates at children's hospitals over ten years and the association with patient outcomes. DESIGN, SETTINGS, AND PARTICIPANTS: We performed a multi-center, retrospective cohort study of children aged 0-18 hospitalized with common, lower-severity diagnoses at 28 children's hospitals in the Pediatric Health Information Systems database. MAIN OUTCOMES AND MEASURES: We calculated average annual testing rates for complete blood counts, electrolytes, and inflammatory markers between 2010 and 2019 for each hospital. A > 2% average testing rate change per year was defined as clinically meaningful and used to separate hospitals into groups: increasing, decreasing, and unchanged testing rates. Groups were compared for differences in length of stay, cost, and 30-day readmission or ED revisit, adjusted for demographics and case mix index. RESULTS: Our study included 576,572 encounters for common, low-severity diagnoses. Individual hospital testing rates in each year of the study varied from 0.3 to 1.4 tests per patient day. The average yearly change in hospital-specific testing rates ranged from -6% to +7%. Four hospitals remained in the lowest quartile of testing and two in the highest quartile throughout all ten years of the study. We grouped hospitals with increasing (8), decreasing (n = 5), and unchanged (n = 15) testing rates. No difference was found across subgroups in costs, length of stay, 30-day ED revisit, or readmission rates. Comparing resource utilization trends over time provides important insights into achievable rates of testing reduction.

Early Real-World Patient and Staff Experience with an Intracanalicular Dexamethasone Insert.

Purpose: To evaluate both the early experience of real-world patients treated with dexamethasone ophthalmic insert (0.4 mg; DEXTENZA®), hereafter referred to as DEX, after cataract surgery as well as staff/practice integration of DEX relative to eyedrops. Patients and Methods: This was a cross-sectional survey study of 23 cataract practices in the United States. Respondents were patients and practice staff who had experience with DEX following cataract surgery. Both patients and practice staff completed an online survey. Descriptive statistics summarized the survey responses to portray the experience of the respondents. Results: Surveys were completed by 62 patients and 19 practice staff. Almost all patients (93%) were satisfied or extremely satisfied with DEX. Patients highly preferred DEX (93%) to topical steroid drops (7%) based on past experiences with topical steroid drops. Most practice staff (95%) were satisfied or highly satisfied with DEX, reporting a 45% reduction in time spent educating patients on postoperative drop use and a 46% decrease in time spent addressing calls from pharmacies regarding postoperative medications. Conclusion: Incorporating the DEX insert into clinical practice in cataract surgery practices can improve patient adherence, while potentially providing significant savings to practices in terms of time spent educating patients and responding to patient and pharmacy call-backs.

Unilateral Periorbital Swelling in a Pediatric Patient.

Infratemporal fossa (ITF) tumors are rare in children and may present with a variety of symptoms. Teratomas are neoplasms derived from the 3 germ layers and approximately 6% to 10% are within the head and neck. Our study discusses one of the first reported cases of teratoma in the ITF in a pediatric patient. A 3-year-old girl presents with 2 years of recurrent monthly left periorbital swelling accompanied by fevers, skin discoloration, and pain. Prior episodes were treated with antibiotics with incomplete resolution. Imaging revealed a cystic lesion centered in the ITF. She was taken for endoscopic endonasal biopsy of the lesion and had no complications. Pathology revealed a mature teratoma composed primarily of pancreatic tissue. Providers should consider masses such as teratoma in the differential for ITF tumors and periorbital edema unresponsive to typical treatment.

Differences in testing for drugs of abuse amongst racial and ethnic groups at children's hospitals.

OBJECTIVES: Racial and ethnic differences in drug testing have been described among adults and newborns. Less is known regarding testing patterns among children and adolescents. We sought to describe the association between race and ethnicity and drug testing at US children's hospitals. We hypothesized that non-Hispanic White children undergo drug testing less often than children from other groups. METHODS: We conducted a retrospective cohort study of emergency department (ED)-only encounters and hospitalizations for children diagnosed with a condition for which drug testing may be indicated (abuse or neglect, burns, malnutrition, head injury, vomiting, altered mental status or syncope, psychiatric, self-harm, and seizure) at 41 children's hospitals participating in the Pediatric Health Information System during 2018 and 2021. We compared drug testing rates among (non-Hispanic) Asian, (non-Hispanic) Black, Hispanic, and (non-Hispanic) White children overall, by condition and patient cohort (ED-only vs. hospitalized) and across hospitals. RESULTS: Among 920,755 encounters, 13.6% underwent drug testing. Black children were tested at significantly higher rates overall (adjusted odds ratio [aOR]: 1.18; 1.05-1.33) than White children. Black-White testing differences were observed in the hospitalized cohort (aOR: 1.42; 1.18-1.69) but not among ED-only encounters (aOR: 1.07; 0.92-1.26). Asian, Hispanic, and White children underwent testing at similar rates. Testing varied by diagnosis and across hospitals. CONCLUSIONS: Hospitalized Black children were more likely than White children to undergo drug testing at US children's hospitals, though this varied by diagnosis and hospital. Our results support efforts to better understand and address healthcare disparities, including the contributions of implicit bias and structural racism.