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The chemotherapeutic agent, cisplatin, accumulates in the kidneys leading to acute kidney injury (AKI). Pre-clinical and clinical studies have demonstrated sex-dependent outcomes of cisplatin-AKI. Deranged histone deacetylase (HDAC) activity is hypothesized to promote the pathogenesis of male murine cisplatin-AKI; however, it is unknown if there are sex differences in the kidney HDACs. We hypothesized that there would be sex specific Hdac expression, localization, or enzymatic activity and this may explain sexual-dimorphic responses to cisplatin-AKI. In normal human kidney RNA samples, HDAC10 was significantly greater in the kidney of women compared to men, while HDAC1, HDAC6, HDAC10, and HDAC11 were differentially expressed between the kidney cortex and medulla, regardless of sex. In a murine model of cisplatin-AKI (3 days post a 15 mg/kg injection) we found few sex- or cisplatin- Hdac kidney transcript differences among the mice. Although Hdac9 was significantly greater in female mice compared to males, HDAC9 protein localization did not differ. Hdac7 transcripts were greater in the inner medulla of cisplatin-AKI mice, regardless of sex, and this agreed with a greater HDAC7 abundance. HDAC activity within the cortex, outer, and inner medullae was significantly lower in cisplatin-AKI mice but did not differ between the sexes. In agreement with these findings a class I HDAC inhibitor didn't improve kidney injury or function. In conclusion, even though cisplatin-AKI was evident and there were transcript level differences among the different kidney regions in this model, there were few sex or cisplatin-dependent effects on kidney HDAC localization or activity.
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BACKGROUND: Periodontitis (PD) is a known risk factor for rheumatoid arthritis (RA) and there is increasing evidence that the link between the two diseases is due to citrullination by the unique bacterial peptidylarginine deiminase (PAD) enzyme expressed by periodontal pathogen Pophyromonas gingivalis (PPAD). However, the precise mechanism by which PPAD could generate potentially immunogenic peptides has remained controversial due to lack of information about the structural and catalytic mechanisms of the enzyme. OBJECTIVES: By solving the 3D structure of PPAD we aim to characterise activity and elucidate potential mechanisms involved in breach of tolerance to citrullinated proteins in RA. METHODS: PPAD and a catalytically inactive mutant PPAD(C351A) were crystallised and their 3D structures solved. Key residues identified from 3D structures were examined by mutations. Fibrinogen and α-enolase were incubated with PPAD and P. gingivalis arginine gingipain (RgpB) and citrullinated peptides formed were sequenced and quantified by mass spectrometry. RESULTS: Here, we solve the crystal structure of a truncated, highly active form of PPAD. We confirm catalysis is mediated by the following residues: Asp130, His236, Asp238, Asn297 and Cys351 and show Arg152 and Arg154 may determine the substrate specificity of PPAD for C-terminal arginines. We demonstrate the formation of 37 C-terminally citrullinated peptides from fibrinogen and 11 from α-enolase following incubation with tPPAD and RgpB. CONCLUSIONS: PPAD displays an unequivocal specificity for C-terminal arginine residues and readily citrullinates peptides from key RA autoantigens. The formation of these novel citrullinated peptides may be involved in breach of tolerance to citrullinated proteins in RA.
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Artrite Reumatoide/imunologia , Hidrolases/química , Modelos Moleculares , Porphyromonas gingivalis/enzimologia , Sequência de Aminoácidos , Autoimunidade , Catálise , Citrulina/química , Cristalização , Cristalografia por Raios X , Humanos , Hidrolases/imunologia , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Porphyromonas gingivalis/imunologia , Desiminases de Arginina em Proteínas , Relação Estrutura-Atividade , Especificidade por SubstratoRESUMO
BACKGROUND: Many United States veterans utilize prescription opioids to treat chronic pain symptoms and are subsequently at risk for opioid and alcohol misuse. As more states legalized the use of cannabis for medical use, increasing numbers of people are using cannabis pharmacotherapy for pain. The veterans Health Administration (VHA) Directive 1315, July 28, 2023 prohibits any medical staff on recommending, making referral to, and complete forms for a state approved program. Also, a veterans medical center does not provide marijuana to veterans. State laws do not change the status of CBD under federal law. CBD is illegal in the federal system. OBJECTIVES: Our aim was to investigate the prevalence of cannabidiol product usage in Veterans and the association with changes in self-reported pain. METHODS: We conducted a cross-sectional descriptive survey offering questionnaires to patients greater than 18 years of age receiving care at the Fargo Veteran Health Administration medical center Pain Clinic (2101 Elm St N, Fargo ND, 58102). RESULTS: A total of 218 veterans participated of which 81.2% were male and 52.3% were in the age range of 60-80 years. Twenty-one participants reported cannabidiol usage (9.6%), with 52.4% using to treat pain symptoms. Average pain scores pre-usage of 6.37 were reduced to 4.05 post-usage indicating a statistically significant reduction in pain (p < 0.001). CONCLUSION: Our study broadened the baseline knowledge of cannabidiol use in the Veteran population. Limitations include results being self-reported and the inability to verify cannabinoid constituents.
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We present a case study on the design and implementation of a value-based bundled package of care for patients with early-stage breast cancer treated in the private health sector in Australia. Value-based healthcare is an essential change to how we deliver healthcare, shifting the focus from paying for individual services provided to a focus on the health outcomes gained over a full cycle of care. The Australian health system has unintentionally created barriers to value-based cancer care through fragmented care pathways and complex funding arrangements where patients can unexpectedly encounter high out-of-pocket costs. A team of clinicians, service providers, health systems and funding experts, private health insurers and consumers have collaborated to design and pilot a complete bundled package of care for breast cancer patients which aims to address these challenges. With 40 patients recruited to date, early evaluation results show positive patient experience of 'joined-up' care and financial transparency. This case study provides a high-level overview of the approach taken to design and implement the Breast Cancer Bundle and the lessons learned for its expansion in both public and private settings.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/terapia , Projetos Piloto , Austrália , Atenção à Saúde , Instalações de SaúdeRESUMO
Myositis-specific autoantibodies (MSAs) are highly specific biomarkers for idiopathic inflammatory myopathies (IIMs). We investigated whether self-reported race and ethnicity were associated with the presence of specific MSAs. Charts of patients with IIM seen at 3 large healthcare systems in the same US city were reviewed. Demographic data and MSA test results were abstracted. Associations between race and ethnicity and presence of MSAs were analyzed using bivariate analysis and further characterized using separate unadjusted and adjusted logistic regression models. One hundred twenty-one subjects were included (19% Asian, 10% Black or African American, 27% Latinx or Hispanic, 36% non-Hispanic White, and 7% Other). In a bivariate analysis, anti-Jo-1 and anti-MDA5 autoantibodies were associated with race and ethnicity (p = 0.03 and 0.02, respectively). Black or African American subjects had increased odds of a positive anti-Jo-1 result compared to non-Hispanic White subjects on unadjusted logistic regression analysis (OR 8.61, 95% CI 1.61-46.07), although after adjustment for age and gender this finding was not significant. Subjects categorized as Other had increased odds of a positive anti-MDA5 result compared to non-Hispanic White subjects on both unadjusted (OR 55.0, 95% CI 2.02-1493) and adjusted analyses (OR 44.8, 95% CI 1.55-1298). Anti-Jo-1 and anti-MDA5 autoantibodies were significantly associated with race and ethnicity on bivariate analysis. Black or African American subjects had increased odds of positive anti-Jo-1 autoantibody on unadjusted, but not adjusted, logistic regression analysis. Subjects characterized as Other had increased odds of positive anti-MDA5 autoantibody, although confidence intervals were wide. Key Points ⢠Association found between MSAs and race and ethnicity in diverse US cohort ⢠Anti-Jo-1 and anti-MDA5 associated with race and ethnicity in bivariate analyses.
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Autoanticorpos , Miosite , Humanos , Etnicidade , Autorrelato , BiomarcadoresRESUMO
BACKGROUND: Clostridioides difficile (C. difficile) is a common hospital-acquired infection which can lead to major implications for patients and our health care system. In this study, we examine a policy change at a single-site Veterans Affairs Healthcare system that allowed bedside nurses to order C. difficile testing in addition to physicians on the time to obtain test results and initiate treatment. METHODS: The time to receive results and initiate treatment were analyzed before and after the policy change, and between physicians and nurses using descriptive statistics and paired student t-tests. Variables associated with lower ordering times were also analyzed using logistic regression while adjusting for patient admission location and length of inpatient hospital stay. RESULTS: The difference in time to obtain the result both before and after the policy change and between ordering provider type were both statistically significant (P < .05). In unadjusted models, nurses were associated with faster test results compared to physicians (OR (95% CI) 1.72 (1.45-2.05). CONCLUSIONS: Allowing bedside nurses more autonomy to order the stool sample significantly decreased the amount of time to receive the results, potentially decreasing the risk of additional infections among patients and decreasing the economic burden on the hospital.
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Clostridioides difficile , Infecções por Clostridium , Infecção Hospitalar , Humanos , Infecções por Clostridium/diagnóstico , Pacientes , Clostridioides , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/prevenção & controleRESUMO
OBJECTIVES: Guidelines recommend screening for latent hepatitis B virus (HBV), hepatitis C virus (HCV), and tuberculosis (TB) before initiating biologics or targeted synthetic disease-modifying antirheumatic drugs (b/ts DMARDs) to avoid reactivation of life-threatening infections. The extent to which such screening occurs in the national Veterans Health Administration (VA) healthcare system is unknown. METHODS: Using data from the Veterans Affairs' (VA) Corporate Data Warehouse, we performed a cross-sectional analysis of veterans receiving b/ts DMARDs between October 1, 2017, and September 30, 2019. We calculated the proportion of patients with screening completed for latent HBV, HCV, and TB between October 1, 1999 and September 30, 2019. Patient characteristics associated with complete screening were evaluated using mixed-effects multivariate logistic regression models. We also examined facility-level factors associated with high versus lower performance. RESULTS: A total of 51,764 unique patients from 129 VA facilities received b/ts DMARDs from 2017 to 2019. Of these, 63% had complete screening. Among the 11,006 patients identified as new users, 64% had complete screening. Higher screening rates were observed among Hispanic/Latinx and Black/African American patients, users of B-cell therapies, and patients who had seen oncology subspecialists. Substantial variation was observed across facilities, with complete screening ranging from 13% to 98% of patients. Higher screening rates were associated with highly complex, urban, and higher-volume facilities. CONCLUSIONS: Approximately two-thirds of veterans taking b/ts DMARDs have received guideline-recommended screening for HBV, HCV, and TB, but substantial facility variation was observed. Performance measures, robust multidisciplinary workflows, and electronic health record-based tools to feed information back to providers may improve screening rates for low-performing facilities.
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Antirreumáticos , Hepatite C , Infecção Latente , Humanos , Estados Unidos , Estudos Transversais , Saúde dos Veteranos , Imunossupressores/efeitos adversos , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Hepatite C/complicações , Infecção Latente/complicações , Infecção Latente/tratamento farmacológico , Antirreumáticos/efeitos adversos , Atenção à Saúde , United States Department of Veterans AffairsRESUMO
BACKGROUND: Hydroxychloroquine (HCQ) is commonly used for patients with autoimmune conditions. Long-term use of HCQ can cause retinal toxicity, but this risk can be reduced if high doses are avoided. OBJECTIVE: We developed and piloted an electronic health record-based dashboard to improve the safe prescribing of HCQ within the Veterans Health Administration (VHA). We observed pilot facilities over a 1-year period to determine whether they were able to improve the proportion of patients receiving inappropriate doses of HCQ. METHODS: Patients receiving HCQ were identified from the VHA corporate data warehouse. Using PowerBI (Microsoft Corp), we constructed a dashboard to display patient identifiers and the most recent HCQ dose and weight (flagged if ≥5.2 mg/kg/day). Six VHA pilot facilities were enlisted to test the dashboard and invited to participate in monthly webinars. We performed an interrupted time series analysis using synthetic controls to assess changes in the proportion of patients receiving HCQ ≥5.2 mg/kg/day between October 2020 and November 2021. RESULTS: At the start of the study period, we identified 18,525 total users of HCQ nationwide at 128 facilities in the VHA, including 1365 patients at the 6 pilot facilities. Nationwide, at baseline, 19.8% (3671/18,525) of patients were receiving high doses of HCQ. We observed significant improvements in the proportion of HCQ prescribed at doses ≥5.2 mg/kg/day among pilot facilities after the dashboard was deployed (-0.06; 95% CI -0.08 to -0.04). The difference in the postintervention linear trend for pilot versus synthetic controls was also significant (-0.06; 95% CI -0.08 to -0.05). CONCLUSIONS: The use of an electronic health record-based dashboard reduced the proportion of patients receiving higher than recommended doses of HCQ and significantly improved performance at 6 VHA facilities. National roll-out of the dashboard will enable further improvements in the safe prescribing of HCQ.
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Background: Due to geographic isolation and border controls Aotearoa New Zealand (AoNZ) attained high levels of population coronavirus disease-19 (COVID-19) vaccination before widespread transmission of COVID-19. We describe outcomes of SARS-CoV-2 infection (Omicron variant) in people with inflammatory rheumatic diseases in this unique setting. Methods: This observational study included people with inflammatory rheumatic disease and SARS-CoV-2 infection in AoNZ between 1 February and 30 April 2022. Data were collected via the Global Rheumatology Alliance Registry including demographic and rheumatic disease characteristics, and COVID-19 vaccination status and outcomes. Multivariable logistic regression was used to explore associations of demographic and clinical factors with COVID-19 hospitalisation and death. Findings: Of the 1599 cases included, 96% were from three hospitals that systematically identified people with inflammatory rheumatic disease and COVID-19. At time of COVID-19, 1513 cases (94.6%) had received at least two COVID-19 vaccinations. Hospitalisation occurred for 104 (6.5%) cases and 10 (0.6%) patients died. Lower frequency of hospitalisation was seen in cases who had received at least two vaccinations (5.9%), compared to the unvaccinated (20.6%) or those with a single vaccine dose (10.7%). In multivariable adjusted models, people with gout or connective tissue diseases (CTD) had increased risk of the combined outcome of hospitalisation/death, compared to people with inflammatory arthritis. Glucocorticoid and rituximab use were associated with increased rates of hospitalisation/death. All patients who died had three or more co-morbidities or were over 60 years old. Interpretation: In this cohort with inflammatory rheumatic diseases and high vaccination rates, severe outcomes from SARS-CoV-2 Omicron variant were relatively infrequent. The outcome of Omicron variant infection among vaccinated but SARS-CoV-2 infection-naive people with inflammatory rheumatic disease without other known risk factors were favourable. Funding: Financial support from the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) included management of COVID-19 Global Rheumatology Alliance funds.
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Monocytes are abundant immune cells that infiltrate inflamed organs. However, the majority of monocyte studies focus on circulating cells, rather than those in tissue. Here, we identify and characterize an intravascular synovial monocyte population resembling circulating non-classical monocytes and an extravascular tissue-resident monocyte-lineage cell (TR-MC) population distinct in surface marker and transcriptional profile from circulating monocytes, dendritic cells, and tissue macrophages that are conserved in rheumatoid arthritis (RA) patients. TR-MCs are independent of NR4A1 and CCR2, long lived, and embryonically derived. TR-MCs undergo increased proliferation and reverse diapedesis dependent on LFA1 in response to arthrogenic stimuli and are required for the development of RA-like disease. Moreover, pathways that are activated in TR-MCs at the peak of arthritis overlap with those that are downregulated in LFA1-/- TR-MCs. These findings show a facet of mononuclear cell biology that could be imperative to understanding tissue-resident myeloid cell function in RA.
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Artrite Reumatoide , Monócitos , Humanos , Monócitos/metabolismo , Membrana Sinovial , Inflamação/metabolismoRESUMO
OBJECTIVE: To determine the association between race/ethnicity and COVID-19 outcomes in individuals with systemic lupus erythematosus (SLE). METHODS: Individuals with SLE from the US with data entered into the COVID-19 Global Rheumatology Alliance registry between March 24, 2020 and August 27, 2021 were included. Variables included age, sex, race, and ethnicity (White, Black, Hispanic, other), comorbidities, disease activity, pandemic time period, glucocorticoid dose, antimalarials, and immunosuppressive drug use. The ordinal outcome categories were: not hospitalized, hospitalized with no oxygenation, hospitalized with any ventilation or oxygenation, and death. We constructed ordinal logistic regression models evaluating the relationship between race/ethnicity and COVID-19 severity, adjusting for possible confounders. RESULTS: We included 523 patients; 473 (90.4%) were female and the mean ± SD age was 46.6 ± 14.0 years. A total of 358 patients (74.6%) were not hospitalized; 40 patients (8.3%) were hospitalized without oxygen, 64 patients (13.3%) were hospitalized with any oxygenation, and 18 (3.8%) died. In a multivariable model, Black (odds ratio [OR] 2.73 [95% confidence interval (95% CI) 1.36-5.53]) and Hispanic (OR 2.76 [95% CI 1.34-5.69]) individuals had higher odds of more severe outcomes than White individuals. CONCLUSION: Black and Hispanic individuals with SLE experienced more severe COVID-19 outcomes, which is consistent with findings in the US general population. These results likely reflect socioeconomic and health disparities and suggest that more aggressive efforts are needed to prevent and treat infection in this population.
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COVID-19 , Lúpus Eritematoso Sistêmico , Reumatologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Etnicidade , Hispânico ou Latino , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Estados Unidos/epidemiologia , Brancos , Negro ou Afro-AmericanoRESUMO
Background: Adenosine triphosphate (ATP)-based monitoring systems can detect the amount of organic matter that remains on hospital surfaces after cleaning. We evaluated an ATP-based monitoring system in assessing contamination of high touched objects in rooms occupied by patients on methicillin resistant S. aureus precautions. Methods: We compared the ATP to standard aerobic cultures as well as to gloved hand culture to predict risk of healthcare-worker hand contamination. Results: More than a third of high touch object surfaces were measured unclean with ATP yet only reflects about 5% chance of contaminating healthcare-workers' hands. Conclusions: Our study emphasizes the shortcomings of using the ATP system even in pathogen specific environment such as surfaces in methicillin resistant S. aureus rooms.
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Objective: The purpose of this case study is to describe chiropractic care of the cervical spine for a patient who previously underwent cervical total disk replacement (CTDR) of the C5-6 and C6-7 disks. Clinical Features: A 42-year-old female veteran of the U.S. Army presented to a Veterans Affairs chiropractic clinic with chronic cervical pain and radiculopathy. She had previously undergone CTDR surgery of the C5-6 disk 9 years earlier, but the pain had become severe and radicular symptoms had returned in the upper left extremity. Imaging taken before the chiropractic referral demonstrated significant joint space narrowing and disk herniation of the C6-7 disk with protrusion to the left side. Intervention and Outcome: The patient received spinal manipulative therapy, trigger-point therapy, and manual traction to the cervical spine. However, these treatments were not effective in reducing her cervical pain and radiculopathy. She then opted for CTDR of the C6-7 disk. After surgery, the patient reported that radicular symptoms were mostly relieved and cervical pain had decreased by 50%. After 6 additional spinal manipulative therapy treatments, she reported having no neurologic symptoms and that her pain had decreased more than 70% from presurgery levels. Conclusion: This case report is the first reported example of chiropractic care after CTDR within an integrated health care environment. The patient's cervical pain and radiculopathy improved with CTDR along with postsurgical chiropractic care.
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OBJECTIVE: To describe people with gout who were diagnosed with coronavirus disease 2019 (COVID-19) and hospitalized and to characterize their outcomes. METHODS: Data on patients with gout hospitalized for COVID-19 between March 12, 2020, and October 25, 2021, were extracted from the COVID-19 Global Rheumatology Alliance registry. Descriptive statistics were used to describe the demographics, comorbidities, medication exposures, and COVID-19 outcomes including oxygenation or ventilation support and death. RESULTS: One hundred sixty-three patients with gout who developed COVID-19 and were hospitalized were included. The mean age was 63 years, and 85% were male. The majority of the group lived in the Western Pacific Region (35%) and North America (18%). Nearly half (46%) had two or more comorbidities, with hypertension (56%), cardiovascular disease (28%), diabetes mellitus (26%), chronic kidney disease (25%), and obesity (23%) being the most common. Glucocorticoids and colchicine were used pre-COVID-19 in 11% and 12% of the cohort, respectively. Over two thirds (68%) of the cohort required supplemental oxygen or ventilatory support during hospitalization. COVID-19-related death was reported in 16% of the overall cohort, with 73% of deaths documented in people with two or more comorbidities. CONCLUSION: This cohort of people with gout and COVID-19 who were hospitalized had high frequencies of ventilatory support and death. This suggests that patients with gout who were hospitalized for COVID-19 may be at risk of poor outcomes, perhaps related to known risk factors for poor outcomes, such as age and presence of comorbidity.
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In this study, we conducted a prospective survey of a convenience sample of high touch objects using adenosine triphosphate bioluminescence surface sample readings, aerobic cultures, and gloved hand methicillin-resistant Staphylococcus aureus imprint cultures to assess inpatient room cleanliness. We demonstrated that thoroughness of cleaning is improved with housekeeping education and feedback and that the addition of automated decontamination with pulsed UV irradiation provides further benefit in decontamination and subsequent risk for health care worker hand contamination.
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Infecção Hospitalar , Staphylococcus aureus Resistente à Meticilina , Infecção Hospitalar/prevenção & controle , Desinfecção , Pessoal de Saúde , Humanos , Estudos Prospectivos , Raios Ultravioleta , XenônioRESUMO
OBJECTIVE: Individuals with autoimmune rheumatic disease (RD) are considered to be at increased risk for infection. However, few US population-based studies have assessed whether these patients are at increased risk of hospitalization or death due to COVID-19 compared with those without RD. METHODS: We performed a retrospective cohort study using national Veterans Affairs Health Care System data for individuals who tested positive for SARS-CoV-2. Outcomes of interest were hospitalization or death due to any cause within 30 days of COVID-19 diagnosis. Outcomes were compared among veterans with RD and those without RD by using propensity score matching (PSM) and mixed-effects multivariate logistic regression. RESULTS: Of 26,116 veterans with COVID-19, 501 (1.9%) had an underlying RD. Prior to matching, patients with RD were more likely to have poor outcomes compared with controls (37.7% vs. 28.5% hospitalized; 6.4% vs. 4.5% died). In the PSM analysis, RD was not a significant predictor for poor outcomes; however, patients with prescriptions for glucocorticoids had increased odds of poor outcomes in a dose-dependent manner (odds ratio [95% confidence interval] for hospitalization or death: 1.33 [1.20-1.48] for doses >0 and ≤10 mg/day; 1.29 [1.09-1.52] for doses >10 mg/day). CONCLUSION: Among US veterans with COVID-19, we did not find a significant association between RD and hospitalization or death. Poor outcomes appear to be mostly driven by age and other comorbidities, similar to the general veteran population. However, we observed an increased risk for poor outcomes among patients who received glucocorticoids, even at daily doses less than or equal to 10 mg.
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BACKGROUND & AIMS: Limited understanding of the role for specific macrophage subsets in the pathogenesis of cholestatic liver injury is a barrier to advancing medical therapy. Macrophages have previously been implicated in both the mal-adaptive and protective responses in obstructive cholestasis. Recently two macrophage subsets were identified in non-diseased human liver; however, no studies to date fully define the heterogeneous macrophage subsets during the pathogenesis of cholestasis. Here, we aim to further characterize the transcriptional profile of macrophages in pediatric cholestatic liver disease. METHODS: We isolated live hepatic immune cells from patients with biliary atresia (BA), Alagille syndrome (ALGS), and non-cholestatic pediatric liver by fluorescence activated cell sorting. Through single-cell RNA sequencing analysis and immunofluorescence, we characterized cholestatic macrophages. We next compared the transcriptional profile of pediatric cholestatic and non-cholestatic macrophage populations to previously published data on normal adult hepatic macrophages. RESULTS: We identified 3 distinct macrophage populations across cholestatic liver samples and annotated them as lipid-associated macrophages, monocyte-like macrophages, and adaptive macrophages based on their transcriptional profile. Immunofluorescence of liver tissue using markers for each subset confirmed their presence across BA (n = 6) and ALGS (n = 6) patients. Cholestatic macrophages demonstrated reduced expression of immune regulatory genes as compared to normal hepatic macrophages and were distinct from macrophage populations defined in either healthy adult or pediatric non-cholestatic liver. CONCLUSIONS: We are the first to perform single-cell RNA sequencing on human pediatric cholestatic liver and identified three macrophage subsets with distinct transcriptional signatures from healthy liver macrophages. Further analyses will identify similarities and differences in these macrophage sub-populations across etiologies of cholestatic liver disease. Taken together, these findings may allow for future development of targeted therapeutic strategies to reprogram macrophages to an immune regulatory phenotype and reduce cholestatic liver injury.
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Atresia Biliar/metabolismo , Colestase/metabolismo , Fígado/metabolismo , Macrófagos/metabolismo , Transcriptoma , Atresia Biliar/genética , Atresia Biliar/patologia , Criança , Pré-Escolar , Colestase/genética , Colestase/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Lactente , Fígado/patologia , MasculinoRESUMO
OBJECTIVE: To characterise the counselling behaviour of practitioners providing a pharmaceutical care (PC) service in community pharmacy, and to describe the content of the consultations. SETTING: Community pharmacies in Sweden. METHODS: Non-participant observations, including audio recording, of five practitioners in five different pharmacies counselling 16 patients, were analysed qualitatively using an iterative, stepwise, interpretivist approach. MAIN OUTCOME MEASURE: Descriptions of counselling behaviour and content of consultations. RESULTS: The counselling behaviour was characterised by attempts to understand the patients' narratives by listening and asking questions and a willingness to help. The computer often had an important role in consultations, being used for documentation and as a supportive tool for identification of drug-drug interactions. The practitioners often took command in the initial phase of the consultation, and omitted to determine the patients' most urgent drug-related needs. However, counselling behaviour that identified and focused on the patient's needs, giving the computer little attention during the consultation was also observed. Practitioners provided vague descriptions of the purpose and outline of the service. Consultations included a wide variety of issues, which potentially could help patients' achieve optimal outcomes of medical treatment. CONCLUSION: The practitioners provided important advice and different forms of support to patients. Focus on the computer screen limited their abilities to practise patient centred care.
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Comunicação , Serviços Comunitários de Farmácia/organização & administração , Aconselhamento , Educação de Pacientes como Assunto , Farmácias , Relações Profissional-Paciente , Adulto , Atitude do Pessoal de Saúde , Feminino , Humanos , Masculino , Sistemas Computadorizados de Registros Médicos , Pessoa de Meia-Idade , Assistência Centrada no Paciente , Farmacêuticos , Prática Profissional/organização & administração , Papel Profissional , SuéciaRESUMO
Objectives: Battlefield Acupuncture (BFA) is a unique auricular acupuncture procedure utilized by many Veterans Affairs Healthcare Administration facilities. Several previous studies have shown an immediate reduction in pain for up to 2 weeks post BFA. The long-term effects of BFA and its potential to decrease opioid use had yet to be analyzed. This study was conducted to analyze the effectiveness of BFA to decrease chronic pain immediately and 6 months after treatment and to decrease the number of opioids needed for management of chronic pain. Materials and Methods: This was a retrospective cohort study comparing veterans who received BFA and were prescribed opioids for their chronic pain to veterans who did not receive BFA. The treatment group included 24 veterans who received BFA and had opioid contracts. The comparison group consisted of 23 randomly selected veterans who had opioid contracts but did not receive BFA. A numeric rating scale (NRS) was used to measure pain before and after treatment, as well as 3 months prior and 6 months post. The average morphine mg equivalents for opioids 3 months prior and 6 months post treatment were also compared. Differences between groups were statistically analyzed by an analysis of variance and a Student's t-test. Results: Significant average decreases of 1.3 points on the NRS occurred in 66.1% immediately after the procedure. No significant decreases in pain were found. No significant changes of the average number of opioids over the 9 months analyzed were found. Conclusions: BFA is effective for immediate pain reduction. Further research with a randomized controlled trial in a larger population is needed to assess BFA effects on chronic pain and opioid dependency.
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Background: There is limited previous English-language literature on acupuncture's ability to treat idiopathic scoliosis. This report shows the potential effectiveness of a combination of acupuncture and cupping therapies to treat curvature progression and thoracic back pain in adult idiopathic scoliosis. Intervention: A 34-year-old male veteran of the U.S. Armed Forces with thoracic back pain and muscle spasms originally presented to the chiropractic clinic at the Fargo Veterans Affairs Healthcare System, Fargo, ND. Per radiographs taken prior to the consultation, the chiropractor determined that the patient had an idiopathic right-convex scoliosis curve of â¼21°. Due to immobility of the thoracic spinal vertebra upon adjustment, he was referred to acupuncture care. After a clinical review, the acupuncturist hypothesized that a combination of utilizing acupuncture and cupping techniques would help relax the muscles along the thoracic spine, allowing correction of the patient's abnormal spinal curvature. Combination Traditional Chinese Medicine (TCM), using acupuncture with cupping therapy was given â¼2 times per week for several weeks, resulting in a total of 15 treatments. Results: After 15 treatments, this patient's subjective pain decreased by 85%. Anecdotally, he reported "feeling a bit looser." He continued to receive acupuncture and cupping treatments when his schedule allowed. Conclusions: The combination therapy was effective for treating musculoskeletal pain but was inconclusive with respect to its ability to treat adult idiopathic scoliosis. More research is needed on the efficacy of TCM for treating adult idiopathic scoliosis.