Steroids as treatment for glomerulonephritis: time for a rethink

Glucocorticoids have been a cornerstone of treatment for inflammatory and autoimmune kidney diseases for almost 70 years, yet it is fair to say, we still do not know how 'best' to use them. Significant adverse events are associated with their continued use, which contribute to premature patient mortality. Steroid avoidance or minimization is possible and has been tested in various glomerular diseases, as a result of novel agents or innovative regimens using established therapeutics. It is now time to seriously address our use of steroids and educate physicians on better ways of managing inflammatory kidney diseases

Characteristics of Frailty in Haemodialysis Patients

© The Author(s) 2022. This article is distributed under the terms of the Creative Commons Attribution-Non Commercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/Background: Both frailty and cachexia increase mortality in haemodialysis (HD) patients. The clinical frailty score (CFS) is a seven-point scale and less complex than other cachexia and frailty assessments. We wished to determine the characteristics of frail HD patients using the CFS.  Methods: Single centre cross-sectional study of HD patients completing physical activity questionnaires with bioimpedance measurements of body composition and hand grip strength (HGS).  Results: We studied 172 HD patients. The CFS classified 54 (31.4%) as frail, who were older (70.4±12.2 vs 56.2 ± 16.1 years, p < 0.001), greater modified Charlson co-morbidity (3 (2–3) versus 1.5 (0–3), p < 0.001), and body fat (33 (25.4–40.2) versus 26.2 (15.8–34) %, p < 0.01), but lower total energy expenditure (1720 (1574–1818) versus 1870 (1670–2194) kcal/day, p < 0.01), lean muscle mass index (9.1 (7.7–10.1) versus 9.9 (8.9–10.8) kg/m2), and HGS (15.3 (10.3–21.9) versus 23.6 (16.7–34.4) kg), both p < 0.001. On multivariable logistic analysis, frailty was independently associated with lower active energy expenditure (odds ratio (OR) 0.98, 95% confidence limits (CL) 0.98–0.99, p = 0.001), diabetes (OR 5.09, CL 1.06–16.66) and HGS (OR 0.92, CL 0.86–0.98).  Discussion: Frail HD patients reported less active energy expenditure, associated with reduced muscle mass and strength. Frail patients were more likely to have greater co-morbidity, particularly diabetes. Whether physical activity programmes can improve frailty remains to be determined.Peer reviewedFinal Published versio

Diferensiasi Produk dan Kualitas Pelayanan terhadap Kepuasan Konsumen pada Rumah Makan Manalagi di Manado

Indonesia sebagai salah satu negara di kawasan Asean yang jumlah penduduk menempati urutan keempat terbanyak merupakan potensi besar bagi produk-produk dan jasa-jasa usaha kecil menengah. Hal inilah yang mendorong perlunya dikembangkan usaha-usaha atau bisnis di wilayah ini seperti usaha rumah makan. Tujuan penelitian adalah untuk menganalisis pengaruh diferensiasi produk dan kualitas pelayanan terhadap kepuasan konsumen usaha rumah makan. Penelitian ini menggunakan metode kuantitatif pada rumah makan Manalagi di Manado. Jumlah sampel sebanyak 100 responden. Pengukuran data menggunakan skala Likert dan menggunakan kuesioner sebagai instrument pengumpulan data. Analisis data dan uji hipotesis menggunakan analisis regresi, uji F dan uji t. Hasil uji statistik ditemukan bahwa secara simultan diferensiasi produk dan kualitas pelayanan berpengaruh positif dan signifikan terhadap kepuasan konsumen. Secara parsial diferensiasi produk dan kualitas pelayanan berpengaruh terhadap kepuasan konsumen usaha rumah makan Manalagi. Selain itu variabel yang paling dominan berpengaruh terhadap kepuasan konsumen adalah diferensiasi produk. Pihak manajemen Perusahaan sebaiknya meningkatkan kualitas pelayanan karena variabel ini berpengaruh lemah bagi kepuasan konsumen. Kata kunci: diferensiasi produk, kualitas pelayanan, kepuasan konsume

Impact of CYP2B6 983T>C polymorphism on non-nucleoside reverse transcriptase inhibitor plasma concentrations in HIV-infected patients

Objectives The aim of this study was to investigate the frequency of CYP2B6 polymorphisms (according to ethnicity) and the influence of heterozygosity and homozygosity on plasma concentrations of efavirenz and nevirapine. Methods Following written informed consent, 225 Caucasians and 146 Blacks were recruited from the German Competence Network for HIV/AIDS. Plasma concentrations of efavirenz and nevirapine were assessed by HPLC, and genotyping for 516G>T, 983T>C and 1459T>C polymorphisms in CYP2B6 was conducted by real-time PCR-based allelic discrimination. Results The minor allele frequency for 516G>T, 983T>C and 1459T>C was 0.29, 0 and 0.08 in Caucasians and 0.34, 0.07 and 0.02 in Blacks, respectively. Two Black patients with the 983C allele receiving efavirenz were identified and both were withdrawn from therapy within 1 week of sampling due to toxicity. In multivariate analyses, efavirenz and nevirapine plasma concentrations were significantly associated with 983T>C (P T (P T was not associated with plasma concentrations of either drug (P > 0.05 for both drugs). Conclusions This is the first report that the 983T>C genotype (part of the CYP2B6*18 haplotype) impacts on nevirapine plasma concentrations and the first study to assess the impact of 983C homozygosity on efavirenz concentrations. These data have implications for administration of non-nucleoside reverse transcriptase inhibitors to Black patient

Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens

Objectives Cytochrome P450 2B6 (CYP2B6) is responsible for the metabolic clearance of efavirenz and single nucleotide polymorphisms (SNPs) in the CYP2B6 gene are associated with efavirenz pharmacokinetics. Since the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) correlate with CYP2B6 in liver, and a CAR polymorphism (rs2307424) and smoking correlate with efavirenz plasma concentrations, we investigated their association with early (<3 months) discontinuation of efavirenz therapy. Methods Three hundred and seventy-three patients initiating therapy with an efavirenz-based regimen were included (278 white patients and 95 black patients; 293 male). DNA was extracted from whole blood and genotyping for CYP2B6 (516G → T, rs3745274), CAR (540C → T, rs2307424) and PXR (44477T → C, rs1523130; 63396C → T, rs2472677; and 69789A → G, rs763645) was conducted. Binary logistic regression using the backwards method was employed to assess the influence of SNPs and demographics on early discontinuation. Results Of the 373 patients, 131 withdrew from therapy within the first 3 months. Black ethnicity [odds ratio (OR) = 0.27; P = 0.0001], CYP2B6 516TT (OR = 2.81; P = 0.006), CAR rs2307424 CC (OR = 1.92; P = 0.007) and smoking status (OR = 0.45; P = 0.002) were associated with discontinuation within 3 months. Conclusions These data indicate that genetic variability in CYP2B6 and CAR contributes to early treatment discontinuation for efavirenz-based antiretroviral regimens. Further studies are now required to define the clinical utility of these association

A high impact intervention for a high impact intervention: Improving documentation of peripheral venous access insertion in theatre

The Department of Health’s ‘High Impact Intervention (HII) – Peripheral intravenous cannula care bundle’ lists six actions to be performed at the time of peripheral intravenous cannulation. Audit of compliance to these requires documentation. We assessed documentation on the anaesthetic charts of 50 surgical patients. Purpose-made stickers were then placed on all anaesthetic charts. Re-assessment of a further 50 patients’ charts demonstrated a significant improvement in documentation of the bundle post intervention (Fisher’s exact test P < 0.0001). This is an example of how a low-tech intervention can produce a high impact improvement in documentation

The use of life-saving extracorporeal membrane oxygenation (ECMO) for pregnant woman with status asthmaticus

INTRODUCTION: Status asthmaticus can develop into a life-threatening disorder that requires mechanical ventilation. Severe respiratory failure during pregnancy can worsen maternal and fetal outcomes. Previous case studies have demonstrated extracorporeal membrane oxygenation (ECMO) as a life-saving measure for pregnant women with acute respiratory distress syndrome (ARDS) as well as non-pregnant patients with status asthmaticus. CASE STUDY: A 25-year-old woman, who was 5 weeks pregnant, was admitted with status asthmaticus and severe hypercapnic respiratory failure. Despite rescue therapies such as pressure control ventilation with high inspiratory pressures, inhaled beta2 agonists and antimuscarinic drugs, intravenous salbutamol, methylprednisolone and magnesium sulfate, her condition gradually deteriorated. Veno-venous ECMO was initiated for respiratory support and the patient's clinical condition as well as the gas exchange improved within the next few days. ECMO was removed and the patient was extubated after 2 days. Sonography, however, revealed a retrochorial hematoma; the patient was diagnosed with abortus imminens and successfully treated with magnesium substitution and bed rest. Finally, she gave birth to a healthy boy at 38 weeks of gestation. CONCLUSIONS: This is the first case report on the successful use of ECMO in a pregnant woman with severe respiratory insufficiency due to status asthmaticus, who failed to respond to invasive mechanical ventilation and maximum pharmacological treatment. Despite this life-threatening condition, the use of ECMO in our patient has greatly improved the chance of survival for the mother and the baby, who was born without any complications

Identifying prognostic risk factors for poor outcome following COVID-19 disease among in-centre haemodialysis patients: role of inflammation and frailty

Introduction: The pandemic of coronavirus disease (COVID-19) has highly affected patients with comorbidities and frailty who cannot self-isolate, such as individuals undergoing haemodialysis. The aim of the study was to identify risk factors for mortality and hospitalisation, which may be useful in future disease spikes. Methods: We collected data retrospectively from the electronic medical records of all patients receiving a diagnosis of COVID-19 between 11th March and 10th May 2020 undergoing maintenance haemodialysis at four satellite dialysis units from the Royal Free London NHS Foundation Trust, London, UK. Mortality was the primary outcome, and the need for hospitalization was the secondary one. Results: Out of 746 patients undergoing regular haemodialysis, 148 symptomatic patients tested positive for SARS-CoV-2 by RT-PCR and were included in the analysis. The overall mortality rate was 24.3%. By univariate analysis, older age, ischaemic heart disease, lower systolic blood pressure, lower body mass index (BMI) and higher frailty scores were associated with higher rates of mortality (all p value < 0.05). The laboratory factors associated with mortality were higher values of WBC, neutrophil counts, neutrophil to lymphocyte ratios (NLR), C-reactive protein (CRP), bilirubin, ferritin, troponin, and lower serum albumin level (all p value < 0.05). In the logistic regression, mortality was associated with older age and higher CRP, while high levels of NLR and CRP were associated with the need for hospitalization. Discussion: Haemodialysis patients are susceptible to COVID-19 and have a high mortality rate. Our study identifies prognostic risk factors associated with poor outcome including age, frailty and markers of inflammation, which may support more informed clinical decision-making. Graphic abstract: [Figure not available: see fulltext.