Optimising prednisolone or prednisone replacement in adrenal insufficiency

CONTEXT: Patients with adrenal insufficiency (AI) have higher mortality than the general population, possibly because of excess glucocorticoid exposure at inappropriate times. The cortisol circadian rhythm is difficult to mimic with twice or thrice-daily hydrocortisone. Prednisolone is a once-daily alternative which may improve patient compliance and convenience. OBJECTIVES: Prednisolone day curves can be used to accurately down-titrate patients to the minimum effective dose. We aimed to review prednisolone day curves and determine therapeutic ranges at different timepoints after administration. METHODS: Between August 2013 and May 2021, 108 prednisolone day curves from 76 individuals receiving prednisolone replacement were analysed. Prednisolone concentrations were determined by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Spearman's correlation coefficient was used to determine the relationship between 2-, 4- and 6-hour prednisolone levels compared to the validated standard 8-hour prednisolone level (15-25 μg/L). RESULTS: The median dose was 4mg prednisolone once daily. There was strong correlation between the 4-hour and 8-hour (R=0.8829, p ≤0.0001), and 6-hour and 8-hour prednisolone levels (R=0.9530, p ≤ 0.0001). Target ranges for prednisolone were 37-62 μg/L at 4-hours, 24-39 μg/L at 6-hours and 15-25 μg/L at 8-hours. Prednisolone doses were successfully reduced in 21 individuals and of these, three were reduced to 2mg once daily. All patients were well upon follow-up. CONCLUSION: This is the largest evaluation of oral prednisolone pharmacokinetics in humans. Low dose prednisolone of 2-4mg is safe and effective in most patients with AI. Doses can be titrated with either 4-hour, 6-hour, or 8-hour single timepoint drug levels

Development and validation of an RP-HPLC method for determination of Cefixime and Dicloxacillin in tablet dosage form

A simple, specific and accurate reverse phase high performance liquid chromatographic method was developed for simultaneous estimation of Cefixime and Dicloxacillin in bulk drug and tablet dosage form. Sepration was achieved by capcell pack C-18 column having 250 mm4.6 mm i.d. in isocratic mode, with mobile phase containing 0.05 M potassium dihydrogen phosphate: methanol (25:75), adjusted to pH 4.5 using ortho phosphoric acid. The flow rate was 1.0 ml/min and effluents were monitored at 232 nm. The retention time of Cefixime and Dicloxacillin were 3.19 min and 6.68 min respectively. The linearity for Cefixime and Dicloxacillin were in the range of 10-100 g/ml. The recoveries of Cefixime and Dicloxacillin were found in the range of 99.63-99.95 % and 99.58-99.98 % respectively. The proposed method was validated as per ICH and USP guidelines and successfully applied to the estimation of Cefixime and Dicloxacillin in bulk drug and tablet dosage form

Late night salivary cortisol and cortisone should be the initial screening test for Cushing’s syndrome

Endogenous Cushing’s syndrome (CS) poses considerable diagnostic challenges. Although late night salivary cortisol (LNSC) is recommended as a first line screening investigation, it remains the least widely used test in many countries. The combined measurement of LNSC and late-night salivary cortisone (LNS cortisone) has shown to further improve diagnostic accuracy1. We present a retrospective study in a tertiary referral centre comparing LNSC, LNS cortisone, overnight dexamethasone suppression test, low dose dexamethasone suppression test and 24-hour urinary free cortisol results of patients investigated for CS. Patients were categorised into those who had CS (21 patients) and those who did not (33 patients).LNSC had a sensitivity of 95% and a specificity of 91%. LNS cortisone had a specificity of 100% and a sensitivity of 86%. With an optimal cut-off for LNS cortisone of >14.5 nmol/l the sensitivity was 95.2%, and the specificity was 100% with an area under the curve of 0.997, for diagnosing CS. Saliva collection is non-invasive and can be carried out at home.We therefore advocate simultaneous measurement of LNSC and LNS cortisone as the first-line screening test to evaluate patients with suspected CS

Diagnostic confusion resolved by being upbeat

The classical stroke presentation – captured by the public health campaign mnemonic FAST (face, arm, speech, time) – does not apply in a large number of stroke cases; yet establishing a prompt diagnosis is imperative for optimal management. Here, we describe a patient with acute bulbar weakness, numbness in all extremities and an apparently normal magnetic resonance imaging (MRI) of the brain upon admission for whom even the fundamental question of whether this reflected a central or peripheral nervous system process was unclear. The critical localizing sign was upbeat nystagmus that denotes a brainstem cause. MRI of the brain in the second week confirmed a diagnosis of medial medullary infarction

The gut microbiota and metabolome are associated with diminished COVID-19 vaccine-induced antibody responses in immunosuppressed inflammatory bowel disease patients

Background: Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. Methods: Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination. Findings: Forty-three infliximab-treated patients with IBD were recruited (30 Crohn's disease, 12 ulcerative colitis, 1 IBD-unclassified; 26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.037). Bilophila abundance was associated with better serological response, while Streptococcus was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R2X 0.25, R2Y 0.26, Q2 0.15; CV-ANOVA p = 0.038). Trimethylamine, isobutyrate and omega-muricholic acid were associated with better response, while succinate, phenylalanine, taurolithocholate and taurodeoxycholate were associated with poorer response. Interpretation: Our data suggest that there is an association between the gut microbiota and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine may be important in mitigating anti-TNF-induced attenuation of the immune response. Funding: JLA is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-502), funded by Imperial College London and The Joyce and Norman Freed Charitable Trust. BHM is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-002). The Division of Digestive Diseases at Imperial College London receives financial and infrastructure support from the NIHR Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. Metabolomics studies were performed at the MRC-NIHR National Phenome Centre at Imperial College London; this work was supported by the Medical Research Council (MRC), the National Institute of Health Research (NIHR) (grant number MC_PC_12025) and infrastructure support was provided by the NIHR Imperial Biomedical Research Centre (BRC). The NIHR Exeter Clinical Research Facility is a partnership between the University of Exeter Medical School College of Medicine and Health, and Royal Devon and Exeter NHS Foundation Trust. This project is supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care

Application of film marketing tools in Kannada film industry: An empirical analysis

Film marketing process has been enriched by the revolutionary changes in the field of communication science and technology. The article is based on empirical study of application of film marketing tools in Kannada film industry. The Kannada film industry has achieved commendable progress during the last eight decades. The film marketing strategies have undergone revolutionary changes consequent on several media campaigns, fairs and festivals in India. The review of literature clearly indicates that not even a single scientific investigation has been carried out on film marketing with special reference to Kannada film industry. The present investigation was carried out on the basis of systematic survey research method. Several advanced film marketing tools have been used by the various stakeholders in Kannada film industry according to the present investigation. The study envisages that Kannada film industry should get rid of the age old formula which glorifies sex, romance, violence, music and dance. The Kannada film marketing strategies should be based on meaningful corporate tie-ups and merchandising in the present times. The stakeholders of Kannada film industry are required to inculcate innovative and creative film marketing strategies which would boost Kannada film industry in the new millennium

Individual participants

Any software made available via TimeCenter is provided \as is " and without any express or implied warranties, including, without limitation, the implied warranty of merchantability and tness for a particular purpose. The TimeCenter icon on the cover combines two \arrows. " These \arrows " are letters in the so-called Rune alphabet used one millennium ago by the Vikings, as well as by their precedessors and successors, The Rune alphabet (second phase) has 16 letters. They all have angular shapes and lack horizontal lines because the primary storage medium was wood. However, runes may also be found on jewelry, tools, and weapons. Runes were perceived by many ashaving magic, hidden powers. The two Rune arrows in the icon denote \T " and \C, " respectively. Real-Time Database Systems (RTDBSs), have attracted considerable amount of research attention in the recent past and a number of important applications have been identi ed for such systems, such as telecommunications network management, automated air tra c control, automated nancial trading, process control and military command and control systems. Due to th

Multiclass Transaction Scheduling and Overload Management in Firm Real-Time Database Systems

Real-Time Database Systems (RTDBSs), have attracted considerable amount of research attention in the recent past and a number of important applications have been identified for such systems, such as telecommunications network management, automated air traffic control, automated financial trading, process control and military command and control systems. Due to the rapidity of change of the system state in such applications, as well as the inherent complexities in controlling such systems (which result in frequent violation of consistency requirements and consequent repeated firings of control actions), it is likely that the transaction load in these systems would be fairly high. Thus RTDBSs need to be equipped with overload management mechanisms. Unfortunately overload management has been a fairly neglected area in real-time systems research in general and real-time database research in particular. In this paper we introduce Adaptive Access Parameter (AAP), a scheduling mechanism for m..