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1.
Obes Rev ; : e13759, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38710656

ABSTRACT

OBJECTIVES: To evaluate the impact of bariatric surgery on the pharmacokinetic (PK) parameters of orally administered medications and supplements. METHODS: Systematic searches of bibliographic databases were conducted to identify studies. Pooled effect estimates from different surgical procedures were calculated using a random-effects model. RESULTS: Quantitative data were synthesized from 58 studies including a total of 1985 participants. Whilst 40 medications and 6 supplements were evaluated across these studies, heterogeneity and missing information reduced the scope of the meta-analysis to the following medications and supplements: atorvastatin, paracetamol, omeprazole, midazolam, vitamin D, calcium, zinc, and iron supplements. There were no significant differences in PK parameters post-surgery for the drugs atorvastatin and omeprazole, and supplements calcium, ferritin, and zinc supplements. Paracetamol showed reduced clearance (mean difference [MD] = -15.56 L/hr, p = 0.0002, I2 = 67%), increased maximal concentration (MD = 6.90 µg/ml, p = 0.006, I2 = 92%) and increased terminal elimination half-life (MD = 0.49 hr, p < 0.0001, I2 = 3%) post-surgery. The remaining 36 medications and 2 supplements were included in a systematic review. Overall, 18 of the 53 drugs and supplements showed post-operative changes in PK parameters. CONCLUSION: This study demonstrates heterogeneity in practice and could not reach conclusive findings for most PK parameters. Prospective studies are needed to inform best practice and enhance patient healthcare and safety following bariatric surgery.

2.
BJOG ; 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38497098

ABSTRACT

OBJECTIVE: To assess the clinical utility of point-of-care (POC) capillary blood glucose (CBG) testing in the assessment of gestational diabetes mellitus (GDM) during oral glucose tolerance test (OGTT). DESIGN: Prospective cohort study. SETTING: Antenatal clinics at King's College Hospital. POPULATION: Women screened for GDM between March and June 2020. METHODS: The CBG was measured using the POC StatStrip® test and the venous plasma glucose (VPG) was measured by Roche analyser (Cobas 8000 c702). GDM was diagnosed based on the 2015 National Institute for Health and Clinical Excellence (NICE) Clinical Guideline criteria. The two methods were compared statistically using Analyse-It 5.40.2. MAIN OUTCOME MEASURES: Diagnostic sensitivity, specificity, positive and negative predictive values (PPV and NPV) for the POC StatStrip® test, compared with VPG measured by reference laboratory method. RESULTS: A total of 230 women were included. The number and percentage of women with glucose concentrations above the GDM threshold using the POC StatStrip® test versus laboratory VPG measurement was 15 (6.5%) versus eight (3.4%) at fasting and 105 (45.6%) versus 72 (31.1%) at 2 h, respectively. The sensitivity and specificity values (and 95% CIs) for the POC StatStrip® test were 88% (52%-99%) and 97% (93%-98%) at fasting and 97% (91%-99%) and 79% (71%-84%) at 2 h, respectively. However, the specificity and the NPV for the POC StatStrip® test for concentrations of ≤5.0 mmol/L at fasting or <7.5 mmol/L at 2 h were 100%, and the sensitivity and the PPV for concentrations of >9.5 mmol/L at 2 h were 100%. CONCLUSIONS: In our cohort the POC measurement of CBG cannot entirely replace the laboratory method for the OGTT; however, it can be used to rule out/rule in GDM for glucose concentrations of ≤5.0 mmol/L at fasting or <7.5/>9.5 mmol/L at 2 h.

3.
Int J STD AIDS ; : 9564624241233036, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38377277

ABSTRACT

BACKGROUND: There are no validated waist circumference (WC) cut-offs to define metabolic syndrome in Black people with HIV. METHODS: Cross-sectional analyses within the CKD-AFRICA study. We used Pearson correlation coefficients and receiver operating characteristic (ROC) curves to describe the relationship between WC and cardiometabolic parameters including triglycerides, cholesterol, glucose, glycated haemoglobin (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR), and to identify optimal WC cut-offs for each of these outcomes. RESULTS: We included 383 participants (55% female, median age 52 years) with generally well controlled HIV. Female and male participants had similar WC (median 98 vs. 97 cm, p = .16). Generally weak correlations (r2 < 0.2) between WC and other cardiometabolic parameters were observed, with low (<0.7) areas under the ROC curves. The optimal WC cut-offs for constituents of the metabolic syndrome, HbA1c and HOMA-IR ranged from 92 to 101 cm in women and 89-98 cm in men, respectively; these cut-offs had variable sensitivity (52%-100%) and generally poor specificity (28%-72%). CONCLUSIONS: In this cohort of Black people with HIV, WC cut-offs for cardiometabolic risk factors in male participants were in line with the recommended value of 94 cm while in female participants they vastly exceeded the recommended 80 cm for white women.

4.
Endocr Connect ; 13(3)2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38236710

ABSTRACT

Introduction: Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex. Whilst surgery is the preferred treatment, adjunctive therapy with mitotane may be offered post-surgically to minimise the risk of recurrence or, in the absence of surgery, to attenuate progression. Aim: The objective was to evaluate the effects of mitotane treatment on serum protein concentrations in patients treated for ACC with mitotane therapy and compare this to patients with other adrenal neoplasms and a normal pregnant cohort. Methods: Serum cortisol, thyroid function tests, adrenocorticotrophic hormone (ACTH), cortisol-binding globulin (CBG), thyroxine-binding globulin (TBG), gonadotrophins and androgens were measured on plasma and serum samples. Thirty-five patients with ACC were included, and mitotane levels were noted to be sub-/supra-therapeutic. Data were tested for normality, reported as mean ± s.d., and compared to other two cohorts using paired-sample t-test with a 5% P-value for significance and a 95% CI. Results: Patients on mitotane therapy had a higher mean serum CBG concentration compared to the adrenal neoplasm group (sub-therapeutic: 79.5 (95% CI: 33.6, 125.4 nmol/L), therapeutic: 85.3 (95% CI: 37.1-133.6 nmol/L), supra-therapeutic: 75.7 (95% CI: -19.3, 170.6 nmol/L) and adrenal neoplasm: 25.5 (95% CI: 17.5, 33.5 nmol/L). Negative correlations between serum cortisol and CBG concentration were demonstrated within the supra-therapeutic plasma mitotane and adrenal neoplasm groups. Conclusion: Patients with ACC and therapeutic plasma mitotane concentrations had higher serum CBG concentrations compared to those with adrenal neoplasms or pregnant women, and higher serum cortisol. Whilst there was no direct correlation with cortisol and mitotane level, the negative correlation of cortisol with CBG may suggest that the direct effect of mitotane in increasing cortisol may also reflect that mitotane has a direct adrenolytic effect.

5.
J Clin Pathol ; 76(7): 442-449, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37164629

ABSTRACT

Accurate diagnosis, classification and risk stratification for chronic kidney disease (CKD) allow for early recognition and delivering optimal care. Creatinine-based glomerular filtration rate (GFR), urinary albumin: creatinine ratio (UACR) and the kidney failure risk equation (KFRE) are important tools to achieve this, but understanding their limitations is important for optimal implementation.When accurate GFR is required (eg, chemotherapy dosing), GFR is measured using an exogenous filtration marker. In routine clinical practice, in contrast, estimated GFR (eGFR) from serum creatinine (SCr), calculated using the enzymatic method±UACR, is recommended. Limitations of SCr include non-GFR determinants such as muscle mass, diet and tubular handling. An alternative or additional endogenous filtration marker is cystatin C, which can be used alongside SCr for confirmatory testing of CKD. However, its role in the UK is more limited due to concerns regarding false positive results.The recommended creatinine-based eGFR equation in the UK is the CKD Epidemiology Collaboration 2009 equation. This was recently updated to a race-neutral 2021 version and demonstrated reduced bias in people of Black ethnicity, but has not been validated in the UK. Limitations are extremes of age, inaccuracy at greater GFRs and reduced generalisability to under-represented ethnicity groups.The KFRE (based on age, sex, SCr and UACR) has recently been developed to help determine 2-year and 5-year risk of progression to end-stage kidney disease. It has been validated in over 30 countries and provides meaningful quantitative information to patients. However, supporting evidence for their performance in ethnic minority groups and kidney diseases such as glomerulonephritis remains modest.In conclusion, early identification, risk stratification of kidney disease and timely intervention are important to impact kidney disease progression. However, clinician awareness of the limitations and variability of creatinine, cystatin C and the eGFR equations, is key to appropriate interpretation of results.


Subject(s)
Cystatin C , Renal Insufficiency, Chronic , Humans , Glomerular Filtration Rate/physiology , Creatinine , Ethnicity , Biomarkers , Minority Groups , Renal Insufficiency, Chronic/diagnosis
6.
AIDS ; 37(5): 753-758, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36728909

ABSTRACT

BACKGROUND: To reduce health inequalities, the creatinine-based chronic kidney disease epidemiology collaboration 2021 formula for estimated glomerular filtration rate (eGFR) is replacing the 2009 formula, which required adjustment specifically for Black individuals. We compared the 2021 and 2009 creatinine-based formulae with cystatin C-based eGFR in Black people on antiretroviral therapy (ART) with HIV RNA <200 c/ml. METHODS: Cross-sectional analysis of paired serum creatinine and cystatin C measurements. Bias, imprecision, accuracy, and performance for identifying individuals with eGFR cystatin C <60 (units: ml/min per 1.73 m 2 ) were determined. The effects of ART with no, mild-moderate, or marked effect on tubular creatinine secretion on the performance of the 2021 formula was assessed. RESULTS: We included 362 individuals (mean age 51 years, 56% female, mean eGFR-cystatin C 88.3). Overall, the 2021 (vs. the 2009 race-adjusted) formula was less biased and had improved imprecision and accuracy compared with eGFR-cystatin C but underestimated eGFR-cystatin C in those with eGFR ≥90 and overestimated eGFR-cystatin C in those with eGFR <60. The 2021 (vs. the 2009) formula had high specificity (95% vs. 97%) and negative predictive value (97% vs. 96%), but low sensitivity (56% vs. 52%) and positive predictive value (44% vs. 54%) for identifying individuals with eGFR-cystatin C <60 ( P  > 0.25). Performance at the eGFR <60 cut-off was minimally affected by ART exposure group. CONCLUSION: The CKD-EPI 2021 creatinine-based formula was better aligned with eGFR-cystatin C than the 2009 formula. eGFR-cystatin C may provide clinically useful information in Black people with eGFR <60 irrespective of ART regimen.


Subject(s)
HIV Infections , Renal Insufficiency, Chronic , Humans , Female , Middle Aged , Male , Glomerular Filtration Rate , Creatinine , HIV Infections/drug therapy , Cystatin C , Cross-Sectional Studies , Kidney
7.
J Nephrol ; 36(3): 777-787, 2023 04.
Article in English | MEDLINE | ID: mdl-36635580

ABSTRACT

BACKGROUND: The incidence of acute kidney injury in pregnancy (P-AKI) is rising and is associated with detrimental maternal and foetal outcomes. Ethnic disparities in pregnancy outcomes are well recognized, with females who identify as Black or Asian being more likely to die during pregnancy compared to females who identify as White ethnicity. METHODS: This study reports rates of P-AKI and associated risk factors in pregnant females of different ethnicities. All pregnancies were recorded between 2016 and 2020. AKI episodes were identified using electronic alerts. Ethnicity, AKI stage (1-3), obstetric outcomes and risk factors for P-AKI (chronic hypertension, pregnancy-induced hypertension and pre-eclampsia, and haemorrhage) were assessed. RESULTS: There were 649 P-AKI episodes from 16,943 deliveries (3.8%). Black females were more likely to have P-AKI (5.72%) compared to those who were White (3.12%), Asian (3.74%), mixed ethnicity (2.89%) and Other/Not Stated (3.10%). Black females, compared to White females, were at greater risk of developing P-AKI if they had haemorrhage requiring blood transfusion (OR 2.44, 95% CI 1.31,4.54; p < 0.001) or pregnancy-induced hypertension (OR 1.79, 95% CI 1.12, 2.86; p < 0.001). After adjusting for risk factors, Black females had increased risk of developing P-AKI (OR 1.52, 95% CI 1.22, 1.80; p < 0.001) compared to White females. Black females were at increased risk of developing P-AKI compared to White females. Mode of delivery, pregnancy-induced hypertension and haemorrhage are likely to have contributed. The increased risk persists despite accounting for these variables, suggesting that other factors such as socioeconomic disparities need to be considered. CONCLUSIONS: The incidence of P-AKI is likely higher than previously stated in the literature. However, caution must be exercised, particularly with AKI stage 1, as the KDIGO system is not validated in pregnancy and gestational changes in renal physiology need to be considered. Pregnancy-specific AKI definitions are needed.


Subject(s)
Acute Kidney Injury , Hypertension, Pregnancy-Induced , Pre-Eclampsia , Pregnancy , Female , Humans , Pregnancy Outcome/epidemiology , Ethnicity , Acute Kidney Injury/epidemiology
8.
Obesity (Silver Spring) ; 31(1): 20-30, 2023 01.
Article in English | MEDLINE | ID: mdl-36502288

ABSTRACT

OBJECTIVE: Postprandial hyperinsulinemic hypoglycemia with neuroglycopenia is an increasingly recognized complication of Roux-en-Y gastric bypass and gastric sleeve surgery that may detrimentally affect patient quality of life. One likely causal factor is glucagon-like peptide-1 (GLP-1), which has an exaggerated rise following ingestion of carbohydrates after bariatric surgery. This paper sought to assess the role of GLP-1 receptor agonists (GLP-1RAs) in managing postprandial hypoglycemia following bariatric surgery. METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Scopus were systematically and critically appraised for all peer-reviewed publications that suitably fulfilled the inclusion criteria established a priori. This systematic review was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P). It followed methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions and is registered with PROSPERO (International Prospective Register of Systematic Reviews; identifier CRD420212716429). RESULTS AND CONCLUSIONS: Postprandial hyperinsulinemic hypoglycemia remains a notoriously difficult to manage metabolic complication of bariatric surgery. This first, to the authors' knowledge, systematic review presents evidence suggesting that use of GLP-1RAs does not lead to an increase of hypoglycemic episodes, and, although this approach may appear counterintuitive, the findings suggest that GLP-1RAs could reduce the number of postprandial hypoglycemic episodes and improve glycemic variability.


Subject(s)
Bariatric Surgery , Glucagon-Like Peptide-1 Receptor , Hypoglycemia , Humans , Bariatric Surgery/adverse effects , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide-1 Receptor/therapeutic use , Hypoglycemia/etiology , Hypoglycemia/prevention & control , Quality of Life
9.
PLoS One ; 17(5): e0266652, 2022.
Article in English | MEDLINE | ID: mdl-35500008

ABSTRACT

OBJECTIVES: Procalcitonin (PCT) is an acute-phase reactant with concentrations ≥0.5 µg/L indicative of possible bacterial infection in patients with SARS-CoV-2 infection (COVID-19). Some with severe COVID-19 develop cytokine storm secondary to virally driven hyper-inflammation. However, increased pro-inflammatory cytokines are also seen in bacterial sepsis. This study aimed to assess the clinical utility of a cytokine panel in the assessment of COVID-19 with bacterial superinfections along with PCT and C-reactive protein (CRP). METHODS: The retrospective analysis included serum cytokines (interleukins; IL-1ß, IL-6, IL-8 and tumour necrosis factor (TNFα)) measured using Ella™ (Bio-Techne, Oxford, UK) and PCT measured by Roche Cobas (Burgess Hill, UK) in patients admitted with COVID-19 between March 2020 and January 2021. Patients enrolled into COVID-19 clinical trials, treated with Remdesivir/IL-6 inhibitors were excluded. The cytokine data was compared between intensive care unit (ICU) patients, age matched non-ICU patients and healthy volunteers as well as ICU patients with high and normal PCT (≥0.5 vs. <0.5 µg/L). RESULTS: Cytokine concentrations and CRP were higher in COVID-19 patients (76; ICU & non-ICU) vs. healthy controls (n = 24), all p<0.0001. IL-6, IL-8, TNFα and were higher in ICU patients (n = 46) vs. non-ICU patients (n = 30) despite similar CRP. Among 46 ICU patients, the high PCT group (n = 26) had higher TNFα (p<0.01) and longer ICU stay (mean 47 vs. 25 days, p<0.05). There was no difference in CRP and blood/respiratory culture results between the groups. CONCLUSIONS: Pro-inflammatory cytokines and PCT were higher in COVID-19 patients requiring ICU admission vs. non-ICU admissions despite no difference in CRP. Furthermore, TNFα was higher in those with high PCT and requiring longer ICU admission despite no difference in CRP or rate of bacterial superinfection.


Subject(s)
COVID-19 , Procalcitonin , C-Reactive Protein/metabolism , Calcitonin , Calcitonin Gene-Related Peptide , Critical Care , Cytokines , Humans , Intensive Care Units , Interleukin-6 , Interleukin-8 , Retrospective Studies , SARS-CoV-2 , Tumor Necrosis Factor-alpha
11.
Article in English | MEDLINE | ID: mdl-35264463

ABSTRACT

Summary: A 49-year-old teacher presented to his general physician with lethargy and lower limb weakness. He had noticed polydipsia, polyuria, and had experienced weight loss, albeit with an increase in central adiposity. He had no concomitant illnesses and took no regular medications. He had hypercalcaemia (adjusted calcium: 3.34 mmol/L) with hyperparathyroidism (parathyroid hormone: 356 ng/L) and hypokalaemia (K: 2.7 mmol/L) and was admitted for i.v. potassium replacement. A contrast-enhanced CT chest/abdomen/pelvis scan revealed a well-encapsulated anterior mediastinal mass measuring 17 × 11 cm with central necrosis, compressing rather than invading adjacent structures. A neck ultrasound revealed a 2 cm right inferior parathyroid lesion. On review of CT imaging, the adrenals appeared normal, but a pancreatic lesion was noted adjacent to the uncinate process. His serum cortisol was 2612 nmol/L, and adrenocorticotrophic hormone was elevated at 67 ng/L, followed by inadequate cortisol suppression to 575 nmol/L from an overnight dexamethasone suppression test. His pituitary MRI was normal, with unremarkable remaining anterior pituitary biochemistry. His admission was further complicated by increased urine output to 10 L/24 h and despite three precipitating factors for the development of diabetes insipidus including hypercalcaemia, hypokalaemia, and hypercortisolaemia, due to academic interest, a water deprivation test was conducted. An 18flurodeoxyglucose-PET (FDG-PET) scan demonstrated high avidity of the mediastinal mass with additionally active bilateral superior mediastinal nodes. The pancreatic lesion was not FDG avid. On 68Ga DOTATE-PET scan, the mediastinal mass was moderately avid, and the 32 mm pancreatic uncinate process mass showed significant uptake. Genetic testing confirmed multiple endocrine neoplasia type 1. Learning points: In young patients presenting with primary hyperparathyroidism, clinicians should be alerted to the possibility of other underlying endocrinopathies. In patients with multiple endocrine neoplasia type 1 (MEN-1) and ectopic adrenocorticotrophic hormone syndrome (EAS), clinicians should be alerted to the possibility of this originating from a neoplasm above or below the diaphragm. Although relatively rare compared with sporadic cases, thymic carcinoids secondary to MEN-1 may also be associated with EAS. Electrolyte derangement, in particular hypokalaemia and hypercalcaemia, can precipitate mild nephrogenic diabetes insipidus.

12.
Ann Clin Biochem ; 59(1): 7-14, 2022 01.
Article in English | MEDLINE | ID: mdl-32429677

ABSTRACT

Prealbumin is a small protein which has been widely evaluated as a nutritional and a prognostic marker. The small size and concentration of prealbumin in blood proposes challenges on measuring it with high sensitivity and specificity. Over the years, a number of analytical methodologies have been developed, which may help establish prealbumin as a useful biomarker in routine clinical practice. The aim of the short review was to explore the current literature on the clinical utility of prealbumin and the advances made in the analytical methodologies of prealbumin. We searched MEDLINE, EMBASE and the Cochrane Library for articles published between January 1980 and July 2019, with the general search terms of 'prealbumin', 'prognostic marker', 'nutritional marker', 'analytical methodologies' and 'malnutrition'. Additionally, we selected relevant articles and comprehensive overviews from reference lists of identified studies. The routine use of prealbumin in clinical practice remains debatable; however; it can complement clinical history, anthropometric assessment and physical examination to assess malnutrition with more certainty. Consensus on the clinical applications of prealbumin in the management of malnutrition is warranted.


Subject(s)
Malnutrition , Prealbumin , Anthropometry , Biomarkers , Humans , Malnutrition/diagnosis , Nutritional Status , Prealbumin/metabolism
14.
Ther Adv Endocrinol Metab ; 12: 20420188211066210, 2021.
Article in English | MEDLINE | ID: mdl-34900218

ABSTRACT

BACKGROUND: Metabolic syndrome (MetS) is defined by at least three of the following five criteria: blood pressure ⩾130/85 mmHg, fasting blood glucose ⩾5.6 mmol/l, triglycerides concentration ⩾1.7 mmol/l, waist circumference ⩾102 cm (for men), and high-density lipoprotein cholesterol concentration <1.03 mmol/l (for men). MetS has been associated with worse lower urinary tract symptoms (LUTS) and higher International Prostate Symptom questionnaire scores. MATERIALS AND METHODS: MEDLINE, Cochrane, ClinicalTrials.gov, and SCOPUS were critically appraised for all peer-reviewed manuscripts that suitably fulfilled our protocol's inclusion criteria established a priori. Meta-analytical and meta-regression calculations were performed in R using the Sidik-Jonkman and Hartung-Knapp random effects model and predefined covariates. RESULTS: A total of 70 studies (n = 90,206) were included in qualitative synthesis. From these, 60 studies focused on MetS and LUTS: 44 reported positive correlations, 5 reported negative correlations, 11 reported no association, and 10 studies focused on MetS and total prostate volume (TPV). MetS positively correlated with moderate LUTS [odds ratio (OR) = 1.56, 95% confidence interval (CI) = 1.35-1.80], severe LUTS (OR = 2.35, 95% CI = 1.82-3.03), overactive bladder (OAB; OR = 3.2, 95% CI = 1.6-5.8), and nocturia severity (OR = 2.509, 95% CI = 1.571-4.007) at multivariate analysis. A total of 30 studies (n = 22,206) were included in meta-analysis; MetS was significantly associated with higher TPV (mean differences = 4.4450 ml, 95% CI = 2.0177-6.8723), but no significant predictive factors for effect sizes were discovered. CONCLUSION: Our meta-analysis demonstrates a significant association between the aggravating effects of MetS, which commonly coexists with obesity and benign prostate enlargement.

15.
PLoS One ; 16(8): e0255869, 2021.
Article in English | MEDLINE | ID: mdl-34383841

ABSTRACT

Assessment in African populations suggest adjustment for ethnicity in estimated glomerular filtration rate (eGFR) equations derived from African Americans lead to overestimation of GFR and failure to determine severity in chronic kidney disease (CKD). However, studies in African Europeans are limited. We aimed to assess accuracy of eGFR equations, with and without ethnicity adjustment compared with measured GFR in people of Black ethnicity in the United Kingdom. Performance of MDRD, CKD-EPI (with and without ethnicity adjustment), Full Age Spectrum (FAS), revised Lund Malmö (LM Revised), and European Kidney Function Consortium (EKFC) eGFR equations were assessed compared to 51Cr-EDTA GFR studies extracted from hospital databases. Participants with albumin <30g/l, liver disease, <18 years, of non-Black or non-White self-reported ethnicity were excluded. Agreement was assessed by bias, precision and 30%-accuracy and was stratified for ethnicity and GFR. 1888 51Cr-EDTA studies were included (Mean age-53.7yrs; 43.6% female; 14.1% Black ethnicity). Compared to White participants, eGFR-MDRD and eGFR-CKD-EPI equations in Black participants significantly overestimated GFR (bias 20.3 and 19.7 ml/min/1.73m2 respectively, p<0.001). Disregarding the ethnicity adjustment significantly improved GFR estimates for Black participants (bias 6.7 and 2.4ml/min/1.73m2 for eGFR-MDRD and eGFR-CKD-EPI respectively, p<0.001). The LM Revised equation had the smallest bias for both White and Black participants (5.8ml and -1.1ml/min/1.73m2 respectively). 30%-accuracy was superior for GFR≥60ml/min/1.73m2 compared to <60ml/min/1.73m2 using eGFR-CKD-EPI equation for both White and Black participants (p<0.001). Multivariate regression methodology with adjustment for age, sex and log(serum creatinine) in the cohort yielded an ethnicity coefficient of 1.018 (95% CI: 1.009-1.027). Overestimation of measured GFR with eGFR equations using ethnicity adjustment factors may lead to reduced CKD diagnosis and under-recognition of severity in people of Black ethnicity. Our findings suggest that ethnicity adjustment for GFR estimation in non-African Americans may not be appropriate for use in people of Black ethnicity in the UK.


Subject(s)
Algorithms , Glomerular Filtration Rate/physiology , Renal Insufficiency, Chronic/physiopathology , Adult , Aged , Black People , Creatinine/blood , Cross-Sectional Studies , Databases, Factual , Female , Humans , Linear Models , Male , Middle Aged , Odds Ratio , Renal Insufficiency, Chronic/ethnology , Self Report , United Kingdom , White People
16.
Clin Obes ; 11(4): e12450, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33955687

ABSTRACT

Women with obesity are at risk of pelvic floor dysfunction with a 3-fold increased incidence of urge urinary incontinence (UUI) and double the risk of stress urinary incontinence (SUI). The National Institute for Health and Care Excellence (NICE) and European Association of Urology (EAU) recommend that women with a body mass index ≥30 kg/m2 should consider weight loss prior to consideration for incontinence surgery. This systematic review and meta-analysis will assess this recommendation to aid in the counselling of women with obesity-related urinary incontinence (UI). Medical Literature Analysis and Retrieval System online (MEDLINE), EMBASE, Cochrane, ClinicalTrials.gov, and SCOPUS were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori and presented original, empirical data relevant to weight loss intervention in the management of urinary incontinence. Thirty-three studies and their outcomes were meta-analysed. Weight loss interventions were associated in a decreased prevalence in UI (OR 0.222, 95% CI [0.147, 0.336]), SUI (OR 0.354, 95% CI [0.256, 0.489]), UUI (OR 0.437, 95% CI [0.295, 0.649]) and improved quality of life (PFDI-20, SMD -0.774 (95% CI [-1.236, -0.312]). This systematic review and meta-analysis provide evidence that weight loss interventions are effective in reducing the prevalence of obesity-related UI symptoms in women. Bariatric surgery in particular shows greater sustained weight loss and improvements in UI prevalence. Further large scale, randomized control trials assessing the effect of bariatric surgery on women with obesity-related UI are needed to confirm this study's findings.


Subject(s)
Bariatric Surgery , Obesity , Urinary Incontinence , Weight Loss , Behavior Therapy , Female , Humans , Obesity/complications , Obesity/epidemiology , Obesity/surgery , Quality of Life , Urinary Incontinence/epidemiology , Urinary Incontinence/etiology
17.
J Clin Pathol ; 2021 May 19.
Article in English | MEDLINE | ID: mdl-34011620

ABSTRACT

AIMS: Public Health England has identified that in COVID-19, death rates among ethnic minorities far exceeds that of the white population. While the increase in ethnic minorities is likely to be multifactorial, to date, no studies have looked to see whether values for routine clinical biochemistry parameters differ between ethnic minority and white individuals. METHODS: Baseline biochemical data for 22 common tests from 311 SARS-CoV-2 positive patients presenting to hospital in April 2020 in whom ethnicity data were available was retrospectively collected and evaluated. Data comparisons between ethnic minority and white groups were made for all patient data and for the subset of patients subsequently admitted to intensive care. RESULTS: When all patient data were considered, the ethnic minority population had statistically significant higher concentrations of C reactive protein (CRP), aspartate aminotransferase and gamma-glutamyl transferase, while troponin T was higher in the white group. A greater proportion of ethnic minority patients were subsequently admitted to intensive care, but when the presenting biochemistry of this subset of patients was compared, no significant differences were observed between ethnic minority and white groups. CONCLUSION: Our data show for the first time that routine biochemistry at hospital presentation in COVID-19 differs between ethnic minority and white groups. Among the markers identified, CRP was significantly higher in the ethnic minority group pointing towards an increased tendency for severe inflammation in this group.

18.
Endocr Connect ; 10(4): 447-461, 2021 Apr 26.
Article in English | MEDLINE | ID: mdl-33764887

ABSTRACT

Calcitonin-secreting neuroendocrine neoplasms of the lung are rare, with few cases reported in the literature. Differentiating between medullary thyroid carcinoma and an ectopic source of calcitonin secretion can represent a complex diagnostic conundrum for managing physicians, with cases of unnecessary thyroidectomy reported in the literature. This manuscript reports a case of ectopic hypercalcitonaemia from a metastatic neuroendocrine neoplasm of the lung with concurrent thyroid pathology and summarises the results of a systematic review of the literature. Medical Literature Analysis and Retrieval System Online, Excerpta Medica, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and SCOPUS databases were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori. The protocol for this systematic review was developed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols, and followed methods outlined in The Cochrane Handbook for Systematic Reviews of Interventions. This systematic review is registered with PROSPERO. It is vital to consider diagnoses other than medullary thyroid carcinoma when presented with a patient with raised calcitonin, as it is not pathognomonic of medullary thyroid carcinoma. Lung neuroendocrine neoplasms can appear similar to medullary thyroid carcinoma histologically, they can secrete calcitonin and metastasize to the thyroid. Patients with medullary thyroid carcinoma may show stimulated calcitonin values over two or more times above the basal values, whereas calcitonin-secreting neuroendocrine neoplasms may or may not show response to stimulation tests. The present review summarises existing evidence from cases of ectopic hypercalcitonaemia to lung neuroendocrine neoplasms.

19.
Am J Physiol Endocrinol Metab ; 320(4): E671-E679, 2021 04 01.
Article in English | MEDLINE | ID: mdl-33459181

ABSTRACT

Bile acids (BA) regulate postprandial metabolism directly and indirectly by affecting the secretion of gut hormones like glucagon-like peptide-1 (GLP-1). The postprandial effects of BA on the secretion of other metabolically active hormones are not well understood. The objective of this study was to investigate the effects of oral ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on postprandial secretion of GLP-1, oxyntomodulin (OXM), peptide YY (PYY), glucose-dependent insulinotropic peptide (GIP), glucagon, and ghrelin. Twelve healthy volunteers underwent a mixed meal test 60 min after ingestion of UDCA (12-16 mg/kg), CDCA (13-16 mg/kg), or no BA in a randomized crossover study. Glucose, insulin, GLP-1, OXM, PYY, GIP, glucagon, ghrelin, and fibroblast growth factor 19 were measured prior to BA administration at -60 and 0 min (just prior to mixed meal) and 15, 30, 60, 120, 180, and 240 min after the meal. UDCA and CDCA provoked differential gut hormone responses; UDCA did not have any significant effects, but CDCA provoked significant increases in GLP-1 and OXM and a profound reduction in GIP. CDCA increased fasting GLP-1 and OXM secretion in parallel with an increase in insulin. On the other hand, CDCA reduced postprandial secretion of GIP, with an associated reduction in postprandial insulin secretion. Exogenous CDCA can exert multiple salutary effects on the secretion of gut hormones; if these effects are confirmed in obesity and type 2 diabetes, CDCA may be a potential therapy for these conditions.NEW & NOTEWORTHY Oral CDCA and UDCA have different effects on gut and pancreatic hormone secretion. A single dose of CDCA increased fasting secretion of the hormones GLP-1 and OXM with an accompanying increase in insulin secretion. CDCA also reduced postprandial GIP secretion, which was associated with reduced insulin. In contrast, UDCA did not change gut hormone secretion fasting or postprandially. Oral CDCA could be beneficial to patients with obesity and diabetes.


Subject(s)
Bile Acids and Salts/pharmacology , Gastrointestinal Hormones/metabolism , Postprandial Period/drug effects , Administration, Oral , Adult , Bile Acids and Salts/administration & dosage , Bile Acids and Salts/blood , Chenodeoxycholic Acid/administration & dosage , Chenodeoxycholic Acid/pharmacology , Cross-Over Studies , Eating/physiology , Female , Healthy Volunteers , Humans , Male , Middle Aged , Secretory Pathway/drug effects , United Kingdom , Ursodeoxycholic Acid/administration & dosage , Ursodeoxycholic Acid/pharmacology , Young Adult
20.
Nephrol Dial Transplant ; 36(6): 1023-1030, 2021 05 27.
Article in English | MEDLINE | ID: mdl-33089321

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) in pregnancy (Pr-AKI) is associated with substantial maternal morbidity and mortality. E-alerts are routinely used for detection of AKI in non-pregnant patients but their role in maternity care has not been explored. METHODS: All pregnant or postpartum women with AKI e-alerts for AKI Stages 1-3 (Kidney Disease Improving Global Outcomes (KDIGO) criteria) were identified at a tertiary centre >2 years. Two women matched by delivery date for each case were selected as controls. AKI stage, recognition of AKI, pregnancy outcomes, renal recovery, AKI aetiology and risk factors were extracted from electronic patient records. RESULTS: 288 of 11 922 (2.4%) women had AKI e-alerts, of which only 118 (41%) were recognized by the obstetric team. Common Pr-AKI causes included infection (48%), pre-eclampsia (26%) and haemorrhage (25%), but no cause was identified in 15% of women. Renal function recovered in 213 (74%) women, but in 47 (17%) repeat testing was not undertaken and 28 (10%) did not recover function. Hypertensive disorders of pregnancy and Caesarean section were associated with increased incidence of Pr-AKI compared with controls. CONCLUSIONS: Pr-AKI e-alerts were identified in ∼1 in 40 pregnancies. However, a cause for Pr-AKI was not identified in many cases and e-alerts may have been triggered by gestational change in serum creatinine. Pregnancy-specific e-alert algorithms may be required. However, 1 in 10 women with Pr-AKI had not recovered kidney function on repeat testing. Better understanding of long-term impacts of Pr-AKI on pregnancy and renal outcomes is needed to inform relevant Pr-AKI e-alert thresholds.


Subject(s)
Acute Kidney Injury , Maternal Health Services , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Cesarean Section , Creatinine , Female , Humans , Pregnancy , Pregnancy Outcome , Risk Factors
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