• Gangrenous digital infarcts in a severe case of cutaneous polyarteritis nodosa

      Mahmood-Rao, Hamzah; Ding, Tina; Gandhi, Nirav (2017-05)
      Cutaneous polyarteritis nodosa (CPAN) is a rare diagnosis which is distinct from polyarteritis nodosa (PAN). PAN is a medium-vessel vasculitis which can affect multiple organs and classically produces microaneurysms in the vasculature. CPAN is limited to the skin mainly affecting small vessels. There is an absence of microaneurysms in CPAN and it does not affect internal organs. However, the histopathological findings on the skin are similar to PAN. CPAN rarely progresses to PAN but relapses more often. We will illustrate a challenging case of a patient with CPAN who developed gangrenous infarcts despite initial immunosuppressive treatment with high-dose steroids and azathioprine. His treatment had to be escalated to intravenous cyclophosphamide which induced disease remission
    • Gastric band erosion, infection and migration causing jejunal obstruction.

      Salar, Omer; Waraich, Naseem; Singh, Rajeev; Awan, Altaf (2013-01)
      Complications of laparoscopic adjustable gastric bands (LAGB) are well documented and may include migration, erosion, slippage, infection, pouch dilatation and, rarely, gastric perforation. We describe a rare case involving three such complications simultaneously, namely, gastric erosion, infection and migration through the pylorus-causing proximal jejunal obstruction. As LAGB is now the commonest performed bariatric procedure for the treatment of morbid obesity, we encourage the practising surgeon to be vigilant of these rare but potentially life-threatening complications.
    • General practitioners’ perspectives on campaigns to promote rapid help-seeking behaviour at the onset of rheumatoid arthritis

      Deighton, Chris (2014-03)
      Objective: To explore general practitioners’ (GPs’) perspectives on public health campaigns to encourage people with the early symptoms of rheumatoid arthritis (RA) to seek medical help rapidly. Design: Nineteen GPs participated in four semistructured focus groups. Focus groups were audio-recorded, transcribed verbatim, and analysed using thematic analysis. Results: GPs recognised the need for the early treatment of RA and identified that facilitating appropriate access to care was important. However, not all held the view that a delay in help seeking was a clinically significant issue. Furthermore, many were concerned that the early symptoms of RA were often non-specific, and that current knowledge about the nature of symptoms at disease onset was inadequate to inform the content of a help-seeking campaign. They argued that a campaign might not be able to specifically target those who need to present urgently. Poorly designed campaigns were suggested to have a negative impact on GPs’ workloads, and would "clog up" the referral pathway for genuine cases of RA. Conclusions: GPs were supportive of strategies to improve access to Rheumatological care and increase public awareness of RA symptoms. However, they have identified important issues that need to be considered in developing a public health campaign that forms part of an overall strategy to reduce time to treatment for patients with new onset RA. This study highlights the value of gaining GPs’ perspectives before launching health promotion campaigns.
    • Gentamicin-associated acute kidney injury

      Selby, Nicholas; Fluck, Richard; Kolhe, Nitin; Shaw, Susan; Woodier, Nicholas (2009-12)
      BACKGROUND: The incidence of gentamicin-associated acute kidney injury (AKI) as defined by the RIFLE criteria is unknown. AIM AND DESIGN: We performed a retrospective observational study to examine this and the predictive value of RIFLE stage on patient outcome in this setting. METHODS: We included all patients who were treated with gentamicin at our centre over a 1-month period. Data on 228 patients across all specialities were collected by manual searching of hospital notes and electronic pathology reporting systems. Information collected included baseline and peak serum creatinine results, gentamicin dose and serum levels, the presence of additional renal insults and the Stoke co-morbidity index. RESULTS: AKI occurred in 51 (24.4%) patients; 37 (17.7%) 'Risk', 9 (4.3%) 'Injury', 5 (2.4%) 'Failure'. Independent predictors of gentamicin associated AKI were number of gentamicin levels >2 mg/l (OR 1.845, 95% CI 1.22 to 2.79) and higher baseline serum creatinine (OR 1.014, 95% CI 1.001-1.028). There was a greatly increased risk of in-hospital mortality in the AKI group as compared to those without AKI (45.1% vs. 19.1%, OR 3.48, 95% CI 1.8-6.9, P = 0.0004). Risk of in hospital mortality increased with each RIFLE stage (P < 0.0001). CONCLUSION: This study shows that gentamicin-associated AKI remains a common and potentially serious clinical problem. There is a strong correlation between RIFLE class and in-hospital mortality.
    • Glucagon-like peptide 1 infusions overcome anabolic resistance to feeding in older human muscle.

      Williams, John P; Idris, Iskandar (2020-08)
      BACKGROUND: Despite its known insulin-independent effects, glucagon-like peptide-1 (GLP-1) role in muscle protein turnover has not been explored under fed-state conditions or in the context of older age, when declines in insulin sensitivity and protein anabolism, as well as losses of muscle mass and function, occur. METHODS: Eight older-aged men (71 ± 1 year, mean ± SEM) were studied in a crossover trial. Baseline measures were taken over 3 hr, prior to a 3 hr postprandial insulin (~30 mIU ml-1 ) and glucose (7-7.5 mM) clamp, alongside I.V. infusions of octreotide and Vamin 14 (±infusions of GLP-1). Four muscle biopsies were taken, and muscle protein turnover was quantified via incorporation of 13 C6 phenylalanine and arteriovenous balance kinetics, using mass spectrometry. Leg macro- and microvascular flow was assessed via ultrasound and anabolic signalling by immunoblotting. GLP-1 and insulin were measured by ELISA. RESULTS: GLP-1 augmented muscle protein synthesis (MPS; fasted: 0.058 ± 0.004% hr-1 vs. postprandial: 0.102 ± 0.005% hr-1 , p < 0.01), in comparison with non-GLP-1 trials. Muscle protein breakdown (MPB) was reduced throughout clamp period, while net protein balance across the leg became positive in both groups. Total femoral leg blood flow was unchanged by the clamp; however, muscle microvascular blood flow (MBF) was significantly elevated in both groups, and to a significantly greater extent in the GLP-1 group (MBF: 5 ± 2 vs. 1.9 ± 1 fold change +GLP-1 and -GLP-1, respectively, p < 0.01). Activation of the Akt-mTOR signalling was similar across both trials. CONCLUSION: GLP-1 infusion markedly enhanced postprandial microvascular perfusion and further stimulated muscle protein metabolism, primarily through increased MPS, during a postprandial insulin hyperaminoacidaemic clamp.
    • Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed by JDRF and supported by the American Diabetes Association (ADA)

      Wilmot, Emma (2020-12)
      Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (ie, before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes.
    • Glycaemic variability: The under-recognized therapeutic target in type 1 diabetes care.

      Wilmot, Emma (2019-07)
      Type 1 diabetes mellitus (T1DM) remains one of the most challenging long-term conditions to manage. Despite robust evidence to demonstrate that near normoglycaemia minimizes (but does not completely eliminate) the risk of complications, its achievement has proved almost impossible to attain in a real-world setting. HbA1c to date has been used as the gold standard marker of glucose control and has been shown to reflect directly the risk of diabetes complications. However, it has been recognized that HbA1c is a crude marker of glucose control. Continuous glucose monitoring (CGM) provides the ability to measure and observe inter- and intraday glycaemic variability (GV), a more meaningful measure of glycaemic control, more relevant to daily living for those with T1DM. This paper reviews the relationship between GV and hypoglycaemia, and micro- and macrovascular complications. It also explores the impact of CGM, insulin pumps, closed-loop technologies, and newer insulins and adjunctive therapies on GV. Looking to the future, there is an argument that GV should become a key determinant of therapeutic success. Further studies are required to investigate the pathological and psychological benefits of reducing GV.
    • A guideline for the use of variable rate intravenous insulin infusion in medical inpatients.

      Hayat, Haleema (2015-06)
      The present paper summarizes the key recommendations in a recent publication produced by the Joint British Diabetes Societies for Inpatient Care on the use of variable rate i.v. insulin infusion in 'medical' inpatients. The full guideline is available at http://www.diabetologists-abcd.org.uk/JBDS/JBDS_IP_VRIII.pdf and is designed to be a practical guide that can used by any healthcare professional who manages medical inpatients with hyperglycaemia. Its main aim is to allow variable rate i.v. insulin infusion to be used safely, effectively and efficiently for this specific group of inpatients.
    • Guidelines for the management of iron deficiency anaemia.

      Goddard, Andrew (2011-10)
      BACKGROUND: Iron deficiency anaemia (IDA) occurs in 2-5% of adult men and postmenopausal women in the developed world and is a common cause of referral to gastroenterologists. Gastrointestinal (GI) blood loss from colonic cancer or gastric cancer, and malabsorption in coeliac disease are the most important causes that need to be sought. DEFINING IRON DEFICIENCY ANAEMIA: The lower limit of the normal range for the laboratory performing the test should be used to define anaemia (B). Any level of anaemia should be investigated in the presence of iron deficiency (B). The lower the haemoglobin the more likely there is to be serious underlying pathology and the more urgent is the need for investigation (B). Red cell indices provide a sensitive indication of iron deficiency in the absence of chronic disease or haemoglobinopathy (A). Haemoglobin electrophoresis is recommended when microcytosis and hypochromia are present in patients of appropriate ethnic background to prevent unnecessary GI investigation (C). Serum ferritin is the most powerful test for iron deficiency (A). INVESTIGATIONS: Upper and lower GI investigations should be considered in all postmenopausal female and all male patients where IDA has been confirmed unless there is a history of significant overt non-GI blood loss (A). All patients should be screened for coeliac disease (B). If oesophagogastroduodenoscopy (OGD) is performed as the initial GI investigation, only the presence of advanced gastric cancer or coeliac disease should deter lower GI investigation (B). In patients aged >50 or with marked anaemia or a significant family history of colorectal carcinoma, lower GI investigation should still be considered even if coeliac disease is found (B). Colonoscopy has advantages over CT colography for investigation of the lower GI tract in IDA, but either is acceptable (B). Either is preferable to barium enema, which is useful if they are not available. Further direct visualisation of the small bowel is not necessary unless there are symptoms suggestive of small bowel disease, or if the haemoglobin cannot be restored or maintained with iron therapy (B). In patients with recurrent IDA and normal OGD and colonoscopy results, Helicobacter pylori should be eradicated if present. (C). Faecal occult blood testing is of no benefit in the investigation of IDA (B). All premenopausal women with IDA should be screened for coeliac disease, but other upper and lower GI investigation should be reserved for those aged 50 years or older, those with symptoms suggesting gastrointestinal disease, and those with a strong family history of colorectal cancer (B). Upper and lower GI investigation of IDA in post-gastrectomy patients is recommended in those over 50 years of age (B). In patients with iron deficiency without anaemia, endoscopic investigation rarely detects malignancy. Such investigation should be considered in patients aged >50 after discussing the risk and potential benefit with them (C).Only postmenopausal women and men aged >50 years should have GI investigation of iron deficiency without anaemia (C). Rectal examination is seldom contributory, and, in the absence of symptoms such as rectal bleeding and tenesmus, may be postponed until colonoscopy. Urine testing for blood is important in the examination of patients with IDA (B). MANAGEMENT: All patients should have iron supplementation both to correct anaemia and replenish body stores (B). Parenteral iron can be used when oral preparations are not tolerated (C). Blood transfusions should be reserved for patients with or at risk of cardiovascular instability due to the degree of their anaemia.
    • H1-antihistamines for chronic spontaneous urticaria: an abridged Cochrane Systematic Review.

      Sharma, Maulina (2015-10)
      BACKGROUND: Chronic spontaneous urticaria is characterized by recurrent itchy wheals. First-line management is with H1-antihistamines. OBJECTIVE: We sought to conduct a Cochrane Review of H1-antihistamines in the treatment of chronic spontaneous urticaria. METHODS: A systematic search of major databases for randomized controlled trials was conducted. RESULTS: We included 73 studies with 9759 participants; 34 studies provided outcome data for 23 comparisons. Compared with placebo, cetirizine 10 mg daily in the short and intermediate term (RR 2.72; 95% confidence interval [CI] 1.51-4.91) led to complete suppression of urticaria. Levocetirizine 20 mg daily was effective for short-term use (RR 20.87; 95% CI 1.37-317.60) as was 5 mg for intermediate-term use (RR 52.88; 95% CI 3.31-843.81). Desloratadine 20 mg was effective for the short term (RR 15.97; 95% CI 1.04-245.04) as was 5 mg in the intermediate term (RR 37.00; 95% CI 2.31-593.70). There was no evidence to suggest difference in adverse event rates between treatments. LIMITATIONS: Some methodological limitations were observed. Few studies for each comparison reported outcome data that could be incorporated in meta-analyses. CONCLUSIONS: At standard doses, several antihistamines are effective and safe in complete suppression of chronic spontaneous urticaria. Research on long-term treatment using standardized outcome measures and quality of life scores is needed.
    • Hailey-Hailey Disease With Coexistent Herpes Virus Infection: Insights Into the Diagnostic Conundrum of Herpetic/Pseudoherpetic Features in Cutaneous Acantholytic Disorders.

      Panthagani, Anusha (2018-10)
      The specific histopathologic diagnosis of a primary acantholytic disorder takes into account the distribution and extent of acantholysis, presence or absence of dyskeratosis, nature of the dermal inflammatory cell infiltrate, and immunofluorescence findings. Herpes virus infection is a common cause of secondary acantholysis where distinctive viral cytopathic changes aid in making it a clear-cut diagnosis in majority of cases. We present a case of coexistence of Hailey-Hailey disease and herpes simplex virus infection to compare and contrast their histopathologic features. This is imperative because acantholytic cells from primary acantholytic disorders may occasionally show cytological features traditionally associated with herpes virus infection (pseudoherpetic changes). The objective of this article is to create a greater awareness of pseudoherpetic changes and also to explore the clinical significance of coexistence of a primary acantholytic disorder and herpes virus infection, as in this case.
    • Health-related utility values of patients with primary Sjögren's syndrome and its predictors.

      Regan, Marian (2014-07)
      OBJECTIVES: EuroQoL-5 dimension (EQ-5D) is a standardised preference-based tool for measurement of health-related quality of life and EQ-5D utility values can be converted to quality-adjusted life years (QALYs) to aid cost-utility analysis. This study aimed to evaluate the EQ-5D utility values of 639 patients with primary Sjögren's syndrome (PSS) in the UK. METHODS: Prospective data collected using a standardised pro forma were compared with UK normative data. Relationships between utility values and the clinical and laboratory features of PSS were explored. RESULTS: The proportion of patients with PSS reporting any problem in mobility, self-care, usual activities, pain/discomfort and anxiety/depression were 42.2%, 16.7%, 56.6%, 80.6% and 49.4%, respectively, compared with 5.4%, 1.6%, 7.9%, 30.2% and 15.7% for the UK general population. The median EQ-5D utility value was 0.691 (IQR 0.587-0.796, range -0.239 to 1.000) with a bimodal distribution. Bivariate correlation analysis revealed significant correlations between EQ-5D utility values and many clinical features of PSS, but most strongly with pain, depression and fatigue (R values>0.5). After adjusting for age and sex differences, multiple regression analysis identified pain and depression as the two most important predictors of EQ-5D utility values, accounting for 48% of the variability. Anxiety, fatigue and body mass index were other statistically significant predictors, but they accounted for <5% in variability. CONCLUSIONS: This is the first report on the EQ-5D utility values of patients with PSS. These patients have significantly impaired utility values compared with the UK general population. EQ-5D utility values are significantly related to pain and depression scores in PSS.
    • Healthcare reconsultation in working-age adults following hospitalisation for community-acquired pneumonia.

      Bewick, Tom (2018-02)
      Community-acquired pneumonia (CAP) is associated with prolonged symptom persistence during recovery. However, the effect of the residual symptom load on healthcare utilisation is unknown. The aim of this study was to quantify healthcare reconsultation within 28 days of hospital discharge for an index episode of CAP, and explore reasons for these reconsultations. Adults of working age admitted to any of four hospitals in the UK, with a primary diagnosis of CAP, were prospectively studied. Of 108 patients, 71 (65.7%) reconsulted healthcare services within 28 days of discharge; of these, 90.1% consulted their GP. Men were less likely to reconsult than women (adjusted odds ratio [aOR] 0.34, 95% confidence interval 0.13-0.91, p=0.032). Persistence of respiratory symptoms accounted for the majority of these reconsultations. Healthcare utilisation is high in working-age adults after an episode of hospitalised CAP and, in most cases, is due to failure to resolve index symptoms.
    • High magnesium dialysate does not improve intradialytic hemodynamics or abrogate myocardial stunning.

      Jefferies, Helen (2020-08)
      BACKGROUND: Hemodialysis (HD) induces myocardial stunning and is associated with adverse cardiovascular outcomes. Intradialytic hypotension is a modifiable determinant of myocardial stunning. Magnesium (Mg) is reported to be valuable in maintaining intradialytic blood pressure, which potentially would protect against demand myocardial ischemia. This study aimed to compare high vs. low dialysate Mg effects on intradialytic hemodynamics and HD-induced myocardial stunning. METHODS: Twenty stable prevalent HD patients entered a randomized cross-over trial of low (0.5 mmol/L) vs. high (1.0 mmol/L) dialysate Mg. Patients were studied after 2 weeks of standard HD with each Mg concentration. Serial echocardiography assessed myocardial stunning, measured by left ventricular regional wall motion abnormalities (RWMAs). Continuous intradialytic hemodynamics were measured noninvasively using thoracic bioimpedance. FINDINGS: Median predialysis serum Mg was higher with high dialysate Mg (1.45[1.29-1.55] vs. 1.03[0.98-1.1] mmol/L, P < 0.0001). There was no significant difference in maximum intradialytic reduction in systolic BP. There was no significant difference in stroke volume, total peripheral resistance, and cardiac output. Overall ventricular global longitudinal strain (GLS) (as a sensitive marker of contractile function) was higher before dialysis in high Mg group, but there was no difference in GLS at peak stress. However, we showed a significant correlation between Mg changes and GLS changes, r = -0.47, P = 0.02. There was no difference in mean number of peak stress RWMAs per patient (4.0 ± 2.2 vs. 4.3 ± 2.9, P = 0.5). Ultrafiltration volume, a critical determinant of stunning, was not different between high and low dialysate Mg studies (1.35[0-3.3] vs. 1.5[0-2.8], P = 0.49). DISCUSSION: Manipulation of magnesium by altering dialysate magnesium concentration does not influence intradialytic hemodynamic response or HD-induced myocardial stunning in the short term. However, decreasing Mg changes appears to decrease GLS changes.
    • High Riding Prostate: Epidemiology of Genitourinary Injury in Motorcyclists from a UK Register of over 12,000 Victims

      Moss, BF (2020-06)
      Background: The mechanism of motorcycle accidents (high speeds, pelvis behind fuel tank) may predispose to genitourinary injury (GUI) but the epidemiology is poorly understood. Previous studies have assessed GUI patterns in cyclists, and road traffic accident victims in general, but no study has analyzed GUI patterns in a large cohort of motorcyclists. Objectives: We aimed to better understand patterns of urological injuries among motorcyclists admitted to hospital. We aimed to determine any relationship between pelvic fracture and GUI patterns or severity. Methods: The Trauma Audit Research Network was reviewed to identify motorcyclists admitted between January 2012 and December 2016 (n = 12,374). Cases were divided into riders (n = 11,926) and pillion passengers (n = 448), and the data analyzed to identify urological injuries and their associations. The associations between pelvic fracture and other injury types were tested for significance by one- and two-way χ2. Results: GUI was identified in 6%. Renal trauma was the most common GUI among riders (4%) and pillions (2%). There was no statistically significant relationship between grade of renal trauma and presence of pelvic fracture. Urethral injury occurred in 0.2% of riders and passengers, and bladder injury in 0.4% of riders and 0.7% of pillions. Urethral and bladder injuries were positively associated with pelvic fracture, which was present in 81 and 92%, respectively. Tes¬ticular trauma occurred in 0.4% of riders and 0.7% of pillions. Body armor was recorded in 3% of casualties with urological trauma, and 3% overall. Conclusions: A significant propor¬tion of motorcyclists brought to accident and emergency department have GUI, most commonly renal trauma. Pelvic fracture is more common in pillion passengers than riders, and associated with urethral and bladder injuries, but it does not predict severity of renal trauma. External genital inju¬ries are rare, but we recommend examination in the tertiary survey, as consequences of missed injury are severe. Further research is needed to explore protective effects of motorcyclist clothing
    • High sodium intake is associated with important risk factors in a large cohort of chronic kidney disease patients.

      McIntyre, Natasha; McIntyre, Christopher; Taal, Maarten (2015-07)
      BACKGROUND/OBJECTIVES: An increased risk of mortality and cardiovascular disease (CVD) is observed in people with chronic kidney disease (CKD) even in early stages. Dietary sodium intake has been associated with important CVD and CKD progression risk factors such as hypertension and proteinuria in this population. We aimed to investigate the relationship between sodium intake and CVD or CKD progression risk factors in a large cohort of patients with CKD stage 3 recruited from primary care. SUBJECTS/METHODS: A total of 1733 patients with previous estimated glomerular filtration rate (eGFR) of 30-59 ml/min/1.73m(2), with a mean age 72.9±9.0 years, were recruited from 32 general practices in primary care in England. Medical history was obtained and participants underwent clinical assessment, urine and serum biochemistry testing. Sodium intake was estimated from three early-morning urine specimens using an equation validated for this study population. RESULTS: Sixty percent of participants who had estimated sodium intake above recommendation (>100 mmol/day or 6 g salt/day) also had higher diastolic blood pressure, mean arterial pressure (MAP), urinary albumin-to-creatinine ratio, high-sensitive C-reactive protein and uric acid and used a greater number of anti-hypertensive drugs. In multivariable regression analysis, excessive sodium intake was an independent predictor of MAP (B=1.57, 95% confidence interval (CI) 0.41-2.72; P=0.008) and albuminuria (B=1.35, 95% CI 1.02-1.79; P=0.03). CONCLUSIONS: High sodium intake was associated with CVD and CKD progression risk factors in patients with predominantly early stages of CKD followed up in primary care. This suggests that dietary sodium intake could afffect CVD risk even in early or mild CKD. Intervention studies are warranted to investigate the potential benefit of dietary advice to reduce sodium intake in this population.