RSS 1.0Pathology
Recent Submissions
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Is Clostridioides difficile diarrhoea associated with greater social deprivation in England?No abstract available.
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Isolated Fusobacterium nucleatum growth in the blood culture of a middle-aged man with lumbar discitis, surrounding psoas abscesses and an inferior vena cava thrombusPyogenic spinal infections (PSI) have an incidence of 0.5-2.2 cases per 100,000 population, though diagnosis can be delayed by up to three months. The incidence of Fusobacterium nucleatum bacteremia is rare, occurring in 0.22-0.34 cases per 100,000 population, whilst its implication in spinal infections is rarer still. A man in his 60s with a background of chronic lower back pain presented to the emergency department with a two-week history of worsening back pain associated with fever and difficulty voiding. He was initially managed as pyelonephritis due to the recent history of urinary tract infection (UTI) with fever and flank pain. However, there were radiculopathy and bilateral pain on hip flexion with reduced power on the right side. The light-touch sensation was reduced over the right hallux and distal L4 dermatome. These neurological deficits associated with deranged infective markers made a diagnosis of discitis plausible. Discitis and native vertebral osteomyelitis (NVO) should be suspected in patients reporting a fever and back pain of recent onset or increasing in severity. Once discitis was confirmed, the patient was subsequently tested for tuberculosis (TB) using a T-SPOT, human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, with no positive findings, but in the days following, blood cultures yielded F. nucleatum. Guided by knowing the natural reservoirs in the body, establishing the source of F. nucleatum could be achieved through head and neck imaging and investigating the gastrointestinal tract for malignant or inflammatory processes.
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Macroprolactin over time : is there any point in rechecking it in people with a persistently elevated serum prolactin?Objective and design: Macroprolactinemia may influence the interpretation of serum prolactin levels-a recognised phenomenon since 1981. The degree of macroprolactinaemia over time is less well described. We determined how macroprolactin status (based on polyethylene glycol (PEG) precipitation) varied by analysing serial measurements in hyperprolactinaemic individuals over a period of 9 years. Patients and measurements: Results from 1810 individuals were included. All serum total prolactin results (measured using Roche Cobas 8000 analyser) were extracted from the laboratory information system for the period 1 January 2012 to 1 April 2021, along with relevant patient demographic/test data. Samples with a macroprolactin screening test performed (on samples with prolactin > 700 miu/L) were included in the main analysis. Results: During the study period, 2782 macroprolactin checks were performed (12.5% of all prolactin tests) in 1810 individuals (599 males/2183 females, median-age: 35, interquartile range: 25-47, range: 16-93 years). Multiple macroprolactin checks were carried out on 465 patients (1437 measurements) with 94 patients (141 measurements) screening positive (<60% recovery). Only 19 patients (18 female) had at least one result above and one below the 60% screening cut-off, with 10 of these patients having results close to the 60% cut-off; in 9 patients, results were clearly different between repeat samples. In seven cases, the adjusted monomeric prolactin showed a potentially clinically significant difference. Conclusions: In this study, only 19/465 patients appeared to change macroprolactin status based on a 60% PEG recovery cut-off. The majority of these 19 patients were on antipsychotic/antidepressant medication(s) or had a prolactinoma; in only 7 did monomeric prolactin change significantly. This suggests that once macroprolactin status has been determined, clinical decision making is rarely affected by repeating it. Keywords: longitudinal trend; macroprolactin; monitoring; prolactin.
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Testosterone therapy reduces insulin resistance in men with adult-onset testosterone deficiency and metabolic syndrome. Results from the Moscow Study, a randomized controlled trial with an open-label phaseAims: To describe changes in homeostasis model assessment of insulin resistance index (HOMA-IR) following testosterone therapy in men with hypogonadism and metabolic syndrome (MetS). Materials and methods: A randomized, placebo-controlled, double-blind randomized controlled trial (RCT) comprising 184 men with MetS and hypogonadism (testosterone undecanoate [TU]: 113 men, placebo: 71 men) was conducted. This was followed by an open-label phase in which all men were given TU. We focused on men who were not receiving antiglycaemic agents (TU: 81 men; placebo: 54 men) as these could affect HOMA-IR. Inter-group comparison of HOMA-IR was restricted to the RCT (30 weeks), whilst intra-group comparison was carried out on men provided TU during the RCT and open-label phases (study cohort) and men given placebo during the RCT and then switched to TU during the open-label phase (confirmatory cohort). Regression analysis was performed to identify factors associated with change in HOMA-IR (∆HOMA-IR). Results: The median HOMA-IR was significantly reduced at almost every time point (after 18 weeks) compared to baseline in men receiving TU in both the study and confirmatory cohorts. There was a significant decrease in median values of fasting glucose (30 weeks: -2.1%; 138 weeks: -4.9%) and insulin (30 weeks: -10.5%; 138 weeks: -35.5%) after TU treatment. Placebo was not associated with significant ∆HOMA-IR. The only consistent predictor of HOMA-IR decrease following TU treatment was baseline HOMA-IR (r2 ≥ 0.64). Conclusions: Baseline HOMA-IR predicted ΔHOMA-IR, with a greater percentage change in insulin than in fasting glucose. In men with MetS/type 2 diabetes (T2DM) not on antiglycaemic therapy, improvements in HOMA-IR may be greater than suggested by change in fasting glucose. Our results suggest that hypogonadism screening be included in the management of men with MetS/T2DM.
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General practice (GP) level analysis shows that patients' own perceptions of support within primary care as reported in the GP patient survey (GPPS) are as important as medication and services in improving glycaemic controlBackground: The way that GP practices organize their services impacts as much on glycaemia in type 2 diabetes as does prescribing. Aim: Our aim was to evaluate the link between patients' own perception of support within primary care and the % patients at each GP practice at target glycaemic control (TGC) and at high glycaemic risk (HGR). Design and setting: Utilisation of National Diabetes Audit (NDA) available data combined with the General practitioner patient survey (GPPS). Method: The NDA 2016_17 published data on numbers of type 2 patients, levels of local diabetes services and the target glycaemic control (TGC) % and high glycaemic risk (HGR) % achieved. The GPPS 2017 published % "No" responses from long term condition (LTC) patients to the question "In the last 6 months, had you enough support from local services or organisations to help manage LTCs?". Multivariate regression was used on the set of indicators capturing patients' demographics and services provided. Results: 6498 practices were included (with more than 2.5 million T2DM patients) and median values with band limits that included 95% practices for % "No" response to the question above was 12% (2%-30%), for TGC 67% (54%-78%) and for HGR 6% (2%-13%). The model accounted for 25% TGC variance and 26% HGR variance. The standardised β values shown as (TGC/HGR) (+=more people; -=less people) for older age (+0.24/-0.25), sulphonylurea use (-0.21/+0.14), greater social disadvantage (-0.09/+0.21), GPPS Support %No (-0.08/+0.12), %Completion 8 checks (+0.09/-0.12) and metformin use (+0.11/-0.05). Conclusion: The relation between the person with diabetes and clinician in primary care is shown to be quantitatively potentially as important in influencing glycaemic outcome as the services provided and medication prescribed. We suggest that all of us in who work in the health care system can bear this in mind in our everyday work.
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Cost of hospital treatment of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) compared to the non-diabetes population : a detailed economic evaluationObjectives: Other than age, diabetes is the largest contributor to overall healthcare costs and reduced life expectancy in Europe. This paper aims to more exactly quantify the net impact of diabetes on different aspects of healthcare provision in hospitals in England, building on previous work that looked at the determinants of outcome in type 1 diabetes (T1DM) and type 2 diabetes (T2DM). Setting: NHS Digital Hospital Episode Statistics (HES) in England was combined with the National Diabetes Audit (NDA) to provide the total number in practice of people with T1DM/T2DM. Outcome measures: We compared differences between T1DM/T2DM and non-diabetes individuals in relation to hospital activity and associated cost. Results: The study captured 90% of hospital activity and £36 billion/year of hospital spend. The NDA Register showed that out of a total reported population of 58 million, 2.9 million (6.5%) had T2DM and 240 000 (0.6%) had T1DM. Bed-day analysis showed 17% of beds are occupied by T2DM and 3% by T1DM. The overall cost of hospital care for people with diabetes is £5.5 billion/year. Once the normally expected costs including the older age of T2DM hospital attenders are allowed for this fell to £3.0 billion/year or 8% of the total captured secondary care costs. This equates to £560/non-diabetes person compared with £3280/person with T1DM and £1686/person with T2DM. For people with diabetes, the net excess impact on non-elective/emergency work is £1.2 billion with additional estimated diabetes-related accident & emergency attendances at 440 000 costing the NHS £70 million/year. T1DM individuals required five times more secondary care support than non-diabetes individuals. T2DM individuals, even allowing for the age, require twice as much support as non-diabetes individuals. Conclusions: This analysis shows that additional cost of provision of hospital services due to their diabetes comorbidities is £3 billion above that for non-diabetes, and that within this, T1DM has three times as much cost impact as T2DM. We suggest that supporting patients in diabetes management may significantly reduce hospital activity.
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Androgen receptor-reduced sensitivity is associated with increased mortality and poorer glycaemia in men with type 2 diabetes mellitus : a prospective cohort studyIntroduction: Hypogonadism is associated with poorer glycaemic outcomes/increased all-cause and cardiovascular morbidity/mortality in type 2 diabetes mellitus (T2DM). Increasing CAG repeat number within exon-1 of the androgen receptor (AR) gene is associated with increased AR resistance/insulin resistance. Methods: We determined in a long-term 14-year follow-up cohort of 423 T2DM Caucasian men, the association between baseline androgen status/CAG repeat number (by PCR then Sequenom sequencing) and metabolic/cardiovascular outcomes. Results: Metabolic outcomes: Lower total testosterone was associated with higher BMI (kg/m2) at 14-year-follow-up: regression coefficient -0.30 (95% confidence interval -0.445 to -0.157), P = 0.0001. The range of CAG repeat number was 9-29 repeats. Higher CAG repeat number in exon-1 of the AR gene was associated with higher follow-up HbA1c2016 - each unit increase in CAG repeat-associated with an increment of 0.1% in HbA1C2016 (P = 0.04), independent of baseline testosterone. Cardiovascular outcomes and mortality: At an average of 14-year-follow-up, 55.8% of hypogonadal men had died vs 36.1% of eugonadal men (P = 0.001). There was a 'u' shaped relation between number of CAG repeats and mortality. Twenty-one CAG repeats were associated with an up to nearly 50% lower mortality rate than <21 CAG repeats and >21 CAG repeats - independent of baseline testosterone level. Conclusion: A higher number of CAG repeats at the AR gene associates with higher future HbA1c. There was a 'u' shaped relation between CAG repeat number and mortality rate. Determination of CAG repeat number may become part of assessment of androgen status/its consequences for men with T2DM.
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The treatment rate of erectile dysfunction (ED) in younger men with type 2 diabetes is up to four times higher than the equivalent non-diabetes populationIntroduction: Erectile dysfunction (ED) is common in older age and in diabetes mellitus (DM). Phosphodiesterase type 5-inhibitors (PDE5-is) are the first-line for ED. We investigated how the type of diabetes and age of males affect the PDE5-i use in the primary care setting. Methods: From 2018 to 2019, the general practice level quantity of all PDE5-i agents was taken from the general practice (GP) Prescribing Dataset in England. The variation in outcomes across practices was examined across one year, and for the same practice against the previous year. Results: We included 5761 larger practices supporting 25.8 million men of whom 4.2 million ≥65 years old. Of these, 1.4 million had T2DM, with 0.8 million of these >65. About 137 000 people had T1DM. About 28.8 million tablets of PDE5-i were prescribed within the 12 months (2018-2019) period in 3.7 million prescriptions (7.7 tablets/prescription), at total costs of £15.8 million (£0.55/tablet). The NHS ED limit of one tablet/user/wk suggests that 540 000 males are being prescribed a PDE5-i at a cost of £29/y each. With approximately 30 000 GPs practising, this is equivalent to one GP providing 2.5 prescriptions/wk to overall 18 males. There was a 3x variation between the highest decile of practices (2.6 tablets/male/y) and lowest decile (0.96 tablets/male/y). The statistical model captured 14% of this variation and showed that T1DM males were the largest users, while men age <65 with T2DM were being prescribed four times as much as non-DM. Those T2DM >65 were prescribed 80% of the non-DM amount. Conclusion: There is a wide variation in the use of PDE5-is. With only 14% variance capture, other factors including wide variation in patient awareness, prescribing rules of local health providers, and recognition of the importance of male sexual health by GP prescribers might have a significant impact.
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People with type diabetes mellitus (T1DM) self-reported views on their own condition management reveal links to potentially improved outcomes and potential areas for service improvementBackground: The self-management of type 1 diabetes (T1DM) has moved forward in many areas over the last 40 years. Our study asked people with T1DM what is their experience of blood glucose (BG) monitoring day to day and how this influences decisions about insulin dosing. Methods: An on-line self-reported questionnaire containing 44 questions prepared after consultation with clinicians and patients was circulated to people with T1DM 116 responders provided completed responses. Fixed responses were allocated specific values (e.g. not confident = 0 fairly confident = 1). Multivariate regression analysis was carried out. Only those 5 factors with p-value <0.05 were retained. Results: 59% of respondents were >50 years old and 66% had diabetes for >20 years, with 63% of patients reporting HbA1c results ≤8% or 64 mmol/mol. Findings included; 75% used only 1 m; 56% had used the same meter for ≥3 years; 10% had tried flash monitors; 47% were concerned about current BG level; 85% were concerned about long-term impact of higher BG. 72% of respondents keep BG level high to avoid hypoglycaemia; 25% used ≥7 mmol/L as pre-meal BG target to calculate dose; 65% were concerned they might be over/under-dosing; 83% did not discuss accuracy when choosing meter. However 85% were confident in their meter's performance. The factors that linked to LOWER HbA1c included LESS units of basal insulin (p < 0.001), HIGHER number of daily BG tests (p = 0.008), LOWER bedtime blood glucose (p = 0.009), HIGHER patient's concern over long-term impact of high BG (BG) (p < 0.009 but LOWER patient's concern over current BG values (p = 0.009). The final statistical model could explain 41% of the observed variation in HbA1c. Conclusion: Many people still run their BG high to avoid hypoglycaemia. Concern about the longer-term consequences of suboptimal glycaemic control was associated with a lower HbA1c and is an area to explore in the future when considering how to help people with T1DM.
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Self-reported views on managing type 1 diabetes mellitusNo abstract available
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Recalibration of thinking about adrenocortical function assessment : how the 'random' cortisol relates to the short synacthen test resultsBackground: The short synacthen test (SST) is the most commonly performed investigation to assess adrenal function. Appropriate criteria for when an SST is performed are subject to debate. We investigated how random serum cortisol levels relate to SST response. Methods: We examined random cortisol measurements taken between 04.40-23.55 p.m. results of SST baseline and 30-/60-min cortisol performed over 12 months (225 SSTs) at Salford Royal Hospital. Serum cortisol was measured on the Siemens Centaur Analyser.A 30-60-min cortisol concentration of ≥450 nmol/L defined a pass; 350-449 nmol/L defined borderline. Results: Patients only proceeded to SST if random cortisol was <400 nmol/L. For those not on corticosteroids for at least 2 weeks, 42/43 (97.7%) cases with random cortisol concentration of ≥200 nmol/L had an SST 'pass'. The relation was less clear with corticosteroid treatment (19/35 cases; 54%).For those not taking glucocorticoid treatment (including inhaled/topical corticosteroids) in the previous 2 weeks, 91.8% of SSTs were pass/2.7% borderline/5.5% fail. For those on steroids, 51.9% of SSTs were a pass/11.4% were borderline.In relation to the postsynacthen cortisol pass cut-off of ≥450 nmol/L, in 15/207 (7.2%) of cases, the 60-min cortisol was ≥450 nmol/L (adequate adrenocortical function), but 30-min cortisol was below this. In all cases where the 30-min cortisol did indicate a pass (i.e. was ≥450 nmol/L) the 60-min cortisol was also ≥450 nmol/L. Conclusion: Our findings suggest that if the random cortisol level is ≥200 nmol/L, regardless of the time of day and the person was not taking corticosteroid treatment in the previous 2 weeks, SST may not be needed. Our data also suggests that 60-min cortisol retains utility.
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Is there a role for natural desiccated thyroid in the treatment of levothyroxine unresponsive hypothyroidism? Results from a consecutive case seriesIntroduction: Some levothyroxine unresponsive individuals with hypothyroidism are prescribed a natural desiccated thyroid (NDT) preparation such as Armour Thyroid® or ERFA Thyroid® . These contain a mixture of levothyroxine and liothyronine in a fixed ratio. We evaluated the response to NDT in individuals at a single endocrine centre in terms of how the change from levothyroxine to NDT impacted on their lives in relation to quality of life (QOL) and thyroid symptoms. Methods: The ThyPRO39 (thyroid symptomatology) and EQ-5D-5L-related QoL/EQ5D5L (generic QOL) questionnaires were administered to 31 consecutive patients who had been initiated on NDT, before initiating treatment/6 months later. Results: There were 28 women and 3 men. The dose range of NDT was 60-180 mg daily. Age range was 26-77 years with length of time since diagnosis with hypothyroidism ranging from 2 to 40 years. One person discontinued the NDT because of lack of response; two because of cardiac symptoms. EQ-5D-5L utility increased from a mean (SD) of 0.214 (0.338) at baseline, to 0.606 (0.248) after 6 months; corresponding to a difference of 0.392 (95% CI 0.241-0.542), t = 6.82, P < .001. EQ-VAS scores increased from 33.4 (17.2) to 71.1 (17.5), a difference of 37.7 (95% CI 25.2-50.2), t = -4.9, P < .001. ThyPRO scores showed consistent fall across all domains with the composite QoL-impact Score improving from 68.3 (95% CI 60.9-75.7) to 25.2 (95% CI 18.7-31.7), a difference of 43.1 (95% CI 33-53.2) (t = 5.6, P < .001). Conclusion: Significant symptomatic benefit and improvement in QOL was experienced by people with a history of levothyroxine unresponsive hypothyroidism treated with NDT, suggesting the need for further evaluation of NDT in this context.
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Dapagliflozin : an effective adjunctive treatment in type 1 diabetesIntroduction: Many people with type 1 diabetes (T1DM) continue to run high HbA1c levels with an associated elevated risk of cardiovascular events and increased mortality. We describe here how adjunctive prescription of an SGLT2 inhibitor has improved the glycaemic control of several people with T1DM, where the new technology has been intensively deployed. Methods: We report outcomes of six adults with T1DM who have been given dapagliflozin in East Cheshire, UK. Initiation was with education/support from the diabetes specialist nurses. All had an HbA1c of 70 mmol/mol (8.6%) or more before this was initiated. All had been monitoring glycemia with a FreeStyle Libre monitor for at least 6 months prior to this. Results: The age range was 30-68 years. The mean duration of T1DM was 23.3 ± 5.5 years. All were on a basal-bolus regime. Over a 6 month period, HbA1c fell from 78.5 mmol/mol (9.3%) to 55 mmol/mol (7.2%). The greatest reduction in HbA1c was 57 mmol/mol (7.4%). Analysis of the FreeStyle Libre blood glucose records showed that the proportion of blood glucose readings on target (4-10 mmol/L) increased from 33.1 to 65.2% with the addition of dapagliflozin(P = 0.007). The proportion of blood glucose readings above target (>10 mmol/L) decreased from 68.0 to 26.4%, 6 months after initiation of dapagliflozin (P = 0.005). There was no increase in symptomatic hypoglycemia. Conclusion: Dapagliflozin as adjunctive therapy to basal-bolus regime insulin in individuals with T1DM was well tolerated and improved glycemic control with no increase in hypoglycemia. We provide further evidence of the value of this intervention.
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Management of patients symptomatically unresponsive to levothyroxine : natural desiccated thyroid extract or the combination of levothyroxine and liothyronine? A research priorityAround 5-10% of hypothyroid patients continue to experience profound and sometimes disabling symptoms, including fatigue, depression and impaired cognition, in spite of being adequately replaced biochemically. The use of the combination of levothyroxine and liothyronine and natural desiccated thyroid extract is controversial for reasons of costs, a lack of evidence of additional benefit over levothyroxine alone, and potential safety concerns. Clinical guidelines caution against the use of both, and advise that only in exceptional cases may a short trial be considered. Natural desiccated thyroid extract is not licensed for use in the UK. However, key deficiencies in the existing evidence-base together with improved understanding of the pharmacology of levothyroxine resistance, indicates that now is the right time for a definitive clinical trial to address this important area of uncertainty.
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Applying Parkes grid method to evaluate impact of variation in blood glucose monitoring (BGM) strip accuracy performance in type 1 diabetes highlights the potential for amplification of imprecision with less accurate BGM stripsBackground: The National Health Service spends £170 million on blood glucose monitoring (BGM) strips each year and there are pressures to use cheaper less accurate strips. Technology is also being used to increase test frequency with less focus on accuracy.Previous modeling/real-world data analysis highlighted that actual blood glucose variability can be more than twice blood glucose meter reported variability (BGMV). We applied those results to the Parkes error grid to highlight potential clinical impact. Method: BGMV is defined as the percent of deviation from reference that contains 95% of results. Four categories were modeled: laboratory (<5%), high accuracy strips (<10%), ISO 2013 (<15%), and ISO 2003 (<20%) (includes some strips still used).The Parkes error grid model with its associated category of risk including "alter clinical decision" and "affect clinical outcomes" was used, with the profile of frequency of expected results fitted into each BGM accuracy category. Results: Applying to single readings, almost all strip accuracy ranges derived in a controlled setting fell within the category: clinically accurate/no effect on outcomes areas.However modeling the possible blood glucose distribution in more detail, 30.6% of longer term results of the strips with current ISO accuracy would fall into the "alter clinical action" category. For previous ISO strips, this rose to 44.1%, and for the latest higher accuracy strips, this fell to 12.8%. Conclusion: There is a minimum standard of accuracy needed to ensure that clinical outcomes are not put at risk. This study highlights the potential for amplification of imprecision with less accurate BGM strips.