Tristan Richardson

Skin-Related Complications of Insulin Therapy

The incidence and prevalence of all types of diabetes mellitus is increasing at an alarming rate. Modern therapy involves greater and earlier use of intensive insulin regimens in order to achieve better control of blood glucose levels and reduce the long-term risks associated with the condition. Insulin therapy is associated with important cutaneous adverse effects, which can affect insulin absorption kinetics causing glycemic excursions above and below target levels for blood glucose.Common complications of subcutaneous insulin injection include lipoatrophy and lipohypertrophy. The development of lipoatrophy may have an immunological basis, predisposed by lipolytic components of certain insulins. Repeated use of the same injection site increases the risk of lipoatrophy — with time, patients learn that these areas are relatively pain free and continue to use them. However, the absorption of insulin from lipoatrophic areas is erratic leading to frequent difficulties in achieving ideal blood glucose control. With the increasing use of modified, rapidly absorbed analog insulins (e.g. insulin lispro, insulin aspart) the incidence of lipoatrophy occurring has decreased over recent years. The likelihood of lipoatrophy can be reduced by regular rotation of injection sites but once developed, practical benefits may be obtained by insulin injection into the edge of the area, co-administration of dexamethasone with insulin, or changing the mode of insulin delivery.Lipohypertrophy is the most common cutaneous complication of insulin therapy. Newer insulins have also reduced its prevalence considerably, although its adverse effect on diabetic control is similar to lipoatrophy through impaired absorption of insulin into the systemic circulation. Experience with liposuction at these sites is limited, although good cosmetic results have been achieved.Local allergic reactions to insulin are usually erythema, pruritus, and induration. These allergic reactions are usually short-lived, and resolve spontaneously within a few weeks. Useful adjuncts to managing allergic reactions include addition of dexamethasone to the insulin injection, desensitization to insulin, or a change in delivery system utilizing insulin pump therapy or potentially inhaled insulins when these become available. The use of insulin pump therapy in managing cutaneous complications of insulin therapy is increasing, but this method itself carries risks of abscess formation and scarring. Fortunately, with improved education of patients these are relatively uncommon.Although many of the cutaneous manifestations are decreasing with the use of newer insulins, they may still influence glycemic control and increase the risk of hypoglycemia as well as have a cosmetic impact on a patient. The introduction of novel therapies and newer delivery systems is likely to reduce the cutaneous problems associated with long-term insulin use.

Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype–phenotype correlations, codon bias and dominant-negative effects

The adaptor protein-2 sigma subunit (AP2σ2) is pivotal for clathrin-mediated endocytosis of plasma membrane constituents such as the calcium-sensing receptor (CaSR). Mutations of the AP2σ2 Arg15 residue result in familial hypocalciuric hypercalcaemia type 3 (FHH3), a disorder of extracellular calcium (Ca2+o) homeostasis. To elucidate the role of AP2σ2 in Ca2+o regulation, we investigated 65 FHH probands, without other FHH-associated mutations, for AP2σ2 mutations, characterized their functional consequences and investigated the genetic mechanisms leading to FHH3. AP2σ2 mutations were identified in 17 probands, comprising 5 Arg15Cys, 4 Arg15His and 8 Arg15Leu mutations. A genotype–phenotype correlation was observed with the Arg15Leu mutation leading to marked hypercalcaemia. FHH3 probands harboured additional phenotypes such as cognitive dysfunction. All three FHH3-causing AP2σ2 mutations impaired CaSR signal transduction in a dominant-negative manner. Mutational bias was observed at the AP2σ2 Arg15 residue as other predicted missense substitutions (Arg15Gly, Arg15Pro and Arg15Ser), which also caused CaSR loss-of-function, were not detected in FHH probands, and these mutations were found to reduce the numbers of CaSR-expressing cells. FHH3 probands had significantly greater serum calcium (sCa) and magnesium (sMg) concentrations with reduced urinary calcium to creatinine clearance ratios (CCCR) in comparison with FHH1 probands with CaSR mutations, and a calculated index of sCa × sMg/100 × CCCR, which was ≥ 5.0, had a diagnostic sensitivity and specificity of 83 and 86%, respectively, for FHH3. Thus, our studies demonstrate AP2σ2 mutations to result in a more severe FHH phenotype with genotype–phenotype correlations, and a dominant-negative mechanism of action with mutational bias at the Arg15 residue.

Randomized control trial investigating the influence of coffee on heart rate variability in patients with ST-segment elevation myocardial infarction

BACKGROUND Cardiac autonomic dysfunction post ST-segment elevation myocardial infarction (STEMI) has been linked to an excess risk of premature cardiovascular morbidity and mortality above those with normal autonomic function post-STEMI. AIM The aim of this study was to evaluate the effect of acute ingestion of coffee on autonomic function and cardiovascular outcomes in patients with acute STEMI. DESIGN Randomized control trial. METHODS We randomized 103 patients with acute STEMI, admitted to our Coronary Care Unit, to receive regular coffee (caffeinated) or de-caffeinated coffee using a randomized controlled double-blinded design. Heart rate variability was assessed 5 days post-STEMI to assess the effect of caffeine on autonomic function. RESULTS In the group randomized to regular coffee, parasympathetic activity increased by up to 96% (P = 0.04) after 5 days. There was no detrimental effect of regular coffee on cardiac rhythm post-STEMI. CONCLUSION Coffee ingestion is associated with an increase in parasympathetic autonomic function immediately post-STEMI. Coffee was found to be safe and not associated with any adverse cardiovascular outcomes in the short term.

Cinacalcet for Symptomatic Hypercalcemia Caused by AP2S1 Mutations

The authors show that cinacalcet, which mediates allosteric modulation of the calcium-sensing receptor, corrects loss of function of AP2S1 mutations that cause familial hypocalciuric hypercalcemia type 3 and ameliorates symptomatic hypercalcemia.

Compartment Syndrome: An Unusual Complication of Influenza AInfection

Abstract This case report discusses a 43-year-old man who presented with 4-limb compartment syndrome secondary to influenza A myositis. We describe the clinical features that were present and the course of this unusual complication. We review the clinical features central to early diagnosis and treatment of compartment syndrome in order to increase awareness of this potentially life-threatening complication.

Insulin errors in hospital: time for a radical re-think on risk?:

Despite having been first used in 1922, insulin prescription errors for hospitalized patients remain common. Improper use of insulin for people hospitalized with diabetes can lead to serious adverse clinical outcomes, prolonged length of stay with important health economic consequences, and a poor patient experience of their hospital treatment. Although the problem of insulin prescription errors is widely appreciated, the approach to reducing the risk of these occurring is variable and subject to local influences and interpretation of current guidance. In addition, risk management in this area appears to be based upon the actual consequences of the error at an individual level rather than the error itself and the potential for harm in others. It may be of more benefit to recognize the potential for harm from insulin errors as a driver to delivering change within NHS service delivery for people with diabetes admitted to hospital.

Reducing insulin prescription errors in hospital: more stick than carrot?

People with diabetes are more likely to be admitted to hospital and have longer stays in hospital than people without diabetes. Data from the National Diabetes Inpatient Audit suggest that people with diabetes experience avoidable prescription errors such as wrong insulin, incorrect doses and omitted doses. These errors result in increased length of stay and harm to the patient. Many of the errors occur due to deficiencies in knowledge. Our aim was to reduce prescription errors and improve health care professionals’ knowledge by introducing the following initiatives: (1) redesign of the diabetes prescription chart; and (2) implementing a root cause analysis prescription error pathway which involves a targeted approach to education for the individual who made the error. Following introduction of the changes to the insulin prescription chart, data from our participation in the National Diabetes Inpatient Audit reported that prescription errors were reduced from 65% to 14% and management errors from 40% to 14% from 2009 to the beginning of 2012. The results of the internal audit during 2012–2013 demonstrated a further reduction in prescription/management errors to 2% following the introduction of the root cause analysis pathway. The changes have demonstrated a significant reduction in prescription errors and an increased awareness of diabetes following the targeted approach to education. Copyright

Cyclical Cushing's: how best to catch the ups and downs.

A 68-year-old man with a background of hypertension and type 2 diabetes presented with fluctuating symptoms of muscle aches and pains and tiredness. His initial work-up for the possibility of hypercortisolaemia showed a completely variable pattern, with 24-hour cortisol excretion and serum cortisol post 1 mg dexamethasone suppression test ranging from normal to significantly elevated. A series of salivary cortisol with symptom diary confirmed the cyclical nature of hypercortisolaemia, and his concomitant adrenocorticotropic hormone (ACTH) levels were elevated. An inferior petrosal sinus sampling, performed during hypercortisolaemic phase of his cycle,suggested a central source of ACTH secretion. He had unsuccessful exploration of his pituitary and was eventually treated with bilateral adrenalectomy followed by lifelong steroid replacement. His symptoms improved immediately, and he came off his oral hypoglycaemic and antihypertensive agents within 6 months following his surgery.

Fever of unknown origin in a patient initially presenting with traveller's diarrhoea

A 17-year-old male presented with diarrhoea and malaise following his return from Kenya and Tunisia. He was managed as a case of travellers diarrhoea. Stool cultures were negative for pathogenic bacterial growth. Two weeks later he presented with worsening lower back pain. MRI of lumbosacral spine suggested L1 osteomyelitis. CT-guided spinal aspirate grew no organisms and repeat viral serology and blood cultures (including tuberculosis screening) were negative. He was treated with a 6-week course of ceftriaxone. Back pain did not improve and a repeat MRI scan 8 weeks after his antibiotic course indicated progressive changes in L1 extending to L2 with an intradiscal abscess. Repeat CT-guided spinal aspirate grew Salmonella arizonae sensitive to cotrimoxazole and ceftriaxone. He was treated with intravenous ceftriaxone and cotrimoxazole for 12 weeks. A 4-month follow-up MRI scan showed progressive improvement of the L1/L2 discitis with resolution of intradiscal fluid.

Escherichia coli and mycotic thoracic aortic aneurysm: a case report

We report a case of an 85-year-old lady with repeated hospital admissions secondary to presumed urosepsis with blood cultures positive for Escherichia coli. Chest radiographs during the final admission had changed dramatically and computed tomography scan of the aorta confirmed mycotic thoracic aortic aneurysm.