Insulinoma and Tuberous Sclerosis: A Possible Mechanistic Target of Rapamycin (mTOR) Pathway Abnormality?

A 23-year-old New Zealand Maori male with tuberous sclerosis (TSC) and associated neurocognitive abnormalities presented with altered behavior and increasing seizure frequency. Endogenous hyperinsulinemia from an underlying insulinoma was confirmed and this was managed surgically. This case represents only the sixth description of insulinoma in TSC to date. The role of the hamartin-tuberin complex in regulation of the mechanistic target of rapamycin pathway provides a plausible pathogenetic mechanism between insulinoma and TSC. This rare disease association should be considered in TSC patients who present with otherwise unexplained worsening neurocognitive symptoms.

A win for the patient: Direct patient notification improves treatment rates of active Helicobacter pylori infection.

BACKGROUND: Current international guidelines recommend the commencement of effective eradication therapy as soon as active Helicobacter pylori (H. pylori) infection is confirmed. At our institution, all positive Campylobacter-like Organism (CLO) test results were automatically communicated to general practitioners (GPs) via a standardised letter, which also advised the commencement of eradication therapy. Despite this endeavour, a clinical audit conducted in 2011 demonstrated that only 66 per cent of confirmed H. pylori-positive South Auckland patients received eradication treatment and only 83 per cent of these patients received treatment within one month. AIMS: Improve the timely initiation of H. pylori eradication therapy through direct patient notification. METHOD: A prospective clinical audit of 109 consecutive outpatients with a positive CLO test identified at gastroscopy. In addition to standard general practitioner notification, patients were also directly notified of their positive CLO test result via a standardised letter, which provided information about H. pylori and its disease associations as well as advising patients to seek consultation with their GP to commence eradication therapy. Dispensing data was examined using Test Safe electronic records to determine the total uptake and timing of treatment compared to data from a preliminary 2011 audit. RESULTS: Ninety-five per cent of H. pylori-positive patients received standard triple therapy; therefore, treatment of active H. pylori infection was significantly higher when patients were directly notified in addition to standard GP notification, when compared to GP notification alone (95 per cent vs 66 per cent, p<0.001). All patients who received eradication therapy did so within one month of notification, a significant improvement compared to data from the previous audit in 2011 (100 per cent vs. 83 per cent, p<0.001). CONCLUSION: Direct patient notification using a standardised letter is a simple and economical strategy that significantly improves the timely initiation of eradication therapy for active H. pylori infection. This has since been integrated into standard practice at our District Health Board (DHB).

Increasing primary antibiotic resistance and ethnic differences in eradication rates of Helicobacter pylori infection in New Zealand--a new look at an old enemy.

AIMS: To determine the current prevalence, primary antibiotic resistance and eradication rate with standard triple therapy of Helicobacter pylori (H. pylori) infection in South Auckland, New Zealand (NZ). METHODS: Consecutive patients undergoing gastroscopy in 2012 were prospectively enrolled. The prevalence of primary H. pylori infection was determined from all Campylobacter-like organism (CLO) tests performed. Antibiotic susceptibility testing was performed for a range of relevant antibiotics and the success of eradication therapy was determined by stool antigen clearance. RESULTS: The prevalence of H. pylori infection by ethnic group; European (7.7%), Maori (34.8%), Pacific People (31.3%) and Orientals (23.8%). Metronidazole resistance was found in 49.3% of isolates, clarithromycin resistance in 16.4%, and moxifloxacin resistance in 9.5%. No isolates were resistant to tetracycline. Clarithromycin resistance (greater than and equal to 15%) was prevalent among Maori, Pacific People and Orientals. Metronidazole resistance has increased significantly from 32.7% in 1999 to 49.3% in 2012 (p=0.011), and clarithromycin resistance from 7% in 1999 to 16.4% in 2012 (p=0.021). The eradication rate (intention to treat) with standard omeprazole, amoxicillin and clarithromycin (OAC) therapy in ethnic groups where clarithromycin resistance was <15% was 85.7% versus 64.9% in groups where clarithromycin resistance was greater than and equal to 15% (p=0.024). CONCLUSION: H. pylori infection is very common among certain ethnic groups living in South Auckland. Resistance to clarithromycin and metronidazole have increased significantly among treatment naive patients compared to historical NZ data. Ethnic groups with clarithromycin resistance of greater than and equal to 15% were associated with lower eradication rates with OAC therapy. This suggests a need to review the current NZ H. pylori eradication guidelines to accommodate ethnic differences in the response to first-line regimens.

Clinical trial participation improves outcome: a matched historical cohort study.

BACKGROUND: Well-conducted, investigator-led randomized controlled trials (RCTs) are the gold standard for evaluating the efficacy of new treatments and are a key component of evidence-based medicine. It is unclear whether participating in an RCT is beneficial to the individual before the results of RCTs are known. PURPOSE: In a matched historical cohort study, we examined whether participation in RCTs was associated with improved health outcomes. METHODS: Participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE), Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET), or Telmisartan Randomized Assessment Study in ACE-intolerant Subjects with Cardiovascular Disease (TRANSCEND) studies and non-participant controls were selected from patients attending outpatient clinics at Middlemore Hospital between 2001 and 2003. RESULTS: A total of 251 RCT participants and 502 randomly selected patients not enrolled in a trial but who met study entry criteria were matched for age, gender, and ethnicity. There was a significant difference in all-cause mortality for trial participants versus non-participants over the study period (unadjusted relative risk reduction (RRR) = 63%; 95% confidence interval (CI) = 28%-81%) and a significant reduction in cardiovascular mortality (unadjusted RRR = 81%; 95% CI = 17%-95%) favouring RCT participants. Allowing for co-morbidity, the adjusted RRR of all-cause mortality associated with trial participation was 55% (95% CI = 10%-77%). Active treatment in an RCT was found to be less explanatory than trial participation. The adjusted RRR for cardiovascular mortality associated with active treatment in a trial was 86% (95% CI = -2% to 98%), with trial participation found to be less explanatory than active treatment. LIMITATIONS: The main limitations of this trial relate to its design as a retrospective study with a historical cohort comparison group. Limitations include lack of complete data for some patients, bias in selection of the comparison group, and the effects of confounding variables. However, the study design and analysis were planned so as to minimize these as much as possible. CONCLUSION: This study revealed significantly lower all-cause mortality among participants in industry-sponsored RCTs compared with non-participants who received routine hospital outpatient care. This effect was independent of study drug.

An uncommon complication of infective bacterial endocarditis.

Coronary artery septic embolisation resulting in cardioembolic myocardial infarction (MI) is a rare complication of bacterial infective endocarditis (IE), representing <1% of complications related to IE. Diagnosis requires a combination of high clinical suspicion, coronary angiography, echocardiography and cultures of peripheral blood and/or embolic material. The associated mortality rate remains high despite early diagnosis. Optimal interventional therapy is unknown with published international experience over the past two decades limited to very small case series and individual case reports. We present a case of ST elevation MI resulting from coronary artery septic embolisation with an accompanying comprehensive review of the literature.

Unusually rapid beta-cell failure in a patient newly diagnosed with type 2 diabetes presenting acutely with unprovoked severe hyperglycaemic hyperosmolar state: a case report.

Pancreatic beta-cell failure on a background of insulin resistance results in the inability to compensate for fasting hyperglycaemia and eventually produces type 2 diabetes mellitus. We describe an interesting case of a patient who presented acutely with unprovoked severe hyperglycaemic hyperosmolar state and was subsequently diagnosed with type 2 diabetes mellitus on a background of only impaired first phase insulin secretion 4 months prior. Glucagon stimulation test detected significant beta-cell failure necessitating long term exogenous insulin therapy which is highly unusual by virtue of the rapid apparent deterioration.

Get a handle on HaNDL (headache, neurological deficit, and lymphocytosis).

In the aftermath of an adverse event, an apology can bring comfort to the patient, forgiveness to the health practitioner, and help restore trust to their relationship. According to the Health and Disability Commissioner: "The way a practitioner handles the situation at the outset can influence a patient's decision about what further action to take, and an appropriate apology may prevent the problem escalating into a complaint to HDC". Yet, for many health practitioners saying "I'm sorry" remains a difficult and uncomfortable thing to do. We can help to bring down this wall of silence by developing a clear understanding of the importance of apologies to patients and health practitioners; appreciating the difference between expressing empathy and accepting legal responsibility for an adverse outcome; knowing the key elements of a full apology and when they should be used; and supporting those who have the honesty and courage to say "I'm sorry" to patients who have been harmed while receiving healthcare.

Lisfranc fracture-dislocation precipitating acute Charcot arthopathy in a neuropathic diabetic foot: a case report.

The Lisfranc injury is relatively uncommon yet remains popular in the literature due to its variable causative mechanisms and subtleties in radiographic features despite its potential for disabling long term outcomes if treatment is inadequate, inappropriate or delayed. These injuries are especially pertinent in diabetic patients, especially those with neuropathy, since they are more common, can lead to Charcot neuropathic joint, ulcers and have different causative mechanisms compared to the general population. We describe the case of a neuropathic diabetic patient who presented with a Lisfranc injury which precipitated the development of acute Charcot arthropathy in the right foot. The case serves to illustrate several salient points about the Lisfranc joint and related injuries in diabetic patients.