Metformin doses to ensure efficacy and safety in patients with reduced kidney function.

We aimed to develop a metformin dosing strategy to optimise efficacy and safety in patients with reduced kidney function. Metformin data from two studies stratified by kidney function were analysed. The relationship between metformin clearance and kidney function estimates was explored using a regression analysis. The maintenance dose range was predicted at different bands of kidney function to achieve an efficacy target of 1 mg/L for steady-state plasma concentrations. The dosing strategy was evaluated using simulations from a published metformin pharmacokinetic model to determine the probability of concentrations exceeding those associated with lactic acidosis risk, i.e. a steady-state average concentration of 3 mg/L and a maximum (peak) concentration of 5 mg/L. A strong relationship between metformin clearance and estimated kidney function using the Cockcroft and Gault (r2 = 0.699), MDRD (r2 = 0.717) and CKD-Epi (r2 = 0.735) equations was found. The probability of exceeding the safety targets for plasma metformin concentration was <5% for most doses and kidney function levels. The lower dose of 500 mg daily was required to maintain concentrations below the safety limits for patients with an eGFR of 15-29 mL/min. Our analysis suggests that a maximum daily dose of 2250, 1700, 1250, 1000, and 500 in patients with normal kidney function, CKD stage 2, 3a, 3b and 4, respectively, will provide a reasonable probability of achieving efficacy and safety. Our results support the cautious of use metformin at appropriate doses in patients with impaired kidney function.

Prevalence and characteristics of post-colonoscopy colorectal cancers in a New Zealand regional centre: a 10-year analysis.

BACKGROUND: Post-colonoscopy colorectal cancers (PCCRC) are cancers that appear following a colonoscopy in which no cancer is diagnosed. The occurrence of PCCRC is thought to be multifactorial, reflecting both endoscopy quality and potential differences in tumour biology between detected colorectal cancers and PCCRC. AIM: To identify the prevalence and characteristics of PCCRC in a New Zealand regional centre over a 10-year period. METHOD: All cases of colorectal cancer (n = 1055) in the Bay of Plenty region between 1 February 2009 and 1 February 2019 were cross-referenced with endoscopy coding records to identify patients who had undergone colonoscopy within the preceding 6-60 months in which cancer was not identified. RESULTS: A total of 46 patients were identified to have PCCRC, giving a prevalence of 4.4%. The majority of these patients were older (80% aged 65 years or over) and female (67%). The mean interval between index colonoscopy and diagnosis of PCCRC was 3.03 years. Most (80%) patients had existent pathology (diverticular disease or colonic polyps) at index colonoscopy, and a significant proportion (43%) developed cancer in the same colonic segment. PCCRC were evenly distributed between the left (50%) and right (50%) colon. The majority of patients (63%) had early-stage cancer. CONCLUSIONS: The prevalence of PCCRC in a New Zealand cohort is consistent with other international reports. Most patients with PCCRC are older, female and have early-stage disease. Of interest, a high proportion of patients developed cancer within a colonic segment with existent pathology, suggesting either missed lesions or incomplete polyp resection.

Physiological responses to a five-day adventure race: Continuous blood glucose, hemodynamics and metabolites the 2012 GODZone field-study.

BACKGROUND/OBJECTIVE: Adventure racing is an ultra-endurance activity that imposes a unique multifaceted stress on the human body. The purpose of this field study was to examine the physiological responses to a 5-day adventure race. METHODS: Eight competitors, two teams (1 female each) in the 2012 GODZone adventure race volunteered. Competitors trekked, cycled and paddled ∼326 km in ∼116 hours. Continuous glucose was measured the day before and throughout. Body mass, urinary solutes, and blood pressure and heart rate during resting, standing, and repeated squat-stand conditions, were assessed pre and post. RESULTS: Despite no changes in mean blood glucose levels, there was increased glycemic variability (Standard deviation glucose; Pre: 0.5 ±â€¯0.1 vs Race: 1.0 ±â€¯0.2 mmol/L, p = 0.02) and periods of hypoglycemia (i.e., Min glucose Pre: 4.1 ±â€¯0.3 vs Race: 3.6 ±â€¯0.5 mmol/L, p = 0.05) during the race. After the race, the blood pressure during resting, standing and squat-stand conditions was significantly lower, by 14 ±â€¯14 mmHg, 16 ±â€¯15 mmHg and 18 ±â€¯15 mmHg (all p < 0.05), respectively, with no change in heart rate. During five-days of adventure racing there is increased glycemic variability and more frequent periods of low blood glucose levels. Additionally, following the race pronounced hypotension is observed in competitors. CONCLUSION: We observed more frequent glucose fluctuations, lower glucose levels and significant perturbations in blood pressure control. Further research is warranted to examine the long-term impact of adventure racing on metabolic and cardiovascular function.

Fluid and electrolyte balance during two different preseason training sessions in elite rugby union players.

The purpose of this study was to compare fluid balance between a resistance and an aerobic training sessions, in elite rugby players. It is hypothesized that resistance exercise will result in a higher prevalence of overdrinking, whereas during the aerobic session, underdrinking will be more prevalent. As with previous fluid balance studies, this was an observational study. Twenty-six players completed the resistance training session, and 20 players completed the aerobic training session. All players were members of an elite rugby union squad competing in the southern hemisphere's premier competition. For both sessions, players provided a preexercise urine sample to determine hydration status, pre- and postexercise measures of body mass, and blood sodium concentration were taken, and the weight of drink bottles were recorded to calculate sweat rates and fluid intake rates. Sweat patches were positioned on the shoulder of the players, and these remained in place throughout each training session and were later analyzed for sodium concentration. The percentage of sweat loss replaced was higher in the resistance (196 ± 130%) than the aerobic training session (56 ± 17%; p = 0.002). Despite this, no cases of hyponatremia were detected. The results also indicated that more than 80% of players started training in a hypohydrated state. Fluid intake seems to differ depending on the nature of the exercise session. In this group of athletes, players did not match their fluid intakes with their sweat loss, resulting in overdrinking during resistance training and underdrinking in aerobic training. Therefore, hydration strategies and education need to be tailored to the exercise session. Furthermore, given the large number of players arriving at training hypohydrated, improved hydration strategies away from the training venue are required.

Sodium supplementation has no effect on endurance performance during a cycling time-trial in cool conditions: a randomised cross-over trial.

BACKGROUND: Sodium ingestion during exercise may exert beneficial effects on endurance performance by either its ability to attenuate the decrease in plasma volume or reduce the risk of Exercise Associated Hyponatremia (EAH). This study aimed to investigate the effect of sodium supplements on endurance performance during a 72 km road cycling time-trial in cool conditions (13.8 ± 2.0°C). METHODS: Nine well-trained cyclists (5 male, 4 female) participated in this randomized, double-blinded cross-over study, receiving either a 700 mg(.)h(-1) salt capsule, or a corn flour placebo during the time trial. Water was ingested ad-libitum throughout the time trial. Measurements were taken pre, post, and 40 min following time-trials, analysing blood, sweat, and urinary hydration and sodium concentration. RESULTS: Sodium supplements had no effect on time-trial performance (overall time = 171 min sodium vs. 172 min placebo; p = 0.46). There was also no effect on the change in plasma sodium concentration from pre to post time trial between trials (relative plasma [Na(+)] change (pre-post): sodium = 0.56%, placebo = 0.47%; p = 0.60). The greatest difference observed was a significantly change in plasma volume from pre to post exercise between the salt and the placebo trial (p = 0.02), which corresponded with an increased thirst with sodium supplementation. CONCLUSION: Sodium supplements therefore do not improving performance during exercise of approximately 3 h duration in cool conditions.