It's never too late - balance and endurance training improves functional performance, quality of life, and alleviates neuropathic symptoms in cancer survivors suffering from chemotherapy-induced peripheral neuropathy: results of a randomized controlled trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) can affect functional performance and quality of life considerably. Since balance training has proven to enhance physical function, it might be a promising strategy to manage CIPN-induced functional impairments. METHODS: Fifty cancer survivors with persisting CIPN after finishing their treatment were randomly allocated to an intervention (IG) or active control group (CG). The IG did endurance plus balance training, the CG only endurance training (twice weekly over 12 weeks). Pre- and post-assessments included functional performance, cardiorespiratory fitness, vibration sense, and self-reported CIPN symptoms (EORTC QLQ-CIPN20). RESULTS: Intention-to-treat analyses (n = 41) did not reveal a significant group difference (CG minus IG) for sway path in semi-tandem stance after intervention (primary endpoint), adjusted for baseline. However, our per-protocol analysis of 37 patients with training compliance ≥70% revealed: the IG reduced their sway path during semi-tandem stance (- 76 mm, 95% CI -141 - -17; CG: -6 mm, 95% CI -52 - 50), improved the duration standing on one leg on instable surface (11 s, 95% CI 8-17; CG: 0 s, 95%CI 0-5) and reported decreased motor symptoms (-8points, 95% CI -18 - 0; CG: -2points 95% CI -6 - 2). Both groups reported reduced overall- (IG: -10points, 95% CI -17 - -4; CG: -6points, 95% CI -11 - -1) and sensory symptoms (IG: -7points, 95% CI -15 - 0; CG: -7points, 95% CI -15 - 0), while only the CG exhibited objectively better vibration sense (knuckle: 0.8points, 95% CI 0.3-1.3; IG: 0.0points, 95% CI -1.1 - 0.9; patella: 1.0points, 95% CI 0.4-1.6: IG: -0.8points, 95% CI -0.2 - 0.0). Furthermore, maximum power output during cardiopulmonary exercise test increased in both groups (IG and CG: 0.1 W/kg, 95% CI 0.0-0.2), but only the CG improved their jump height (2 cm, 95% CI 0.5-3.5; IG: 1 cm, 95% CI -0.4 - 3.2). CONCLUSION: We suppose that endurance training induced a reduction in sensory symptoms in both groups, while balance training additionally improved patients' functional status. This additional functional effect might reflect the IG's superiority in the CIPN20 motor score. Both exercises provide a clear and relevant benefit for patients with CIPN. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) number: DRKS00005419 , prospectively registered on November 19, 2013.

Medium-chain acyl-CoA dehydrogenase deficiency associated with a novel splice mutation in the ACADM gene missed by newborn screening.

BACKGROUND: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common disorder of mitochondrial fatty acid ß-oxidation and a target disease of newborn screening in many countries. CASE PRESENTATION: We report on two siblings with mild MCAD deficiency associated with a novel splice site mutation in the ACADM gene. The younger sibling was detected by newborn screening, while the older sister was missed, but diagnosed later on by genetic family testing. Both children were found to be compound heterozygous for the common c.985A > G (p.K329E) mutation and a novel splice site mutation, c.600-18G > A, in the ACADM gene. To determine the biological consequence of the c.600-18G > A mutation putative missplicing was investigated at RNA level in granulocytes and monocytes of one of the patients. The splice site mutation was shown to lead to partial missplicing of the ACADM pre-mRNA. Of three detected transcripts two result in truncated, non-functional MCAD proteins as reflected by the reduced octanoyl-CoA oxidation rate in both patients. In one patient a decrease of the octanoyl-CoA oxidation rate was found during a febrile infection indicating that missplicing may be temperature-sensitive. CONCLUSIONS: Our data indicate that the c.600-18G > A variant activates a cryptic splice site, which competes with the natural splice site. Due to only partial missplicing sufficient functional MCAD protein remains to result in mild MCADD that may be missed by newborn screening.

Balance training and multi-task performance in seniors.

Age-related impairment in gait patterns when simultaneously performing cognitive (CI) and/or motor (MI) interference tasks are associated with an increased risk of falling in seniors. The objective of this study was to investigate the impact of balance training (BT) on walking performance with and without concurrently performing a CI and/or MI task in seniors. Twenty healthy women (n=14) and men (n=6) were assigned to either an intervention (n=11, age 71.9+/-4.8 yrs) or a control group (n=9, age 74.9+/-6.3 yrs). The intervention group conducted a six week BT (3/week). Pre and post tests included the assessment of stride-to-stride variability during single (walking), dual (CI or MI+walking), and triple (CI+MI+walking) task walking on an instrumented walkway. BT resulted in statistically significant reductions in stride time variability under single (p=0.02, Delta34.8%) but not dual or triple-task walking. Significant improvements in the MI task (p=0.05, Delta39.1%), but not in the CI task were found while walking. Findings showed that improved performance during single-task walking did not transfer to walking under dual or triple-task conditions suggesting multi-task BT as an alternative training modality. Improvement of the secondary motor but not cognitive task may indicate the need for the involvement of motor and particularly cognitive tasks during BT.

Pharmacokinetics of meropenem in critically ill patients with acute renal failure treated by continuous hemodiafiltration.

The pharmacokinetics of meropenem were studied in nine anuric critically ill patients treated by continuous venovenous hemodiafiltration. Peak levels after infusion of 1,000 mg over 30 min amounted to 103.2 +/- 45.9 microgram/ml, and trough levels at 12 h were 9.6 +/- 3.8 microgram/ml. A dosage of 1,000 mg of meropenem twice a day provides plasma drug levels covering intermediately susceptible microorganisms. Further reductions of the dosage might be appropriate for highly susceptible bacteria or when renal replacement therapies with lower clearances are applied.