The burden of neutropenic sepsis in patients with advanced non-small cell lung cancer treated with single-agent docetaxel: A retrospective study.

OBJECTIVES: To describe rates of confirmed and suspected neutropenic sepsis (NS) and associated hospital resource utilisation in patients with non-small cell lung cancer (NSCLC) treated with docetaxel monotherapy following relapse after ≥1 line of chemotherapy in routine UK clinical practice. MATERIALS AND METHODS: A multi-centre, retrospective, observational research study was conducted in seven centres across England and Wales. Adult patients with stage III/IV NSCLC initiated on docetaxel monotherapy between 2010 and 2016 in routine clinical practice (aged ≥18 years at initiation) following failure of first-line chemotherapy were eligible. Data were collected from hospital medical records between May 2016 and July 2016, on all episodes of confirmed or suspected NS related to docetaxel monotherapy, including patient characteristics. Episodes of confirmed NS were defined as documented absolute neutrophil count <1.0×109/L, plus temperature >38°C or other signs/symptoms of sepsis, otherwise episodes were classified as suspected NS. RESULTS: 121 patients were included (median age 65.5 years; 57.9% male; median 4.0 cycles of docetaxel; 19.8% treated with prophylactic granulocyte-colony stimulating factor). Episodes of confirmed or suspected NS were recorded in 21/121 (17.4%) patients (11 confirmed episodes in 11 [9.1%] patients and 11 suspected episodes in 10 [8.3%] patients). Resource utilisation data were available for 21/22 episodes; the mean length of stay for confirmed NS admissions (n=11) was 9.2 (SD: 9.2) days and for suspected NS admissions (n=10) was 4.7 (SD: 4.6) days. The most commonly prescribed treatment for NS was piperacillin/tazobactam therapy (46.5% of all documented treatments). The mean total costs of managing patients with confirmed NS (n=11) and suspected NS (n=9) were £3163 (SD: £2921) and £1790 (SD: £1585) per patient, respectively. CONCLUSION: Rates of confirmed NS in UK clinical practice were broadly similar to those reported in clinical trials; however, the burden of suspected NS, not routinely reported elsewhere, is also substantial.

Post-activation potentiation: underlying physiology and implications for motor performance.

The response of muscle to volitional or electrically induced stimuli is affected by its contractile history. Fatigue is the most obvious effect of contractile history reflected by the inability of a muscle to generate an expected level of force. However, fatigue can coexist with post-activation potentiation (PAP), which serves to improve muscular performance, especially in endurance exercise and activities involving speed and power. The measured response of muscular performance following some form of contractile activity is the net balance between processes that cause fatigue and the simultaneous processes that result in potentiation. Optimal performance occurs when fatigue has subsided but the potentiated effect still exists. PAP has been demonstrated using electrically induced twitch contractions and attributed to phosphorylation of myosin regulatory light chains, which makes actin and myosin more sensitive to Ca(2+). The potentiated state has also been attributed to an increase in alpha-motoneuron excitability as reflected by changes in the H-reflex. However, the significance of PAP to functional performance has not been well established. A number of recent studies have applied the principles of PAP to short-term motor performance as well as using it as a rationale for producing long-term neuromuscular changes through complex training. Complex training is a training strategy that involves the execution of a heavy resistance exercise (HRE) prior to performing an explosive movement with similar biomechanical characteristics, referred to as a complex pair. The complex pair is then repeated for a number of sets and postulated that over time will produce long-term changes in the ability of a muscle to generate power. The results of these studies are equivocal at this time and, in fact, no training studies have actually been undertaken. The discrepancies among the results of the various studies is due in part to differences in methodology and design, with particular reference to the mode and intensity of the HRE, the length of the rest interval within and between the complex pairs, the type of explosive activity, the training history of the participants, and the nature of the dependent variables. In addition, few of the applied studies have actually included measures of twitch response or H-reflex to determine if the muscles of interest are potentiated. There is clearly more research required in order to clarify the functional significance of PAP and, in particular, the efficacy of complex training in producing long-term neuromuscular adaptations.