A Clinical Evaluation of the Accuracy of an Intrathecal Drug Delivery Device.

INTRODUCTION: Implantable intrathecal drug delivery (ITDD) devices are used to treat severe pain and spasticity refractory to conventional medical management. Although off-label medications and drug admixtures are commonly used in clinical practice and recommended by international guidelines, manufacturers state that this practice can result in device failure. The impact of off-label drugs and drug combinations on pump accuracy has hitherto never been assessed. MATERIALS AND METHODS: A multinational, three-center, retrospective review of patient records was undertaken. The inclusion criterion was the presence of an ITDD device implantation in adult patients, with the pump in situ for the expected battery lifespan. Residual drug volumes at each refill, drug mixtures and concentrations, and rate and flow pattern of the pump (simple or flex) were recorded. A normalized flow rate ratio was calculated (actual to theoretical flow rate). The impact of nonapproved drugs, battery life, pump size, and flow program on drug delivery accuracy was assessed. RESULTS: Data from 1402 pump refills were collected (73 patients). The overall mean accuracy ratio was 0.995 (95% CI = 0.986-1.004). The ratio for approved drug status was 0.990 vs 0.997 in nonapproved, with a difference of -0.007 (-0.032 to 0.017). At the tenth centile for remaining battery life (14 months), the ratio was 0.983 vs 1.009 for the 90th centile (69 months), with a difference of -0.026 (-0.038 to -0.014). The ratio for flex administration was 0.982 vs 1.006 for simple, with a difference of -0.024 (-0.040 to -0.008). For pump size of 40 mL, the ratio was 0.975 vs 1.010 for 20 mL, with a difference of -0.035 (-0.063 to -0.008). The 95% prediction interval for individual refill ratios was ±0.15. CONCLUSION: In a clinical setting, the ITDD pumps retained high levels of accuracy and acceptable precision across their lifespan despite using unapproved drugs or admixtures and under various flow modes and rates.

Age- and sex-specific reference intervals for visceral fat mass in adults.

BACKGROUND/OBJECTIVES: Dual-energy X-ray absorptiometry (DXA) is becoming a method of choice for the assessment of visceral adipose tissue (VAT) but the lack of robust reference ranges presents a challenge to the interpretation of VAT in clinical practice, research settings, and the athletic environment. The objective of this study was to develop age- and sex-specific reference intervals for DXA-derived VAT mass. SUBJECTS/METHODS: The reference group comprised 3219 adults (1886 general population, 42% women; 1333 athletes, 11% women) in the United Kingdom, aged 18-83 years. Total body scans were performed using a GE Lunar iDXA and VAT analyses were enabled through Corescan software (Encore version 15.0). Age-specific reference ranges were derived in samples stratified by sex and general population/ athlete status. We modelled the mean and SD of Box-Cox transformed VAT mass as a function of age with a generalised least squares method using fractional polynomials (Stata® -xrigls- program). Centile values were then back-transformed to provide reference intervals on the original scale. RESULTS: In general population samples, average VAT mass increases with age up until around 65-70 years, and then begins to decline at older ages, though data are relatively sparse at the upper end of the age range. In athletes, on average, VAT mass increases with advancing age in men and women. Both 95 and 98% reference ranges are presented in 5-year increments in all samples, and we provide equations to enable the calculation of any centile, for any age within the range. CONCLUSIONS: These reference data can aid the interpretation of VAT mass specific to an individual's sex, age, and athletic status, increasing the utility and applicability of DXA-derived VAT assessments. Additional research is needed in adults over 65 years and female athletes, with different DXA devices, across different ethnic groups and specific sports.

Bolus intrathecal injection of ziconotide (Prialt®) to evaluate the option of continuous administration via an implanted intrathecal drug delivery (ITDD) system: a pilot study.

OBJECTIVES: This study evaluated efficacy and safety of bolus doses of ziconotide (Prialt®, Eisai Limited, Hertfordshire, UK) to assess the option of continuous administration of this drug via an implanted intrathecal drug delivery system. MATERIALS AND METHODS: Twenty adults with severe chronic pain who were under consideration for intrathecal (IT) therapy were enrolled in this open label, nonrandomized, pilot study. Informed consent was obtained. Demographics, medical/pain history, pain scores, and concomitant medications were recorded. A physical examination was performed. Creatine kinase was measured. Initial visual analog scale (VAS), blood pressure, heart rate, and respiratory rate were recorded. All patients received an initial bolus dose of 2.5 mcg ziconotide; the dose in the subsequent visits was modified according to response. Subsequent doses were 2.5 mcg, 1.2 mcg, or 3.75 mcg as per protocol. A good response (≥30% reduction in baseline pain VAS) with no side-effects on two occasions was considered a successful trial. Data were analyzed using a generalized estimating equations model, with pain VAS as the outcome and time (seven time points; preinjection and one to six hours postinjection) as the predictor. RESULTS: Generalized estimating equations analysis of summary measures showed a mean reduction of pain VAS of approximately 25% at the group level; of 11 responders, seven underwent pump implantation procedure, two withdrew because of adverse effects, one refused an implant, and one could not have an implant (lack of funding from the Primary Care Trust). CONCLUSIONS: Our data demonstrated that mean VAS was reduced by approximately 25% at the group level after IT ziconotide bolus. Treatment efficacy did not vary with sex, center, age, or pain etiology. Ziconotide bolus was generally well tolerated. Larger studies are needed to determine if bolus dosing with ziconotide is a good predictor of response to continuous IT ziconotide via an intrathecal drug delivery system.

Habitual physical activity levels of adults with heart failure: systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to quantify habitual physical activity (PA) levels of patients with heart failure (HF) and assess the quality of reporting of device-assessed PA. METHODS: Eight electronic databases were searched up to 17 November 2021. Data on the study and population characteristics, method of PA measurement and PA metrics were extracted. A random-effects meta-analysis (restricted maximum likelihood with Knapp-Hartung SE adjustment) was conducted. RESULTS: Seventy-five studies were included in the review (n=7775 patients with HF). Meta-analysis was restricted to mean steps per day, encompassing 27 studies (n=1720 patients with HF). Pooled mean steps per day were 5040 (95% CI: 4272 to 5807). The 95% prediction interval for mean steps per day in a future study was 1262 to 8817. Meta-regression at the study level revealed that a 10-year increment in the mean age of patients was associated with 1121 fewer steps per day (95% CI: 258 to 1984). CONCLUSIONS: Patients with HF are a low-active population. These findings have implications for the way in which PA is targeted in patients with HF, and interventions should focus on addressing the age-related decline observed as well as increasing PA to improve HF symptoms and quality of life. PROSPERO REGISTRATION NUMBER: CRD42020167786.

Maturational effect on Functional Movement Screen™ score in adolescent soccer players.

OBJECTIVES: The effect of maturity on Functional Movement Screen (FMS) scores in elite, adolescent soccer players was examined. DESIGN: A cross-sectional observational study was completed. METHODS: Participants were 1163 male English Football League soccer players (age 8-18 years). Players were mid-foundation phase (MF) (U9); late foundation phase (LF) (U10 and U11); early youth development phase (EYD) (U12 and U13); mid-youth development (MYD) phase (U14-U15); Late Youth Development Phase (LYD) (U16) and early professional development phase (EPD) (U18). Age from peak height velocity was estimated and players were categorized as pre- or post-peak height velocity (PHV). To analyse where differences in FMStotal score existed we separated the screen into FMSmove (3 movement tests); FMSflex (2 mobility tests) and FMSstab (2 stability tests). RESULTS: FMStotal median score ranged from 11 at MF to 14 for EPD. There was a substantial increase (10%) in those able to achieve a score of ≥14 on FMStotal in those who were post-PHV compared to pre-PHV. This was explained by a substantial increase in those achieving a score of ≥4 on FMSstab (21%). There was a substantial increase in the proportion of players who achieved the FMStotal threshold of ≥14 with an increase of 47.5 (41.4-53.6)% from the MF phase to the EPD phase due to improvements in FMSmove and FMSstab. CONCLUSIONS: PHV and maturity have substantial effects on FMS performance. FMS assessment appears to be invalid for very young players. Findings are relevant to those analyzing movement in soccer players.