Implementation of an integrated primary care prevention and management program for chronic low back pain (LBP): patient-reported outcomes and predictors of pain interference after six months.

BACKGROUND: Integrated primary care programs for patients living with chronic pain which are accessible, interdisciplinary, and patient-centered are needed for preventing chronicity and improving outcomes. Evaluation of the implementation and impact of such programs supports further development of primary care chronic pain management. This study examined patient-reported outcomes among individuals with low back pain (LBP) receiving care in a novel interdisciplinary primary care program. METHODS: Patients were referred by primary care physicians in four regions of Quebec, Canada, and eligible patients received an evidence-based interdisciplinary pain management program over a six-month period. Patients were screened for risk of chronicity. Patient-reported outcome measures of pain interference and intensity, physical function, depression, and anxiety were evaluated at regular intervals over the six-month follow-up. A multilevel regression analysis was performed to evaluate the association between patient characteristics at baseline, including risk of chronicity, and change in pain outcomes. RESULTS: Four hundred and sixty-four individuals (mean age 55.4y, 63% female) completed the program. The majority (≥ 60%) experienced a clinically meaningful improvement in pain intensity and interference at six months. Patients with moderate (71%) or high risk (81%) of chronicity showed greater improvement in pain interference than those with low risk (51%). Significant predictors of improvement in pain interference included a higher risk of chronicity, younger age, female sex, and lower baseline disability. CONCLUSION: The outcomes of this novel LBP program will inform wider implementation considerations by identifying key components for further effectiveness, sustainability, and scale-up of the program.

Evolution of a biological thermocouple by adaptation of cytochrome c oxidase in a subterrestrial metazoan.

In this study we report a naturally evolved temperature-sensing electrical regulator in the cytochrome c oxidase of the Devil Worm, Halicephalobus mephisto. This extremophile metazoan was isolated 1.3 km underground in a South African goldmine, where it adapted to heat and potentially to hypoxia, making its mitochondrial sequence a likely target of adaptational change. We obtained the full mitochondrial genome sequence of this organism, and show through dN/dS analysis statistically robust evidence of positive selection in H. mephisto cytochrome c oxidase subunits. Seventeen of these positively-selected amino acid substitutions were localized in proximity to the H- and K-pathway proton channels of the complex. Surprisingly, the H. mephisto cytochrome c oxidase proton pump completely shuts down at low temperatures (20°C) leading to approximately a 4.8-fold reduction in the transmembrane proton gradient voltage (ΔΨm) compared to optimal temperature (37°C). Direct measurement of oxygen consumption found a corresponding 4.7-fold drop at 20°C compared to 37°C. Correspondingly, the lifecycle of H. mephisto takes four-fold longer at the low temperature compared to higher. This elegant evolutionary adaptation creates a finely-tuned mitochondrial temperature sensor, allowing this ectothermic organism to maximize its reproductive success in varying environmental temperatures. Our study shows that evolutionary innovation may remodel core metabolism to make it more accurately map onto environmental variation.