No description available.

No description available.

Background: An increasing number of mixed methods studies have been conducted across health care professions in recent years. However, little is known about the methodological reporting quality among mixed methods studies involving chiropractic research. Objective: To examine the methodological quality of published chiropractic mixed methods studies, provide recommendations for improving future chiropractic mixed methods research, and apply these recommendations in two mixed methods health services evaluations of chiropractic integration and prescription opioid use for spinal pain. Methods: We conducted a meta-epidemiological review of the chiropractic mixed methods literature and examined reporting quality using the Good Reporting of A Mixed Methods Study guideline and risk of bias using the Mixed Methods Appraisal Tool. We used generalized estimating equations to explore factors associated with higher methodological quality. We applied our findings in two sequential explanatory mixed methods investigations of the association between chiropractic care and opioid prescribing for non-cancer spinal pain. Results: Among eligible mixed methods studies, we found that many were both poorly reported and at risk of bias. Publication in journals with an impact factor and/or more recent publication were significantly associated with higher methodological quality. In our sequential explanatory analyses, we found that receipt of chiropractic care was associated with decreases in initial opioid prescribing and long-term opioid use, and our qualitative results suggested these relationships were multi-factorial. Conclusion: We identified areas for improvement in the methodological reporting quality of chiropractic mixed methods research. Our mixed methods studies suggest that integration of chiropractic services into primary care centres may reduce the use of opioids for spinal pain. / Thesis / Doctor of Philosophy (PhD) / We reviewed the literature to assess the methodological reporting quality of mixed methods studies involving chiropractic research and found that most studies had important omissions. We applied these results to optimize methodologic reporting of two mixed methods studies on the association between chiropractic care and opioid prescribing. We found that patients with non-cancer spinal pain were less likely to receive an initial prescription for opioids if they accessed chiropractic care. Further, among chronic pain patients receiving opioids, we found that providing access to chiropractic care reduced their chances of continuing to receive opioids. The qualitative aspect of our studies provided important context to inform how patients and their primary care providers felt access to chiropractic care had reduced reliance on prescription opioids. These findings will increase awareness among researchers for opportunities to improve reporting quality of mixed methods research and highlight the potential role of chiropractic care in helping to address the opioid crisis.

Thesis advisor: Donald Cox / Can Vitamin D deficiency contribute to opioid use? Though seemingly unrelated substances, the two interestingly mirror each other in effects and metabolism. Vitamin D deficiency can lead to weakness, pain, and depression. Both can interact with addiction receptors in the brain. For these reasons, some evolutionary thinkers argue sunlight, the primary source of Vitamin D, may have emerged as the very first addiction. In this framework, modern opioid use could mirror sun exposure, but without the benefits and regulation which Vitamin D provides. Thus, one's natural Vitamin D levels may be very important to explaining their interactions with opioids. This paper parallels previous medical and epidemiological literature attempting to demonstrate how Vitamin D mediates the strength of opioids. Using 2003--2004 U.S. NHANES prescription use, health, and demographic data for individuals aged 20 to 84, this paper measures the impact of Vitamin D deficiency on the propensity of opioid use. A control function approach is used, leveraging milk consumption to relieve endogeneity concerns in previous studies. Unlike previous findings, we do not observe any significant effect from Vitamin D levels. / Thesis (BA) — Boston College, 2024. / Submitted to: Boston College. Morrissey School of Arts and Sciences. / Discipline: Economics. / Discipline: Departmental Honors.

Six studies were conducted to examine the role of endogenous opioid peptides in the regulation of ingestive behavior in the domestic fowl. In the first study, the dose-response relationships of two opioid antagonists, naloxone and naltrexone, were evaluated in Rock-Comish (RC) and Single-Comb White Leghorn (SCWL) cockerels. Naloxone and naltrexone decreased food and water intake in both stocks. In a separate experiment, the effect of naloxone on water intake was evaluated independent of food intake. Naloxone depressed water intake in normally hydrated and saline-loaded chicks. These results indicate endogenous opioid peptides influence food and water consumption independently in the domestic fowl. The sensitivities of RC and SCWL stocks to naloxone were compared in a second investigation. There was no difference in the efficacy of naloxone in attenuating ingestive behavior when the stocks were compared at either the same age or similar body weight. Therefore, genetic selection for meat or egg production has not significantly altered naloxone-sensitive opioid mechanisms regulating food and water intake in the domestic fowl. A third study extended the investigation of opioid regulation of ingestive behavior to Japanese quail (Coturnix coturnix japonica). Administration of naloxone attenuated feeding, but not drinking, suggesting that water in Japanese quail is not influenced by endogenous opioids. The fourth study was performed to determine whether opioid regulation of ingestive behavior in the domestic fowl is mediated at sites within the central nervous system or peripheral tissues. An initial experiment examined the effects of two opioid antagonists with differing ability to traverse the blood-brain barrier (bbb). Food and water intake were attenuated by both antagonists. However, at equally potent doses the antagonist which does not readily traverse the bbb (quaternary naloxone) was more effective than its congener which crosses the bbb (tertiary naloxone). Central administration of tertiary naloxone attenuated water consumption, but not feeding. No alterations in ingestive behavior were observed when these levels of tertiary naloxone were injected im. Therefore, these results suggest that opioid regulation of food intake occurs at sites outside the bbb, whereas water intake is at least, in part, centrally mediated. The remaining studies were conducted to identify the specific opioid receptor subtypes which mediate ingestive behavior in the domestic fowl. In the fifth study, ingestive responses to central (intracerebroventricular; ICV) and peripheral (im) administration of the mu agonist, morphiceptin, and the delta agonist, [Met⁵]·enkephalin, were studied. The mu and delta-opioid receptors are the receptors for which naloxone has the highest and lowest affinity, respectively. ICV administration of morphiceptin stimulated drinking, whereas im administration stimulated feeding. [Met⁵]·enkephalin stimulated food intake by both routes of administration. These results indicate that the mu opioid receptor mediates water intake in the central nervous system and food intake peripherally, while the delta-opioid receptor mediates food intake centrally and peripherally. Failure to detect central opioid mediation of food intake in previous studies was likely due to the low-affinity naloxone exhibits for the delta receptor. The final study examined the feeding, drinking, and temperature responses to ICV administration of ß-endorphin. ß-endorphin has equal affinity for the mu, delta, and epsilon opioid receptors. ICV administration of ß·endorphin induced increases in feeding, drinking, and colonic temperature in RC and SCWL. These studies indicate that endogenous opioid peptides influence food and water intake in the domestic fowl. Opioids appear to influence food and water consumption at sites within and outside the bbb, and via different receptor subtypes. Furthermore, there seems to be no difference in naloxone·sensitive opioid systems influencing ingestive behavior in meat and egg stocks of chickens. / Ph. D. / incomplete_metadata

published_or_final_version / abstract / Anaesthesiology / Master / Master of Philosophy

Morphine has been and continues to be one of the most potent and widely used drugs for the treatment of pain. Clinical and animal models investigating sex differences in pain and analgesia demonstrate that morphine is a more potent analgesic in males than in females; indeed, we report the effective dose of morphine for female rats is twice that of male rats. In addition to binding to the neuronal mu opioid receptor, morphine binds to the innate immune receptor toll-like receptor 4 (TLR4) on microglia. Morphine action at TLR4 initiates a neuroinflammatory response and directly opposes morphine analgesia. Our recent studies demonstrate that administration of chronic morphine activates microglia within the ventrolateral periaqueductal gray (vlPAG), a critical brain region for the antinociceptive effects of morphine, while blockade of vlPAG microglia increases morphine analgesia and suppresses the development of tolerance in male rats. Despite increasing evidence of the involvement of microglia in altering morphine efficacy, no studies have examined sex differences in microglia within the PAG. The present experiments seek to characterize the distribution and activity of vlPAG microglia in males and females using behavioral, immunohistochemical and molecular techniques, while demonstrating the sufficiency and necessity of vlPAG microglia to produce sex differences in morphine analgesia using site-specific pharmacological manipulation of TLR4. We also investigate a novel pharmacokinetic mechanism underlying the sexually dimorphic effects of morphine administration on microglial activity. Here, we address a fundamental gap in our current understanding of sex differences in morphine analgesia and establish a mechanistic understanding of how the activation of vlPAG microglia sex-specifically influences morphine analgesia.

Introduction The main objectives of this study were: 1) to examine the prevalence and characteristics of opioid exposures, 2) to estimate the economic costs associated with opioid poisonings, and 3) to examine the characteristics associated with opioid poisoning-related health care resource use (HCRU) and costs in children. Methods Data from the National Poison Data System from January 1, 2010 to December 31, 2014 were utilized to examine the prevalence and characteristics of opioid exposures and poisonings in children <18 years. Economic costs were estimated using the 2012 Nationwide Emergency Department Sample, Kids’ Inpatient Database, Multiple Cause-of-Death file and other published sources, applying a societal perspective. Direct costs included costs associated with ED visits, hospitalizations and ambulance transports. Indirect cost included productivity costs due to caregivers’ absenteeism and premature mortality among children. Results There were a total of 83,418 pediatric opioid exposures and nearly half of them resulted in poisoning. The epidemiology of opioid exposures differed considerably by age. Opioid exposures were more prevalent and mainly accidental in young children. Exposures in adolescents were more likely to be intentional and severe. The total economic costs of pediatric opioid poisonings in the United States were calculated at $230.8 million in 2012. Total direct costs were estimated to be over $21.1 million. Total productivity costs were calculated at $209.7 million, and 98.6% of these costs were attributed to opioid poisoning-related mortality. Conclusions Opioid exposures and poisonings in children continue to occur and impose an economic burden on the society.

Opioid medications are medicine's best weapon against severe intractable pain, but prolonged use of these medications can be complicated by side effects like tolerance and mental clouding which, themselves, can be disabling. The present study examined the independent and combined effects of inflammatory pain and opioid medication on spatial memory for a well learned task in Sprague-Dawley rats. The Hargreaves method was used to verify the pain state of the animals after complete Freund's adjuvant injection and morphine treatment. Whereas pain had little effect on spatial memory, morphine had profound detrimental effects that persisted beyond the analgesic effectiveness of the drug. However, morphine-induced cognitive deficits were absent when morphine was provided to animals in chronic pain. Also, analgesic tolerance was significantly attenuated in these animals. Taken together, these results suggest that chronic pain activates a neural mechanism that antagonizes the unwanted effects of opioids.

Orientador: Paulo Sérgio Patto dos Santos / Resumo: Objetivou-se avaliar os efeitos hemodinâmicos, hemogasométricos e sedativos da associação de xilazina e nalbufina em equinos hígidos. Foram utilizados 7 equinos adultos (385 ± 82kg), de ambos os sexos, com idade média de 7 ± 3 anos. Após a administração de bolus sequenciais de xilazina (0,8 mg/kg) e nalbufina (0,025 mg/kg), pela via intravenosa (IV), iniciou-se a infusão contínua de xilazina (0,7 mg/kg/hora) e nalbufina (0,03 mg/kg/hora). As variáveis FC, PAS, PAD, PAM, DC, PVC, PAPM, IS, IC, IRVS, FR, pH, PaO2, PaCO2, HCO3-, BE, temperatura corporal, sedação, ataxia e motilidade intestinal foram avaliadas antes do início da administração dos fármacos (Basal) e a cada vinte minutos após o início da infusão contínua até 80 minutos (T20, T40 e T60 e T80). Houve redução da FC, IC, FR e aumento do IRVS e da PaCO2 após o início da infusão contínua dos fármacos. Com os resultados obtidos é possível concluir que a associação de xilazina e nalbufina, nas doses empregadas neste estudo, promoveu sedação e manteve a motilidade reduzida, sem causar alterações clinicamente significativas nos parâmetros hemodinâmicos e hemogasométricos. / Abstract: The aim of this study was to evaluate the hemodynamic, hemogasometric and sedative effects of xylazine and nalbuphine in healthy horses. Seven adult horses (385 ± 82 kg), with a mean age of 7 ± 3 years, were used. Administration of sequential doses of xylazine (0.8 mg kg-1) and nalbuphine (0.025 mg kg-1), both intravenous (IV), continuous rate infusion of xylazine (0.7 mg kg-1 hour-1) and nalbuphine (0.03 mg kg-1 hour-1). The variables HR, RR SAP, DAP, MAP, CO, CVP, MPAP, SI, CI, SVRI RR pH, PaO2, PaCO2, HCO3-, BE, body temperature, sedation, ataxia and motility were taken immediately before the administration of the drugs (Basal) and then at 20-minute intervals during 80 minutes (T20, T40, T60 and T80). Reduction of HR, CI, respiratory rate (RR) and increase of ISVR and PaCO2 were observed after the administration of xylazine and nalburphine combination. The results allow us to conclude that the xylazine and nalbuphine association, at the doses used in this study, promoted sedation and maintenance of motility reduction without causing clinically significant changes in hemodynamic and hemogasometric parameters. / Mestre