In forensic toxicology, opioids are frequently associated with drug abuse or drug-related death cases. An optimal method for use in the identification and quantification of opioids in a complex blood matrix is of paramount importance. Along with the ability to identify and quantitate opioids, this method should be accurate, sensitive, and selective. The application of sample pre-treatment and solid-phase extraction are common to purify and concentrate the target analytes before analyzing with liquid chromatography-tandem mass spectrometry. The purpose of this study was to compare the performance of two standard operating procedures, adopted by the Massachusetts State Police Crime Laboratory Toxicology and the Biomedical Forensic Sciences– Toxicology Laboratory at Boston University School of Medicine, for detecting opioids in blood. A total of eight drugs were analyzed: 6-monoacetylmorphine, codeine, fentanyl, hydrocodone, morphine, norhydrocodone, oxycodone, and oxymorphone. Comparison was performed using the parameters studied as part of method validation, including calibration model, bias, precision, carryover, interferences, ionization suppression/enhancement, and recovery. The results indicated that the method from Massachusetts State Police provided a better performance with between-run precision, interferences from matrix and other commonly encountered drugs, matrix effect at high concentration (250 ng/mL) and matrix recovery. Meanwhile, the method from Biomedical Forensic Sciences showed less bias, within-run precision, and matrix effect at low concentrations. Carryover and internal standard interference were comparable in both standard operating procedures. The calibration models were adjusted by altering the selection of regression model for improved quantification method performance. The volume of solvents, sample matrix, as well as time, were taken into consideration in accessing the overall performance of identification and quantitation. Both procedures were comparable yet the one from Massachusetts State Police was more beneficial in identifying the target analytes with greater sensitivity and selectivity and the one from Biomedical Forensic Sciences was more economical and efficient.

This study explored the roles and responsibilities of social workers providing services to nonmedical prescription drug users (NMPDU). Researchers have indicated NMPDU disproportionately affects people living in rural communities. The overarching research question sought to explore the concerns of social workers when providing services to patients coping with NMPDU in the rural community of Ulster County, New York. The intention was to examine systemic challenges facing rural social workers when attempting to decrease morbidity risks and increase the health of Ulster County residents. A total of 7 social workers participated in 3 focus groups to explore their ideas for defining, clarifying, and identifying solutions to the problem. The social exchange theory was used to frame the roles and responsibilities of social workers within rural communities at the macro, mezzo, and micro levels. Qualitative content analysis identified 5 themes: roles and responsibilities, barriers, education, treatment interventions, NMPDU and illicit substances of use. The results of the study included advocating for the fair and equitable distribution of resources for all residents coping with NMPDU in Ulster County, their responsibility to collaborate on pressing matters and educate physicians, community service providers, local legislators, individuals, and families of the warning signs and harmful effects of NMPDU. Findings may effect social change by enhancing the role of social workers by reducing overdose and death rates of NMPDUs.

No description available.

Existing research on health disparities in breast cancer is heavily focused on outcomes for poor or low-income women. Little is known about the experience of privately insured Black breast cancer patients that have moderate to high SES. As a result, the present study was conducted to learn more about their experiences. It examines differences in physician prescribing of two breast cancer pain treatments, peripheral nerve block (PNB) and opioids, for Black and White women with like levels of health insurance coverage and socioeconomic status (SES). Three specific questions are addressed: 1. What, if any, race-based disparities exist in usage of PNBs at time of total mastectomy? 2. What, if any, race based disparities exist in the prescription of opioids for postoperative pain following total mastectomy? 3. What, if any, changes have occurred in the frequency of orders placed for PNBs and prescription opioids over time, to treat postoperative pain resulting from mastectomy? A cross-sectional designed was used relying on an existing national dataset, Optum Clinformatics Data Mart. The study period was January 1, 2012, through December 31, 2019. Study results revealed that while moderate to higher SES Black women have equitable access to PNB and opioids - a kind of shield from long established physician bias against Black women – this protection is quite porous. They still do not have open and ready access to PNB as a more advanced pain treatment. Nor do they have assurance that they are protected from the overprescribing of opioids, a class of drugs with serious and well-known safety risks. Therefore, on the surface, it appears that equity and racial inclusion are hallmarks of physician prescribing of postoperative breast cancer pain treatment. However, further interrogation reveals that ‘separate and somewhat equal’ is a more accurate characterization of their prescribing practices, based both on race and SES.

Chronic pain is common and a burden for both the individual and society. In chronic pain, the pain has lost its function as a warning system and instead has become a disease in itself. Neurobiologically, several areas of the brain are involved, but to gain a broader understanding of the long-term pain, the biopsychosocial model is the best starting point. In line with thisand many scientific studies since the late 90's, psychological factors have proven to be an important factor in the development and maintenance of chronic pain. Interdisciplinary multimodal rehabilitation programs (IMMRP) are the treatment currently given to patients with long-term pain in the specialized pain rehabilitation. When the IMMRP has been reviewed, patients have shown improvement over time, but it is not possible to say whether it is the IMMRP or which parts of the IMMRP that explain the improvement (1). In this licentiate thesis, I have studied the importance of psychological factors in the rehabilitation of patients with chronic pain. This has been done in three studies reported in three published articles. All the studies have been close to the clinic and have been performed on patients in the specialized pain rehabilitation care in Sweden. The first article studied the effect of the multimodal investigation (MMI). More specifically, it was investigated whether alliance building and feelings of validation in patients with chronic pain affected their acceptance of pain, pain management, catastrophic thoughts, and depression. This was performed in a "single case" study on six patients in MMI. The results showed that despite good alliance and sense of validation, acceptance increased only in one patient and no improvement was seen in pain management, catastrophizing, and depression. In study two, subgroups of patients with chronic pain were studied. The subgroup analysis showed that patients referred for IMMRP could be divided into groups with different profiles regarding emotional problems and pain avoidance. These profiles were important for how the patients relatedto their pain and the results of IMMRP. The results of the study can increase the understanding of which patients should be selected for IMMRP and how the treatment can be adapted to the patients' needs. In study three, opioid treatment in patients with long-term pain who were referred to IMMRP was studied. The result showed that opioid prescribing was common and 55% of the participants received at least one prescription for opioids during the two years after the first assessment. It also turns out that there was a connection between individual patient characteristics (especially pain and depressive symptoms) and opioid prescription. Understanding how individual patient characteristics relate to prescribing patterns and long-term opioid use is an important prerequisite for managing opioid prescribing and the basics for preventing overuse. Overall, this licentiate thesis shows that MMU has no therapeutic effect on patients with long-term pain. It also shows that patients with chronic pain are a heterogeneous group that can be divided into subgroups based on psychological characteristics. The subgroups, in turn, had different ways of managing their pain and absorbing the treatment offered. In addition, it emerged that opioid prescribing was common among patients with long-term pain and that there was a link between opioids and patient characteristics.

No description available.

Acute and chronic pain conditions cause significant patient distress, interference with daily activities, and increased health care costs. It is important to evaluate analgesic interventions to improve pain relief, function, quality of life, and also to prevent persisting pain after surgery. This thesis is a combination of studies evaluating analgesic interventions in the setting of acute surgical pain; prevention of persistent post-surgical pain; and chronic low back pain. In part 1, we report our comparison of morphine and hydromorphone in 402 ambulatory surgery patients, for their ability to achieve satisfactory analgesia with minimal emesis using a design of multicentre randomized controlled trial. We observed no differences in their analgesic potential and common side effects and note that appearance of side effects is likely to be idiosyncratic. In part 2, we report our 2×2 factorial feasibility trial to prevent persistent post-surgical pain in patients having elective video-assisted thoracic surgery lobectomies, comparing N-methyl-D-aspartate antagonists versus placebo, and intravenous steroids versus placebo. As our feasibility outcomes were not met, we suggest appropriate considerations for protocol changes before embarking on a definitive larger trial. In part 3, we report on our systematic review and meta-analysis assessing the effectiveness and safety of gabapentinoids (gabapentin and pregabalin) in adult patients with chronic low back pain. We observed that the existing evidence is small and there is minimal improvement in pain and other outcomes with potential for adverse events. We suggest that the use of gabapentinoids for chronic low back pain merits caution and there is need for large high-quality trials. / Thesis / Doctor of Philosophy (PhD) / It is important to evaluate analgesic interventions to decrease pain, improve function, and lessen health care costs. In a randomized controlled trial of day surgery patients, we demonstrate that there are no differences between morphine and hydromorphone in achieving pain relief and common side effects. To prevent persistent post-surgical pain in patients having elective video-assisted thoracic surgery lobectomies, we performed a 2×2 factorial, feasibility randomized controlled trial, to compare N-methyl-D-aspartate antagonists versus placebo, and intravenous steroids versus placebo. We observe that appropriate protocol changes must be made before embarking on a larger trial. Finally, we report our systematic review and meta-analysis on the use of gabapentinoids in adult patients with chronic low back pain and observe that the existing evidence is small and not supportive, and the use of gabapentinoids for chronic low back pain merits caution.

Deep brain stimulation (DBS) is a neurosurgical intervention now established for the treatment of movement disorders. For the treatment of chronic pain refractory to medical therapies, several prospective case series have been reported, but few centres worldwide have published findings from patients treated during the last decade using current standards of technology. This thesis seeks to survey the current clinical status of DBS for pain, investigate its mechanisms and their interactions with autonomic function, its clinical limitations and ablative alternatives. Presented first is a review of the current status of analgesic DBS including contemporary clinical studies. The historical background, scientific rationale, patient selection and assessment methods, surgical techniques and results are described. The clinical outcomes of DBS of the sensory thalamus and periventricular / periaqueductal grey (PAVG) matter in two centres are presented including results from several pain and quality of life measures. A series of translational investigations in human subjects receiving DBS for pain elucidating mechanisms of analgesic DBS and its effects upon autonomic function are then presented. Single photon emission tomography comparing PAVG, VP thalamus and dual target stimulation is described. Somatosensory and local field potential (LFP) recordings suggesting PAVG somatotopy are shown. ABPM results demonstrating changes with PAVG DBS are given and Portapres studies into heart rate variability changes with ventral PAVG DBS are detailed. Investigations using naloxone are then shown to hypothesise separate dorsal opioidergic and ventral parasympathetic analgesic streams in the PAVG. Finally, cingulotomy in lung cancer to relieve pain and dyspnoea results are discussed in the context of altering pain and autonomic function by functional neurosurgery. Pain and autonomic interactions and mechanisms in deep brain surgery for pain are then discussed alongside its limitations with proposals made for optimising treatment and improving outcomes.

Growth hormone (GH) stimulates growth and metabolism but also displays profound effects on the central nervous system (CNS). GH affects neurogenesis and neuroprotection, and has been shown to counteract drug-induced apoptosis in the brain. Anabolic androgenic steroids (AAS), mainly abused for their anabolic and performance-enhancing properties, can cause several adverse effects, such as cardiovascular complications, sterility, depression, and aggression. GH and AAS are both believed to interact with several signaling systems in the CNS. The aim of this thesis was to further investigate the impact of GH and AAS on neurochemistry and cognitive functions. Recombinant human GH (rhGH) and the steroid nandrolone decanoate (ND) were administered, separately and in combination with each other, to male rats. The results demonstrated that administration of GH improved spatial memory, assessed in a water maze test. Furthermore, GH induced alterations of the GABAB receptor mRNA expression, density, and functionality in the brain, for example in regions associated with cognition. GH also altered the mu opioid peptide (MOP) receptor, but not the delta opioid peptide (DOP) receptor functionality in the brain. Thus, some of the GH effects on cognition may involve effects on the GABAB receptors and MOP receptors. ND, on the contrary, seemed to induce impairments of memory and also altered the GABAB receptor mRNA expression in the brain. Furthermore, ND lowered the IGF-1 plasma concentrations and attenuated the IGF-1, IGF-2, and GHR mRNA expression in the pituitary. In addition, significant effects of GH and ND were found on plasma steroid concentrations, organ weight, as well as body weight. In conclusion, this thesis contributes with further knowledge on the cognitive and neurochemical consequences of GH and ND use. The findings regarding ND are worrying considering the common use of AAS among adolescents. GH improves memory functions and affects signaling systems in the brain associated with cognition, hence the hypothesis that GH can reverse drug-induced impairments is further strengthened.

Pain is a significant health problem. Mu opioid receptor agonists are used clinically as analgesics, but their use is constrained by high abuse liability. Intracranial self-stimulation (ICSS) is a preclinical behavioral procedure that has been used to assess abuse potential of opioids, and drug-induced facilitation of ICSS is interpreted as an abuse-related effect. ICSS can also be used as a behavioral baseline to detect affective dimensions of pain. Specifically, pain-related depression of ICSS can model pain-related depression of behavior and mood, and drug-induced blockade of pain-related ICSS depression can serve as a measure of affective analgesia. This dissertation used mu agonists that vary in efficacy at the mu receptor (methadone> fentanyl> morphine> hydrocodone> buprenorphine> nalbuphine) and compared their effects on ICSS in the absence (phase one) or presence (phase 2) of pain. Adult male Sprague-Dawley rats were equipped with intracranial electrodes targeting the medial forebrain bundle and trained to lever press for brain stimulation. Different frequencies of stimulation maintained a frequency-dependent increase in ICSS rates, and permitted detection of both rate-increasing and rate-decreasing treatment effects. During phase 1, medium- and high-efficacy mu agonists produced initial rate-decreasing effects, followed by abuse-related rate-increasing effects at later time points. Repeated morphine administration produced tolerance to its own rate-decreasing effects, cross-tolerance to rate-decreasing effects of other mu agonists, and enhanced expression of rate-increasing effects. Low efficacy mu agonists only produced rate-increasing effects, which were enhanced after repeated morphine. These results suggest that previous opioid exposure increases expression of abuse-related facilitation of ICSS by mu agonists regardless of efficacy. During phase 2, intraperitoneal administration of lactic acid (1.8%) served as a noxious stimulus to depress ICSS. All mu agonists blocked acid-induced depression of ICSS at doses similar to those that facilitated ICSS in the absence of pain. A higher intensity noxious stimulus (5.6 % acid) produced further depression of ICSS and reduced the antinociceptive potency of both methadone and nalbuphine. Morphine antinociception was resistant to tolerance in the assay of acid-depressed ICSS. Overall, these results provide a basis for comparing determinants of abuse-related opioid effects in the absence of pain with their affective analgesic effects in the presence of pain.