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The neurologist has become increasingly involved in the multidisciplinary treatment of patients with chronic noncancer pain (CNP). Chronic noncancer pain affects a diverse patient population with multiple underlying diagnoses and associated therapies. Following the model of the American Board of Anesthesiology and the American Society of Anesthesiologists for practice guidelines and subspecialty requirements, neurologic pain management is now recognized as a subspecialty of neurology by the American Academy of Neurology and the American Board of Psychiatry and Neurology. Current basic and clinical research into the neuropathology, neurophysiology, neurochemistry, and neuropharmacology of chronic pain continues to expand diagnostic and therapeutic options. Informed regulatory agencies and professional organizations such as the American Academy of Neurology recognize the undertreatment of patients with CNP and provide clear recommendations to help neurologists in the ethical and effective treatment of patients with pain. Improved education of neurologists, other health care professionals, patients, and the media about evolving standards of pain care and therapy will produce a more supportive environment for the compassionate and ethical treatment of patients with CNP. [ABSTRACT FROM AUTHOR]

Importance: Acute urinary retention (UR) is common, yet variations in diagnosis and management can lead to inappropriate catheterization and harm., Objective: To develop an algorithm for screening and management of UR among adult inpatients., Design, Setting, and Participants: In this mixed-methods study using the RAND/UCLA Appropriateness Method and qualitative interviews, an 11-member multidisciplinary expert panel of nurses and physicians from across the US used a formal multi-round process from March to May 2015 to rate 107 clinical scenarios involving diagnosis and management of adult UR in postoperative and medical inpatients. The panel ratings informed the first algorithm draft. Semistructured interviews were conducted from October 2020 to May 2021 with 33 frontline clinicians-nurses and surgeons from 5 Michigan hospitals-to gather feedback and inform algorithm refinements., Main Outcomes and Measures: Panelists categorized scenarios assessing when to use bladder scanners, catheterization at various scanned bladder volumes, and choice of catheterization modalities as appropriate, inappropriate, or uncertain. Next, qualitative methods were used to understand the perceived need, usability, and potential algorithm uses., Results: The 11-member expert panel (10 men and 1 woman) used the RAND/UCLA Appropriateness Method to develop a UR algorithm including the following: (1) bladder scanners were preferred over catheterization for UR diagnosis in symptomatic patients or starting as soon as 3 hours since last void if asymptomatic, (2) bladder scanner volumes appropriate to prompt catheterization were 300 mL or greater in symptomatic patients and 500 mL or greater in asymptomatic patients, and (3) intermittent was preferred to indwelling catheterization for managing lower bladder volumes. Interview findings were organized into 3 domains (perceived need, feedback on algorithm, and implementation suggestions). The 33 frontline clinicians (9 men and 24 women) who reviewed the algorithm reported that an evidence-based protocol (1) was needed and could be helpful to clinicians, (2) should be simple and graphically appealing to improve rapid clinician review, and (3) should be integrated within the electronic medical record and prominently displayed in hospital units to increase awareness. The draft algorithm was iteratively refined based on stakeholder feedback., Conclusions and Relevance: In this study using a systematic, multidisciplinary, evidence- and expert opinion-based approach, a UR evaluation and catheterization algorithm was developed to improve patient safety by increasing appropriate use of bladder scanners and catheterization. This algorithm addresses the need for practical guidance to manage UR among adult inpatients.

Background: Migraine is a prevalent disabling condition often associated with comorbid physical and psychological symptoms that contribute to impaired quality of life and disability. Studies suggest that increasing dietary omega-3 fatty acid is associated with headache reduction, but less is known about the effects on quality of life in migraine., Methods: After a 4-week run-in, 182 adults with 5-20 migraine days per month were randomized to one of the 3 arms for sixteen weeks. Dietary arms included: H3L6 (a high omega-3, low omega-6 diet), H3 (a high omega-3, an average omega-6 diet), or a control diet (average intakes of omega-3 and omega-6 fatty acids). Prespecified secondary endpoints included daily diary measures (stress perception, sleep quality, and perceived health), Patient-Reported Outcome Measurement Information System Version 1.0 ([PROMIS©) measures and the Migraine Disability Assessment (MIDAS). Analyses used linear mixed effects models to control for repeated measures., Results: The H3L6 diet was associated with significant improvements in stress perception [adjusted mean difference (aMD): -1.5 (95% confidence interval: -1.7 to -1.2)], sleep quality [aMD: 0.2 (95% CI:0.1-0.2)], and perceived health [aMD: 0.2 (0.2-0.3)] compared to the control. Similarly, the H3 diet was associated with significant improvements in stress perception [aMD: -0.8 (-1.1 to -0.5)], sleep quality [aMD: 0.2 (0.1, 0.3)], and perceived health [aMD: 0.3 (0.2, 0.3)] compared to the control. MIDAS scores improved substantially in the intervention groups compared with the control (H3L6 aMD: -11.8 [-25.1, 1.5] and H3 aMD: -10.7 [-24.0, 2.7]). Among the PROMIS-29 assessments, the biggest impact was on pain interference [H3L6 MD: -1.8 (-4.4, 0.7) and H3 aMD: -3.2 (-5.9, -0.5)] and pain intensity [H3L6 MD: -0.6 (-1.3, 0.1) and H3 aMD: -0.6 (-1.4, 0.1)]., Discussion: The diary measures, with their increased power, supported our hypothesis that symptoms associated with migraine attacks could be responsive to specific dietary fatty acid manipulations. Changes in the PROMIS© measures reflected improvements in non-headache pain as well as physical and psychological function, largely in the expected directions. These findings suggest that increasing omega-3 with or without decreasing omega-6 in the diet may represent a reasonable adjunctive approach to reducing symptoms associated with migraine attacks. Trial Registration: ClinicalTrials.gov NCT02012790., Competing Interests: The National Institutes on Aging claims intellectual property related to stable analogs of oxidized lipid mediators (PCT/US2018/041086) with CR and Gregory Keyes as inventors. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Faurot, Park, Miller, Honvoh, Domenichiello, Mann, Gaylord, Lynch, Palsson, Ramsden, MacIntosh, Horowitz and Zamora.)

A previous report showed that 12-week lowering of dietary omega-6 linoleic acid (LA) coupled with increased omega-3 polyunsaturated fatty acid (PUFA) intake (H3-L6 diet) reduced headache frequency and improved quality of life in patients with chronic daily headaches (CDHs) compared to dietary LA reduction alone (L6 diet). The trial also showed that targeted dietary manipulation alters PUFA-derived lipid mediators and endocannabinoids. However, several additional classes of lipid mediators associated with pain in preclinical models were not measured. The current secondary analysis investigated whether the clinical benefits of the H3-L6 diet were related to changes in plasma unesterified PUFA-derived lipid mediators known to be involved in nociception, including prostanoids. Lipid mediators were measured by ultra-high-pressure liquid chromatography coupled with tandem mass-spectrometry. Compared to baseline, dietary LA lowering with or without added omega-3 fatty acids did not alter unesterified n-6 PUFA-derived lipid mediators, although several species derived from LA, di-homo-gamma-linolenic acid, and arachidonic acid were positively associated with headache frequency and intensity, as well as mental health burden. Alpha-linolenic acid (ALA)-derived metabolites were also associated with increased headache frequency and intensity, although they did not change from the baseline in either dietary group. Compared to baseline, docosahexaenoic acid (DHA)-derived epoxides were more elevated in the H3-L6 group compared to the L6 group. Diet-induced elevations in plasma DHA-epoxides were associated with reduced headache frequency, better physical and mental health, and improved quality of life ( p < 0.05). Prostanoids were not detected, except for PGF2-alpha, which was not associated with any outcomes. This study demonstrates that diet-induced changes in DHA-epoxides were associated with pain reduction in patients with chronic headaches, whereas n-6 PUFA and ALA metabolites were associated with nociception. Lipid mediator associations with mental health and quality of life paralleled pain management outcomes in this population. The findings point to a network of multiple diet-modifiable lipid mediator targets for pain management in individuals with CDHs.

Background: Migraine is a neurological condition characterized by chronic inflammation. However, not much is known about the potential role of peripheral blood immune cells in the pathophysiology of migraine., Methods: We investigated the status of peripheral blood immune cells of 15 adults with frequent episodic or chronic migraine recruited chronologically from a randomized clinical trial (RCT) on Nutrition for Migraine (NCCIH 5R01AT007813-05) and 15 non-migraine, healthy volunteers (control) matched by age, gender, and Body Mass Index (BMI). Continuous variables were presented as means ± standard deviationas well as medians, and comparisons between patients and healthy volunteers were performed with non-parametric Wilcoxon signed rank tests. Statistical analysis was performed using Stata (StataCorp. 2019. Stata Statistical Software). Fluorescence-Activated Cell Sorting (FACS) data were processed using FlowJo software (Ashland, OR: Becton, Dickenson and Company; 2019)., Results: We observed that migraineurs had a significantly lower percentage of non-classical monocytes (CD14 + CD16 ++ ) in blood circulation, compared to the control group. In addition, Migraineurs also showed a significantly lower percentage of blood CD3 + CD4 + helper T cells and CD4 + CD25 + regulatory T cells, compared to controls. Differences in leukocyte surface markers between chronic migraine patients and their matched controls were more prominent than those between episodic migraine patients and their matched controls., Conclusions: Our results suggest that migraine is associated with dysregulated peripheral immune homeostasis and that inflammation and autoimmunity may play a role in its pathophysiology., (© 2022. The Author(s).)

Context.—: Coronavirus disease 2019 (COVID-19) has been shown to have effects outside of the respiratory system. Placental pathology in the setting of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains a topic of great interest because earlier studies have shown mixed results., Objective.—: To ascertain whether maternal SARS-CoV-2 infection is associated with any specific placental histopathology, and to evaluate the virus's propensity for direct placental involvement., Design.—: Placentas from 65 women with polymerase chain reaction-proven SARS-CoV-2 infection underwent histologic evaluation using Amsterdam consensus group criteria and terminology. Another 85 placentas from women without SARS-CoV-2 constituted the negative control group. A total of 64 of the placentas from the SARS-CoV-2-positive group underwent immunohistochemical staining for SARS-CoV-2 nucleocapsid protein., Results.—: Pathologic findings were divided into maternal vascular malperfusion, fetal vascular malperfusion, chronic inflammatory lesions, amniotic fluid infection sequence, increased perivillous fibrin, intervillous thrombi, increased subchorionic fibrin, meconium-laden macrophages (M-LMs) within fetal membranes, and chorangiosis. There was no statistically significant difference in prevalence of any specific placental histopathology between the SARS-CoV-2-positive and SARS-CoV-2-negative groups. There was no immunohistochemical evidence of SARS-CoV-2 virus in any of the 64 placentas that underwent staining for viral nucleocapsid protein., Conclusions.—: Our study results and a literature review suggest that there is no characteristic histopathology in most placentas from women with SARS-CoV-2 infection. Likewise, direct placental involvement by SARS-CoV-2 is a rare event.

Objectives: To formally assess the appropriateness of different timings of urethral catheter removal after transurethral prostate resection or ablation. Although urethral catheter placement is routine after this common treatment for benign prostatic hyperplasia (BPH), no guidelines inform duration of catheter use., Study Design: RAND/UCLA Appropriateness Methodology., Methods: Using a standardized, multiround rating process (ie, the RAND/UCLA Appropriateness Methodology), an 11-member multidisciplinary panel reviewed a literature summary and rated clinical scenarios for urethral catheter duration after transurethral prostate surgery for BPH as appropriate (ie, benefits outweigh risks), inappropriate, or of uncertain appropriateness. We examined appropriateness across 4 clinical scenarios (no preexisting catheter, preexisting catheter [including intermittent], difficult catheter placement, significant perforation) and 5 durations (postoperative day [POD] 0, 1, 2, 3-6, or ≥7)., Results: Urethral catheter removal and first trial of void on POD 1 was rated appropriate for all scenarios except clinically significant perforations. In this case, waiting until POD 3 was deemed the earliest appropriate timing. Waiting 3 or more days to remove the catheter for patients with or without preexisting catheter needs, or for those with difficult catheter placement in the operating room, was rated as inappropriate., Conclusions: We defined clinically relevant guidance statements for the appropriateness of urethral catheter duration after transurethral prostate surgery. Given the lack of guidelines and this robust expert panel approach, these ratings may help clinicians and healthcare systems improve the consistency and quality of care for patients undergoing transurethral surgery for BPH.

African Americans have disproportionately high rates of stress-related conditions, including diabetes and diabetes-related morbidity. Psychological stress may negatively influence engagement in risk-reducing lifestyle changes (physical activity and healthy eating) and stress-related physiology that increase diabetes risk. This study examined the feasibility of conducting a randomized trial comparing a novel mindfulness-based stress management program combined with diabetes risk-reduction education versus a conventional diabetes risk-reduction education program among African American adults with prediabetes and self-reported life stress. Participants were recruited in collaboration with community partners and randomized to the mindfulness-based diabetes risk-reduction education program for prediabetes (MPD; n  = 38) or the conventional diabetes risk-reduction education program for prediabetes (CPD; n  = 30). The mindfulness components were adapted from the Mindfulness-based Stress Reduction Program. The diabetes risk-reduction components were adapted from the Power to Prevent Program and the Diabetes Prevention Program . Groups met for eight weeks for 2.5 hours, with a half-day retreat and six-monthly boosters. Mixed-methods strategies were used to assess feasibility . Psychological, behavioral, and metabolic data were collected before the intervention and at three and six months postintervention to examine within-group change and feasibility of collecting such data in future clinical efficacy research. Participants reported acceptability, credibility, and cultural relevance of the intervention components. Enrollment of eligible participants (79%), intervention session attendance (76.5%), retention (90%), and postintervention data collection attendance (83%, 82%, and 78%, respectively) demonstrated feasibility, and qualitative data provided information to further enhance feasibility in future studies. Both groups exhibited an A1C reduction. MPD participants had reductions in perceived stress, BMI, calorie, carbohydrate and fat intake, and increases in spiritual well-being. Considering the high prevalence of diabetes and diabetes-related complications in African Americans, these novel findings provide promising guidance to develop a larger trial powered to examine efficacy of a mindfulness-based stress management and diabetes risk-reduction education program for African Americans with prediabetes., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper.

Prostate cancer (PCa) is the most common non-cutaneous cancer in the United States. There is currently a lack of safe and effective radiosensitizers that can enhance the effectiveness of radiation treatment (RT) for Pca. Clonogenic assay, PCNA staining, Quick Cell Proliferation assay, TUNEL staining and caspase-3 activity assay were used to assess proliferation and apoptosis in DU145 Pca cells. RT-PCR/IHC were used to investigate the mechanisms. We found that the percentage of colonies, PCNA staining intensity, and the optical density value of DU145 cells were decreased (RT/GT vs. RT). TUNEL + cells and the relative caspase-3 activity were increased (RT/GT vs. RT). Compared to RT, the anti-proliferative effect of RT/GT correlated with increased expression of the anti-proliferative molecule p16. Compared to RT, the pro-apoptotic effect of RT/GT correlated with decreased expression of the anti-apoptotic molecule Bcl-2. GT enhances RT sensitivity of DU145 by inhibiting proliferation and promoting apoptosis.

Interleukin-33 (IL-33), a damage-associated molecular pattern molecule, is a cytokine within the IL-1 interleukin family that binds to the plasma membrane receptor suppression of tumorigenicity 2 on numerous cell types. IL-33 has been extensively studied in its role in autoimmune diseases, host responses to pathogens and allergens, and has been associated with tumorigenic effects in cancer research. The present study was performed to investigate the effects of IL-33 on colon cancer cells, based off the previous data that have demonstrated an anti-tumor effect of IL-33 on pancreatic cancer cells. The effects of IL-33 on proliferation, cell survival and apoptosis on human HCT-116 colon cancer cells were examined using clonogenic survival assays, proliferation and caspase-3 activity kits, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and immunocytochemistry. It was determined that the HCT-116 cells demonstrated an notable decrease in optical density value upon incubation with IL-33, along with a decrease in the number of colonies, compared with the controls. It was further determined that the anti-proliferative effect of IL-33 on HCT-116 cells was associated with downregulation of the pro-proliferative molecules cyclin B, cyclin D and cyclin dependent kinase 2. An apoptosis-inducing effect of IL-33 on HCT-116 cells was associated with downregulation of the anti-apoptotic molecules Flice-like inhibitory protein and B-cell lymphoma 2. Taken together, the results indicated that IL-33 inhibits the growth of colon cancer by suppressing cellular proliferation, whilst simultaneously promoting apoptosis.

Unlabelled: Omega-3 and omega-6 fatty acids are biosynthetic precursors of endocannabinoids with antinociceptive, anxiolytic, and neurogenic properties. We recently reported that targeted dietary manipulation-increasing omega-3 fatty acids while reducing omega-6 linoleic acid (the H3-L6 intervention)-reduced headache pain and psychological distress among chronic headache patients. It is not yet known whether these clinical improvements were due to changes in endocannabinoids and related mediators derived from omega-3 and omega-6 fatty acids. We therefore used data from this trial (N = 55) to investigate 1) whether the H3-L6 intervention altered omega-3- and omega-6-derived endocannabinoids in plasma and 2) whether diet-induced changes in these bioactive lipids were associated with clinical improvements. The H3-L6 intervention significantly increased the omega-3 docosahexaenoic acid derivatives 2-docosahexaenoylglycerol (+65%, P < .001) and docosahexaenoylethanolamine (+99%, P < .001) and reduced the omega-6 arachidonic acid derivative 2-arachidonoylglycerol (-25%, P = .001). Diet-induced changes in these endocannabinoid derivatives of omega-3 docosahexaenoic acid, but not omega-6 arachidonic acid, correlated with reductions in physical pain and psychological distress. These findings demonstrate that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids in humans and suggest that 2-docosahexaenoylglycerol and docosahexaenoylethanolamine could have physical and/or psychological pain modulating properties., Trial Registration: ClinicalTrials.gov (NCT01157208) PERSPECTIVE: This article demonstrates that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids and that these changes are related to reductions in headache pain and psychological distress. These findings suggest that dietary interventions could provide an effective, complementary approach for managing chronic pain and related conditions., (Published by Elsevier Inc.)

Few trials have evaluated the metabolic effects and health outcomes of lowering dietary n-6 PUFA. The objectives of the present paper were (1) to report the methods employed to lower dietary n-6 PUFA, while either increasing or maintaining n-3 PUFA intake and (2) to validate our methods with 24 h recalls and erythrocyte fatty acid analyses. A total of sixty-seven subjects were randomised to either (1) an average-n-3 PUFA, low-n-6 PUFA (L6) intervention designed to lower linoleic acid (LA; #2·5% of energy (en%)) and arachidonic acid (#60 mg/d), while maintaining an average US intake of n-3 PUFA or (2) a high-n-3 PUFA, low-n-6 PUFA (H3-L6) intervention designed to lower n-6 LA, while increasing the n-3 PUFA a-linolenic acid (ALA; $1·5 en%) and EPA þ DHA ($1000 mg/d). Pre- and intraintervention nutrient intakes were estimated with six 24 h dietary recalls per subject. Both groups achieved the targeted reductions in dietary LA to #2·5 en% (median LA 2·45 (2·1, 3·1); P,0·001). Intakes of n-3 PUFA did not change for the L6 group. Target increases in n-3 ALA (median 1·6 en%, (1·3, 2·0), P,0·001) and EPA þ DHA (1482 mg, (374, 2558), P,0·001) were achieved in the H3-L6 group. Dietary changes were validated by corresponding changes in erythrocyte n-6 and n-3 fatty acid composition. Dietary LA can be lowered to #2·5 en%, with or without concurrent increases in dietary n-3 PUFA, in an outpatient clinical trial setting using this integrated diet method.

Background: Targeted analgesic dietary interventions are a promising strategy for alleviating pain and improving quality of life in patients with persistent pain syndromes, such as chronic daily headache (CDH). High intakes of the omega-6 (n-6) polyunsaturated fatty acids (PUFAs), linoleic acid (LA) and arachidonic acid (AA) may promote physical pain by increasing the abundance, and subsequent metabolism, of LA and AA in immune and nervous system tissues. Here we describe methodology for an ongoing randomized clinical trial comparing the metabolic and clinical effects of a low n-6, average n-3 PUFA diet, to the effects of a low n-6 plus high n-3 PUFA diet, in patients with CDH. Our primary aim is to determine if: A) both diets reduce n-6 PUFAs in plasma and erythrocyte lipid pools, compared to baseline; and B) the low n-6 plus high n-3 diet produces a greater decline in n-6 PUFAs, compared to the low n-6 diet alone. Secondary clinical outcomes include headache-specific quality-of-life, and headache frequency and intensity., Methods: Adults meeting the International Classification of Headache Disorders criteria for CDH are included. After a 6-week baseline phase, participants are randomized to a low n-6 diet, or a low n-6 plus high n-3 diet, for 12 weeks. Foods meeting nutrient intake targets are provided for 2 meals and 2 snacks per day. A research dietitian provides intensive dietary counseling at 2-week intervals. Web-based intervention materials complement dietitian advice. Blood and clinical outcome data are collected every 4 weeks., Results: Subject recruitment and retention has been excellent; 35 of 40 randomized participants completed the 12-week intervention. Preliminary blinded analysis of composite data from the first 20 participants found significant reductions in erythrocyte n-6 LA, AA and %n-6 in HUFA, and increases in n-3 EPA, DHA and the omega-3 index, indicating adherence., Trial Registration: ClinicalTrials.gov (NCT01157208).

Aims: Fine particles (PM10) in the air in Christchurch have been estimated to be a considerable health hazard, and 9.1% of all deaths have been attributed to them. Concentrations often exceed the national standard. The particles come from wood-burning stoves and hydrocarbon-burning traffic and industry. This study asks whether the particles from these sources are equally toxic, and whether a standard based on concentration of particles is appropriate as a measure for devising regulatory controls to safeguard public health., Methods: Recorded concentrations of PM10 in Christchurch are much higher in winter than in summer. Published estimates show that 25% of the summer PM10 comes from home fires, and 75% from traffic and industry. It has been estimated that in winter 80% comes from home fires. Other published estimates show that in summer PM10 is 5 to 10 times more toxic than in winter. In this article these estimates are used together to estimate of the relative toxicity of PM10 from home fires compared with PM10 from traffic and industry., Results: The calculations imply that the PM10 from home fires is less toxic than the PM10 from traffic and industry, and despite its predominance as a component in the winter PM10 it may be relatively harmless. An alternative explanation is that toxicity varies seasonally for each kind of PM10., Conclusions: Reducing total PM10 by reducing the component which comes from home fires may not reduce the incidence of premature deaths from PM10 pollution.

Background: Irritable bowel syndrome (IBS), a functional bowel disorder with symptoms of abdominal pain and disturbed defecation experienced by 10% of U.S. adults, results in significant disability, impaired quality of life, and health-care burden. Conventional medical care focusing on pharmacological approaches, diet, and lifestyle management has been partially effective in controlling symptoms. Behavioral treatments, such as cognitive-behavioral therapy and hypnosis, are promising. This paper describes an on-going feasibility study to assess the efficacy of mindfulness training, a behavioral treatment involving directing and sustaining attention to present-moment experience, for the treatment of IBS., Methods/design: The study design involves randomization of adult women with IBS according to Rome II criteria, to either an eight-week mindfulness training group (based on a Mindfulness-based Stress Reduction [MBSR] format) or a previously validated IBS social-support group as an attention-control condition. The primary hypothesis is that, compared to Support Group participants, those in the Mindfulness Program will demonstrate significant improvement in IBS symptoms as measured by the IBS Symptom Severity Scale [1]., Discussion: 214 individuals have been screened for eligibility, of whom 148 were eligible for the study. Of those, 87 were enrolled, with 21 withdrawing after having given consent. 66 have completed or are in the process of completing the interventions. It is feasible to undertake a rigorous randomized clinical trial of mindfulness training for people with IBS, using a standardized MBSR protocol adapted for those experiencing IBS, compared to a control social-support group previously utilized in IBS studies., Trial Registration: Clinical Trials.gov Identifier: NCT00680693.

Objective: To examine the longitudinal use of methadone in a pain clinic., Design: Follow-up study of 40 patients initially treated with methadone and re-evaluated 2 years later, comparing those maintained on methadone with those who were switched to other opioids., Setting: Pain clinic at a university hospital., Results: The 14 patients (35%) who stayed on methadone for the duration of the study, had higher employment rates (P <.05) and higher functional ratings (P <.02) than those on other opioids. Side effects were the most common reason (33.4%) for discontinuation of methadone. Dose escalation occurred in 11 of 14 patients (78.6%)., Conclusions: Chronic pain patients may be safely and effectively treated with methadone. Those not responding or tolerating methadone may be benefited by treatment with other opioids.

An educational program designed to change knowledge in order to change pain management practices and patient outcomes was offered to nurses who provide day-to-day care to patients with cancer in communities in a predominantly rural state. A quasi-experimental time-series design was used to measure the effectiveness of the program in changing nurse knowledge, attitude and behavior, and to evaluate the relationships between the outcomes. Data were collected from nurses (N = 29) and patient charts before (N = 209) and after (N = 163) the program. Nurses' knowledge increased, but the change was not statistically significant; the mean percent of correct answers on the three subtests were different and differences persisted throughout the study. Nurses believed that patients should be "pain free." Documentation of behaviors, for example, practice activities, occurred infrequently and showed little change until 6 months after the program. Increase in documentation of pain-intensity ratings, pain location, number of sites of pain, presence of confusion, anxious or depressed mood, sleep, nausea and vomiting, constipation, and general activity were noted. Documentation of the use of a propoxyphene-containing analgesic decreased; increase in the use of hydromorphone methadone and transdermal fentanyl was noted. Analysis of the relationships between correct responses to nurse knowledge questions and documentation of behavior provided interesting, statistically insignificant results that need to be reexamined in future research. Future programs should emphasize analgesic dosing and calculation of equianalgesic doses. Current practices in chart documentation may provide incomplete information regarding change in practice behaviors; more detailed documentation of pain management practices is needed. Nurses who participated in the program anecdotally reported feelings of increased credibility and effectiveness. Although change in behavior is slow to occur, education does make a difference.

A great deal of effort is being expended at national, state and local levels to improve cancer pain management in the United States. The fact that cancer patients continue to experience "unrelieved pain" is of concern to professional caregivers and families, as well as to the patients themselves. This article describes the content and scope of an educational program for nurses who work in predominantly rural areas. Content of the program and the evaluation process are described in detail in order to provide other caregivers with a model that could be implemented in similar settings.

Trisomic codominant expression of the HLA antigens was observed in an infant with duplication of a part of 6p occurring as a result of crossing over within a paternally transmitted pericentric inversion. The HLA-A and B loci were linked absolutely with the inversion chromosome in a four generation pedigree.

Published methods for isolation of 3-indoleacetic acid (IAA) were found to give low yields due to losses at specific steps. Loss during extraction was minimized by grinding tissue under a nitrogen atmosphere, using 0.02% sodium diethyldithiocarbamate in 80% ethanol as the extractant. When ethereal solutions of IAA were concentrated in vacuo, the hormone was lost, presumably by sublimation. This significant source of loss was eliminated by concentration at atmospheric pressure. Oxidative losses during application of extracts to chromatograms were reduced by prior application of an antioxidant to the origin of chromatograms. These precautions permitted development of a method where 10-50 μg of IAA could be recovered from soybean leaves with approximately 60% yield.

Subsequent production of amylase is severely inhibited if barban [4-chloro-2-butynyl N-(3-chlorophenyl) carbamate] is added to embryo-free half seeds of barley within 4 to 5 hours after gibberellic acid treatment of these seeds. Thirty to 50 mg/L concentrations of barban are effective. Barban inhibition is non-competitive with respect to gibberellic acid. Addition of barban 7 hours or more after gibberellic acid treatment is almost without effect. The delay between gibberellic acid treatment and amylase formation tends to become shorter with more prolonged imbibition periods. Regardless of imbibition period, susceptibility to barban is lost within 7 hours after gibberellic acid treatment. Other herbicidally active phenylurethanes are also inhibitors, but none are as effective as barban. Phenethyl alcohol and 2 arylcarbamates can act as inhibitors.