Understanding Myeloma-Related Information Needs and Communication Preferences Within Black American Communities: An Exploratory Study.

Myeloma is the third most common blood cancer and one of the most complex and expensive cancers to treat. Black Americans face health disparities related to myeloma incidence, age at diagnosis, access to novel treatments, and mortality. To help reduce health disparities among Black Americans through education and outreach, the Leukemia & Lymphoma Society has implemented its Myeloma Link initiative. In 2022, a formative, qualitative evaluation was conducted across the 15 U.S. cities that implemented Myeloma Link to better understand the information and communication needs and preferences of three groups: patients, community members, and primary care providers (PCPs). Data collection included interviews with eight patients, two focus groups with a total of ten community members, and interviews with six PCPs. Patients expressed wanting information about treatment experiences, including clinical trials, and emotional and peer support services, particularly from other Black American patients. Community members were largely unfamiliar with myeloma and desired outreach via trusted community organizations about disease signs and symptoms. Both groups discussed the importance of self-advocacy within the current healthcare system and wanted actionable messaging, rather than messaging leading with disparities statistics. PCPs described systemic capacity and time challenges in the context of needing to address more frequently encountered health conditions; nonetheless, PCPs welcomed information and brief trainings about myeloma diagnosis and treatment options, referrals to specialists, and how to improve care, prognosis, and caregiver support. Findings underscore the importance of outreach initiatives such as Myeloma Link to help meet these needs and reduce health disparities.

Fast Bayesian Variable Screenings for Binary Response Regressions with Small Sample Size.

Screening procedures play an important role in data analysis, especially in high-throughput biological studies where the datasets consist of more covariates than independent subjects. In this article, a Bayesian screening procedure is introduced for the binary response models with logit and probit links. In contrast to many screening rules based on marginal information involving one or a few covariates, the proposed Bayesian procedure simultaneously models all covariates and uses closed-form screening statistics. Specifically, we use the posterior means of the regression coefficients as screening statistics; by imposing a generalized g-prior on the regression coefficients, we derive the analytical form of their posterior means and compute the screening statistics without Markov chain Monte Carlo implementation. We evaluate the utility of the proposed Bayesian screening method using simulations and real data analysis. When the sample size is small, the simulation results suggest improved performance with comparable computational cost.

Ultra-low dose naloxone restores the antinociceptive effect of morphine in pertussis toxin-treated rats by reversing the coupling of mu-opioid receptors from Gs-protein to coupling to Gi-protein.

Pertussis toxin (PTX) treatment results in ADP-ribosylation of Gi-protein and thus in disruption of mu-opioid receptor signal transduction and loss of the antinociceptive effect of morphine. We have previously demonstrated that pretreatment with ultra-low dose naloxone preserves the antinociceptive effect of morphine in PTX-treated rats. The present study further examined the effect of ultra-low dose naloxone on mu-opioid receptor signaling in PTX-treated rats and the underlying mechanism. Male Wistar rats implanted with an intrathecal catheter received an intrathecal injection of saline or PTX (1 microg in 5 microl of saline), then, 4 days later, were pretreated by intrathecal injection with either saline or ultra-low dose naloxone (15 ng in 5 microl of saline), followed, 30 min later, by saline or morphine (10 microg in 5 microl of saline). Four days after PTX injection, thermal hyperalgesia was observed, together with increased coupling of excitatory Gs-protein to mu-opioid receptors in the spinal cord. Ultra-low dose naloxone pretreatment preserved the antinociceptive effect of morphine, and this effect was completely blocked by the mu-opioid receptor antagonist CTOP, but not by the kappa-opioid receptor antagonist nor-BNI or the delta-opioid receptor antagonist naltrindole. Moreover, a co-immunoprecipitation study showed that ultra-low dose naloxone restored mu-opioid receptor/Gi-protein coupling and inhibited the PTX-induced mu-opioid receptor/Gs-protein coupling. In addition to the anti-neuroinflammatory effect and glutamate transporter modulation previously observed in PTX-treated rats, the re-establishment of mu-opioid receptor Gi/Go-protein coupling is involved in the restoration of the antinociceptive effect of morphine by ultra-low dose naloxone pretreatment by normalizing the balance between the excitatory and inhibitory signaling pathways. These results show that ultra-low dose naloxone preserves the antinociceptive effect of morphine, suppresses spinal neuroinflammation, and reduces PTX-elevated excitatory Gs-coupled opioid receptors in PTX-treated rats. We suggest that ultra-low dose naloxone might be clinically valuable in pain management.

Ultra-low dose naloxone restores the antinociceptive effect of morphine in pertussis toxin-treated rats and prevents glutamate transporter downregulation by suppressing the p38 mitogen-activated protein kinase signaling pathway.

We previously demonstrated that ultra-low dose naloxone restores the antinociceptive effect of morphine in rats with pertussis toxin (PTX)-induced thermal hyperalgesia by reversing the downregulation of glutamate transporter (GT) expression and suppressing spinal neuroinflammation. In the present study, we examined the underlying mechanisms of this anti-inflammatory effect in PTX-treated rats, particularly on the expression of GTs. Male Wistar rats were implanted with an intrathecal catheter and, in some cases, with a microdialysis probe. All rats were injected intrathecally with saline (5 microl) or PTX (1 microg), then, 4 days later, were randomly assigned to receive a single injection of saline, ultra-low dose naloxone (15 ng), or the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (5 microg), followed by morphine injection (10 microg) 30 min later. Our results showed that PTX injection induced activation of microglia and a significant increase in P-p38 MAPK expression in the spinal cord. Ultra-low dose naloxone plus morphine significantly inhibited the effect of PTX on P-p38 MAPK expression in the spinal cord, while the p38 MAPK inhibitor SB203580 attenuated the PTX-induced mechanical allodynia, thermal hyperalgesia, increase in spinal cerebrospinal fluid excitatory amino acids, and downregulation of GTs. These results show that the restoration of the antinociceptive effect of morphine and GT expression in PTX-treated rats by ultra-low dose naloxone involves suppression of the p38 MAPK signal transduction cascade.

Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo.

Major depressive disorder (MDD) is a common complex trait with enormous public health significance. As part of the Genetic Association Information Network initiative of the US Foundation for the National Institutes of Health, we conducted a genome-wide association study of 435 291 single nucleotide polymorphisms (SNPs) genotyped in 1738 MDD cases and 1802 controls selected to be at low liability for MDD. Of the top 200, 11 signals localized to a 167 kb region overlapping the gene piccolo (PCLO, whose protein product localizes to the cytomatrix of the presynaptic active zone and is important in monoaminergic neurotransmission in the brain) with P-values of 7.7 x 10(-7) for rs2715148 and 1.2 x 10(-6) for rs2522833. We undertook replication of SNPs in this region in five independent samples (6079 MDD independent cases and 5893 controls) but no SNP exceeded the replication significance threshold when all replication samples were analyzed together. However, there was heterogeneity in the replication samples, and secondary analysis of the original sample with the sample of greatest similarity yielded P=6.4 x 10(-8) for the nonsynonymous SNP rs2522833 that gives rise to a serine to alanine substitution near a C2 calcium-binding domain of the PCLO protein. With the integrated replication effort, we present a specific hypothesis for further studies.

Genomewide association for schizophrenia in the CATIE study: results of stage 1.

Little is known for certain about the genetics of schizophrenia. The advent of genomewide association has been widely anticipated as a promising means to identify reproducible DNA sequence variation associated with this important and debilitating disorder. A total of 738 cases with DSM-IV schizophrenia (all participants in the CATIE study) and 733 group-matched controls were genotyped for 492,900 single-nucleotide polymorphisms (SNPs) using the Affymetrix 500K two-chip genotyping platform plus a custom 164K fill-in chip. Following multiple quality control steps for both subjects and SNPs, logistic regression analyses were used to assess the evidence for association of all SNPs with schizophrenia. We identified a number of promising SNPs for follow-up studies, although no SNP or multimarker combination of SNPs achieved genomewide statistical significance. Although a few signals coincided with genomic regions previously implicated in schizophrenia, chance could not be excluded. These data do not provide evidence for the involvement of any genomic region with schizophrenia detectable with moderate sample size. However, a planned genomewide association study for response phenotypes and inclusion of individual phenotype and genotype data from this study in meta-analyses hold promise for eventual identification of susceptibility and protective variants.

Low-dose haloperidol prevents post-operative nausea and vomiting after ambulatory laparoscopic surgery.

BACKGROUND: We evaluated the prophylactic effect of low-dose haloperidol (1 mg) on post-operative nausea and vomiting (PONV) in women undergoing ambulatory laparoscopic surgery. Droperidol (0.625 mg) and saline were controls. METHODS: One hundred and fifty women undergoing ambulatory laparoscopic surgery under general anaesthesia were enrolled in this randomized, double-blind, and placebo-controlled study. After tracheal intubation, the haloperidol group (n=50) received intravenous haloperidol (1 mg), the droperidol group (n=50) received intravenous droperidol (0.625 mg), and the saline group (n=50) received intravenous saline. RESULTS: Haloperidol- and droperidol-group patients reported a lower incidence of PONV [24% and 23% vs. 49% (saline group); P<0.05] and requested fewer doses of rescue antiemetics [13% and 16% vs. 38% (saline group); P<0.05] during the first four post-operative hours. During the 24-h post-operative period, haloperidol- and droperidol-group patients also reported a lower incidence of PONV [31% and 32% vs. 62% (saline group); P<0.01]. No differences were found between the haloperidol and droperidol groups. CONCLUSION: Like droperidol (0.625 mg), prophylactic intravenous haloperidol (1 mg) significantly reduced the incidence of PONV in women undergoing ambulatory laparoscopic surgery.

Mammary gouty tophus: a case report and review of the literature.

We present an uncommon presentation of a common disease in a completely asymptomatic woman. She presented with a solitary breast nodule incidentally found on her first mammography. A step-by-step evaluation of the breast nodule, including fine-needle aspiration and excisional biopsy, was done which revealed mammary gouty tophus.

Antinociceptive effect of a novel long-acting nalbuphine preparation.

BACKGROUND: A long-acting analgesic may be particularly desirable in patients suffering from long-lasting pain. The aim of the study was to evaluate the antinociceptive effect of a novel nalbuphine preparation and to determine its duration of action. METHODS: The antinociceptive effects of i.m. nalbuphine HCl in saline and nalbuphine base in sesame oil were evaluated in rats. The in vitro drug-releasing profiles of nalbuphine HCl and base in different preparations were also evaluated. RESULTS: We found that i.m. nalbuphine HCl 25, 50 and 100 micromol kg(-1) produced dose-related antinociceptive effects with a duration of action of 1.5, 2 and 3 h, respectively. i.m. nalbuphine base 100, 200 and 400 micromol kg(-1) also produced dose-related antinociceptive effects but with longer durations of action: 27, 49 and 55 h, respectively. In vitro studies demonstrated that nalbuphine base in sesame oil had the slowest drug-releasing profile of the different preparations. CONCLUSIONS: i.m. injection of an oil formulation of nalbuphine base produced a long-lasting antinociceptive effect.

Low-dose dexamethasone effectively prevents postoperative nausea and vomiting after ambulatory laparoscopic surgery.

PURPOSE: To evaluate the prophylactic effect of low-dose dexamethasone (5 mg) on postoperative nausea and vomiting (PONV) in women undergoing ambulatory laparoscopic surgery. Metoclopramide and saline served as controls. METHODS: One hundred twenty women (n=40 in each of the three groups) undergoing ambulatory laparoscopic tubal ligation under general anesthesia were enrolled in this randomized, double-blinded, placebo-controlled study. After tracheal intubation, group I received i.v. dexamethasone 5 mg, whereas groups II and III received i.v. metoclopramide 10 mg and saline, respectively. RESULTS: Patients in group I reported a lower incidence of PONV and requested less rescue antiemetics than those in group III during the first four postoperative hours (P <0.01). Patients in group I reported a lower incidence of PONV than those in groups II (P <0.05) and III (P <0.01) during the 24-hr postoperative period. Groups II and III did not differ from each other in the incidence of PONV and the proportion of patients who requested rescue antiemetics. CONCLUSION: Prophylactic iv dexamethasone 5 mg significantly reduces the incidence of PONV in women undergoing ambulatory laparoscopic tubal ligation. At this dose, dexamethasone is more effective than metoclopramide 10 mg or placebo.

Prolonged fractionation of paced right atrial electrograms in patients with atrial flutter and fibrillation.

OBJECTIVES: This study investigated the extent of fractionation of paced right atrial electrograms in patients with and without paroxysmal atrial flutter (AFL) or atrial fibrillation (AF). BACKGROUND: Slow conduction through nonuniform anisotropic atrial muscles, represented by fractionated electrograms, may favor the generation of atrial tachyarrhythmias. METHODS: This study included 10 control patients (Group 1), 8 patients with documented paroxysmal AFL (Group 2) and 10 patients with documented paroxysmal AF (Group 3). Five electrode catheters were placed in the different sites of the right atrium and one catheter was positioned at the coronary sinus ostium. Atrial pacing from one site was done by a constant drive train with an extrastimulus inserted every fourth beat while recording at the other five sites was performed. The delay of each fractionated potential in the high-pass filtered atrial electrogram in response to extrastimulation was determined and used to construct conduction curves of delay versus the S1S2 interval. RESULTS: The mean increase in electrogram duration between a coupling interval of 350 ms and 10 ms above atrial refractoriness was significantly greater in Groups 2 and 3 compared with that in Group 1 (8.5 +/- 2.5 vs. 11.0 +/- 2.7 vs. 5.9 +/- 2.3 ms, respectively, p < 0.001). The mean S1S2 interval at which delay increased suddenly was also longer in Groups 2 and 3 compared with Group 1 (326 +/- 9 vs. 343 +/- 12 vs. 307 +/- 17 ms, respectively, p < 0.001). CONCLUSIONS: Increased delays in the individual potential of the fractionated atrial electrograms may be related to the development of AFL and AF.

Dexamethasone prophylaxis of nausea and vomiting after epidural morphine for post-Cesarean analgesia.

PURPOSE: To determine the minimum effective dose of dexamethasone in preventing nausea and vomiting associated with epidural morphine for post-Cesarean analgesia. METHOD: One hundred and eighty parturients (n=45 in each of four groups) requiring epidural morphine for post-Cesarean analgesia were enrolled in this randomized, double-blinded, placebo-controlled study. At the end of surgery, parturients received either dexamethasone, at doses of 10 mg, 5 mg, 2.5 mg, or saline i.v.. Three milligrams epidural morphine were given to all parturients for postoperative analgesia. The incidence of PONV and side effects were estimated for 24 hr after delivery by blinded, trained nurse anesthetists. RESULTS: Parturients who received dexamethasone, either 10 mg or 5 mg were different from those who received saline alone in the following parameters: the total incidence of nausea and vomiting, incidence of > 4 vomiting episodes, number the of parturients requiring rescue antiemetics, and the total number of parturients with no vomiting and/or no antiemetic medication (P < 0.05 to P < 0.01). The differences between dexamethasone 10 mg and 5 mg were not significant. Dexamethasone 2.5 mg was partially effective. CONCLUSION: Dexamethasone, 5 mg i.v., is suggested as the minimum effective dose in preventing nausea and vomiting associated with epidural morphine for post-Cesarean analgesia.

Dexamethasone for preventing nausea and vomiting associated with epidural morphine: a dose-ranging study.

UNLABELLED: We conducted a dose-ranging study of dexamethasone for preventing nausea and vomiting within the first 24 h after the administration of epidural morphine. Two hundred twenty-five women (n = 45 in each of the five groups) undergoing simple abdominal total hysterectomy under epidural anesthesia were enrolled in this randomized, double-blind, placebo-controlled study. When the incision closure was completed, patients received IV dexamethasone, 10 mg, 5 mg, or 2.5 mg; IV droperidol 1.25 mg; or saline 2 mL. All patients received epidural morphine 3 mg for postoperative analgesia. We found that patients who received dexamethasone 5 mg or 10 mg or droperidol 1.25 mg were significantly different from those who received saline alone in the following variables: the total incidence of nausea and vomiting, the incidence of more than four vomiting episodes, the number of patients requiring rescue antiemetics, the total number of patients with no vomiting and/or no antiemetic medication (P < 0.05 to P < 0.01). The differences among dexamethasone 10 mg and 5 mg and droperidol 1.25 mg were not significant. Dexamethasone 2.5 mg was ineffective. In conclusion, because dexamethasone 5 mg was as effective as 10 mg as an antiemetic, we recommend the smaller dose for preventing nausea and vomiting associated with epidural morphine. IMPLICATIONS: We conducted a dose-ranging study of dexamethasone for preventing nausea and vomiting within the first 24 h after the administration of epidural morphine. We found that dexamethasone 5 mg was as effective as 10 mg. We recommend the smaller dose for this purpose.