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Introduction: Many surgeons require patients to quit smoking prior to elective surgeries to reduce the risk of postoperative complications. Our aim was to qualitatively evaluate the communication and care experiences of patients and clinicians involved in conversations about quitting smoking prior to elective orthopaedic surgery., Methods: A qualitative interview study of rural-residing Veterans, primary care providers (PCPs), and Veterans Administration (VA) orthopaedic surgery staff and pharmacists, who care for rural Veterans. We performed a combination of deductive and inductive approaches to support conventional content analysis using a Patient-Centered Care framework., Results: Patients appreciated a shared approach with their PCP on the plan and reasons for cessation. Despite not knowing if the motivation for elective surgeries served as a teachable moment to facilitate long-term abstinence, almost all clinicians believed it typically helped in the short-term. There was a lack of standardized workflow between primary care and surgery, especially when patients used care delivered outside of VA., Conclusions: While clinician-provided information about the reasons behind the requirement to quit smoking preoperatively was beneficial, patients appreciated the opportunity to collaborate with their care teams on developing a plan for cessation and abstinence. Other aspects of patient-centered care need to be leveraged, such as the therapeutic alliance or patient-as-person, to build trust and improve communication surrounding tobacco use treatment. System-level changes may need to be made to improve coordination and connection of clinicians within and across disciplines., Implications: This study included perspectives from patients, primary care teams, and surgical teams and found that, in addition to providing information, clinicians need to address other aspects of patient-centered care such as the therapeutic alliance and patient-as-person domains to promote patient engagement in tobacco use treatment. This, in turn, could enhance the potential of surgery as a teachable moment and patient success in quitting smoking., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Few cancer patients receive guideline-concordant care for treatment of tobacco dependence. The purpose of this pilot trial was to obtain preliminary estimates of effectiveness of an evidence-based practice intervention on the delivery of tobacco treatment and cessation outcomes in cancer patients. We conducted a pragmatic implementation trial with a before-after design in 119 current or recently quit adult smokers with cancer who met with a clinician at a single National Cancer Institute designated comprehensive cancer center (CCC) (n = 61 pre-implementation, n = 58 post-implementation). We used a multi-component strategy based on the Chronic Care Model to implement National Comprehensive Cancer Network (NCCN) guidelines for smoking cessation. Smoking cessation counseling during the index visit was assessed by exit interview and patients were interviewed by phone to assess cessation outcomes at 3-month follow-up. Performance of cessation counseling and 7-day point prevalence abstinence (PPA) were compared across the pre- and post-implementation periods using log-logistic regression, accounting for clustering by nursing staff. More patients had received assistance in quitting at the index visit during the post-implementation period compared to the pre-implementation period (30 vs. 10%, p < .01). At 3-month follow-up, 38 and 14% of participants had discussed smoking cessation medication with a CCC healthcare professional and 57 and 27% of participants had used pharmacotherapy, respectively (p < .01 for both comparisons). Seven-day PPA at 3-month follow-up was similar in both periods, however (14 vs. 12%, respectively). A multi-component tobacco treatment intervention increased the proportion of smokers who received assistance in quitting smoking during usual cancer care but did not improve cessation outcomes., (© Society of Behavioral Medicine 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Chlamydia trachomatis is the most common reportable infection in the United States and can cause pelvic inflammatory disease (PID) and tubal factor infertility (TFI)., Methods: We created life tables to estimate the "lifetime" risk of chlamydia diagnosis among women aged 15-34 years in King County, Washington, between 1992 and 2014. We estimated the lifetime risk of chlamydia-associated PID and TFI incorporating published estimates of the risk of sequelae., Results: There were 51464 first chlamydia diagnoses in 1992-2014. For women born between 1980 and 1984, the lifetime risk of chlamydia diagnosis was 19.8% overall and 14.0% for non-Hispanic white, 64.9% for non-Hispanic black, and 32.6% for Hispanic women. The cumulative risk of chlamydia by age 24 increased overall from 13.9% to 17.3% among women born between 1975 and 1994 but declined among non-Hispanic black women, among whom risk by age 24 declined from 57.3% among women born between 1980 and 1984 to 38.6% among women born between 1990 and 1994. The lifetime risk of chlamydia-associated PID among women born between 1980 and 1984 ranged from 0.33% to 1.14%. Among non-Hispanic white, non-Hispanic black, and Hispanic women, the lifetime risk of chlamydia-associated TFI was 0.04%, 0.20%, and 0.10%, respectively., Conclusions: Over 60% of non-Hispanic black women had at least 1 chlamydia diagnosis by age 34 in the birth cohorts most affected, a risk almost 5 times that in non-Hispanic whites. An estimated 1 in 500 non-Hispanic black women develops chlamydia-associated TFI. More effective control measures are needed.

Background: Antimicrobial-resistant Neisseria gonorrhoeae is a major public health threat. The Centers for Disease Control and Prevention (CDC) recommends ceftriaxone 250 mg plus azithromycin (AZM) 1 g for gonorrhea treatment. Resistance to AZM could affect gonorrhea control efforts., Methods: Using gonococcal isolates collected at the Public Health-Seattle & King County (PHSKC) Sexually Transmitted Disease (STD) Clinic from 2012 to 2016, focusing on 2014-2016, we compared cases with the CDC AZM alert value minimum inhibitory concentration (MIC) (≥2 µg/mL) to those with AZM MIC ≤1 µg/mL, antimicrobial susceptibility profiles and clinical outcomes., Results: In 2012 and 2013, none of the 263 patients from whom we isolated N. gonorrhoeae from the urethra were infected with organisms with an AZM MIC ≥2 µg/mL. Between 2014 and 2016, 4.4% of 926 gonorrhea cases demonstrated reduced susceptibility to AZM; 93% of these cases occurred among men who have sex with men (MSM). Among MSM, 5.0% of 2014-2016 cases demonstrated reduced susceptibility to AZM. No AZM alert value isolates had concomitant cephalosporin resistance. There were 2 potential treatment failures: 1 pharyngeal infection treated with AZM 2 g alone, and 1 pharyngeal infection that persisted after study drug., Conclusions: Among MSM with gonorrhea in Seattle, 5% have gonorrhea with reduced susceptibility to AZM. The World Health Organization recommends changing treatment guidelines when >5% of isolates are resistant to a recommended drug. The emergence of resistant AZM gonorrhea should prompt reconsideration of current treatment recommendations, and highlights the need for new therapies for gonorrhea., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Many hospitalized smokers do not receive guideline-recommended tobacco treatment, but little is known about the perceptions of inpatient nurses with regard to tobacco treatment. We used a sequential explanatory mixed methods design to help explain the findings of an academic detailing intervention trial on the inpatient medicine units of four Veterans Affairs (VA) hospitals. We surveyed 164 nurses and conducted semistructured interviews in a purposeful sample of 33 nurses with different attitudes toward cessation counseling. Content analysis was used to inductively characterize the issues raised by participants. Emerging themes were categorized using the knowledge-attitudes-behavior framework of guideline adherence. Knowledge-related and attitudinal barriers included perceived lack of skills in cessation counseling and skepticism about the effectiveness of cessation guidelines in hospitalized veterans. Nurses also reported multiple behavioral and organizational barriers to guideline adherence: resistance from patients, insufficient time and resources, the presence of smoking areas on VA premises, and lack of coordination with primary care. VA hospitals should train inpatient staff how to negotiate behavior change, integrate cessation counseling into nurses' workflow, develop alternative referral mechanisms for post-discharge cessation counseling, and adopt hospital policies to promote inpatient abstinence., (Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.)

Introduction: The focus on acute care, time pressure, and lack of resources hamper the implementation of smoking cessation guidelines in the emergency department (ED). The purpose of this study was to determine whether an emergency nurse- initiated intervention based on the 5A's (Ask-Advise-Assess-Assist-Arrange) framework improves quit rates., Methods: We conducted a pre-post implementation trial in 789 adult smokers who presented to two EDs in Iowa between August 13, 2008 and August 4, 2010. The intervention focused on improving delivery of the 5A's by ED nurses and physicians using academic detailing, charting/reminder tools, and group feedback. Performance of ED cessation counseling was measured using a 5A's composite score (ranging from 0 to 5). Smoking status was assessed by telephone interview at 3- and 6-month follow-up (with biochemical confirmation in those participants who reported abstinence at 6-month follow-up)., Results: Based on data from 650 smokers who completed the post-ED interview, there was a significant improvement in the mean 5A's composite score for emergency nurses during the intervention period at both hospitals combined (1.51 vs. 0.88, difference = 0.63, 95% confidence interval [CI] [0.41, 0.85]). At 6-month follow-up, 7-day point prevalence abstinence (PPA) was 6.8 and 5.1% in intervention and preintervention periods, respectively (adjusted odds ratio [OR] = 1.7, 95% CI [0.99, 2.9])., Conclusions: It is feasible to improve the delivery of brief smoking cessation counseling by ED staff. The observed improvements in performance of cessation counseling, however, did not translate into statistically significant improvements in cessation rates. Further improvements in the effectiveness of ED cessation interventions are needed.

Dopamine D3 receptors are preferentially localized in the limbic system and midbrain, and thus may be involved in the pathophysiology of neuropsychiatry disorders. [11C](+)-PHNO is the first preferential D3 receptor radioligand in humans, yet there are no blockade studies with a D3 receptor antagonist in humans. This study characterized the blockade of [11C](+)-PHNO binding by ABT-925, a D3 receptor antagonist, in healthy male subjects. Sixteen subjects underwent 2-3 positron emission tomography (PET) scans, at baseline and following one or two doses of ABT-925 ranging from 50 mg to 600 mg. Receptor occupancies were estimated for globus pallidus, substantia nigra, caudate, putamen, and ventral striatum. At the 600-mg dose (n=9), ABT-925 receptor occupancy (mean+/-s.d.) was higher in substantia nigra (75+/-10%) and globus pallidus (64+/-22%) than in ventral striatum (44+/-17%), caudate (40+/-18%) and putamen (38+/-17%) (ANOVA: F4,140=15.02, p<0.001). The fractions of [11C](+)-PHNO binding attributable to D3 receptors in D3 receptor-rich regions were 100% (substantia nigra) and 90% (globus pallidus), and in D2 receptor-rich regions were 55% (caudate) and 53% (putamen). The ED50 of ABT-925 was 4.37 microg/ml across regions. Our results demonstrate that [11C](+)-PHNO binding can be blocked by a D3 receptor antagonist and confirm preclinical findings that [11C](+)-PHNO signal in the substantia nigra and globus pallidus is mainly reflective of its binding to D3 receptors. Thus, [11C](+)-PHNO seems a suitable PET radiotracer to estimate D3 receptor occupancy in humans.

Background: The Agency for Healthcare Research and Quality (AHRQ) Smoking Cessation Clinical Practice Guideline recommends that all clinicians strongly advise their patients who use tobacco to quit., Methods: We conducted a randomized, controlled trial of the effectiveness of Guideline implementation at eight community-based primary care clinics in southern Wisconsin (four test sites, four control sites) among 2163 consecutively enrolled adult patients who smoked at least one cigarette per day and presented for nonemergency care during the baseline period (June 16, 1999, to June 20, 2000) or the intervention period (from June 21, 2000, to May 3, 2001). After collecting baseline data, staff at test sites implemented the intervention over a 2-month period. The intervention included a tutorial for intake clinicians, group and individual performance feedback for intake clinicians, use of a modified vital signs stamp, an offer of free nicotine replacement therapy, and proactive telephone counseling. Staff at control sites received only general information about the AHRQ Guideline. Self-reported abstinence from smoking was determined by telephone interviews at 2- and 6-month follow-up assessments. Hierarchical logistic regression models were used to estimate the odds ratios (ORs) for treatment assignment after adjustment for patient characteristics. All statistical tests were two-sided., Results: There were no statistically significant differences in smoking cessation rates between participants at test and control sites during the baseline period. Among participants treated during the intervention period, those at test sites were more likely than those at control sites to report being abstinent at the 2-month (16.4% versus 5.8%; adjusted OR = 3.3, 95% confidence interval [CI] = 1.9 to 5.6; P<.001) and 6-month (15.4% versus 9.8%; adjusted OR = 1.7, 95% CI = 1.2 to 2.6; P =.009) follow-up assessments and to report continuous abstinence, that is, abstinence at both 2 and 6 months (10.9% versus 3.8%; adjusted OR = 3.4, 95% CI = 1.8 to 6.3; P<.001)., Conclusion: Implementation of a guideline-based smoking cessation intervention by intake clinicians in primary care is associated with higher abstinence among smokers.

Negative sellar exploration (despite the results of endocrine evaluation indicating Cushing's disease), the high incidence of failure of total hypophysectomy, and remission of Cushing's syndrome after unsuccessful hypophysectomy and sellar irradiation suggest that the etiology of refractory Cushing's disease, in some patients, lies near the sella but not in the pituitary gland. We present 5 patients, out of 626 who received surgery for Cushing's disease, in whom an ACTH-secreting extrapituitary parasellar adenoma was identified: 2 after unsuccessful total hypophysectomy for the treatment of refractory Cushing's disease, 2 after unsuccessful hemihypophysectomy (the first, 2 yr before treatment at the NIH for Nelson's syndrome; and the second, with recurrent Cushing's disease 5 yr after negative transsphenoidal exploration), and 1 with a preoperative diagnosis of an intraclival microadenoma, which was cured by resection of the tumor. In all cases, an extrapituitary parasellar microadenoma was confirmed unequivocally as the cause of the disease, by negative pathology of the resected pituitary gland (patients 1, 2, 3, and 5), and/or the remission of the disease after selective resection of the extrasellar adenoma (patients 3, 4, and 5). Three of 5 patients had a partial empty sella. These patients support the thesis that ACTH-secreting tumors can arise exclusively from remnants of Rathke's pouch, rather than from the adenohypophysis (anterior lobe or pars tuberalis of the pituitary gland) and can be a cause of Cushing's disease. In the sixth presented case, an extrapituitary tumor was suspected at surgery after negative pituitary exploration, but serial sections of the hemihypophysectomy specimen revealed a microscopic focus of tumor at the margin of the resected gland. This case demonstrates the importance of negative pituitary histology to establish the presence of an extrapituitary parasellar tumor as an exclusive source of ACTH, and it supports the value of clinical outcome to establish the diagnosis with selective adenomectomy of an extrapituitary parasellar tumor. In patients with negative pituitary magnetic resonance imaging, especially in the presence of a partial empty sella, the diagnostic and surgical approach in Cushing's disease should consider the identification and resection of extrapituitary parasellar adenoma, which can avoid total hypophysectomy, as was possible in 3 of our 5 patients.

Nelson's syndrome is the appearance and/or progression of ACTH-secreting pituitary macroadenomas in patients who had previously undergone bilateral adrenalectomy for Cushing's disease. Extremely high plasma ACTH levels and aggressive neoplastic growth might be explained by the lack of appropriate glucocorticoid negative feedback due to defective glucocorticoid signal transduction. To study the glucocorticoid receptor (GR) gene in Nelson's syndrome, DNA was extracted from pituitary adenomas and leukocytes of four patients with this condition and amplified by PCR for direct sequence analysis. In one of the tumors, a heterozygous mutation, consisting of an insertion of a thymine between complementary DNA nucleotides 1188 and 1189, was found in exon 2. This frame-shift mutation led to premature termination at amino acid residue 366 of the wild-type coding sequence, excluding the expression of a functioning receptor protein from the defective allele. The mutation was not detected in the sequence of the GR gene in the patient's leukocyte DNA, indicating a somatic origin. By lowering the receptor number in tumorous cells, this defect might have caused local resistance to negative glucocorticoid feedback similar to that caused by the presence of a null allele in a kindred with the generalized glucocorticoid resistance syndrome. P53 protein accumulation, previously reported in 60% of corticotropinomas, could not be detected in any of the four pituitary tumors examined by immunohistochemistry. We suggest that a somatic GR defect might have played a pathophysiological role in the tumorigenesis of the corticotropinoma bearing this mutation.

Levels of human immunodeficiency virus type 1 (HIV-1) DNA and quinolinic acid were examined in areas of the central nervous system (CNS) and lymphoid organs (LN) from 5 AIDS patients with no clinically apparent CNS compromise (group I), 7 with CNS opportunistic diseases (group II), and 8 with HIV encephalopathy (group III). The brains from patients with HIV encephalopathy not only contained higher levels of HIV-1 DNA (cerebrum, P < .01; cerebellum, P < .05) as assessed by quantitative polymerase chain reaction but also showed a higher rate of viral pol region mutations suggestive of zidovudine or didanosine resistance than brains from patients in group I or II (P < .01). CNS quinolinic acid concentrations were significantly higher in group II and III patients than in group I (P = .03), even though quinolinic acid levels in LN were comparable among the 3 groups. These data suggest that CNS inflammatory changes associated with HIV encephalopathy may be triggered by a local productive HIV-1 infection within the CNS.

The 3'-untranslated regions of many labile transcripts contain AU-rich sequences that serve as cis determinants of mRNA stability and translational efficiency. Using a photocrosslinking technique, our laboratory has previously defined three cytoplasmic RNA-binding activities specific for the AUUUA multimers found in the 3'-untranslated regions of lymphokine mRNAs. One of these activities, AU-A, has an apparent molecular mass of 34 kDa, is constitutively expressed in both primary T cells and the Jurkat T cell leukemia line, and binds to a variety of U-rich RNA sequences. Previous studies had shown that AU-A is more prevalent in the nucleus than the cytoplasm, raising the possibility that AU-A is really a nuclear RNA-binding activity that is found in cytoplasmic extracts because of nuclear leakage during cell fractionation. We now show that AU-A shuttles between the cytoplasm and the nucleus. Our results indicate that AU-A is a candidate protein component of ribonucleoprotein complexes that participate in nucleocytoplasmic transport of mRNA and cytoplasmic mRNA metabolism. The properties of AU-A activity are similar to those of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1). However, using monoclonal antibodies to hnRNP A1 and protease digestion patterns, we show that AU-A activity and hnRNP A1 protein are distinct. These studies have also allowed us to define a fourth RNA-binding activity of apparent molecular mass 41 kDa with specificity for AUUUA multimers. This activity is restricted to the nucleus and contains the hnRNP C protein.

Pituitary tumors rarely metastasize outside the central nervous system. Of the more than 100 reported TSH-secreting adenomas, we now describe the first carcinoma. A 40-yr-old woman had transsphenoidal surgery for a large TSH-secreting pituitary adenoma in 1984. She had increased thyroid hormone levels with a TSH that varied from 16-31 microU/mL, and an unusually high alpha-subunit that ranged from 125-150 ng/mL. Because of residual tumor, she had a left craniotomy in 1985 followed by radiation. Despite these therapies, she had a residual tumor that remained stable until January 1989 when her tumor nearly doubled in size. She received radiation therapy and octreotide with marked diminution of the tumor and clinical improvement. In August 1989, she presented with leg weakness, and magnetic resonance imaging revealed a large sacral mass. A biopsy confirmed that the sacral mass was a metastasis from the pituitary tumor. Due to additional metastases in the lung, she received 5-fluorouracil, cytoxan, and adriamycin, with marked decrease in her lesions. Further substantiation of the metastatic pituitary tumor was made when the patient returned in December 1989 with a pleural effusion containing pituitary tumor cells. Of all the reported cases of TSH-secreting adenomas, this case had the highest alpha-subunit portending future metastases. Furthermore, the apparent response to octreotide and response to chemotherapy are encouraging and suggest that new therapies should be explored. Finally, since TSH-secreting adenomas tend to be more invasive than other pituitary tumors, this case underscores the need for early diagnosis and aggressive treatment of these tumors.

The synthesis and secretion of anterior pituitary hormones are subjected to a variety of positive and negative feedback mechanisms. Aberrancies of these highly regulated phenomena may lead to hyperplasia involving multiple cells of the anterior lobe. Alternatively, a rare genetic mutation in a single cell may precede its clonal expansion. Which of these mechanisms is operative in the development of corticotroph adenomas is not known. To examine this question, we studied the clonal composition of ACTH-producing pituitary adenomas from female patients with Cushing's disease by using X-chromosome inactivation analysis. Nine of 27 patients examined were heterozygous at 1 of the 2 X-chromosome-linked polymorphic loci, hypoxanthine-phosphoribosyl-transferase and phosphoglycerate-kinase. The methylation patterns of the hypoxanthine-phosphoribosyl-transferase and phosphoglycerate-kinase genes, distinguishing between the active and inactive alleles, were analyzed in DNA extracted from the central part of the tumor and compared with those of autologous lymphocyte DNA. Six tumors (4 microadenomas and 2 macroadenomas) showed a single active allele of the X-chromosome-linked genes and were monoclonal in nature. The other 3 pituitary adenomas (1 microadenoma and 2 macroadenomas, 1 from a patient with Nelson's syndrome) revealed a polyclonal pattern of X-chromosome inactivation. Our data demonstrate that corticotroph adenomas of the pituitary may arise from a single cell or from more than one cell. Whether fundamentally different endocrine mechanisms underlie the two processes remains to be seen.

The clinical and histologic features of a benign cystic teratoma with histologic evidence of almost full gastrointestinal tract development are discussed. The literature has previously described only bowel epithelium, segments of bowel, appendix, and esophagus separately. This is the first report of almost complete development of the gastrointestinal tract in a benign cystic teratoma. In this teratoma, the entire gastrointestinal tract from esophagus to colon is represented histologically.