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Paru S David,1 Taryn L Smith,2 Hannah C Nordhues,3 Juliana M Kling1 1Department of Internal Medicine, Mayo Clinic, Scottsdale, AZ, USA; 2Department of Internal Medicine, Mayo Clinic, Jacksonville, FL, USA; 3Department of Internal Medicine, Mayo Clinic, Rochester, MN, USACorrespondence: Paru S David, Email david.paru@mayo.eduAbstract: Most women experience vasomotor symptoms (VMS) during their menopausal transition. Menopausal hormone therapy (HT) is the most effective treatment for VMS, but some women choose not to use HT or have contraindications to using HT. Non-hormonal treatment options should be offered to these symptomatic menopausal women. Multiple large randomized controlled trials have demonstrated statistically significant reductions in hot flash severity and/or frequency with the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). To date, paroxetine mesylate remains the only non-hormonal treatment that has been approved by the United States Food and Drug Administration (FDA) for the management of moderate to severe postmenopausal vasomotor symptoms. Lower doses are needed to reduce VMS than those used to treat anxiety or depression, which is beneficial since side effects are typically dose dependent. The recommended dosage is 7.5 mg once daily at bedtime. Dose dependent side effects include nausea, fatigue, and dizziness. Knowing potential medication interactions is critical such as with medications that can lead to serotonin syndrome, concomitant use with monoamine oxidase inhibitors and being aware of p450 drug metabolism is essential for patients taking drugs that utilize the CYP2D6 enzyme for metabolism including tamoxifen. This review discusses in detail the available data supporting the use of paroxetine for the treatment of VMS, including side effects and considerations regarding prescribing. A discussion of other emerging treatments is included as well, including estetrol, oxybutynin and neurokinin 3 (NK3) receptor antagonists.Keywords: menopause, vasomotor symptoms, non-hormonal treatments, paroxetine

BACKGROUND/OBJECTIVE:: Few studies have examined whether chronic heart failure (HF) outcomes can be improved by increasing patient engagement (known as activation) in care and capabilities for self-care management. The objective was to determine the efficacy of a patient activation intervention compared with usual care on activation, self-care management, hospitalizations, and emergency department visits in patients with HF. METHODS:: This study used a randomized, 2-group, repeated-measures design. After consent was given, 84 participants were stratified by activation level and randomly assigned to usual care (n = 41) or usual care plus the intervention (n = 43). The primary outcomes and measures were patient activation using the Patient Activation Measure (PAM), self-management using the Self-Care of Heart Failure Index (SCHFI) and the Medical Outcomes Study (MOS) Specific Adherence Scale, and hospitalizations and emergency department visits. The intervention was a 6-month program to increase activation and improve HF self-management behaviors, such as adhering to medications and implementing health behavior goals. RESULTS:: Participants were primarily male (99%), were white (77%), and had New York Heart Association III stage (52%). The mean (SD) age was 66 (11) years, and 71% reported 3 or more comorbidities. The intervention group compared with the usual care group showed a significant increase in activation/PAM scores from baseline to 6 months. No significant group-by-time interactions were found for the SCHFI scales. Although the baseline MOS Specific Adherence Scale mean was lower in the intervention group, results showed a significant group-by-time effect with the intervention group improving more over time. Participants in the intervention group had fewer hospitalizations compared with the usual care group when the baseline activation/PAM level was low or high. CONCLUSION:: This study supports the importance of targeted interventions to improve patient activation or engagement in HF care. Further work is needed related to HF self-management measurement and outcomes. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the properties of scaffold derived from freeze-dried human Achilles tendon allograft for use in anterior cruciate ligament (ACL) reconstruction. Our hypothesis was that such an allograft could be processed using a method to remove cellular and infectious material, producing a cytocompatible, architecturally modified scaffold possessing tensile properties suitable for ACL reconstruction.Methods: Fifty-two allografts were provided by a tissue bank. Twenty-one were used as controls to assess cellularity, DNA content, microarchitecture, porosity, cytocompatibility, and tensile properties in vitro (n = 13) and in vivo (n = 8). Thirty-one were processed to produce scaffolds that were similarly assessed for these properties in vitro (n = 23) and in vivo (n = 8). The elimination of added enveloped and nonenveloped viruses was also determined in vitro after each processing step.Results: A subjective decrease in cellularity and a significant decrease in DNA content were observed in the scaffolds compared with the allografts from which they had been derived. The porosity was increased significantly, and the scaffolds were cytocompatible in vitro. Processing resulted in significantly increased elongation of the scaffolds (138% of the elongation of the unprocessed allograft) during tensile testing. No other significant differences in tensile properties were observed in vitro or in vivo. The number of infiltrating host cells and the depth to which those cells infiltrated were significantly greater in the scaffolds. No enveloped viruses and only two of 10(8) nonenveloped viruses were detected in the scaffolds after processing, corresponding to a sterility assurance level of 0.2 × 10(-7).Conclusions: Allografts were processed using a method that removed cellular and infectious material to produce a decellularized, cytocompatible, architecturally modified scaffold with tensile properties that differed minimally from those of human allograft tissue both in vitro and in vivo. The scaffold production process also resulted in an increase in porosity that led to increased cell infiltration in vivo. [ABSTRACT FROM AUTHOR]

Melioidosis, an infection caused by the bacterium Burkholderia pseudomallei, is endemic to Southeast Asia and northern Australia but is only very rarely seen in patients in the United States. We report pulmonary B pseudomallei infection in a young girl with cystic fibrosis (CF) who had never traveled to Asia or Australia. Biochemical and epidemiologic investigation determined Aruba as the likely site of disease acquisition. This report highlights the ability of patients with CF to acquire this organism outside of Southeast Asia and describes an aggressive treatment regimen that has kept this patient culture-negative for the organism over a long period of time. [ABSTRACT FROM AUTHOR]

Background: Interactions between the peripheral nervous system and the healing skeleton are poorly understood. Various clinical observations suggest that the nervous system interacts with and promotes fracture-healing. The purpose of this study was to examine the effect of selective sensory denervation on fracture-healing.Methods: Fifty-one Sprague-Dawley rats underwent unilateral placement of an intramedullary rod followed by creation of a standardized femoral fracture. One group of these rats underwent sensory denervation by means of a localized capsaicin injection, and the other did not. Subgroups were allocated for analysis of mRNA expression of collagen I and II and osteocalcin at three, seven, and fourteen days after the fracture. Additionally, histological examination was performed at four weeks; micro-computed tomography, at five weeks; and biomechanical testing, at six weeks.Results: The sensory-denervated group had significantly less collagen-I upregulation than the sensory-intact group at three days after the fracture (difference in means, forty-four-fold [95% confidence interval = 22.7 to 65.5-fold]; p < 0.001) and significantly less collagen-II upregulation at seven days after the fracture (difference in means, ninefold [95% confidence interval = 4.3 to 13.8-fold]; p < 0.001). In the sensory-denervated group, the fracture callus had a significantly larger cross-sectional area (difference in means, 15.6 mm(2) [95% confidence interval = 0.78 to 30.5 mm(2)]; p = 0.043) and was less dense. Biomechanical testing revealed that sensory denervation significantly decreased the load to failure (difference in means, 28.7 N [95% confidence interval = 1.2 to 56.2 N]; p = 0.022).Conclusions: Sensory denervation negatively affects fracture-healing. These results offer insight into the nerve-bone interaction following injury. [ABSTRACT FROM AUTHOR]

AIM: The goals of this paper are to evaluate whether drinking practices among peers mediates the relationship between a low level of response (LR) to alcohol and a person's heavier drinking and alcohol-related problems in 12-14-year-olds. DESIGN: Correlations and structural equation models (SEM) were used to test a hypothesized model of the relationships among key variables in adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC), a longitudinal birth cohort study in Bristol, England. PARTICIPANTS: These included 688 boys (40.4%) and girls who were offspring of the pregnant women who had been selected as ALSPAC participants in 1991 and 1992. The offspring were interviewed at about age 13 years, and those who had ever consumed a full drink completed the Self-Report of the Effects of Alcohol (SRE) questionnaire indicating the number of drinks required for up to four effects early in their drinking histories. A higher number of drinks required for effects indicated a low LR per drink consumed. FINDINGS: The SEM explained 58% of the variance of the alcohol pattern, and had good fit characteristics. A low LR was related to heavier drinking and more alcohol problems both directly and as mediated partially by drinking in peers. The model performed well across the narrow age range, and applied equally well in boys and girls. CONCLUSIONS: The perceived drinking practices of peers is a potentially important mediator of how a low LR to alcohol relates to drinking practices during early adolescence. The findings may be useful in developing approaches to prevent heavier drinking in this young group. [ABSTRACT FROM AUTHOR]

Objective. The national burden of type 2 diabetes mellitus (T2DM) is increasing rapidly. This study investigated a) clinical differences between early onset and later onset T2DM; and b) if specific risk factors were associated with age at diagnosis or clinical outcomes among uninsured adults in a large urban setting. Methods. We compared 417 adults diagnosed under age 30 with 968 adults diagnosed ages 50-58 on clinical and social measures using standard parametric tests. Results. Early onset patients had higher hemoglobin A1c, were more likely to smoke and to be depressed, and had more emergency department visits. Insulin monotherapy was more common in early onset patients (32% vs. 11%). Complications were already present in 11% of early onset patients and 29% of later onset patients within one year of diagnosis. Conclusion. Early onset patients had more acute beta-cell failure and coped less well with their diabetes. It is crucial to expand specialized diabetes resources for young, medically indigent patients. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The purpose of this study was to describe the clinical features of a series of patients in whom sinocutaneous fistula developed in the setting of chronic frontal sinusitis. METHODS: We performed a retrospective case review of patients with sinocutaneous fistula. Clinical records, imaging, and operative reports were carefully examined. A complete literature review for relevant studies was performed to examine similar cases and possible pathophysiology. RESULTS: Three patients with sinocutaneous fistula secondary to frontal sinusitis were identified. All patients underwent successful endoscopic sinus surgery with computer-assisted stereotactic localization and closure of the fistula. CONCLUSIONS: Development of sinocutaneous fistula secondary to frontal sinusitis is rare, but still occurs in the modern antibiotic era. Definitive management of this disease process requires 1) a frontal sinusotomy ensuring patency of the outflow tract and 2) fistula excision and multilayer closure. [ABSTRACT FROM AUTHOR]

Reduction of smoking may increase the likelihood of eventual smoking cessation among those not ready to quit. We describe the development and acceptance of a smoking-reduction intervention that integrates telephone counseling sessions with newsletters. A computer-assisted telephone interviewing program generates real-time-tailored counseling delivered by lay interviewers. Pilot participants (n = 53) were adult smokers scheduled for outpatient procedures in a health maintenance organization, randomized to intervention or a control condition (quarterly mailings). Smoking levels were measured by self-report and biochemically. Among intervention participants continuing at 3 months, all but one rated their telephone support person positively on all dimensions. Counseling calls were 'about right' in number, and newsletters were perceived as quite personal. Intervention recipients reported smoking significantly fewer mean cigarettes per day at 3 months than at baseline, and significantly fewer than control participants. Comparisons were non-significant under intent-to-treat analyses and on biochemical measures. The program was well received by outpatients who were not ready to quit smoking, and was implemented successfully by telephone staff who had no previous smoking cessation counseling experience. An ongoing trial is evaluating effectiveness, cost and relationship to eventual cessation. [ABSTRACT FROM AUTHOR]

Objectives: To compare objective and quality of life (QOL) outcomes after endoscopic sinus surgery (ESS) in aspirin (ASA)-tolerant patients and ASA-intolerant patients over intermediate and long-term follow-up. Study Design: Prospective analysis of a cohort of patients with chronic rhinosinusitis. Methods: Preoperative computed tomography (CT), pre- and postoperative endoscopy, and two validated disease specific QOL instruments, the Rhinosinusitis Disability Index (RSDI) and Chronic Sinusitis Survey (CSS), were collected. Differences in the proportions of patients who improved were analyzed using Pearson's chi-square and Fisher's exact test. Results: Nineteen ASA-intolerant patients and 104 ASA-tolerant patients were followed for a mean of 17.7 months. Patients with ASA intolerance had significantly worse preoperative CT (P < .0001) and endoscopy scores (P < .0001). After ESS, 57% to 74% of patients improved on endoscopy scores, 63% to 71% improved on the RSDI, and 58% to 73% improved on the CSS; improvement did not significantly differ by ASA status. Conclusions: Similar proportions of ASA-tolerant and ASA-intolerant patients showed improvement on endoscopy and QOL measures after ESS. [ABSTRACT FROM AUTHOR]