ONS Guidelines™ for Cancer Treatment-Related Hot Flashes in Women With Breast Cancer and Men With Prostate Cancer.

PURPOSE: Hot flashes are a common and troublesome side effect of surgery or endocrine therapy. They may lead to physical and psychological distress and negatively affect quality of life. This clinical practice guideline presents evidence-based recommendations for pharmacologic, behavioral, and natural health product interventions for treatment-related hot flashes in patients with breast or prostate cancer. METHODOLOGIC APPROACH: An interprofessional panel of healthcare professionals with patient representation prioritized clinical questions and patient outcomes for the management of hot flashes. Systematic reviews of the literature were conducted. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach was used to assess the evidence and make recommendations. FINDINGS: The panel agreed on 14 pharmacologic, behavioral, and natural health recommendations. IMPLICATIONS FOR NURSING: Conditional recommendations include the use of antidepressants rather than no treatment, physical activity rather than no treatment, and the avoidance of gabapentin and dietary supplements in the treatment of hot flashes. SUPPLEMENTARY MATERIAL CAN BE FOUND AT HTTPS: //onf.ons.org/ons-guidelines-hot-flashes-supplementary-material.

Long-term use of antipsychotics and antidepressants is not evidence-based.

BACKGROUND: The widespread use of psychiatric drugs does not appear to be evidence-based but seems to be driven mainly by commercial pressures. I studied whether two widely differing drug classes, antipsychotics and antidepressants, showed similar patterns in long-term usage. METHODS: I constructed usage curves over a ten-year period, from 2006 to 2016, based on data from Statistics Denmark. RESULTS: In 2006, a total of 110,235 patients deemed a prescription for an antipsychotic and 395,018 for an antidepressant, corresponding to 2.0% and 7.3% of the Danish population. Only 21,846 vs. 79,030 of these were first-time users (19.8% vs. 20.0%). The percentage of current users who redeemed a prescription for the same or a similar drug in each of the following years was remarkably similar for the two classes of drugs, and after ten years, it was 35% vs. 33%.Using the requirement that the patients identified in 2006 needed to redeem the prescription only once during the next ten years, 42% vs. 43% were taking a drug in 2016. This suggests that most patients identified at any given point in time as drug users continue taking such drugs for many years, with little or no interruption in drug intake.For first-time users, the drop in usage was much quicker. The percentage of first-time users who redeemed a prescription for the same or a similar drug in each of the following years fell to about one-third (29% vs. 36%) already after two years.Using 2011 as the starting year yielded similar results. CONCLUSIONS: If we accept the evidence-based premises that antipsychotics and antidepressants do not have clinically relevant effects and that the patients dislike them, the data suggest massive overuse of the drugs, to a remarkably similar degree. We need to focus on helping patients withdraw slowly and safely from the drugs they are on instead of telling them that they need to stay on them.

Different Depression Treatment Recommendations and Adherence for Spanish- and English-Speaking Patients.

INTRODUCTION: National guidelines recommend primary care providers (PCPs) screen patients for depression with a standardized tool and address positive screenings. However, depression prevalence is lower in Latinos (8% to 15%, with Spanish speakers at 8%) than non-Latino whites (22%). As a result of these prevalence differences, PCPs may use ethnicity and language of the patient to determine depression screening behaviors. This study examined standard of care (SoC) depression treatment recommendations by ethnicity and language for patients who screened positive for major depression during a medical visit. METHODS: 275 patients scored ≥10 on the Patient Health Questionnaire-9 screening; a chart review assessed treatment referrals, followed by semistructured interviews with 18 patients and 7 PCPs regarding depression treatment behaviors. RESULTS: 138 patients (50%) received SoC treatment recommendations. After controlling for age, gender, and race, a binary logistic regression was performed to determine language and ethnicity effects on SoC depression treatment recommendations (psychotherapy/pharmacotherapy vs other). Spanish-speaking Latinos were 72% less likely to receive SoC recommendations than English speakers (odds ratio [OR] = 0.39). Interviews with Spanish-speaking patients confirmed that negative perceptions about medications, patient noncompliance, and a shortage of bilingual behavioral health providers within the clinic impacted SoC recommendations and uptake. CONCLUSIONS: Spanish-speaking Latinos did not receive or follow through with SoC recommendations as often as English speakers regardless of ethnicity. Future studies should explore reasons why language is a barrier to SoC recommendations for Latinos and explore culturally and linguistically sensitive methods to effectively treat Spanish speakers for depression during a medical visit.

Guidelines for the pharmacological acute treatment of major depression: conflicts with current evidence as demonstrated with the German S3-guidelines.

Several international guidelines for the acute treatment of moderate to severe unipolar depression recommend a first-line treatment with antidepressants (AD). This is based on the assumption that AD obviously outperform placebo, at least in the case of severe depression. The efficacy of AD for severe depression can only be definitely clarified with individual patient data, but corresponding studies have only been available recently. In this paper, we point out discrepancies between the content of guidelines and the scientific evidence by taking a closer look at the German S3-guidelines for the treatment of depression. Based on recent studies and a systematic review of studies using individual patient data, it turns out that AD are marginally superior to placebo in both moderate and severe depression. The clinical significance of this small drug-placebo-difference is questionable, even in the most severe forms of depression. In addition, the modest efficacy is likely an overestimation of the true efficacy due to systematic method biases. There is no related discussion in the S3-guidelines, despite substantial empirical evidence confirming these biases. In light of recent data and with their underlying biases, the recommendations in the S3-guidelines are in contradiction with the current evidence. The risk-benefit ratio of AD for severe depression may be similar to the one estimated for mild depression and thus could be unfavorable. Downgrading of the related grade of recommendation would be a logical consequence.

Clinical depression in untreated obstructive sleep apnea: examining predictors and a meta-analysis of prevalence rates.

OBJECTIVE/BACKGROUND: Patients with obstructive sleep apnea (OSA) experience daytime sleepiness, cognitive impairment and depressive symptoms. However, the measured prevalence of clinical depression in OSA using standardized clinical assessment is currently unclear. The aims of this study were to examine the prevalence of clinical depression and antidepressant use in untreated OSA patients, to examine predictors of depression, and to conduct an exploratory meta-analysis to determine the pooled prevalence of clinical depression in this population. PATIENTS/METHODS: In sum, 109 consecutive patients with diagnosed OSA (mean age (SD) = 52.6 (12.1) years; 43.1% female) who presented to the sleep laboratory completed a structured clinical interview for depression (SCID-IV), the Hospital Anxiety and Depression Scale, the Pittsburgh Sleep Quality Index (PSQI), the Functional Outcomes of Sleep Questionnaire (FOSQ), the Assessment of Quality of Life Questionnaire (AQoL) and the Epworth Sleepiness Scale (EES). An exploratory meta-analysis was also conducted to quantify the risk of clinical depression in untreated OSA. RESULTS: Twenty-five (22.7%) participants had clinical depression based on the SCID-IV, and 24.8% were using antidepressants. Those with clinical depression had significantly poorer sleep quality and impaired quality of life. In a regression model, quality of life impairment was most strongly associated with clinical depression. Results from the meta-analysis revealed a pooled prevalence of 23% of clinical depression in OSA patients across seven studies. CONCLUSION: Clinical depression and antidepressant use is common in patients with OSA. Depression was associated with reduced quality of life and poorer subjective sleep, however it was not associated with polysomnographic measures or daytime sleepiness. Whether CPAP treatment can alleviate the burden of clinical depression needs to be determined in future studies.

The Efficacy of Playing Videogames Compared with Antidepressants in Reducing Treatment-Resistant Symptoms of Depression.

Objective: The goal of this month-long controlled study was to compare the efficacy of a second antidepressant (sAD) medication with a prescribed regimen of Plants vs. Zombies™ (PvZ), a casual videogame, in reducing treatment-resistant depression symptoms (TRDS) and improving heart rate variability (HRV). Materials and Methods: Approximately ∼8 weeks after beginning antidepressant therapy, participants returned to psychiatrists for evaluation and complained of TRDS. The psychiatrist gave them a choice of self-selecting a sAD medication or playing a prescribed regimen of PvZ as part of a research study. Those who agreed were referred to researchers who then screened them for major depression, the criteria for inclusion. PvZ was prescribed four times per week for 30-45 minutes over 4 weeks. Self-reported data were collected at four different times utilizing the Patient Health Questionnaire-9. HRV, an indicator of autonomic nervous system (ANS) functioning, was also recorded each time. Results: The sAD group's TRDS significantly improved. Remarkably, the PvZ group's TRDS improved significantly beyond the control group at all measurement times except for time 1 or baseline. In addition, a single 30-minute session of playing PvZ was significantly more effective in acutely reducing TRDS when compared with the sAD group that surfed the NIHM website on depression. Changes in HRV parameters indicated increased parasympathetic engagement and ANS balance in the PvZ group compared with the sAD group. Discussion: The findings illustrate the potential of PvZ as an acute and chronic intervention for reducing TRDS. Health care practitioners such as physicians and recreational therapists can consider recommending a regimen of prescribed PvZ play as a method to ameliorate symptoms of depression for those clients who self-select this option. Finally, a psychophysiological method for measuring the efficacy of videogames in reducing TRDS and a means to quantify ANS changes during gameplay are presented.

Discontinuation Rates of Antidepressant Use by Dutch Soldiers.

INTRODUCTION: Soldiers have a higher risk for developing psychiatric disorders that require treatment; often with antidepressants. However, antidepressants as well as the psychiatric disorder, may influence military readiness in several ways. In the general population, early discontinuation of antidepressant treatment is often seen. It is yet unknown whether this occurs to a similar extent in soldiers. The objective of this study was to evaluate discontinuation of antidepressant use by Dutch soldiers in the first 12 months after start and determinants thereof. MATERIALS AND METHODS: Data were obtained from the military pharmacy. All Dutch soldiers who started using an antidepressant between 2000 and 2014 were included. Kaplan-Meier curves were constructed to estimate the discontinuation rate over time and the influence of each determinant on discontinuation rate was estimated using Cox regression. RESULTS: About 25.9% of de 2479 starters had discontinued their antidepressant use after 1 month; after 3 and 6 months this number increased to 52.7% and 70.3%, respectively. Early discontinuation was higher in soldiers who received their first prescription from a neurologist or rehabilitation specialist (HR 1.85, 95% CI 1.55-2.21, HR 2.66 95% CI 1.97-3.58) compared to soldiers with a first prescription from a general practitioner. In addition, early discontinuation was lower in soldiers who were prescribed serotonin reuptake inhibitors and other antidepressants (HR 0.57, 95% CI 0.51-0.60, HR 0.63, 95% CI 0.55-0.73) and in soldiers between 40 and 50 years of age (HR 0.79, 95% CI 0.70-0.89). CONCLUSION: More than half of the soldiers discontinued their prescribed antidepressant within 3 months and after 6 months, only 30% were still on antidepressants.

Change in Pain Score after Administration of Analgesics for Lower Extremity Fracture Pain during Hospitalization.

BACKGROUND: Effective acute pain management following injury is critical to improve short-and long-term patient outcomes. Analgesics can effectively reduce pain intensity, yet half of injury patients report moderate to severe pain during hospitalization. PURPOSE: The primary aim of this study was to identify the analgesic, different analgesic combinations, or analgesic and adjuvant analgesic combination that generated the largest percent change from pre- to post-analgesic pain score. DESIGN: This was a descriptive retrospective cohort study of 129 adults admitted with lower extremity fractures to a trauma center. METHODS: Name, dose, and frequency of analgesics and adjuvant analgesics administered from admission to discharge were collected from medical records. Percent change was calculated from pain scores documented on the 0-10 numeric rating scale. RESULTS: The analgesic with largest percent change from pre- to post-administration pain score was hydromorphone 2 mg IV (53%) for the emergency department and morphine 4 mg IV (54%) for the in-patient unit. All analgesics administered in the emergency department and ∼50% administered on the in-patient unit produced a minimal (15%) decrease in pain score. CONCLUSIONS: This study revealed that few analgesics administered in the emergency department and the in-patient unit to patients with lower extremity fractures provide adequate pain relief. In the emergency department, all analgesics administered resulted in at least minimal improvement of pain. On the in-patient unit 13 analgesic doses resulted at least minimal improvement in pain while nine doses did not even reach 20% change in pain. Findings from this study can be used guide the treatment of fracture pain in the hospital.

Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management.

The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. The extract decreased lipid peroxidation and prevented the reduction of superoxide dismutase and catalase activities in the prefrontal cortex, hippocampus and striatum of animals submitted to HPD. We observed a HPD-induced reduction of thiol content in these cerebral structures. The extract prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test. Regarding chemical composition, LC/MS analysis showed the presence of nine anthocyanins as the major compounds. In conclusion, E. uniflora extract showed benefits against metabolic alterations caused by HPD, as well as exhibited antioxidant and antidepressant-like effects.

Caring for dementia: a population-based study examining variations in guideline-consistent medical care.

BACKGROUND: Evidence indicates that early detection and management of dementia care can improve outcomes. We assess variations in dementia care based on processes outlined in clinical guidelines by the BC Ministry of Health. METHOD: A population-based retrospective cohort study of community-dwelling seniors using patient-level administrative data in British Columbia, Canada. Guidelines measured: laboratory testing, imaging, prescriptions, complete examination, counseling, and specialist referral. RESULTS: Older patients were less likely to receive guideline-consistent medical care. Patients in higher income categories had higher odds of receiving counseling (confidence interval or CI 1.13-153) and referrals (15.1 CI 1.18-1.95) compared with those of lower income. Over a quarter of the cohort received an antipsychotic (28%) or nonrecommended benzodiazepine (26%). Individuals living within "rural" health authorities or of low income were more likely to receive antipsychotic treatment. CONCLUSION: Patterns of inequality by age and income may signal barriers to care, particularly for management of dementia care processes.

Ultra high performance supercritical fluid chromatography coupled with tandem mass spectrometry for screening of doping agents. II: Analysis of biological samples.

The potential and applicability of UHPSFC-MS/MS for anti-doping screening in urine samples were tested for the first time. For this purpose, a group of 110 doping agents with diverse physicochemical properties was analyzed using two separation techniques, namely UHPLC-MS/MS and UHPSFC-MS/MS in both ESI+ and ESI- modes. The two approaches were compared in terms of selectivity, sensitivity, linearity and matrix effects. As expected, very diverse retentions and selectivities were obtained in UHPLC and UHPSFC, proving a good complementarity of these analytical strategies. In both conditions, acceptable peak shapes and MS detection capabilities were obtained within 7 min analysis time, enabling the application of these two methods for screening purposes. Method sensitivity was found comparable for 46% of tested compounds, while higher sensitivity was observed for 21% of tested compounds in UHPLC-MS/MS and for 32% in UHPSFC-MS/MS. The latter demonstrated a lower susceptibility to matrix effects, which were mostly observed as signal suppression. In the case of UHPLC-MS/MS, more serious matrix effects were observed, leading typically to signal enhancement and the matrix effect was also concentration dependent, i.e., more significant matrix effects occurred at the lowest concentrations.

Potential antidepressant overtreatment associated with office use of brief depression symptom measures.

BACKGROUND: Use of brief depression symptom measures for identifying or screening cases may help to address depression undertreatment, but whether it also leads to diagnosis and treatment of patients with few or no symptoms-a group unlikely to have major depression or benefit from antidepressants-is unknown. We examined the associations of use of a brief depression symptom measure with depression diagnosis and antidepressant recommendation and prescription among patients with few or no depression symptoms. METHODS: We conducted exploratory observational analyses of data from a randomized trial of depression engagement interventions conducted in primary care offices in California. Analyses focused on participants scoring <10 on a study-administered 9-item Patient Health Questionnaire (PHQ-9) (completed immediately before an office visit and not disclosed to the provider) with complete chart review data (n = 595). We reviewed visit notes for evidence of practice administration of a brief symptom measure (independent of the trial) and whether the provider (1) diagnosed depression or (2) recommended and/or prescribed an antidepressant. RESULTS: Among the 545 patients without a practice-administered measure, 57 (10.5%) had a visit diagnosis of depression; 9 (1.6%) were recommended and another 21 (3.8%) prescribed an antidepressant. Among the 50 patients (8.4% of total sample) with a practice-administered measure, 10 (20%) had a visit diagnosis of depression; 6 (12%) were recommended and another 6 (12%) prescribed an antidepressant. Adjusting for nesting within providers, trial intervention, stratification variables, and sample weighting, use of a brief symptom measure was associated with depression diagnosis (adjusted odds ratio, 3.2; 95% confidence interval, 1.1-9.2) and antidepressant recommendation and/or prescription (adjusted odds ratio, 3.80; 95% confidence interval, 1.0-13.9). Analyses using progressively lower PHQ-9 thresholds (<9 to <5) and examining antidepressant prescription alone yielded consistent findings. Analyses by practice-administered measure (PHQ-9 vs PHQ-2) indicated the study findings were largely associated with PHQ-9 use. CONCLUSIONS: These exploratory findings suggest administration of brief depression symptom measures, particularly the PHQ-9, may be associated with depression diagnosis and antidepressant recommendation and prescription among patients unlikely to have major depression. If these findings are confirmed, researchers should investigate the balance of benefits and risks (eg, overdiagnosis of depression and overtreatment with antidepressants) associated with use of a brief symptom measure.

Standard and emerging treatment options for diabetic neuropathy.

Diabetic neuropathy is a common complication of diabetes mellitus affecting 30-50% of patients and is a major cause for increased costs, morbidity and mortality. Strict diabetes control prevents this complication and may restore neurologic deficits in the early stages. Several efforts have been undertaken to alter the natural history of this complication, including the use of aldose reductase and protein kinase-C inhibitors, as well as antioxidants. Available data so far do not support the use of aldose reductase inhibitors due to safety issues and efficacy. Protein kinase-C inhibitors have provided encouraging initial results but their development has been halted. Antioxidants, like a-lipoic acid, improve some neurological deficits and painful symptoms. There are effective and safe medications such as anticonvulsants, antidepressants and opioids for the management of patients with painful symptoms. In this revew we present standard and emerging treatment modalities for the etiologic and symptomatic treatment of diabetic neuropathy.

Quantification and structural elucidation of potential impurities in agomelatine active pharmaceutical ingredient.

Seven impurities in agomelatine drug substance were determined by a newly developed RP-HPLC method. Structures of potential impurities were confirmed by NMR and IR analysis. Efficient chromatographic separation was achieved on Hypersil BDS C18 column (250 mm × 4.6 mm, 5 µm) in gradient mode by using a binary mixture of potassium dihydrogen phosphate (15 mM, pH adjusted to 3.0) and acetonitrile at a flow rate of 1.0 ml/min. A photodiode array detector set at 230 nm was used for detection. Forced degradation studies showed that the proposed method was specific, and agomelatine was found to be susceptible to acidic and alkaline conditions. The method was validated according to ICH guidelines with respect to specificity, sensitivity, precision, linearity, accuracy, robustness and system suitability. Detection limit of impurities was in the range of 0.0008-0.0047%. Regression analysis showed correlation coefficient value greater than 0.999 for agomelatine and its seven impurities. Accuracy of the method was established based on the recovery obtained between 94.4% and 106.7% for all impurities. The validation results demonstrated that the developed method was suitable for the quantitative determination of potential impurities in agomelatine. A possible mechanism for the formation of impurities was proposed.

Neuroenhancement - perspectives of Swiss psychiatrists and general practitioners.

QUESTIONS UNDER STUDY: Although the ethical and health implications of neuroenhancement have been intensely discussed over the past years, little is known about the experiences and attitudes of physicians confronted with requests for neuroenhancing substances. The aim of this study was to explore general practitioners' and psychiatrists' familiarity with such requests and their willingness to prescribe these products. METHOD: A nation-wide cross-sectional survey among general practitioners and psychiatrists in Switzerland was conducted. A questionnaire was developed, pre-tested and sent out to a pre-defined sample of 1,600 Swiss practising physicians in the fields of psychiatry and general practice/internal medicine in the German-speaking and French-speaking part of Switzerland. RESULTS: A total of 393 questionnaires were returned (response rate: 24.7%). 80.2% of study participants were encountered requests for neuroenhancing products in their own practice, mostly not exceeding 1-2 times a year. A total of 41.1% were undecided when asked if they categorically against neuroenhancement, 49% would decide on a case-by-case basis, and 9.6% would decide according to patients' wishes. CONCLUSIONS: Swiss psychiatrists and general practitioners are confronted with requests for neuroenhancement, albeit not very frequently. Most participants embrace a pragmatic position towards neuroenhancement, although there is also a considerable degree of uncertainty about the appropriateness of a categorical refusal. A minority would follow a consumer model that leaves the decision about the use of neuroenhancers to the client, even though this conflicts with legal requirements regarding drug prescriptions.