Evaluation of extended and continuous use oral contraceptives

Oral contraceptives are classically given in a cyclic manner with 21 days of active pills followed by 7 days of placebo. In the past 4 years, new oral contraceptives have been introduced which either shorten the placebo time, lengthen the active pills (extended cycle), or provide active pills every day (continuous). These concepts are not new; extended and continuous pills were first studied in the 1960s and 1970s and have been provided in an off-label manner by gynecologists to treat menstrual disorders, such as menorrhagia and dysmenorrhea, and gynecologic disorders, such as endometriosis. Now that extended and continuous combined oral contraceptives are available for all patients, it is critical for providers to understand the physiology, dosing, side effects, and benefits of this form of oral contraceptive. This article reviews the history and the potential uses of the new continuous combined oral contraceptive

The Science and Psychology of Infertility

An evidence-based presentation on the science/etiologies of infertility and its psychological impact. Outline: Prevalence and Etiology of Infertility. Basic Evaluation. Treatment Options. Psychological Effects of Infertility. Depression/Anxiety. Social, Cultural, and Gender Issues. Relationship Issues. Patient Distress and Pregnancy Rates. Psychological Support. Evidence-Based Psychological Interventions

General practice palliative care: Patient and carer expectations, advance care plans and place of death-a systematic review

Background: With an increasing ageing population in most countries, the role of general practitioners (GPs) and general practice nurses (GPNs) in providing optimal end of life (EoL) care is increasingly important. Objective: To explore: (1) patient and carer expectations of the role of GPs and GPNs at EoL; (2) GPs’ and GPNs’ contribution to advance care planning (ACP) and (3) if primary care involvement allows people to die in the place of preference. Method: Systematic literature review. Data sources: Papers from 2000 to 2017 were sought from Medline, Psychinfo, Embase, Joanna Briggs Institute and Cochrane databases. Results: From 6209 journal articles, 51 papers were relevant. Patients and carers expect their GPs to be competent in all aspects of palliative care. They valued easy access to their GP, a multidisciplinary approach to care and well-coordinated and informed care. They also wanted their care team to communicate openly, honestly and empathically, particularly as the patient deteriorated. ACP and the involvement of GPs were important factors which contributed to patients being cared for and dying in their preferred place. There was no reference to GPNs in any paper identified. Conclusions: Patients and carers prefer a holistic approach to care. This review shows that GPs have an important role in ACP and that their involvement facilitates dying in the place of preference. Proactive identification of people approaching EoL is likely to improve all aspects of care, including planning and communicating about EoL. More work outlining the role of GPNs in end of life care is required

Advancing Stage of Female Reproductive Life Associated with Bipolar Illness Exacerbation

Introduction: Perimenopause confers an increased risk of depression in the general population, yet bipolar disorder mood course remains unknown. Methods: Clinic visits in 519 premenopausal, 116 perimenopausal including 13 women transitioning from peri- to postmenopause, and 133 postmenopausal women with bipolar disorder who received naturalistic treatment in the multisite STEP-Bipolar Disorder study over 19.8 +/- 15.5 months were analyzed for mood state. Results: Advancing female reproductive stage was associated with significant decline in mood elevation; significant decline in euthymia; no significant difference in major depression; and symptomatic significant increase. Conclusions: Advancing stage of female reproductive life was associated with bipolar illness exacerbation. Women transitioning from peri- to postmenopause had significantly greater depression than other female reproductive groups

Properties of small molecular drug loading and diffusion in a fluorinated PEG hydrogel studied by ^1H molecular diffusion NMR and ^(19)F spin diffusion NMR

R_f-PEG (fluoroalkyl double-ended poly(ethylene glycol)) hydrogel is potentially useful as a drug delivery depot due to its advanced properties of sol–gel two-phase coexistence and low surface erosion. In this study, ^1H molecular diffusion nuclear magnetic resonance (NMR) and ^(19)F spin diffusion NMR were used to probe the drug loading and diffusion properties of the R_f-PEG hydrogel for small anticancer drugs, 5-fluorouracil (FU) and its hydrophobic analog, 1,3-dimethyl-5-fluorouracil (DMFU). It was found that FU has a larger apparent diffusion coefficient than that of DMFU, and the diffusion of the latter was more hindered. The result of ^(19)F spin diffusion NMR for the corresponding freeze-dried samples indicates that a larger portion of DMFU resided in the R_f core/IPDU intermediate-layer region (where IPDU refers to isophorone diurethane, as a linker to interconnect the R_f group and the PEG chain) than that of FU while the opposite is true in the PEG–water phase. To understand the experimental data, a diffusion model was proposed to include: (1) hindered diffusion of the drug molecules in the R_f core/IPDU-intermediate-layer region; (2) relatively free diffusion of the drug molecules in the PEG-water phase (or region); and (3) diffusive exchange of the probe molecules between the above two regions. This study also shows that molecular diffusion NMR combined with spin diffusion NMR is useful in studying the drug loading and diffusion properties in hydrogels for the purpose of drug delivery applications

Chemical abundance gradients from open clusters in the Milky Way disk: results from the APOGEE survey

Metallicity gradients provide strong constraints for understanding the chemical evolution of the Galaxy. We report on radial abundance gradients of Fe, Ni, Ca, Si, and Mg obtained from a sample of 304 red-giant members of 29 disk open clusters, mostly concentrated at galactocentric distances between ~8 - 15 kpc, but including two open clusters in the outer disk. The observations are from the APOGEE survey. The chemical abundances were derived automatically by the ASPCAP pipeline and these are part of the SDSS III Data Release 12. The gradients, obtained from least squares fits to the data, are relatively flat, with slopes ranging from -0.026 to -0.033 dex/kpc for the alpha-elements [O/H], [Ca/H], [Si/H] and [Mg/H] and -0.035 dex/kpc and -0.040 dex/kpc for [Fe/H] and [Ni/H], respectively. Our results are not at odds with the possibility that metallicity ([Fe/H]) gradients are steeper in the inner disk (R_GC ~7 - 12 kpc) and flatter towards the outer disk. The open cluster sample studied spans a significant range in age. When breaking the sample into age bins, there is some indication that the younger open cluster population in our sample (log age < 8.7) has a flatter metallicity gradient when compared with the gradients obtained from older open clusters.Comment: 4 pages, 3 figures, To appear in Astronomische Nachrichten, special issue "Reconstruction the Milky Way's History: Spectroscopic surveys, Asteroseismology and Chemo-dynamical models", Guest Editors C. Chiappini, J. Montalb\'an, and M. Steffen, AN 2016 (in press)

The Open Cluster Chemical Analysis and Mapping Survey: Local Galactic Metallicity Gradient with APOGEE using SDSS DR10

The Open Cluster Chemical Analysis and Mapping (OCCAM) Survey aims to produce a comprehensive, uniform, infrared-based dataset for hundreds of open clusters, and constrain key Galactic dynamical and chemical parameters from this sample. This first contribution from the OCCAM survey presents analysis of 141 members stars in 28 open clusters with high-resolution metallicities derived from a large uniform sample collected as part of the SDSS-III/Apache Point Observatory Galactic Evolution Experiment (APOGEE). This sample includes the first high-resolution metallicity measurements for 22 open clusters. With this largest ever uniformly observed sample of open cluster stars we investigate the Galactic disk gradients of both [M/H] and [alpha/M]. We find basically no gradient across this range in [alpha/M], but [M/H] does show a gradient for R_{GC} < 10 kpc and a significant flattening beyond R_{GC} = 10 kpc. In particular, whereas fitting a single linear trend yields an [M/H] gradient of -0.09 +/- 0.03$ dex/kpc --- similar to previously measure gradients inside 13 kpc --- by independently fitting inside and outside 10 kpc separately we find a significantly steeper gradient near the Sun (7.9 <= R_{GC} <= 10) than previously found (-0.20 +/- 0.08 dex/kpc) and a nearly flat trend beyond 10 kpc (-0.02 +/- 0.09 dex/kpc).Comment: 6 pages, 4 figures, ApJ letters, in pres

Emotions in business-to-business service relationships

Emotion in business-to-business service relationships regarding cargo services is explored. The service relationship is characterised by mutual trust and cooperation. Contact is mainly via telephone or e-mail with some face-to-face interactions and participants providing a complex, multi-skilled seamless service. Experience rather than training plays a vital role with long-term service relationships built up and maintained. Emotional sensitivity is acquired partly by experience and a repeat customer base but mainly through a genuine desire to help and get to know others. In contrast to the view of emotional labour bringing managerial control or adverse affects to service staff, the emotion engendered by this work is authentic expression bringing personal satisfaction

Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis

Background More than 10 years have elapsed since human papillomavirus (HPV) vaccination was implemented. We did a systematic review and meta-analysis of the population-level impact of vaccinating girls and women against human papillomavirus on HPV infections, anogenital wart diagnoses, and cervical intraepithelial neoplasia grade 2+ (CIN2+)to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination.Methods In this updated systematic review and meta-analysis, we used the same search strategy as in our previous paper. We searched MEDLINE and Embase for studies published between Feb 1, 2014, and Oct 11, 2018. Studies were eligible if they compared the frequency (prevalence or incidence) of at least one HPV-related endpoint (genital HPV infections, anogenital wart diagnoses, or histologically confirmed CIN2+) between pre-vaccination and post-vaccination periods among the general population and if they used the same population sources and recruitment methods before and after vaccination. Our primary assessment was the relative risk (RR) comparing the frequency (prevalence or incidence) of HPV-related endpoints between the pre-vaccination and post-vaccination periods. We stratified all analyses by sex, age, and years since introduction of HPV vaccination. We used random-effects models to estimate pooled relative risks.Findings We identified 1702 potentially eligible articles for this systematic review and meta-analysis, and included 65 articles in 14 high-income countries: 23 for HPV infection, 29 for anogenital warts, and 13 for CIN2+.After 5\u20138 years of vaccination, the prevalence of HPV 16 and 18 decreased significantly by 83% (RR 0\ub717, 95% CI 0\ub711\u20130\ub725) among girls aged 13\u201319 years, and decreased significantly by 66% (RR 0\ub734, 95% CI 0\ub723\u20130\ub749) among women aged 20\u201324 years. The prevalence of HPV 31, 33, and 45 decreased significantly by 54% (RR 0\ub746, 95% CI 0\ub733\u20130\ub766) among girls aged 13\u201319 years. Anogenital wart diagnoses decreased significantly by 67% (RR 0\ub733, 95% CI 0\ub724\u20130\ub746) among girls aged 15\u201319 years, decreased significantly by 54% (RR 0\ub746, 95% CI 0.36\u20130.60) among women aged 20\u201324 years, and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub753\u20130\ub789) among women aged 25\u201329 years. Among boys aged 15\u201319 years anogenital wart diagnoses decreased significantly by 48% (RR 0\ub752, 95% CI 0\ub737\u20130\ub775) and among men aged 20\u201324 years they decreased significantly by 32% (RR 0\ub768, 95% CI 0\ub747\u20130\ub798). After 5\u20139 years of vaccination, CIN2+ decreased significantly by 51% (RR 0\ub749, 95% CI 0\ub742\u20130\ub758) among screened girls aged 15\u201319 years and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub757\u20130\ub784) among women aged 20\u201324 years.Interpretation This updated systematic review and meta-analysis includes data from 60 million individuals and up to 8 years of post-vaccination follow-up. Our results show compelling evidence of the substantial impact of HPV vaccination programmes on HPV infections and CIN2+ among girls and women, and on anogenital warts diagnoses among girls, women, boys, and men. Additionally, programmes with multi-cohort vaccination and high vaccination coverage had a greater direct impact and herd effects

Response to the editorial by Dr Geraghty

This article is written in response to the linked editorial by Dr Geraghty about the adaptive Pacing, graded Activity and Cognitive behaviour therapy; a randomised Evaluation (PACE) trial, which we led, implemented and published. The PACE trial compared four treatments for people diagnosed with chronic fatigue syndrome. All participants in the trial received specialist medical care. The trial found that adding cognitive behaviour therapy or graded exercise therapy to specialist medical care was as safe as, and more effective than, adding adaptive pacing therapy or specialist medical care alone. Dr Geraghty has challenged these findings. In this article, we suggest that Dr Geraghty’s views are based on misunderstandings and misrepresentations of the PACE trial; these are corrected