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Objectives/hypothesisPsychosocial distress is common among patients with head and neck cancer (HNC) and is associated with poorer quality of life and clinical outcomes. Despite these risks, distress screening is not widely implemented in HNC care. In this study, we investigated the prevalence of psychosocial distress and its related factors in routine care of patients with HNC.MethodsData from medical records between September 2017 and March 2020 were analyzed. Psychosocial distress was measured by the National Comprehensive Cancer Network's Distress Thermometer (DT), and a modified HNC-specific problem list; depression and anxiety were assessed using the Patient Health Questionnaire-4. Descriptive statistics and logistic regression were conducted to report prevalence of distress, depression and anxiety, and factors associated with clinical distress. Implementation outcomes, including rates of referrals and follow-up for distressed patients, are also reported.ResultsTwo hundred and eighty seven HNC patients completed the questionnaire (age 64.3 ± 14.9 years), with a mean distress score of 4.51 ± 3.35. Of those, 57% (n = 163) reported clinical distress (DT ≥ 4). Pain (odds ratio [OR] = 3.31, 95% CI = 1.75-6.26), fatigue (OR = 2.43, 95% CI = 1.1.7-5.05), anxiety (OR = 1.63, 95% CI = 1.30-2.05), and depression (OR = 1.51, 95% CI = 1.04-2.18) were significantly associated with clinical distress (P < .05). Of patients identified as distressed, 79% received same-day psychosocial evaluation.ConclusionsClinical distress was identified in 57% of patients who completed the questionnaire, suggesting that an ultra-brief psychosocial screening protocol can be implemented in routine ambulatory oncology care, and identifies patients whose distress might otherwise go unrecognized.Level of evidence4 Laryngoscope, 132:1600-1608, 2022.

Provoked vestibulodynia (PVD) is a chronic pain disorder characterized by local hypersensitivity and severe pain with pressure localized to the vulvar vestibule. Despite decades of study, the lack of identified biomarkers has slowed the development of effective therapies. The primary aim of this study was to use metabolomics to identify novel biochemical mechanisms in vagina and blood underlying brain biomarkers and symptoms in PVD, thereby closing this knowledge gap. Using a cross-sectional case-control observational study design, untargeted and unbiased metabolomic profiling of vaginal fluid and plasma was performed in women with PVD compared to healthy controls. In women with PVD, we also obtained assessments of vulvar pain, vestibular and vaginal muscle tenderness, and 24-hour symptom intensity alongside resting-state brain functional connectivity of brain regions involved in pain processing and modulation. Compared to healthy controls, women with PVD demonstrated differences primarily in vaginal (but not plasma) concentrations of metabolites of the sphingolipid signaling pathways, suggesting localized effects in vagina and vulvar vestibule rather than systemic effects. Our findings reveal that dysregulation of sphingolipid metabolism in PVD is associated with increased vulvar pain and muscle tenderness, sexual dysfunction, and decreased functional connectivity strength in pain processing/modulatory brain regions. This data collectively suggests that alterations in sphingolipid signaling pathways are likely an important molecular biomarker in PVD that could lead to new targets for therapeutic intervention. PERSPECTIVE: This manuscript presents the results of a robust, unbiased molecular assessment of plasma and vaginal fluid samples in women with provoked vestibulodynia compared to healthy controls. The findings suggest that alterations in sphingolipid signaling pathways are associated with symptoms and brain biomarkers and may be an important molecular marker t

RationaleNicotine patches may be less effective in female compared with male smokers. However, it is unknown if negative affect and physical symptoms influence transdermal nicotine patch-related effects on smoking behaviors.MethodsEighty-one acutely tobacco-abstinent premenopausal female smokers attended three counter-balanced experimental sessions across the menstrual cycle (early follicular, late follicular, and mid-luteal) and were randomized to patch condition (nicotine [21 mg] vs. placebo [0 mg] transdermal patch). Negative affect and physical symptoms were assessed prior to patch administration. The patch was removed 5 h post-administration, and participants completed a smoking reinstatement task. Multilevel linear models tested associations of patch condition, negative affect and physical symptoms, and their interaction on smoking behavior.ResultsThere was a significant patch condition × Negative Affect and Pain symptoms interaction on the number of cigarettes smoked (p < 0.05). When Negative Affect and Pain were lower-than-usual, females administered a nicotine patch smoked significantly fewer cigarettes than females administered a placebo patch (p < .05), but there were no significant patch differences when Negative Affect and Pain were higher-than-usual. There was also a significant patch condition × Negative Affect interaction on time delay. The effects of patch condition on time delay to smoking were greater during sessions in which Negative Affect was higher-than-usual.ConclusionsResults suggest that among female smokers transdermal nicotine patch effectiveness may interact with negative affect and pain. Understanding and considering female-specific factors that may impact the efficacy of one of the most commonly used cessation medications is important for improving smoking cessation in female smokers.

RationaleNicotine patches may be less effective in female compared with male smokers. However, it is unknown if negative affect and physical symptoms influence transdermal nicotine patch-related effects on smoking behaviors.MethodsEighty-one acutely tobacco-abstinent premenopausal female smokers attended three counter-balanced experimental sessions across the menstrual cycle (early follicular, late follicular, and mid-luteal) and were randomized to patch condition (nicotine [21 mg] vs. placebo [0 mg] transdermal patch). Negative affect and physical symptoms were assessed prior to patch administration. The patch was removed 5 h post-administration, and participants completed a smoking reinstatement task. Multilevel linear models tested associations of patch condition, negative affect and physical symptoms, and their interaction on smoking behavior.ResultsThere was a significant patch condition × Negative Affect and Pain symptoms interaction on the number of cigarettes smoked (p < 0.05). When Negative Affect and Pain were lower-than-usual, females administered a nicotine patch smoked significantly fewer cigarettes than females administered a placebo patch (p < .05), but there were no significant patch differences when Negative Affect and Pain were higher-than-usual. There was also a significant patch condition × Negative Affect interaction on time delay. The effects of patch condition on time delay to smoking were greater during sessions in which Negative Affect was higher-than-usual.ConclusionsResults suggest that among female smokers transdermal nicotine patch effectiveness may interact with negative affect and pain. Understanding and considering female-specific factors that may impact the efficacy of one of the most commonly used cessation medications is important for improving smoking cessation in female smokers.

Laura C Seidman,1 Catherine R Temme,1 Lonnie K Zeltzer,2 Andrea J Rapkin,3 Bruce D Naliboff,4 Laura A Payne1,5 1Division of Women’s Mental Health, McLean Hospital, Belmont, MA, USA; 2Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 3Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 4Oppenheimer Center for Neurobiology of Stress and Resilience, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 5Department of Psychiatry, Harvard Medical School, Boston, MA, USACorrespondence: Laura C SeidmanMcLean Hospital, Mail Stop 306, 115 Mill Street, Belmont, MA 02478, USATel +1 617 855 2746Email LCSeidman@mclean.harvard.eduPurpose: Primary dysmenorrhea (PD; menstrual pain without an identified organic cause) has been proposed as a possible risk factor for the development of chronic pelvic pain, but the mechanism through which this process occurs is unknown. One possible mechanism is central sensitization – alterations in the central nervous system that increase responsiveness to pain leading to hypersensitivity. Repeated episodes of pain, such as those experienced over time with PD, may alter how the brain processes pain. Ecological momentary assessment (EMA; collection of data in real time in participants’ natural environments) is a novel data collection method that may help elucidate pain occurring during non-menstrual cycle phases.Patients and Methods: The current observational study assessed the feasibility and acceptability of using EMA via text messages to collect pelvic pain data during menstrual and non-menstrual cycle phases in a community sample of adolescents and young adults (AYA) aged 16– 24 years with and without PD and explored occurrence rates and intensity of non-menstrual pelvic pain (NMPP) in each of these groups.Results: Thirty-nine AYA with PD and 53 healthy controls reported pelvic pain level via nightly text mess

BackgroundPremenstrual dysphoric disorder (PMDD) is an understudied, debilitating disorder of women. Given evidence for prefrontal cortical and limbic dysfunction in PMDD, we compared intrinsic connectivity of the executive control network (ECN), default mode network (DMN), and amygdala in women with PMDD vs. controls.MethodsThirty-six women (18 PMDD, 18 control) participated in fMRI during the follicular and luteal phases of the menstrual cycle. At each time, resting-state functional connectivity was evaluated both before and after participants performed an emotion regulation task. The ECN was identified using independent components analysis, and connectivity of left and right amygdala seeds was also evaluated.ResultsNonparametric permutation testing identified a cluster in the left middle temporal gyrus (MTG) with significantly stronger connectivity to the left ECN in women with PMDD vs. controls in all four fMRI sessions. Women with PMDD exhibited no difference in functional connectivity between menstrual cycle phases. Amygdala connectivity did not differ between the groups but differed significantly with menstrual phase, with left amygdala connectivity to cingulate cortex being significantly stronger during the follicular vs. luteal phase. Right amygdala connectivity to the middle frontal gyrus was also stronger during the follicular vs. luteal phase, with no group differences. These findings suggest that women with PMDD have different intrinsic network dynamics in the left executive control network compared to healthy controls.

BackgroundPremenstrual dysphoric disorder (PMDD) is an understudied, debilitating disorder of women. Given evidence for prefrontal cortical and limbic dysfunction in PMDD, we compared intrinsic connectivity of the executive control network (ECN), default mode network (DMN), and amygdala in women with PMDD vs. controls.MethodsThirty-six women (18 PMDD, 18 control) participated in fMRI during the follicular and luteal phases of the menstrual cycle. At each time, resting-state functional connectivity was evaluated both before and after participants performed an emotion regulation task. The ECN was identified using independent components analysis, and connectivity of left and right amygdala seeds was also evaluated.ResultsNonparametric permutation testing identified a cluster in the left middle temporal gyrus (MTG) with significantly stronger connectivity to the left ECN in women with PMDD vs. controls in all four fMRI sessions. Women with PMDD exhibited no difference in functional connectivity between menstrual cycle phases. Amygdala connectivity did not differ between the groups but differed significantly with menstrual phase, with left amygdala connectivity to cingulate cortex being significantly stronger during the follicular vs. luteal phase. Right amygdala connectivity to the middle frontal gyrus was also stronger during the follicular vs. luteal phase, with no group differences. These findings suggest that women with PMDD have different intrinsic network dynamics in the left executive control network compared to healthy controls.

Andrea J Rapkin, Yelena Korotkaya, Kathrine C Taylor Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USACorrespondence: Andrea J RapkinDepartment of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, 10833 Le Conte Avenue, CHS 22-184, Los Angeles 90095, CA, USATel +1 310 825 6963Email arapkin@mednet.ucla.eduAbstract: Premenstrual Dysphoric Disorder (PMDD) is a severe form of premenstrual syndrome (PMS) affecting up to 7% of reproductive age women. Women with PMDD are of reproductive age; therefore, contraception and treatment of PMDD are important considerations. The disorder as described in the DSM-V is characterized by moderate to severe psychological, behavioral and physical symptoms beginning up to two weeks prior to menses, resolving soon after the onset of menstruation and significantly interfering with daily functioning. PMDD develops in predisposed individuals after they are exposed to progesterone at the time of ovulation. It has been hypothesized that PMDD is in part attributable to luteal phase abnormalities in serotonergic activity and to altered configuration of ℽ-aminobutyric acid subunit A (GABAA) receptors in the brain triggered by the exposure to the neuroactive steroid progesterone metabolite, allopregnanolone (Allo). A large body of evidence suggests that selective serotonin reuptake inhibitors (SSRIs) can be effective in the treatment of PMDD. Combined hormonal contraceptive (CHC) pills, specifically the 20 mcg ethinyl estradiol/3mg drospirenone in a 24/4 extended cycle regimen has been shown to significantly improve the emotional and physical symptoms of PMDD. Other combined monophasic, extended cycle hormonal contraceptive pills with less androgenic progestins may also be helpful, although not well studied. Copper intrauterine devices (IUDs) are recommended for those not seeking hormonal contraceptives. Progestin-only methods including the

ObjectiveTo evaluate self-administration of vaginal lidocaine gel to decrease pain with intrauterine device (IUD) insertion in nulliparous women.MethodsIn this randomized, double-blind, placebo-controlled trial, women self-administered 2% lidocaine or placebo vaginal gel 5 minutes before IUD insertion. The primary outcome was change in pain from baseline to IUD insertion on a 100-mm visual analog scale. We also assessed pain after speculum insertion, tenaculum placement, uterine sounding, and 5 minutes after IUD insertion. Secondary outcomes included patient acceptability, ease of IUD insertion, and need for pain medication for up to 7 days.ResultsFrom July 2012 to May 2013, 59 women were randomized; 30 received lidocaine gel and 29 placebo. Baseline demographics, including age, race, and body mass index, were similar. There was no difference in median change in pain during IUD insertion in women receiving lidocaine (61 mm [interquartile range 53-71]) compared with placebo (69 mm [interquartile range 63-80], P=.06). Women receiving lidocaine experienced less pain with tenaculum placement (32 mm [interquartile range 18-54]) compared with placebo (56 mm [interquartile range 26-75], P=.02). Most (76%) women were satisfied with their IUD insertion experience and 86% would probably or definitely recommend an IUD to a friend. Thirty-four percent of women required pain medication for at least 3 days after IUD insertion.ConclusionFor nulliparous women, self-administered vaginal lidocaine gel does not reduce pain with IUD insertion, but does decrease pain with tenaculum placement.Clinical trial registrationClinicalTrials.gov, http://clinicaltrials.gov, NCT01534520.

Provoked vestibulodynia (PVD) is a chronic pelvic pain disorder affecting 16% of the female population. Neuroimaging studies have highlighted central abnormalities in PVD, similar to other chronic pelvic pain disorders, including brain regions involved in sensory processing and modulation of pain. The aim of the study was to determine alterations in the subvoxel, microstructural organization within tissues in PVD compared with healthy control participants (HCs) and a disease control group (irritable bowel syndrome [IBS]). Diffusion tensor imaging magnetic resonance imaging was conducted in 87 age-matched premenopausal women (29 PVD, 29 HCs, 29 IBS). Statistical parameter mapping of fractional anisotropy (FA) and mean diffusivity (MD) maps were used to identify microstructural difference in the brain specific to PVD or shared with IBS. PVD alterations in microstructural organization of the brain were predominantly observed in fibers associated with sensorimotor integration and pain processing that relay information between the thalamus, basal ganglia, sensorimotor, and insular cortex. PVD, compared with HCs, showed extensive increases in the FA of somatosensory and basal ganglia regions. In contrast, PVD and IBS subjects did not show any FA-related group differences. PVD subjects showed greater MD in the basal ganglia compared with HCs (higher MD in the internal capsule and pallidum) and IBS (higher MD in the putamen and pallidum). Increases in MD were associated with increased vaginal muscle tenderness and vulvar pain. The current findings highlight possible shared mechanisms between 2 different pelvic pain disorders, but also highlight the widespread alterations observed specifically in PVD compared with HCs. PERSPECTIVE:Alterations in microstructure in PVD were observed in fibers associated with sensorimotor integration and pain processing, which were also associated with increased vaginal muscle tenderness and vulvar pain. These alterations may be contributing to

BackgroundDifficulties in regulating emotions are linked to the core symptoms of premenstrual dysphoric disorder (PMDD). We therefore investigated the neural substrates of emotion-regulation problems in women with PMDD.MethodsOn the basis of self-evaluations over 2 months on the Daily Record of Severity of Problems, eligible participants were assigned to two groups: PMDD and control (18 per group). Functional magnetic resonance imaging (fMRI) and a well-validated task were used to assess brain function during emotion regulation. Participants were tested twice, once during the follicular (asymptomatic) and once in the late luteal (symptomatic) phase of the menstrual cycle.ResultsWomen with PMDD gave higher ratings of negative affect in the luteal phase than in the follicular phase, and compared with healthy control participants during the luteal phase. A region-of-interest fMRI analysis indicated that during the late luteal phase, women with PMDD had hypoactivation in right dorsolateral prefrontal cortex (dlPFC) during all conditions of the emotion-regulation task, not only in the contrast that isolated emotion regulation. An exploratory whole-brain, voxel-wise analysis showed that women with PMDD had less activation in the precentral gyrus during the luteal phase than the follicular phase, and less activation in the postcentral gyrus compared with control participants.ConclusionsDuring the luteal phase of the menstrual cycle, women with PMDD experience difficulty regulating emotions. Hypoactivation in the right dlPFC may contribute to this problem, but may be related more generally to other affective symptoms of PMDD. Hypofunction in the right pre- and postcentral gyri warrants additional study.

Provoked vestibulodynia (PVD) is a chronic pelvic pain disorder affecting 16% of the female population. Neuroimaging studies have highlighted central abnormalities in PVD, similar to other chronic pelvic pain disorders, including brain regions involved in sensory processing and modulation of pain. The aim of the study was to determine alterations in the subvoxel, microstructural organization within tissues in PVD compared with healthy control participants (HCs) and a disease control group (irritable bowel syndrome [IBS]). Diffusion tensor imaging magnetic resonance imaging was conducted in 87 age-matched premenopausal women (29 PVD, 29 HCs, 29 IBS). Statistical parameter mapping of fractional anisotropy (FA) and mean diffusivity (MD) maps were used to identify microstructural difference in the brain specific to PVD or shared with IBS. PVD alterations in microstructural organization of the brain were predominantly observed in fibers associated with sensorimotor integration and pain processing that relay information between the thalamus, basal ganglia, sensorimotor, and insular cortex. PVD, compared with HCs, showed extensive increases in the FA of somatosensory and basal ganglia regions. In contrast, PVD and IBS subjects did not show any FA-related group differences. PVD subjects showed greater MD in the basal ganglia compared with HCs (higher MD in the internal capsule and pallidum) and IBS (higher MD in the putamen and pallidum). Increases in MD were associated with increased vaginal muscle tenderness and vulvar pain. The current findings highlight possible shared mechanisms between 2 different pelvic pain disorders, but also highlight the widespread alterations observed specifically in PVD compared with HCs. PERSPECTIVE:Alterations in microstructure in PVD were observed in fibers associated with sensorimotor integration and pain processing, which were also associated with increased vaginal muscle tenderness and vulvar pain. These alterations may be contributing to

BackgroundDifficulties in regulating emotions are linked to the core symptoms of premenstrual dysphoric disorder (PMDD). We therefore investigated the neural substrates of emotion-regulation problems in women with PMDD.MethodsOn the basis of self-evaluations over 2 months on the Daily Record of Severity of Problems, eligible participants were assigned to two groups: PMDD and control (18 per group). Functional magnetic resonance imaging (fMRI) and a well-validated task were used to assess brain function during emotion regulation. Participants were tested twice, once during the follicular (asymptomatic) and once in the late luteal (symptomatic) phase of the menstrual cycle.ResultsWomen with PMDD gave higher ratings of negative affect in the luteal phase than in the follicular phase, and compared with healthy control participants during the luteal phase. A region-of-interest fMRI analysis indicated that during the late luteal phase, women with PMDD had hypoactivation in right dorsolateral prefrontal cortex (dlPFC) during all conditions of the emotion-regulation task, not only in the contrast that isolated emotion regulation. An exploratory whole-brain, voxel-wise analysis showed that women with PMDD had less activation in the precentral gyrus during the luteal phase than the follicular phase, and less activation in the postcentral gyrus compared with control participants.ConclusionsDuring the luteal phase of the menstrual cycle, women with PMDD experience difficulty regulating emotions. Hypoactivation in the right dlPFC may contribute to this problem, but may be related more generally to other affective symptoms of PMDD. Hypofunction in the right pre- and postcentral gyri warrants additional study.

BackgroundDifficulties in regulating emotions are linked to the core symptoms of premenstrual dysphoric disorder (PMDD). We therefore investigated the neural substrates of emotion-regulation problems in women with PMDD.MethodsOn the basis of self-evaluations over 2 months on the Daily Record of Severity of Problems, eligible participants were assigned to two groups: PMDD and control (18 per group). Functional magnetic resonance imaging (fMRI) and a well-validated task were used to assess brain function during emotion regulation. Participants were tested twice, once during the follicular (asymptomatic) and once in the late luteal (symptomatic) phase of the menstrual cycle.ResultsWomen with PMDD gave higher ratings of negative affect in the luteal phase than in the follicular phase, and compared with healthy control participants during the luteal phase. A region-of-interest fMRI analysis indicated that during the late luteal phase, women with PMDD had hypoactivation in right dorsolateral prefrontal cortex (dlPFC) during all conditions of the emotion-regulation task, not only in the contrast that isolated emotion regulation. An exploratory whole-brain, voxel-wise analysis showed that women with PMDD had less activation in the precentral gyrus during the luteal phase than the follicular phase, and less activation in the postcentral gyrus compared with control participants.ConclusionsDuring the luteal phase of the menstrual cycle, women with PMDD experience difficulty regulating emotions. Hypoactivation in the right dlPFC may contribute to this problem, but may be related more generally to other affective symptoms of PMDD. Hypofunction in the right pre- and postcentral gyri warrants additional study.

The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD), which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS). The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed.

A 2009 survey confirmed the experiences of many end-of-life advocates: Most Californians said they would prefer to die at home, but only 32% of deaths occurred at home that year. A large percentage of survey respondents said it was important to put their end-of-life care wishes in writing, yet only 23% said they had done so.To address this continuing challenge in California, regional coalitions -- which included hospitals, skilled nursing facilities, emergency medical service providers, hospices, nursing homes, senior centers, and consumer groups -- formed in the late 1990s and early 2000s to promote advance care planning through a community-based approach. Advance care planning is a process to help patients consider options and to establish their wishes about future care in legal documents that take effect when those patients lose the capacity to make decisions for themselves. These coalitions readily embraced the Physician Orders for Life-Sustaining Treatment (POLST) process when it was first introduced to California in 2007.To better understand successful community engagement strategies for advance care planning, the California HealthCare Foundation (CHCF) interviewed 10 coalition members in four California communities: Inland Empire, Sacramento, Santa Cruz County, and Sonoma County. This paper describes the experiences and lessons learned from these coalitions in implementing successful advance care planning and POLST initiatives.

The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD), which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS). The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed.

The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD), which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS). The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed.

A 2009 survey confirmed the experiences of many end-of-life advocates: Most Californians said they would prefer to die at home, but only 32% of deaths occurred at home that year. A large percentage of survey respondents said it was important to put their end-of-life care wishes in writing, yet only 23% said they had done so.To address this continuing challenge in California, regional coalitions -- which included hospitals, skilled nursing facilities, emergency medical service providers, hospices, nursing homes, senior centers, and consumer groups -- formed in the late 1990s and early 2000s to promote advance care planning through a community-based approach. Advance care planning is a process to help patients consider options and to establish their wishes about future care in legal documents that take effect when those patients lose the capacity to make decisions for themselves. These coalitions readily embraced the Physician Orders for Life-Sustaining Treatment (POLST) process when it was first introduced to California in 2007.To better understand successful community engagement strategies for advance care planning, the California HealthCare Foundation (CHCF) interviewed 10 coalition members in four California communities: Inland Empire, Sacramento, Santa Cruz County, and Sonoma County. This paper describes the experiences and lessons learned from these coalitions in implementing successful advance care planning and POLST initiatives.

Katharine Rapkin has worked in academic and commercial book publishing. She currently works as an archivist in Savannah. On January 21, 2017, millions of people worldwide took part in marches to protest the inauguration of Donald Trump as the President of the United States. The first protest, which took place in Washington, D.C., was known as the Women's March on Washington and was intended as a response to anti-woman rhetoric and beliefs that were espoused during Trump's campaign. While women's and reproductive rights were at the forefront of marchers' concerns, many also protested the racist, anti-immigrant, anti-science, and other controversial sentiments expressed by the incoming Trump administration., In this interview, Katharine Rapkin discusses her background and how that shaped her current politics. She explains that she became politically involved early in her life, and her attendance at the 2017 March re-started her political activity. She describes the march, gives advice to others, and discusses her issues with the Trump administration.

Laura A Payne,1 Andrea J Rapkin,2 Laura C Seidman,1 Lonnie K Zeltzer,1 Jennie CI Tsao1 1Pediatric Pain and Palliative Care Program, 2Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Abstract: Primary dysmenorrhea (PD) has been the focus of a number of experimental pain studies. Although a number of reviews exist, few have critically evaluated the existing body of research on PD and experimental and procedural pain. Data from 19 published research articles that include women with PD and responses to an experimental or procedural pain stimulus (or stimuli) suggest that women with PD may have elevated pain reactivity, as compared to women without PD. This pattern appears to be true across different phases of the menstrual cycle. However, there is an abundance of conflicting findings, which may be due to significant methodological issues such as inconsistent definitions of PD, wide variation in experimental pain methodologies, and inaccurate assessment of the menstrual cycle. Future research should focus on identifying specific symptoms (i.e., pain threshold ratings) to more clearly define what constitutes PD, establish reliable and valid laboratory testing protocols, and assess the menstrual cycle with greater precision. Keywords: primary dysmenorrhea, menstrual pain, acute pain, menstrual cycle, central pain mechanisms&nbsp

Meryl Alappattu,1,2 Georgine Lamvu,3,4 Jessica Feranec,3,4 Kathryn Witzeman,5 Michael Robinson,2,6 Andrea Rapkin7 1Department of Physical Therapy, 2Center for Pain Research and Behavioral Health, University of Florida, Gainesville, 3Division of Surgery, Gynecology Section, Veteran Affairs Medical Center, 4University of Central Florida, Orlando, FL, 5Women’s Integrated Health Program, Department of OBGYN, Denver Health Medical Center, Denver, CO, 6Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, 7Department of Obstetrics and Gynecology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA Background: Vulvodynia classification is based on the sensory dimensions of pain and does not include psychological factors associated with the pain experience and treatment outcomes. Previous work has shown that individuals with chronic pain can be classified into subgroups based on pain sensitivity, psychological distress, mood, and symptom severity.Objective: The aim of this study was to identify distinct subgroups of women with vulvodynia enrolled in the National Vulvodynia Registry. We hypothesized that women with vulvodynia can be clustered into subgroups based on distress and pain sensitivity.Design: A cross-sectional study.Methods: We conducted an exploratory hierarchical agglomerative cluster analysis using Ward’s cluster method and squared Euclidean distances to identify unique subgroups based on baseline psychological distress and pain sensitivity. The variables included the catastrophizing subscale of the Coping Strategies Questionnaire, the Beck Depression Inventory, the State Trait Anxiety Index-Trait scale, McGill Pain Questionnaire-Affective subscale, and vulvar and pelvic muscle pressure pain sensitivity.Subjects: Eight sites enrolled women who presented with vaginal or vulval pain of at least 3-month duration.Results: Two distinct subgroups, high pain sensitivity with high dis

Whilst professional bodies such as the Royal College and the American College of Obstetricians and Gynecologists have well-established standards for audit of management for most gynaecology disorders, such standards for premenstrual disorders (PMDs) have yet to be developed. The International Society of Premenstrual Disorders (ISPMD) has already published three consensus papers on PMDs covering areas that include definition, classification/quantification, clinical trial design and management (American College Obstetricians and Gynecologists 2011; Brown et al. in Cochrane Database Syst Rev 2:CD001396, 2009; Dickerson et al. in Am Fam Physician 67(8):1743-1752, 2003). In this fourth consensus of ISPMD, we aim to create a set of auditable standards for the clinical management of PMDs. All members of the original ISPMD consensus group were invited to submit one or more auditable standards to be eligible in the inclusion of the consensus. Ninety-five percent of members (18/19) responded with at least one auditable standard. A total of 66 auditable standards were received, which were returned to all group members who then ranked the standards in order of priority, before the results were collated. Proposed standards related to the diagnosis of PMDs identified the importance of obtaining an accurate history, that a symptom diary should be kept for 2 months prior to diagnosis and that symptom reporting demonstrates symptoms in the premenstrual phase of the menstrual cycle and relieved by menstruation. Regarding treatment, the most important standards were the use of selective serotonin reuptake inhibitors (SSRIs) as a first line treatment, an evidence-based approach to treatment and that SSRI side effects are properly explained to patients. A set of comprehensive standards to be used in the diagnosis and treatment of PMD has been established, for which PMD management can be audited against for standardised and improved care.

Premenstrual dysphoric disorder (PMDD) is a psychiatric disorder that causes serious impairments in the functioning and quality of life of affected women. Until recently, research efforts were somewhat hampered by the lack of formal diagnostic criteria, which have now been codified as a category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Better characterization of deficits in socioemotional functioning caused by PMDD may aid in improving treatment efforts. In this investigation, prospective symptom ratings, based on DSM-5 criteria, were used to measure PMDD symptoms in 36 women (18 with PMDD and 18 healthy controls). Two self-report inventories, the Emotion Regulation Questionnaire and the Difficulties in Emotion Regulation Scale, were used to measure ability to regulate emotions, and socioemotional functioning was measured by inventories of social connectedness, perceived stress, and affect. Potential relationships between ability to regulate emotion and PMDD symptom severity, as well as other measures of socioemotional functioning and affective state, were tested. Women with PMDD reported significantly more behavioral impulsivity and greater difficulties in regulating emotion and in socioemotional functioning. Cognitive or behavioral strategies to improve these problems may benefit women with PMDD and help to alleviate distress caused by this disorder.

What does representation mean when applied to international organizations? While many scholars working on normative questions related to global governance often make use of the concept of representation, few have addressed specifics of applying the concept to the rules and practices by which IOs operate. This article examines representation as a fundamental, albeit often neglected, norm of governance which, if perceived to be deficient or unfair, can interfere with other components of governance, as well as with performance of an organization’s core tasks by undermining legitimacy. We argue that the concept of representation has been neglected in the ongoing debates about good governance and democratic deficits within IOs. We aim to correct this by drawing on insights from normative political theory considerations of representation. The article then applies theoretical aspects of representation to the governance of the International Monetary Fund. We determine that subjecting IOs to this kind of conceptual scrutiny highlights important deficiencies in representational practices in global politics. Finally, our conclusion argues scholars of global governance need to address the normative and empirical implications of conceptualizing representation at the supranational level. (author's abstract)

Premenstrual dysphoric disorder (PMDD) is a psychiatric disorder that causes serious impairments in the functioning and quality of life of affected women. Until recently, research efforts were somewhat hampered by the lack of formal diagnostic criteria, which have now been codified as a category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Better characterization of deficits in socioemotional functioning caused by PMDD may aid in improving treatment efforts. In this investigation, prospective symptom ratings, based on DSM-5 criteria, were used to measure PMDD symptoms in 36 women (18 with PMDD and 18 healthy controls). Two self-report inventories, the Emotion Regulation Questionnaire and the Difficulties in Emotion Regulation Scale, were used to measure ability to regulate emotions, and socioemotional functioning was measured by inventories of social connectedness, perceived stress, and affect. Potential relationships between ability to regulate emotion and PMDD symptom severity, as well as other measures of socioemotional functioning and affective state, were tested. Women with PMDD reported significantly more behavioral impulsivity and greater difficulties in regulating emotion and in socioemotional functioning. Cognitive or behavioral strategies to improve these problems may benefit women with PMDD and help to alleviate distress caused by this disorder.

Premenstrual dysphoric disorder (PMDD) is a psychiatric disorder that causes serious impairments in the functioning and quality of life of affected women. Until recently, research efforts were somewhat hampered by the lack of formal diagnostic criteria, which have now been codified as a category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Better characterization of deficits in socioemotional functioning caused by PMDD may aid in improving treatment efforts. In this investigation, prospective symptom ratings, based on DSM-5 criteria, were used to measure PMDD symptoms in 36 women (18 with PMDD and 18 healthy controls). Two self-report inventories, the Emotion Regulation Questionnaire and the Difficulties in Emotion Regulation Scale, were used to measure ability to regulate emotions, and socioemotional functioning was measured by inventories of social connectedness, perceived stress, and affect. Potential relationships between ability to regulate emotion and PMDD symptom severity, as well as other measures of socioemotional functioning and affective state, were tested. Women with PMDD reported significantly more behavioral impulsivity and greater difficulties in regulating emotion and in socioemotional functioning. Cognitive or behavioral strategies to improve these problems may benefit women with PMDD and help to alleviate distress caused by this disorder.

Rachel Rapkin profiles faculty mentor Jennifer Bay, an associate professor in the Department of English. Over the past five years, Bay has integrated service-learning into all of her courses at both the undergraduate and graduate levels. Bay is the only professor within the Professional Writing Program who consistently uses this teaching methodology. She, however, prefers to call her work community engagement.

Rachel Rapkin profiles faculty mentor Jennifer Bay, an associate professor in the Department of English. Over the past five years, Bay has integrated service-learning into all of her courses at both the undergraduate and graduate levels. Bay is the only professor within the Professional Writing Program who consistently uses this teaching methodology. She, however, prefers to call her work community engagement.

ObjectiveTo compare contraceptive knowledge and use among women seeking emergency contraception (EC) before and after an inner-city clinic began providing structured counseling and offering same-day intrauterine device (IUD) or implant placement to all women seeking EC.Study designFor 8 months before and 21 months after this change in clinic policy, women aged 15-45 who wanted to avoid pregnancy for at least 6 months were asked to complete surveys immediately, 3 and 12 months after their clinic visit. In addition, we abstracted electronic medical record (EMR) data on all women who sought EC (n=328) during this period. We used chi-squared tests to assess pre/post differences in survey and EMR data.ResultsSurveys were completed by 186 women. After the clinic began offering structured counseling, more women had accurate knowledge of the effectiveness of IUDs, immediately and 3 months after their clinic visit. In addition, more women initiated IUD or implant use (survey: 40% vs. 17% preintervention, p=0.04; EMR: 22% vs. 10% preintervention, p=0.01), and fewer had no contraceptive use (survey: 3% vs. 17% preintervention, p<0.01; EMR: 32% vs. 68%, p<0.01) in the 3 months after seeking EC. EMR data indicate that when same-day placement was offered, 11.0% of women received a same-day IUD. Of those who received a same-day IUD, 88% (23/26) reported IUD use at 3-months and 80% (12/15) at 12 months.ConclusionsRoutine provision of structured counseling with the offer of same-day IUD placement increases knowledge and use of IUDs 3 months after women seek EC.ImplicationsWomen seeking EC from family planning clinics should be offered counseling about highly effective reversible contraceptives with the option of same-day contraceptive placement.

The purpose of this study was to classify the clinical subtypes of core premenstrual disorders during the International Society for Premenstrual Disorders' second consensus meeting. Multiple iterations were used to achieve consensus between a group of experts; these iterations included a two-generational Delphi technique that was preceded and followed by open group discussions. The first round was to generate a list of all potential clinical subtypes, which were subsequently prioritized using a Delphi methodology and then finalised in a final round of open discussion. On a six-point scale, 4 of the 12 potential clinical subtypes had a mean score of ≥5.0 following the second iteration and only 3 of the 4 still had a mean score of ≥5.0 after the third iteration. The final list consisted of these three subtypes and an additional subtype, which was introduced and agreed upon, in the final iteration. There is consensus amongst experts that core premenstrual disorder is divided into three symptom-based subtypes: predominantly physical, predominantly psychological and mixed. A proportion of psychological and mixed subtypes may meet the DSM-IV diagnostic criteria for premenstrual dysphoric disorder.

The second consensus meeting of the International Society for Premenstrual Disorders (ISPMD) took place in London during March 2011. The primary goal was to evaluate the published evidence and consider the expert opinions of the ISPMD members to reach a consensus on advice for the management of premenstrual disorders. Gynaecologists, psychiatrists, psychologists and pharmacologists each formally presented the evidence within their area of expertise; this was followed by an in-depth discussion leading to consensus recommendations. This article provides a comprehensive review of the outcomes from the meeting. The group discussed and agreed that careful diagnosis based on the recommendations and classification derived from the first ISPMD consensus conference is essential and should underlie the appropriate management strategy. Options for the management of premenstrual disorders fall under two broad categories, (a) those influencing central nervous activity, particularly the modulation of the neurotransmitter serotonin and (b) those that suppress ovulation. Psychotropic medication, such as selective serotonin reuptake inhibitors, probably acts by dampening the influence of sex steroids on the brain. Oral contraceptives, gonadotropin-releasing hormone agonists, danazol and estradiol all most likely function by ovulation suppression. The role of oophorectomy was also considered in this respect. Alternative therapies are also addressed, with, e.g. cognitive behavioural therapy, calcium supplements and Vitex agnus castus warranting further exploration.

The purpose of this study was to classify the clinical subtypes of core premenstrual disorders during the International Society for Premenstrual Disorders' second consensus meeting. Multiple iterations were used to achieve consensus between a group of experts; these iterations included a two-generational Delphi technique that was preceded and followed by open group discussions. The first round was to generate a list of all potential clinical subtypes, which were subsequently prioritized using a Delphi methodology and then finalised in a final round of open discussion. On a six-point scale, 4 of the 12 potential clinical subtypes had a mean score of a parts per thousand yen5.0 following the second iteration and only 3 of the 4 still had a mean score of a parts per thousand yen5.0 after the third iteration. The final list consisted of these three subtypes and an additional subtype, which was introduced and agreed upon, in the final iteration. There is consensus amongst experts that core premenstrual disorder is divided into three symptom-based subtypes: predominantly physical, predominantly psychological and mixed. A proportion of psychological and mixed subtypes may meet the DSM-IV diagnostic criteria for premenstrual dysphoric disorder.

The second consensus meeting of the International Society for Premenstrual Disorders (ISPMD) took place in London during March 2011. The primary goal was to evaluate the published evidence and consider the expert opinions of the ISPMD members to reach a consensus on advice for the management of premenstrual disorders. Gynaecologists, psychiatrists, psychologists and pharmacologists each formally presented the evidence within their area of expertise; this was followed by an in-depth discussion leading to consensus recommendations. This article provides a comprehensive review of the outcomes from the meeting. The group discussed and agreed that careful diagnosis based on the recommendations and classification derived from the first ISPMD consensus conference is essential and should underlie the appropriate management strategy. Options for the management of premenstrual disorders fall under two broad categories, (a) those influencing central nervous activity, particularly the modulation of the neurotransmitter serotonin and (b) those that suppress ovulation. Psychotropic medication, such as selective serotonin reuptake inhibitors, probably acts by dampening the influence of sex steroids on the brain. Oral contraceptives, gonadotropin-releasing hormone agonists, danazol and estradiol all most likely function by ovulation suppression. The role of oophorectomy was also considered in this respect. Alternative therapies are also addressed, with, e.g. cognitive behavioural therapy, calcium supplements and Vitex agnus castus warranting further exploration.

Women seeking walk-in pregnancy testing (WIP) and emergency contraception (EC) are at high risk for unintended pregnancy. We evaluated the effect of structured contraceptive counseling on contraceptive knowledge and use 3 months after women sought WIP or EC from a Title X clinic in Pittsburgh. Women aged 15-45 who sought WIP or EC and wanted to avoid pregnancy for at least 6 months were asked to complete a telephone survey three months after their clinic visit. We compared responses from patients seen before (Jan-Aug 2011) and after the clinic began offering brief structured counseling about highly effective reversible contraceptives to all women seeking EC or WIP (Aug 2011-May 2013). Five hundred ten women enrolled in the study; 168 prior to and 342 following implementation of the counseling intervention. After the introduction of structured counseling, more women had accurate knowledge of the relative effectiveness of intrauterine contraception (IUC) (40% vs 11%, p

The purpose of this study was to classify the clinical subtypes of core premenstrual disorders during the International Society for Premenstrual Disorders' second consensus meeting. Multiple iterations were used to achieve consensus between a group of experts; these iterations included a two-generational Delphi technique that was preceded and followed by open group discussions. The first round was to generate a list of all potential clinical subtypes, which were subsequently prioritized using a Delphi methodology and then finalised in a final round of open discussion. On a six-point scale, 4 of the 12 potential clinical subtypes had a mean score of ≥5.0 following the second iteration and only 3 of the 4 still had a mean score of ≥5.0 after the third iteration. The final list consisted of these three subtypes and an additional subtype, which was introduced and agreed upon, in the final iteration. There is consensus amongst experts that core premenstrual disorder is divided into three symptom-based subtypes: predominantly physical, predominantly psychological and mixed. A proportion of psychological and mixed subtypes may meet the DSM-IV diagnostic criteria for premenstrual dysphoric disorder.

Women seeking walk-in pregnancy testing (WIP) and emergency contraception (EC) are at high risk for unintended pregnancy. We evaluated the effect of structured contraceptive counseling on contraceptive knowledge and use 3 months after women sought WIP or EC from a Title X clinic in Pittsburgh. Women aged 15-45 who sought WIP or EC and wanted to avoid pregnancy for at least 6 months were asked to complete a telephone survey three months after their clinic visit. We compared responses from patients seen before (Jan-Aug 2011) and after the clinic began offering brief structured counseling about highly effective reversible contraceptives to all women seeking EC or WIP (Aug 2011-May 2013). Five hundred ten women enrolled in the study; 168 prior to and 342 following implementation of the counseling intervention. After the introduction of structured counseling, more women had accurate knowledge of the relative effectiveness of intrauterine contraception (IUC) (40% vs 11%, p

BackgroundWhen used within 5 days of unprotected sex, emergency contraception (EC) can reduce the risk of pregnancy. Our objective was to explore how often women seeking clinic-based pregnancy testing who do not desire pregnancy might benefit from EC and examine variables associated with patients asking for EC when use is indicated.Study designWomen seeking pregnancy testing or EC from an inner-city Title-X-funded family planning clinic between January 2011 and June 2012 were invited to complete surveys.ResultsTwenty-seven percent (n=79) of respondents were seeking EC, and 73% (n=215) were seeking pregnancy testing. Of those seeking pregnancy testing, 39% might have benefited from same-day use of EC pills. Women who had never used EC and who had more than one episode of unprotected sex within the past month were less likely to request EC when use was indicated, while single women were more likely to request EC.ConclusionsCounseling regarding EC options is particularly important for women seeking same-day pregnancy testing who do not desire pregnancy.

Women seeking walk-in pregnancy testing (WIP) and emergency contraception (EC) are at high risk for unintended pregnancy. We evaluated the effect of structured contraceptive counseling on contraceptive knowledge and use 3 months after women sought WIP or EC from a Title X clinic in Pittsburgh. Women aged 15-45 who sought WIP or EC and wanted to avoid pregnancy for at least 6 months were asked to complete a telephone survey three months after their clinic visit. We compared responses from patients seen before (Jan-Aug 2011) and after the clinic began offering brief structured counseling about highly effective reversible contraceptives to all women seeking EC or WIP (Aug 2011-May 2013). Five hundred ten women enrolled in the study; 168 prior to and 342 following implementation of the counseling intervention. After the introduction of structured counseling, more women had accurate knowledge of the relative effectiveness of intrauterine contraception (IUC) (40% vs 11%, p

Women seeking walk-in pregnancy testing (WIP) and emergency contraception (EC) are at high risk for unintended pregnancy. We evaluated the effect of structured contraceptive counseling on contraceptive knowledge and use 3 months after women sought WIP or EC from a Title X clinic in Pittsburgh. Women aged 15-45 who sought WIP or EC and wanted to avoid pregnancy for at least 6 months were asked to complete a telephone survey three months after their clinic visit. We compared responses from patients seen before (Jan-Aug 2011) and after the clinic began offering brief structured counseling about highly effective reversible contraceptives to all women seeking EC or WIP (Aug 2011-May 2013). Five hundred ten women enrolled in the study; 168 prior to and 342 following implementation of the counseling intervention. After the introduction of structured counseling, more women had accurate knowledge of the relative effectiveness of intrauterine contraception (IUC) (40% vs 11%, p

This article presents an overview of four studies that evaluated a continuous oral contraceptive (OC) containing levonorgestrel (90 mcg) and ethinyl estradiol (20 mcg; LNG/EE) for managing premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS).

This article presents an overview of four studies that evaluated a continuous oral contraceptive (OC) containing levonorgestrel (90 mcg) and ethinyl estradiol (20 mcg; LNG/EE) for managing premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS).

Premenstrual disorders (PMD) are characterised by a cluster of somatic and psychological symptoms of varying severity that occur during the luteal phase of the menstrual cycle and resolve during menses (Freeman and Sondheimer, Prim Care Companion J Clin Psychiatry 5:30-39, 2003; Halbreich, Gynecol Endocrinol 19:320-334, 2004). Although PMD have been widely recognised for many decades, their precise cause is still unknown and there are no definitive, universally accepted diagnostic criteria. To consider this issue, an international multidisciplinary group of experts met at a face-to-face consensus meeting to review current definitions and diagnostic criteria for PMD. This was followed by extensive correspondence. The consensus group formally became established as the International Society for Premenstrual Disorders (ISPMD). The inaugural meeting of the ISPMD was held in Montreal in September 2008. The primary aim was to provide a unified approach for the diagnostic criteria of PMD, their quantification and guidelines on clinical trial design. This report summarises their recommendations. It is hoped that the criteria proposed here will inform discussions of the next edition of the World Health Organisation's International Classification of Diseases (ICD-11), and the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) criteria that are currently under consideration. It is also hoped that the proposed definitions and guidelines could be used by all clinicians and investigators to provide a consistent approach to the diagnosis and treatment of PMD and to aid scientific and clinical research in this field.