The multifactorial aetiology and management of premenstrual dysphoric disorder with leuprorelin acetate.

Up to 18% of women of reproductive age may experience symptoms during the luteal phase of the menstrual cycle known as premenstrual syndrome (PMS) or its more severe form, premenstrual dysphoric disorder (PMDD). A plethora of symptoms have been described, but both are commonly associated with other mood-related disorders such as major depression causing significant life impairment. Originally known as late luteal phase dysphoric disorder in the DSM-III-R (American Psychiatric Association 1987), the syndrome was renamed PMDD in the DSM-IV (American Psychiatric Association 1994). Between 3% and 8% of women meet the diagnostic criteria for PMDD. Currently, there is no consensus on its aetiology although it is thought to be multifactorial. Biological, genetic, psychological, environmental and social factors have all been suggested. However, an altered sensitivity to the normal hormonal fluctuations that influence functioning of the central nervous system is thought most likely. PMDD is identified in the DSM-5 by the presence of at least five symptoms accompanied by significant psychosocial or functional impairment. During evaluation, it is recommended that clinicians confirm symptoms by prospective patient mood charting for at least two menstrual cycles. Management options include psychotropic agents, ovulation suppression and dietary modification. Selective serotonin reuptake inhibitors (SSRIs) are considered primary therapy for psychological symptoms. Ovulation suppression is another option with the combined oral contraceptive pill (COCP) or GnRH (gonadotropin-releasing hormone) agonists. Rarely symptoms warrant a bilateral oophorectomy and a 6-month trial of GnRH agonists prior to surgery may be prudent to determine its potential efficacy. The authors present the case of a multiparous woman in her mid-30s experiencing severe symptoms during the luteal phase of her menstrual cycle. A trial of the contraceptive pill and SSRIs were unsuccessful. Treatment with leuprorelin acetate (Prostap) improved her symptoms. She therefore elected to undergo a bilateral oophorectomy with resolution of her symptoms. She started hormone replacement therapy (HRT). This case demonstrates the multifactorial aetiology of PMDD and the challenges in its management. Women with PMDD suffer functional impairments comparable with other depressive disorders and yet PMDD and its impact remain under-recognised. As the psychological nature and consequences of PMDD often seem indistinguishable from symptoms of other mental health difficulties, this condition presents distinct diagnostic challenges for healthcare professionals. It is crucial to establish the correct diagnosis using clearly defined criteria because if it is left untreated, it can cause considerable impairment to the woman's quality of life.

Levator Ani Syndrome Presenting with Vaginal Pain.

Levator ani syndrome (LAS), also known as levator ani spasm, puborectalis syndrome, chronic proctalgia, pyriformis syndrome and pelvic tension myalgia, produces chronic anal pain. The levator ani muscle is susceptible to the development of myofascial pain syndrome, and trigger points may be elicited on physical examination. The pathophysiology remains to be fully delineated. The diagnosis of LAS is suggested primarily by the clinical history, physical examination and the exclusion of organic disease that can produce recurrent or chronic proctalgia. Digital massage, sitz bath, electrogalvanic stimulation and biofeedback are the treatment modalities most frequently described in the literature. Pharmacological management includes non-steroidal anti-inflammatory medications, diazepam, amitriptyline, gabapentin and botulinum toxin. The evaluation of these patients can be challenging due to a diversity of causative factors. The authors present the case of a nulliparous woman in her mid-30s presenting with acute onset of lower abdominal and rectal pain radiating to her vagina. There was no history of trauma, inflammatory bowel disease, anal fissure or altered bowel habit. Each pain episode lasted longer than 20 min and was exacerbated by sitting. Neurological examination showed no evidence of neurological dysfunction. Rectal examination was unremarkable. During vaginal examination, palpation of the levator ani muscles elicited pain indicating pelvic floor dysfunction. Laboratory investigations including a full blood count and C reactive protein were within normal range. Further investigation with a transabdominal ultrasound scan, CT of the abdomen and pelvis and MRI of the lumbar spine were unremarkable. She commenced treatment with amitriptyline 20 mg once daily. She was referred for pelvic floor physiotherapy. Functional pain syndromes, such as LAS, should be regarded as diagnoses of exclusion and considered only after a thorough evaluation has been performed to rule out structural causes of pain. Knowledge of the pelvic floor and pelvic wall muscles may enable the physician to identify LAS, a possible cause of chronic pelvic pain.

Ruptured ovarian ectopic pregnancy presenting with an acute abdomen.

An ectopic pregnancy occurs in 2% of all pregnancies. A primary ovarian ectopic (OP) is a rare entity and occurs in <2% of all ectopic gestations. It may present in those individuals who take ovulatory drugs, use an intrauterine device or have undergone in vitro fertilisation or embryo transfer. Multiparity and a younger age are other recognised risk factors. Diagnosing an OP pregnancy remains a challenge and it may be misdiagnosed as a bleeding luteal cyst, a haemorrhagic ovarian cyst or a tubal pregnancy by ultrasound scan. The diagnosis is often only established at laparoscopy following histopathological examination. A ruptured OP is a potentially life-threatening condition due to its potential for haemorrhage and hemodynamic collapse. Hence, early diagnosis is crucial to prevent serious morbidity and mortality. The authors present the case of a multiparous woman in her late 30s presenting with a seizure and lower abdominal pain at 6 weeks gestation. Her beta human chorionic gonadotropin was >9000 Miu/mL. A transvaginal ultrasound scan showed no evidence of an intrauterine pregnancy. There was free fluid in the pelvis. She was hemodynamically stable. She underwent a diagnostic laparoscopy, which showed hemoperitoneum and a ruptured left OP pregnancy. She underwent a left oophorectomy. Histology confirmed chorionic villi within the ovarian stroma. This case demonstrates the challenges in preoperative diagnosis of a ruptured OP pregnancy and acts as a cautionary reminder that individuals can present with hemodynamic stability. Rarely, as in this case, an OP pregnancy can occur without the presence of risk factors. Despite its rarity, a ruptured OP pregnancy should be considered in the differential diagnosis of women of reproductive age presenting to the emergency department with acute abdominal pain and a positive pregnancy test.

Could congressionally mandated incentives lead to deployment of large-scale CO2 capture, facilities for enhanced oil recovery CO2 markets and geologic CO2 storage?

In passing the Bipartisan Budget Act of 2018, Congress reformed and strengthened a section of the tax code, 45Q, which provides tax credits of up to $35/ton CO2 for the capture and utilization of CO2 in qualifying applications such as enhanced oil recovery (EOR) and up to $50/ton CO2 for CO2 that is captured and permanently stored in a geologic repository. Earlier versions of the tax credit with lower credit values generated limited interest. This change to the tax code could potentially alter U.S. energy systems. This paper examines the effect of the increased 45Q credits on CO2 capture, utilization and storage (CCUS) deployment in the United States and on petroleum and power production. A range of potential outcomes is explored using five modeling tools. The paper goes on to explore the potential impact of possible modifications of the current tax credit including extension of its availability in time, the period over which 45Q tax credits can be utilized for any given asset and increases in the value of the credit as well as interactions with technology availability and carbon taxation. The paper concludes that 45Q tax credits could stimulate additional CCUS beyond that which is already underway.

Process evaluation of the impact and acceptability of a polypill for prevention of cardiovascular disease.

IMPORTANCE: The Use of a Multidrug Pill In Reducing cardiovascular Events (UMPIRE) trial has shown improved adherence with the use of a polypill strategy when compared with usual medications for cardiovascular disease (CVD) prevention. To advance from efficacy to impact, we need a better understanding of why and how such a strategy might be deployed in complex health systems. OBJECTIVE: To understand, from the perspective of UMPIRE trial participants and professionals, how and why a polypill strategy improves adherence compared with usual care, why improvement is greater in some subgroups, and to explore the acceptability of a polypill strategy among trial participants and healthcare professionals. DESIGN, SETTING AND PARTICIPANTS: A preplanned process evaluation, based on qualitative interviews, was conducted with a subsample of 102 trial participants and 41 healthcare professionals at the end of the UMPIRE trial in India and Europe. RESULTS: Most patients contrasted the simplicity of the polypill with usual medications that they found complex and, for many in India, expensive. Patients with low baseline adherence struggled most with complex medication lists, and those without established disease described less motivation to adhere when compared with people who had already been diagnosed with CVD; people in the latter group had already undertaken self-directed measures to adhere to CVD preventive medicines prior to entering the trial. Taking medication was one of many adaptations described by patients; these included dietary changes, stopping smoking and maintaining exercise. Most patients liked the polypill strategy, although some participants and health professionals were concerned that it would provide less tailored therapy for individual needs. CONCLUSIONS: Adherence to treatment lists with multiple medications is complex and influenced by several factors. Simplifying medication by using a once-daily polypill is one approach to CVD prevention that may enhance adherence. Prescribers should also consider the wide variety of adjustments that individuals need to make to cope with daily medication.

Peroxisome proliferator-activated receptor ligands reduce aortic dilatation in a mouse model of aortic aneurysm.

OBJECTIVE: Osteopontin (OPN) is associated with human abdominal aortic aneurysms (AAA) and in vitro studies suggest that this cytokine is downregulated by peroxisome proliferator-activated receptor (PPAR) ligation. We examined the effect of two PPAR ligands within a mouse model of aortic aneurysm. METHODS: At 11 weeks of age apolipoprotein E deficient (ApoE(-/-)) mice were given pioglitazone (n=27), fenofibrate (n=27) or vehicle (n=27) in their drinking water. From 13 weeks of age mice received angiotensin II (1 microg/kg/min) infusion via subcutaneous pumps until death or 17 weeks when the aortas were harvested and maximum aortic diameters were recorded. Suprarenal aortic segments were assessed for OPN concentration and macrophage accumulation. Saline infused mice served as negative controls (n=22). RESULTS: Angiotensin II induced marked dilatation in the suprarenal aorta (>2-fold increase compared to controls) associated with upregulation of the cytokines OPN and macrophage infiltration. Suprarenal aortic expansion was significantly reduced by administration of pioglitazone (mean diameter 1.61+/-0.11 mm, p=0.011) and fenofibrate (mean diameter 1.51+/-0.13 mm, p=0.001) compared to the vehicle control group (mean diameter 2.10+/-0.14 mm). Immunostaining for macrophages was reduced in mice treated with pioglitazone (median staining area 6.2%, interquartile range 4.1-7.2, p<0.001) and fenofibrate (median staining area 4.0%, interquartile range 2.2-6.1, p<0.001) compared to mice receiving vehicle control (median staining area 13.2%, interquartile range 8.4-20.0). CONCLUSION: These findings suggest the potential value of peroxisome proliferator-activated receptor ligation as a therapy for human AAAs.

Unprotected left main disease managed with drug-eluting stents: long-term outcome of 100 patients with increased surgical risk.

OBJECTIVES: The purpose of this study was to determine long-term clinical outcomes in high surgical risk patients (pts) with unprotected left main (ULM) disease who were managed with drug-eluting stents (DES). BACKGROUND: The long-term efficacy of unprotected left main (ULM) stenting with DES remains uncertain. METHODS: From June 2003 to December 2005, 100 pts with increased surgical risk underwent ULM stenting with DES. Patient risk was estimated by EuroSCORE. Disease was confined to the ostium/main stem in Group A (31 pts) and involved the bifurcation in Group B (69 pts). Study endpoints were MI, TVR, and death. RESULTS: Mean age was 68 +/- 1 years, EF 52 +/- 1%. Mean EuroSCORE was 5.2 +/- 0.4, and 41% pts had a EuroSCORE of >6. In Group A, 87% of lesions were directly stented. In Group B, 61% of pts received one stent and 39% received two stents. Primary success was 95%. Follow-up data (mean 28 +/- 1 months) were obtained in all patients. Restenosis occurred at the proximal stent margin in 5/9 pts. There were 12 cardiac deaths (88% cardiac survival) and 9 noncardiac deaths (79% total survival). In Group B, 5 pts died suddenly: 3 within the first week and 2 additional pts after 1 year. Sudden death did not occur in Group A. All cause event-free survival was 65% in Group A and 67% in Group B. CONCLUSION: A substantial number of late adverse events occurred in both ostial and bifurcation groups with equal frequency. Until definitive data from randomized trials are available, ULM stenting should be performed only in patients with prohibitive surgical risk.

Technique of left main stenting is dependent on lesion location and distal branch protection.

The purpose of this study was to review our experience with left main stenting and evaluate initial results with drug-eluting stents (DESs). Drug-eluting stents delivered with contemporary techniques could change the traditional surgical approach to patients with significant left main disease. One hundred sixty-one patients underwent left main stenting (100 bare metal, 61 drug-eluting) after being excluded from surgery. In group A, disease was confined to the ostium or main stem; in group B, disease involved the bifurcation. Patients were classified as either unprotected (U) or protected (P) depending on the presence of a patent bypass graft. Study endpoints were any major adverse cardiac event (MACE). In-hospital MACE was 6% with no deaths; 74% of patients in group A underwent direct stenting, whereas 89% of the patients in group B had predilatation performed prior to stent implantation. A total of 98% of patients in BU had kissing balloon inflations after stent deployment; provisional side-branch stenting was required in one patient. V-stenting was performed in 13% of patients in group BU. The 1-year mortality in the bare metal stent group was 9% with the majority of deaths in group BU. There was one noncardiac death in the DES group at 6 months and five patients (8.2%) underwent target vessel revascularization for restenosis. Event-free survival at 6 months in group BU treated with DESs was 87%. Significant left main disease presents a spectrum of angiographic abnormalities and different interventional techniques are required depending on lesion location and distal protection. Although in-hospital complications with left main stenting were low in this single-center study, follow-up events were common in patients treated with bare metal stents. A randomized multicenter trial will be required to determine whether drug-eluting stents will improve survival in patients with left main disease.