This document summarizes information about ENABLEX (darifenacin), an extended-release tablet for treating overactive bladder. It discusses the disease background and risk factors. ENABLEX is a muscarinic receptor antagonist that is M3 selective, targeting bladder smooth muscle with fewer CNS side effects than less selective drugs. Clinical trials showed ENABLEX significantly reduced incontinence episodes and other symptoms and was well tolerated, establishing it as an effective treatment option.
This document discusses modifications made to oral contraceptive regimens to address issues with the standard 21-day regimen that includes a 7-day hormone-free interval. Specifically, it discusses how reducing the hormone-free interval or supplementing it with low-dose estrogen pills can help suppress ovarian follicle development and prevent problems like breakthrough bleeding. The experts describe how our understanding of ovarian physiology informed the development of extended-cycle regimens and the importance of consistent pill-taking, especially during the first week after the hormone-free interval.
DHEA supplementation may improve ovarian reserve and fertility outcomes in women with diminished ovarian reserve (DOR). Studies show DHEA increases egg and embryo counts and quality, and pregnancy rates. It acts before, during or after the recruitment phase of follicle growth, preventing follicle atresia and increasing FSH receptors. DHEA supplementation in women over age 40 or those with elevated FSH or low ovarian reserve based on tests has shown benefits with few side effects at recommended doses of 25mg TID for at least 2 months prior to fertility treatment. Pregnancy loss rates were reduced by 50-80% with DHEA supplementation in studies.
DHEA supplementation can improve ovarian reserve and fertility outcomes in women with diminished ovarian reserve. It acts early in follicle development to stimulate growth and maturation. Studies show DHEA increases levels of AMH, the number of eggs and embryos retrieved in IVF, and pregnancy rates while decreasing cancellation rates. The optimal dosage is 25mg three times daily until pregnancy is achieved. DHEA is not recommended for PCOS patients unless they have low testosterone levels and are poor responders.
Pure DHEA Supplementation For Fertility TreatmentJason Peters
DHEA supplementation is a fertility treatment used mainly for women with diminished ovarian reserve. Studies by the Center for Human Reproduction in New York have found that pure DHEA increases egg and embryo quality and pregnancy rates. It can increase spontaneous conceptions and reduce miscarriages. Potential side effects include emotional changes, insomnia and headaches. Women with certain medical conditions should only take DHEA under a physician's supervision.
This document discusses modifications made to oral contraceptive regimens to address issues with the standard 21-day regimen that includes a 7-day hormone-free interval. Specifically, it discusses how reducing the hormone-free interval or supplementing it with low-dose estrogen pills can help suppress ovarian follicle development and prevent problems like breakthrough bleeding. The experts describe how our understanding of ovarian physiology informed the development of extended-cycle regimens and the importance of consistent pill-taking, especially during the first week after the hormone-free interval.
DHEA supplementation may improve ovarian reserve and fertility outcomes in women with diminished ovarian reserve (DOR). Studies show DHEA increases egg and embryo counts and quality, and pregnancy rates. It acts before, during or after the recruitment phase of follicle growth, preventing follicle atresia and increasing FSH receptors. DHEA supplementation in women over age 40 or those with elevated FSH or low ovarian reserve based on tests has shown benefits with few side effects at recommended doses of 25mg TID for at least 2 months prior to fertility treatment. Pregnancy loss rates were reduced by 50-80% with DHEA supplementation in studies.
DHEA supplementation can improve ovarian reserve and fertility outcomes in women with diminished ovarian reserve. It acts early in follicle development to stimulate growth and maturation. Studies show DHEA increases levels of AMH, the number of eggs and embryos retrieved in IVF, and pregnancy rates while decreasing cancellation rates. The optimal dosage is 25mg three times daily until pregnancy is achieved. DHEA is not recommended for PCOS patients unless they have low testosterone levels and are poor responders.
Pure DHEA Supplementation For Fertility TreatmentJason Peters
DHEA supplementation is a fertility treatment used mainly for women with diminished ovarian reserve. Studies by the Center for Human Reproduction in New York have found that pure DHEA increases egg and embryo quality and pregnancy rates. It can increase spontaneous conceptions and reduce miscarriages. Potential side effects include emotional changes, insomnia and headaches. Women with certain medical conditions should only take DHEA under a physician's supervision.
Evolution of ovarian stimulation for ART - towards an individualized approachSandro Esteves
The presentation discusses the evolution of ovarian stimulation for assisted reproductive technology (ART). It begins with a historical perspective of gonadotropin development from urinary sources to recombinant products. It then examines primary factors affecting IVF success like age, ovarian reserve markers, and cause of infertility. The presentation concludes by exploring more individualized clinical strategies like tailoring gonadotropin doses, flexible GnRH antagonist protocols, and LH supplementation to improve IVF outcomes.
Poor and hyper responders: biomarkers management, strategies
This document discusses the use of biomarkers such as AMH, AFC, and genetic markers to predict ovarian response and tailor IVF stimulation strategies. Key points:
1. AMH and AFC are effective at predicting poor and hyper ovarian response but not live birth rates. They are useful for choosing protocols.
2. Genetic markers of FSH and LH receptors can help explain hypo-sensitivity to FSH in some patients.
3. An integrated approach combining hormonal, functional and genetic biomarkers is needed to select the optimal treatment protocol for each patient.
4. Individualized treatment based on biomarkers can reduce cancellations, OHSS
Effective interventions in ART An overview of Cochrane Reviews 2015Aboubakr Elnashar
This document summarizes the key findings from 95 Cochrane systematic reviews on interventions for assisted reproductive technology published up to July 2015. 32 reviews identified interventions that were effective (19 interventions) or promising (13 interventions) in improving live birth or pregnancy rates. 14 reviews found interventions that were ineffective (2 interventions) or possibly ineffective (12 interventions). The reviews assessed interventions for various steps of ART including pre-ART strategies, ovarian stimulation, embryo transfer, and luteal phase support. Effective interventions included use of growth hormone, metformin, endometrial injury, and single embryo transfer. Ineffective interventions included follicular flushing and preimplantation genetic screening.
This document discusses management strategies for poor responders undergoing assisted reproductive technology. It begins by defining poor responders according to the Bologna criteria. It then reviews biomarkers for predicting poor response, finding AMH and AFC to be similarly accurate. The document outlines an individualized approach to controlled ovarian stimulation for poor responders, discussing adjuvant therapies like growth hormone and testosterone. It reviews evidence that recombinant FSH preparations retrieve more oocytes than urinary FSH or HMG. GnRH antagonists may shorten stimulation duration slightly. LH supplementation, specifically recombinant LH added to FSH, may modestly improve pregnancy rates.
This document discusses the management of poor or hyper ovarian response in IVF treatment. It covers topics such as predicting ovarian reserve, definitions of poor response, protocols for poor and hyper responders, and techniques like coasting to help prevent ovarian hyperstimulation syndrome. Coasting, where gonadotropin administration is stopped but down regulation continued, is an effective way to prevent OHSS while still allowing for embryo retrieval and transfer. GnRH antagonist protocols may also help lower the risk of OHSS compared to long agonist protocols. There is no single best protocol, and treatments should be individualized based on patient factors and expectations.
The document summarizes a systematic review and meta-analysis that evaluated the efficacy of mild ovarian stimulation compared to conventional IVF in poor responder women undergoing IVF/ICSI treatment cycles. The analysis found that various modalities of mild ovarian stimulation resulted in comparable pregnancy rates, number of retrieved follicles, and cancellation rates, but with shorter duration of stimulation, compared to conventional IVF protocols. Therefore, the review concludes that mild ovarian stimulation could replace conventional IVF as a treatment option for poor responder women undergoing IVF/ICSI.
The document discusses recent advances in controlled ovarian stimulation (COS) protocols for infertility treatment. It describes how recombinant gonadotropins are purer and safer than urinary gonadotropins, while having similar clinical efficacy. COS protocols now utilize GnRH antagonists to simplify treatment and decrease the risk of ovarian hyperstimulation syndrome compared to agonists. Overall, novel COS protocols incorporate recombinant gonadotropins and GnRH antagonists to provide patient-friendly stimulation with good outcomes.
Letrozole in assisted reproduction , Prof. Usama M. Foudaumfrfouda
Letrozole is an aromatase inhibitor that is effective for ovulation induction. It works by decreasing estrogen levels and increasing FSH levels, stimulating follicle growth. Studies have shown letrozole to be as effective as clomiphene citrate for inducing ovulation in women with PCOS or unexplained infertility. Letrozole may also improve ovarian response and decrease gonadotropin needs when used as an adjuvant to gonadotropins for ovarian stimulation in IVF. Letrozole is a promising option for fertility preservation in cancer patients undergoing IVF since it maintains lower estrogen levels than standard gonadotropin protocols.
This document provides an update on poor ovarian response and approaches to improving outcomes for women with poor ovarian reserve undergoing IVF treatment. The key points summarized are:
1) The PRIMA study found no difference in pregnancy outcomes between a mild ovarian stimulation protocol using 150 IU of FSH daily versus a conventional stimulation protocol using 450 IU of HMG daily for women with poor ovarian reserve, despite the mild protocol requiring fewer days of stimulation and lower gonadotropin doses.
2) While increasing gonadotropin doses does not improve pregnancy rates, supplementation with LH during stimulation may provide benefits for women with poor ovarian reserve based on prior studies.
3) A new approach called "dual stimulation"
1. The document discusses the evolution of gonadotropins used in assisted reproduction, including their development from urinary sources to recombinant products.
2. It describes how recombinant gonadotropins provide higher purity and more consistent dosage compared to earlier urinary products, with clinical trials demonstrating similar or improved outcomes.
3. The use of recombinant gonadotropins can offer benefits to patients through features such as pre-filled pens, which may improve compliance and reduce stress associated with treatment.
This document discusses the potential use of DHEA as a supplement for women who are poor responders to IVF treatment. It provides background on DHEA, reviews several studies that have investigated its effects, and shares the author's experience. While some studies found benefits like increased oocyte yield and pregnancy rates, the evidence is still inconclusive. The author's own retrospective analysis found no significant differences in outcomes between DHEA users and non-users. They conclude that more randomized controlled trials are still needed before DHEA can be routinely recommended to improve IVF success rates for poor responders.
DHEA is a hormone that decreases with age and may improve fertility. Studies have found that DHEA supplements:
- Increase fertility rates by 300%
- Improve egg quality and rejuvenate ovaries
- Double IVF pregnancy rates, especially for women over 40
- Reduce miscarriage rates by 50-80%
DHEA appears to work by boosting FSH receptors, reducing cell death in ovaries, and improving embryo quality. It is being used successfully to treat infertility at centers worldwide.
This document summarizes various adjuvant therapies used in IVF/ICSI and their evidence and effectiveness. It discusses assisted hatching, which helps the embryo hatch from the zona pellucida, and preimplantation genetic screening, which screens embryos for genetic abnormalities. It also reviews maternal factors like aspirin, glucocorticoids, growth hormone, and their effects on IVF outcomes. The evidence and roles of additional treatments including heparin, immunoglobulin, antibiotics, acupuncture, and endometrial biopsy are summarized.
Role of adjuvants in poor ovarian responders , undergoing infertility treatment , in terms of Intra uterine inseminations ( IUI ) to In Vitro Fertilization ( IVF )
LETROZOLE WITH TIMED INTERCOURSE VERSUS CLOMIPHENE CITRATE WITH IUIJoe Lee
This study compared pregnancy outcomes in 7,764 patients with unexplained infertility who underwent controlled ovarian stimulation (COS) with either letrozole (LET) and timed intercourse (IC) or clomiphene citrate (CC) and intrauterine insemination (IUI). Clinical pregnancy rates were significantly higher in the LET-IC group compared to the CC-IUI group (15.0% vs 11.8% for IC, 12.3% vs 11.5% for IUI). Endometrial thickness and follicular response were also higher in the LET group. The study concluded that unexplained infertility patients have better pregnancy outcomes with LET stimulation and timed IC compared to CC stimulation and timed ICI
The document discusses luteal phase support (LPS) in assisted reproductive technology (ART) cycles. It notes that abnormal luteal function can occur after controlled ovarian stimulation, necessitating LPS. It reviews various LPS options including human chorionic gonadotropin and progesterone administered via different routes. Vaginal progesterone is found to effectively increase endometrial levels while intramuscular progesterone yields the highest serum levels. The document concludes that LPS is necessary to optimize ART outcomes and that intramuscular or vaginal progesterone are equally effective options.
The document discusses pharmacotherapy for overactive bladder. It provides an overview of overactive bladder terminology, prevalence, diagnosis, and differential diagnosis. It then focuses on the rationale for pharmacologic treatment of overactive bladder, including the use of antimuscarinic drugs which are the mainstay of treatment by inhibiting involuntary bladder contractions. Clinical trials demonstrate the efficacy of drugs like tolterodine in reducing overactive bladder symptoms and improving quality of life.
Progesterone rise on the day of hcg administration (ppremature luteinization)...Aboubakr Elnashar
This document discusses premature luteinization (PL), defined as a rise in progesterone on the day of hCG administration in IVF. It outlines that the incidence of PL varies widely in studies from 13-71% due to different definitions and protocols. Several hypotheses for the pathogenesis of PL are presented, including elevated LH levels and increased LH receptor sensitivity. The impact of PL on IVF outcomes is controversial, with some studies finding negative effects and others no effect. The document concludes by recommending prospective studies are needed to better understand the role of progesterone elevation on IVF success rates and provides suggestions for preventing PL during treatment.
Are Reverse Payment Settlements on Reverse Gear?enthu_rajan
The document summarizes recent developments regarding "reverse payment settlements" between brand-name and generic drug companies. It discusses several court cases that considered whether such settlements violate antitrust laws. There is no consensus in the courts, but the DOJ recently stated that reverse payments substantially above litigation costs should be presumptively unlawful. Proposed legislation in Congress would prohibit or place limits on reverse payment settlements.
This was a presentation I gave to an audience at Nature Publishing Group in New York on May 7th 2009. It's a long presentation and over an hour in length. Not much new here relative to other presentations...just a knitting together of many of the others on here.
There is an increasing availability of free and open access resources for scientists to use on the internet. Coupled with an increasing number of Open Source software programs we are in the middle of a revolution in data availability and tools to manipulate these data. ChemSpider is a free access website built with the intention of providing a structure centric community for chemists. As an aggregator of chemistry related information from many sources, at present over 21.5 million unique chemical entities from over 190 separate data sources, ChemSpider has taken on the task of both robotically and manually integrating and curating publicly available data sources. ChemSpider has also provided an environment for users to deposit, curate and annotate chemistry-related information. This has allowed the community to enhance ChemSpider by adding analytical data, associating synthetic pathways and publications and connecting to social networking resources. I will discuss how ChemSpider is fast becoming the premier curated platform and centralized hub for resourcing information about chemical entities and how the platform provides the foundation data for services allowing the analysis of analytical data and collaborative science.
Evolution of ovarian stimulation for ART - towards an individualized approachSandro Esteves
The presentation discusses the evolution of ovarian stimulation for assisted reproductive technology (ART). It begins with a historical perspective of gonadotropin development from urinary sources to recombinant products. It then examines primary factors affecting IVF success like age, ovarian reserve markers, and cause of infertility. The presentation concludes by exploring more individualized clinical strategies like tailoring gonadotropin doses, flexible GnRH antagonist protocols, and LH supplementation to improve IVF outcomes.
Poor and hyper responders: biomarkers management, strategies
This document discusses the use of biomarkers such as AMH, AFC, and genetic markers to predict ovarian response and tailor IVF stimulation strategies. Key points:
1. AMH and AFC are effective at predicting poor and hyper ovarian response but not live birth rates. They are useful for choosing protocols.
2. Genetic markers of FSH and LH receptors can help explain hypo-sensitivity to FSH in some patients.
3. An integrated approach combining hormonal, functional and genetic biomarkers is needed to select the optimal treatment protocol for each patient.
4. Individualized treatment based on biomarkers can reduce cancellations, OHSS
Effective interventions in ART An overview of Cochrane Reviews 2015Aboubakr Elnashar
This document summarizes the key findings from 95 Cochrane systematic reviews on interventions for assisted reproductive technology published up to July 2015. 32 reviews identified interventions that were effective (19 interventions) or promising (13 interventions) in improving live birth or pregnancy rates. 14 reviews found interventions that were ineffective (2 interventions) or possibly ineffective (12 interventions). The reviews assessed interventions for various steps of ART including pre-ART strategies, ovarian stimulation, embryo transfer, and luteal phase support. Effective interventions included use of growth hormone, metformin, endometrial injury, and single embryo transfer. Ineffective interventions included follicular flushing and preimplantation genetic screening.
This document discusses management strategies for poor responders undergoing assisted reproductive technology. It begins by defining poor responders according to the Bologna criteria. It then reviews biomarkers for predicting poor response, finding AMH and AFC to be similarly accurate. The document outlines an individualized approach to controlled ovarian stimulation for poor responders, discussing adjuvant therapies like growth hormone and testosterone. It reviews evidence that recombinant FSH preparations retrieve more oocytes than urinary FSH or HMG. GnRH antagonists may shorten stimulation duration slightly. LH supplementation, specifically recombinant LH added to FSH, may modestly improve pregnancy rates.
This document discusses the management of poor or hyper ovarian response in IVF treatment. It covers topics such as predicting ovarian reserve, definitions of poor response, protocols for poor and hyper responders, and techniques like coasting to help prevent ovarian hyperstimulation syndrome. Coasting, where gonadotropin administration is stopped but down regulation continued, is an effective way to prevent OHSS while still allowing for embryo retrieval and transfer. GnRH antagonist protocols may also help lower the risk of OHSS compared to long agonist protocols. There is no single best protocol, and treatments should be individualized based on patient factors and expectations.
The document summarizes a systematic review and meta-analysis that evaluated the efficacy of mild ovarian stimulation compared to conventional IVF in poor responder women undergoing IVF/ICSI treatment cycles. The analysis found that various modalities of mild ovarian stimulation resulted in comparable pregnancy rates, number of retrieved follicles, and cancellation rates, but with shorter duration of stimulation, compared to conventional IVF protocols. Therefore, the review concludes that mild ovarian stimulation could replace conventional IVF as a treatment option for poor responder women undergoing IVF/ICSI.
The document discusses recent advances in controlled ovarian stimulation (COS) protocols for infertility treatment. It describes how recombinant gonadotropins are purer and safer than urinary gonadotropins, while having similar clinical efficacy. COS protocols now utilize GnRH antagonists to simplify treatment and decrease the risk of ovarian hyperstimulation syndrome compared to agonists. Overall, novel COS protocols incorporate recombinant gonadotropins and GnRH antagonists to provide patient-friendly stimulation with good outcomes.
Letrozole in assisted reproduction , Prof. Usama M. Foudaumfrfouda
Letrozole is an aromatase inhibitor that is effective for ovulation induction. It works by decreasing estrogen levels and increasing FSH levels, stimulating follicle growth. Studies have shown letrozole to be as effective as clomiphene citrate for inducing ovulation in women with PCOS or unexplained infertility. Letrozole may also improve ovarian response and decrease gonadotropin needs when used as an adjuvant to gonadotropins for ovarian stimulation in IVF. Letrozole is a promising option for fertility preservation in cancer patients undergoing IVF since it maintains lower estrogen levels than standard gonadotropin protocols.
This document provides an update on poor ovarian response and approaches to improving outcomes for women with poor ovarian reserve undergoing IVF treatment. The key points summarized are:
1) The PRIMA study found no difference in pregnancy outcomes between a mild ovarian stimulation protocol using 150 IU of FSH daily versus a conventional stimulation protocol using 450 IU of HMG daily for women with poor ovarian reserve, despite the mild protocol requiring fewer days of stimulation and lower gonadotropin doses.
2) While increasing gonadotropin doses does not improve pregnancy rates, supplementation with LH during stimulation may provide benefits for women with poor ovarian reserve based on prior studies.
3) A new approach called "dual stimulation"
1. The document discusses the evolution of gonadotropins used in assisted reproduction, including their development from urinary sources to recombinant products.
2. It describes how recombinant gonadotropins provide higher purity and more consistent dosage compared to earlier urinary products, with clinical trials demonstrating similar or improved outcomes.
3. The use of recombinant gonadotropins can offer benefits to patients through features such as pre-filled pens, which may improve compliance and reduce stress associated with treatment.
This document discusses the potential use of DHEA as a supplement for women who are poor responders to IVF treatment. It provides background on DHEA, reviews several studies that have investigated its effects, and shares the author's experience. While some studies found benefits like increased oocyte yield and pregnancy rates, the evidence is still inconclusive. The author's own retrospective analysis found no significant differences in outcomes between DHEA users and non-users. They conclude that more randomized controlled trials are still needed before DHEA can be routinely recommended to improve IVF success rates for poor responders.
DHEA is a hormone that decreases with age and may improve fertility. Studies have found that DHEA supplements:
- Increase fertility rates by 300%
- Improve egg quality and rejuvenate ovaries
- Double IVF pregnancy rates, especially for women over 40
- Reduce miscarriage rates by 50-80%
DHEA appears to work by boosting FSH receptors, reducing cell death in ovaries, and improving embryo quality. It is being used successfully to treat infertility at centers worldwide.
This document summarizes various adjuvant therapies used in IVF/ICSI and their evidence and effectiveness. It discusses assisted hatching, which helps the embryo hatch from the zona pellucida, and preimplantation genetic screening, which screens embryos for genetic abnormalities. It also reviews maternal factors like aspirin, glucocorticoids, growth hormone, and their effects on IVF outcomes. The evidence and roles of additional treatments including heparin, immunoglobulin, antibiotics, acupuncture, and endometrial biopsy are summarized.
Role of adjuvants in poor ovarian responders , undergoing infertility treatment , in terms of Intra uterine inseminations ( IUI ) to In Vitro Fertilization ( IVF )
LETROZOLE WITH TIMED INTERCOURSE VERSUS CLOMIPHENE CITRATE WITH IUIJoe Lee
This study compared pregnancy outcomes in 7,764 patients with unexplained infertility who underwent controlled ovarian stimulation (COS) with either letrozole (LET) and timed intercourse (IC) or clomiphene citrate (CC) and intrauterine insemination (IUI). Clinical pregnancy rates were significantly higher in the LET-IC group compared to the CC-IUI group (15.0% vs 11.8% for IC, 12.3% vs 11.5% for IUI). Endometrial thickness and follicular response were also higher in the LET group. The study concluded that unexplained infertility patients have better pregnancy outcomes with LET stimulation and timed IC compared to CC stimulation and timed ICI
The document discusses luteal phase support (LPS) in assisted reproductive technology (ART) cycles. It notes that abnormal luteal function can occur after controlled ovarian stimulation, necessitating LPS. It reviews various LPS options including human chorionic gonadotropin and progesterone administered via different routes. Vaginal progesterone is found to effectively increase endometrial levels while intramuscular progesterone yields the highest serum levels. The document concludes that LPS is necessary to optimize ART outcomes and that intramuscular or vaginal progesterone are equally effective options.
The document discusses pharmacotherapy for overactive bladder. It provides an overview of overactive bladder terminology, prevalence, diagnosis, and differential diagnosis. It then focuses on the rationale for pharmacologic treatment of overactive bladder, including the use of antimuscarinic drugs which are the mainstay of treatment by inhibiting involuntary bladder contractions. Clinical trials demonstrate the efficacy of drugs like tolterodine in reducing overactive bladder symptoms and improving quality of life.
Progesterone rise on the day of hcg administration (ppremature luteinization)...Aboubakr Elnashar
This document discusses premature luteinization (PL), defined as a rise in progesterone on the day of hCG administration in IVF. It outlines that the incidence of PL varies widely in studies from 13-71% due to different definitions and protocols. Several hypotheses for the pathogenesis of PL are presented, including elevated LH levels and increased LH receptor sensitivity. The impact of PL on IVF outcomes is controversial, with some studies finding negative effects and others no effect. The document concludes by recommending prospective studies are needed to better understand the role of progesterone elevation on IVF success rates and provides suggestions for preventing PL during treatment.
Are Reverse Payment Settlements on Reverse Gear?enthu_rajan
The document summarizes recent developments regarding "reverse payment settlements" between brand-name and generic drug companies. It discusses several court cases that considered whether such settlements violate antitrust laws. There is no consensus in the courts, but the DOJ recently stated that reverse payments substantially above litigation costs should be presumptively unlawful. Proposed legislation in Congress would prohibit or place limits on reverse payment settlements.
This was a presentation I gave to an audience at Nature Publishing Group in New York on May 7th 2009. It's a long presentation and over an hour in length. Not much new here relative to other presentations...just a knitting together of many of the others on here.
There is an increasing availability of free and open access resources for scientists to use on the internet. Coupled with an increasing number of Open Source software programs we are in the middle of a revolution in data availability and tools to manipulate these data. ChemSpider is a free access website built with the intention of providing a structure centric community for chemists. As an aggregator of chemistry related information from many sources, at present over 21.5 million unique chemical entities from over 190 separate data sources, ChemSpider has taken on the task of both robotically and manually integrating and curating publicly available data sources. ChemSpider has also provided an environment for users to deposit, curate and annotate chemistry-related information. This has allowed the community to enhance ChemSpider by adding analytical data, associating synthetic pathways and publications and connecting to social networking resources. I will discuss how ChemSpider is fast becoming the premier curated platform and centralized hub for resourcing information about chemical entities and how the platform provides the foundation data for services allowing the analysis of analytical data and collaborative science.
Aging beautifully part 2 urinary incontinenceciehortl
The document discusses urinary incontinence and its management. It notes that urinary incontinence affects many adults, especially older adults, and can negatively impact quality of life. There are different types of urinary incontinence, including stress, urge, mixed, overflow, and functional incontinence. Treatment involves non-pharmacological options as well as pharmacological therapies like duloxetine, alpha-adrenergic agonists, anticholinergics, and tricyclic antidepressants. Pharmacists play an important role in helping patients manage urinary incontinence through medication management and addressing adverse effects to improve quality of life.
A presentation by Dr David James, Executive Director of Strategic Innovation at the Royal Society of Chemistry - given at the Open Science Showcase held by the Royal Society of Chemistry on 26 February 2014.
The document provides an overview of an advanced mental health training course. The course covers topics such as identifying mental health problems, developing positive mental health, psychosocial intervention, case studies, and practice skills. It includes sessions on stress and psychosis, the ladder of functioning, statistics on prevalence of mental health issues, and decreasing stress tolerance for those with psychosis.
The document discusses several legal issues regarding tax claims and preferential payments in winding up proceedings under the Companies Act 1956. It summarizes various court judgments and discusses that (1) tax assessments are not legal proceedings under section 446, (2) taxes not due within 12 months of winding up are unsecured claims, (3) interest and penalties require court approval, and (4) rent accrued after winding up is not a preferential payment if the property is not used for winding up purposes. The document provides contact details for the author for any clarifications.
This document discusses obesity, systemic lupus erythematosus (SLE), thyroid disease, and in vitro fertilization (IVF). It summarizes that obesity is associated with lower clinical pregnancy and live birth rates after IVF due to factors like insulin resistance and inflammation. For SLE patients undergoing IVF, aggressive ovarian stimulation should be avoided to prevent thrombosis, and immunosuppressants may be increased. Thyroid disorders must be controlled before conception, and levothyroxine doses may need adjustment during ovarian stimulation due to changes in hormone levels. Screening for thyroid disease is recommended for those with risk factors prior to IVF to optimize treatment.
Fecal Incontinence in the Scleroderma Patient: What We Know and Where We Should Go
Darren M. Brenner, MD Assistant Professor of Medicine and Surgery Northwestern University—Feinberg School of Medicine
Presented at Scleroderma Patient Education Conference - Saturday, October 19, 2013
Conference hosted by the Scleroderma Foundation, Greater Chicago Chapter and the Northwestern Scleroderma Program
This document discusses the medical management of Overactive Bladder (OAB) through the use of anticholinergic drugs such as Vesicare (solifenacin succinate). It provides details on the efficacy, tolerability, and pharmacokinetics of Vesicare based on clinical studies. Vesicare was shown to provide rapid relief of OAB symptoms such as urgency and have a good balance between efficacy and tolerability. It was found to be superior to tolterodine ER in improving OAB parameters and its effects increased over long-term use. The document also discusses alternative therapies for OAB and treatment considerations for different patient populations.
This document discusses Dr. Santosh Agrawal's background and credentials as a urologist and kidney transplant surgeon. It then provides information on overactive bladder (OAB), including definitions, prevalence statistics, quality of life impacts, incidence being underreported, and OAB classification systems. Diagnosis of OAB is discussed, covering patient history, physical exam, lab tests, bladder diaries, and urodynamics. Conservative management options like behavioral modification, bladder training, pelvic floor muscle therapy, and pharmacologic therapies are summarized. Specific drugs for treating detrusor overactivity like tolterodine are also mentioned.
This document provides guidelines for the diagnosis and management of premature ovarian insufficiency (POI). It defines POI as depletion of follicular activity before age 40, characterized by menstrual disturbances, raised gonadotropins, and low estrogen. The prevalence is approximately 1% in the general population. Causes include genetic factors, autoimmune disorders, infections, chemotherapy and radiation. Management focuses on hormone replacement therapy (HRT) to reduce long-term health risks, fertility options, and treatment of symptoms like reduced bone mineral density and increased cardiovascular risk.
AKI in neonates can be caused by prerenal, intrinsic renal, or postrenal factors. It is defined based on changes in creatinine and urine output. Evaluation involves investigating causes and monitoring electrolytes and acid-base status. Management includes supportive care, correcting fluid and electrolyte imbalances, and considering renal replacement therapies like peritoneal dialysis or hemodialysis if indicated. Peritoneal dialysis uses the peritoneum as a dialyzing membrane and allows diffusion and ultrafiltration to remove waste and fluid. Complications can include peritonitis or fluid leaks. Some neonates who experience AKI may later develop chronic kidney disease.
AKI in neonates can be caused by prerenal, intrinsic renal, or postrenal factors. It is defined and classified using creatinine and urine output criteria. Management involves identifying and treating the underlying cause, maintaining fluid/electrolyte balance, and considering renal replacement therapy for refractory cases. Peritoneal dialysis is often preferred for neonates as it is gentler than hemodialysis and can provide both fluid removal and metabolic control. However, peritoneal dialysis also carries risks of peritonitis, mechanical issues, and complications in critically ill infants.
Acute kidney injury (AKI) - a sudden impairment in kidney function, that results in the retention of nitrogenous waste products and alters the regulation of extracellular fluid volume, electrolytes, and acid-base homeostasis.
The document discusses controversies and advances in treating neonatal feeding difficulties, outlining the epidemiology and burden of feeding problems in preterm infants, developmental physiology of feeding, methods to clarify the pathophysiological basis of symptoms, evolving evidence-based management approaches, and the development of individualized feeding programs. It provides objectives for the presentation and details research conducted on evaluating aerodigestive reflexes and developing personalized management plans to improve feeding outcomes in high-risk neonates.
This document summarizes current evidence on medical add-ons used in in vitro fertilization (IVF). It discusses adjuvants used to improve ovarian response and implantation success, including DHEA, growth hormone, antioxidants, artificial oocyte activation, estrogen, and metformin. For each adjuvant, the proposed mechanisms of action and available evidence from studies are summarized. In general, the evidence for most add-ons is limited and inconclusive due to small study sizes and heterogeneity. High-quality randomized controlled trials are still needed to establish efficacy and safety.
Commercial products and compounded options for the treatment of erectile dysfunction. Brief overview regarding the pathophysiology, medical, and physical causes behind these disorders as well as epidemiology and prevalence of the disease.
This document discusses IVF treatment for polycystic ovary syndrome (PCOS). It begins with an overview of PCOS prevalence, definitions, and diagnostic criteria. IVF is indicated for PCOS patients who fail to conceive after ovulation induction or have other fertility factors. Patient preparation, gonadotropin protocols and monitoring, triggering ovulation, embryo transfer, and luteal phase support are discussed. Outcomes are better with GnRH antagonist protocols for PCOS patients due to lower gonadotropin doses and risk of ovarian hyperstimulation syndrome (OHSS). Primary and secondary prevention of OHSS includes metformin use, coasting, cryopreservation of embryos, and GnRH agonist triggering of ovulation.
The Impact of Chinese Herbal Medicine on In Vitro Fertilization Outcomes A Sy...keith644288
Many are familiar with acupuncture and its possible benefits for infertility patients. Numerous studies on IVF and acupuncture have been conducted over the last twenty-five years. In the United States fewer are aware that historically in China the specialty of women’s health in Chinese medicine is almost exclusively herbal. In Vitro Fertilization has now been in use for 40 years, originally developed to help women conceive who had blocked fallopian tubes. Recent advances in freezing embryos and preimplantation genetic testing for aneuploidies (PGT-a) have helped physicians gradually increase their IVF rates of success. Pregnancy rates at some of the nation’s top fertility clinics hover at approximately 65%. Physicians and patients alike continue to seek novel methods to further optimize their IVF cycles. This work seeks to explore mechanisms of action and the impact of one of the world’s most ancient medical systems, Chinese medicine’s Chinese herbal medicine (CHM) on the outcomes of IVF.
Fecal incontinence is more prevalent in patients with scleroderma compared to the general population. It can be caused by structural abnormalities of the internal and external anal sphincters as well as neurological and stool abnormalities. Diagnostic tests like anorectal manometry and endoanal ultrasound can identify abnormalities. Treatment options include lifestyle modifications, biofeedback, bulking agents, sacral nerve stimulation, and surgery. However, no treatment has been proven highly effective for fecal incontinence in scleroderma patients.
Overactive bladder, DR Sharda Jain Lifecare Centre Lifecare Centre
OAB OAB is not synonymous with detrusor overactivity as the former is a symptom based diagnosis whilst the latter is an urodynamic diagnosis.
It has been estimated that 64% of patients with OAB have urodynamically proven detrusor overactivity and that 83% of patient with detrusor overactivity have symptoms suggestive of OAB.
Racecadotril is an intestinal antisecretory agent that inhibits intestinal fluid secretion. It works by inhibiting the enzyme enkephalinase, which breaks down the endogenous opioid peptide enkephalin. Enkephalin binds to delta receptors on intestinal cells and reduces cyclic AMP formation, thereby decreasing intestinal fluid secretion. Clinical trials have shown that racecadotril reduces stool output and shortens the time to recovery in children with acute watery diarrhea when used as an adjunct to oral rehydration therapy. It provides benefits over current diarrhea treatments by inhibiting intestinal hypersecretion while having a rapid onset, limited constipating effects, and good safety profile.
This study evaluated the long-term safety of tegaserod, a 5-hydroxytryptamine-4 receptor partial agonist used to treat constipation-predominant irritable bowel syndrome, in 579 patients over 12 months. The most common adverse events related to tegaserod were mild and transient diarrhea, headache, abdominal pain, and flatulence. The study found that tegaserod appeared to be well tolerated for long-term use with no unexpected safety issues identified.
Treatment of MS Symptoms during pregnancy and whilst breastfeedingMS Trust
This document summarizes key information from a presentation on managing multiple sclerosis during pregnancy. It discusses various drug treatments for MS symptoms like spasticity, pain, and mobility issues. It notes that clinical trials on drug safety during pregnancy are limited. Physiological changes in pregnancy can impact drug absorption and dosage requirements. Major birth defects may occur early in pregnancy before the pregnancy is recognized. The risks and benefits of continuing or adjusting treatments need to be considered. Gabapentin appears to have no contraindications, while drugs like duloxetine and carbamazepine require careful consideration during pregnancy. Non-drug options should also be explored. Close monitoring by an MS team is recommended for pregnant women with MS.
otline of the background;;;;
nephrolithiasis is a condition in whom hard massesform whithin the urinary tract,
formation of kidney stones may occur where
the lifetime incidence of kidney stones is approximately 13 percent for mens and 7 percent for women
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
Are you looking for a long-lasting solution to your missing tooth?
Dental implants are the most common type of method for replacing the missing tooth. Unlike dentures or bridges, implants are surgically placed in the jawbone. In layman’s terms, a dental implant is similar to the natural root of the tooth. It offers a stable foundation for the artificial tooth giving it the look, feel, and function similar to the natural tooth.
Co-Chairs, Val J. Lowe, MD, and Cyrus A. Raji, MD, PhD, prepared useful Practice Aids pertaining to Alzheimer’s disease for this CME/AAPA activity titled “Alzheimer’s Disease Case Conference: Gearing Up for the Expanding Role of Neuroradiology in Diagnosis and Treatment.” For the full presentation, downloadable Practice Aids, and complete CME/AAPA information, and to apply for credit, please visit us at https://bit.ly/3PvVY25. CME/AAPA credit will be available until June 28, 2025.
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdfrightmanforbloodline
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Summer is a time for fun in the sun, but the heat and humidity can also wreak havoc on your skin. From itchy rashes to unwanted pigmentation, several skin conditions become more prevalent during these warmer months.
The skin is the largest organ and its health plays a vital role among the other sense organs. The skin concerns like acne breakout, psoriasis, or anything similar along the lines, finding a qualified and experienced dermatologist becomes paramount.
Breast cancer: Post menopausal endocrine therapyDr. Sumit KUMAR
Breast cancer in postmenopausal women with hormone receptor-positive (HR+) status is a common and complex condition that necessitates a multifaceted approach to management. HR+ breast cancer means that the cancer cells grow in response to hormones such as estrogen and progesterone. This subtype is prevalent among postmenopausal women and typically exhibits a more indolent course compared to other forms of breast cancer, which allows for a variety of treatment options.
Diagnosis and Staging
The diagnosis of HR+ breast cancer begins with clinical evaluation, imaging, and biopsy. Imaging modalities such as mammography, ultrasound, and MRI help in assessing the extent of the disease. Histopathological examination and immunohistochemical staining of the biopsy sample confirm the diagnosis and hormone receptor status by identifying the presence of estrogen receptors (ER) and progesterone receptors (PR) on the tumor cells.
Staging involves determining the size of the tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). The American Joint Committee on Cancer (AJCC) staging system is commonly used. Accurate staging is critical as it guides treatment decisions.
Treatment Options
Endocrine Therapy
Endocrine therapy is the cornerstone of treatment for HR+ breast cancer in postmenopausal women. The primary goal is to reduce the levels of estrogen or block its effects on cancer cells. Commonly used agents include:
Selective Estrogen Receptor Modulators (SERMs): Tamoxifen is a SERM that binds to estrogen receptors, blocking estrogen from stimulating breast cancer cells. It is effective but may have side effects such as increased risk of endometrial cancer and thromboembolic events.
Aromatase Inhibitors (AIs): These drugs, including anastrozole, letrozole, and exemestane, lower estrogen levels by inhibiting the aromatase enzyme, which converts androgens to estrogen in peripheral tissues. AIs are generally preferred in postmenopausal women due to their efficacy and safety profile compared to tamoxifen.
Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant is a SERD that degrades estrogen receptors and is used in cases where resistance to other endocrine therapies develops.
Combination Therapies
Combining endocrine therapy with other treatments enhances efficacy. Examples include:
Endocrine Therapy with CDK4/6 Inhibitors: Palbociclib, ribociclib, and abemaciclib are CDK4/6 inhibitors that, when combined with endocrine therapy, significantly improve progression-free survival in advanced HR+ breast cancer.
Endocrine Therapy with mTOR Inhibitors: Everolimus, an mTOR inhibitor, can be added to endocrine therapy for patients who have developed resistance to aromatase inhibitors.
Chemotherapy
Chemotherapy is generally reserved for patients with high-risk features, such as large tumor size, high-grade histology, or extensive lymph node involvement. Regimens often include anthracyclines and taxanes.
Kosmoderma Academy, a leading institution in the field of dermatology and aesthetics, offers comprehensive courses in cosmetology and trichology. Our specialized courses on PRP (Hair), DR+Growth Factor, GFC, and Qr678 are designed to equip practitioners with advanced skills and knowledge to excel in hair restoration and growth treatments.
Know the difference between Endodontics and Orthodontics.Gokuldas Hospital
Your smile is beautiful.
Let’s be honest. Maintaining that beautiful smile is not an easy task. It is more than brushing and flossing. Sometimes, you might encounter dental issues that need special dental care. These issues can range anywhere from misalignment of the jaw to pain in the root of teeth.
1. ENABLEX ® in the Treatment of Overactive Bladder ENABLEX ® is a registered trademark of Warner Chilcott Company, LLC. ENABLEX ® (darifenacin) extended-release tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency
5. Overactive Bladder Is a Complex Syndrome Coyne KS, et al. Urology. 2011; 77:1081-1087. Urgency 12.6% Urge Urinary Incontinence 9.1% Urgency + Frequency 5.2% 1.2% Urgency + Urge Urinary Incontinence 13.1% Urgency + Urge Urinary Incontinence + Frequency 7.0% Prevalence of Overactive Bladder Symptoms in Poll of 2000 Adults Aged ≥40 Years Urge Urinary Incontinence + Frequency
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8. Comorbidities Associated With Overactive Bladder Brown JS, et al. Am J Manag Care . 2000;6(suppl 11):S574-S579. Falls and Fractures Depression Sleep Disturbances Urinary Tract and Skin Infections
9. Overactive Bladder Negatively Affects QOL * A standardized questionnaire that measures health-related QOL. Modified from Stewart WF, et al. World J Urol . 2003;20:327-336. Decrease in Mean SF-36 Score (%) QOL Areas of Measure Patients With Overactive Bladder Urge Incontinence Compared With Controls (SF-36)*
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11. M 3 Receptor Selectivity Allows for Targeting of Tissue of Intent Abrams P, et al. Br J Pharmacol . 2006;148:565-578.
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16. ENABLEX ® as a Treatment Option for Patients With Overactive Bladder Proven Efficacy and Safety by Clinical Trials
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23. 7.5 mg ENABLEX ® Significantly Reduces Incontinence Episodes by ~70% Chapple C, et al. BJU Int. 2005;95:993-1001. * P =.004 vs placebo; data missing for 2 subjects. Treatment Darifenacin 7.5 mg * Placebo Data from a pooled analysis of 3 phase 3, fixed-dose, double-blind, placebo-controlled, parallel-group, 12-week clinical trials (1001, 1002, 1041). A total of 1059 subjects were included in the analysis (darifenacin 7.5 mg: n=337; darifenacin 15 mg: n=334; placebo: n=388). Absolute changes from baseline (last observation carried forward [LOCF]) to Week 12 for subjects on darifenacin: number of weekly incontinence episodes: –8.8 (7.5 mg) and –10.6 (15 mg). n=335 n=271
24. 15 mg ENABLEX ® Significantly Reduces Incontinence Episodes by >75% Chapple C, et al. BJU Int. 2005;95:993-1001. * P <.001 vs placebo; data missing for 4 subjects. Treatment Darifenacin 15 mg * Placebo Data from a pooled analysis of 3 phase 3, fixed-dose, double-blind, placebo-controlled, parallel-group, 12-week clinical trials (1001, 1002, 1041). A total of 1059 subjects were included in the analysis (darifenacin 7.5 mg: n=337; darifenacin 15 mg: n=334; placebo: n=388). Absolute changes from baseline (last observation carried forward [LOCF]) to Week 12 for subjects on darifenacin: number of weekly incontinence episodes: –8.8 (7.5 mg) and –10.6 (15 mg). n=330 n=384
25. 7.5 mg ENABLEX ® Significantly Reduces the Number of Urgency Episodes Chapple C, et al. BJU Int. 2005;95:993-1001. * P <.005 compared with corresponding placebo. 37% 24%
26. 15 mg ENABLEX ® Significantly Reduces the Number of Urgency Episodes Chapple C, et al. BJU Int. 2005;95:993-1001. 39% 23% * P <.01 compared with corresponding placebo. * 49% 34% *
29. ENABLEX ® Long-term Efficacy Up to 2 Years Haab F, et al . BJU Int . 2006;98:1025-1032. Subjects recruited from 1 of 2 phase 3, randomized, double-blind, 12-week studies ENABLEX ® 7.5 mg Once Daily 12-week Studies Long-term Study (24 months) ENABLEX ® 15 mg Once Daily ENABLEX ® 7.5 mg for 2 Weeks Study 1 (n=526) ENABLEX ® 3.75, 7.5, 15 mg, and Placebo Study 2 (n=357) ENABLEX ® 7.5, 15 mg, and Placebo Multicenter, Long-term, Noncomparative, Open-label Study Primary Objective Assess long-term safety and tolerability Secondary Objective Evaluate long-term efficacy
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33. ENABLEX ® Significantly* Improves Patient -reported Bladder Control Zinner N, et al. Int J Clin Pract. 2008;62:1664-1674 . Results of PPBC p <0.0001.
34. ENABLEX ® : Cognitive Function in Older Subjects Kay G, et al . Eur Urol . 2006;50:317-326. 0 1 2 3 Cognitive Function Tests (weeks) Washout Treatments Multicenter, Randomized, Double-blind, Double-dummy, Placebo-controlled, 3-week Study Primary Efficacy Effect on recent (delayed) memory using Name-Face Association Test at Week 3 Secondary Efficacy Recall on First-Last Name Association Test Misplaced Objects Test Delayed recall scores at weeks 1 and 2 Effects on immediate memory Visual attention Information processing Psychomotor/reaction time
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36. ENABLEX ® : Effect on QT Interval QTcF=Fridericia-corrected QT interval. Serra DB, et al . J Clin Pharmacol . 2005;45:1038-1047. ENABLEX ® 15 mg Once Daily (n=47) Moxifloxacin 400 mg Once Daily (n=48) Treatment Period (Days 1-6) ENABLEX ® 75 mg Once Daily (n=46) Placebo Run-in (Day –1) Placebo (n=47) 7-Day, Single-center, Randomized, Parallel-group Study in Healthy Subjects Primary Efficacy Change from mean baseline in QTcF at T max Secondary Efficacy Mean change from baseline in QT/QTcF Maximum QT interval postdose change from baseline
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63. ENABLEX ® Treatment in a Wide Range of Patients With Overactive Bladder Summary
64. ENABLEX ® : Effective Treatment for Overactive Bladder Patients 1. Chapple C, et al. BJU Int. 2005;95:993-1001. 2. Zinner N, et al. Int J Clin Pract. 2008;62:1664-1674 . 3. ENABLEX ® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. 4. Kay G, et al . Eur Urol . 2006;50:317-326. 5. Serra DB, et al . J Clin Pharmacol . 2005;45:1038-1047. 6. Haab F, et al . BJU Int. 2006;98:1025-1032. 7. Hill S, et al. Curr Med Res Opin . 2007;23:2697-2704.
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Editor's Notes
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Key Points Overactive bladder is considered a complex syndrome and often presents with multiple symptoms Urgency alone occurs in 12.6% of individuals, and urge urinary incontinence occurs in 9.1% of individuals Urgency and urge urinary incontinence occur together in 13% of individuals Urgency, urge urinary incontinence, and frequency occur together in 7.0% of individuals Reference Coyne KS, Sexton CC, Vats V, et al. National community prevalence of overactive bladder in the United States stratified by sex and age. Urology. 2011;77:1081-1087. 09/28/11
Key Points According to results from the National Overactive Bladder Evaluation (NOBLE) Program, overactive bladder affects over 33 million Americans 1 Overactive bladder is among the most common chronic diseases in the United States 1 In fact, overactive bladder is more common than diabetes mellitus, which affects 8.5 million Americans, and cardiovascular (CV) disease, which affects 7.8 million Americans 2 References Kelleher CJ. Economic and social impact of OAB. Eur Urol Suppl. 2002;1:11-16. Wilper AP, Woolhandler S, Lasser KE, et al. A national study of chronic disease prevalence and access to care in uninsured U.S. adults. Ann Intern Med. 2008;149:170-176. 09/28/11
Key Point A number of factors are associated with increased risk of overactive bladder, including Increased age 1 Abnormal metabolic factors 2 Pelvic surgery 3 Pregnancy and vaginal delivery 4 Medications 3 Prostate-related conditions 3,4 References Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol . 2003;20:327-336. Teleman PM, Lidfeldt J, Nerbrand C, et al, for the WHILA study group. Overactive bladder: prevalence, risk factors and relation to stress incontinence in middle-aged women. BJOG . 2004;111:600-604. Rosenberg MT, Newman DK, Tallman CT, et al. Overactive bladder: recognition requires vigilance for symptoms. Cleve Clin J Med . 2007;74(suppl 3):S21-S29. Thüroff JW, Abrams P, Andersson KE, et al. EAU guidelines on urinary incontinence. Eur Urol . 2011;59:387-400. 09/28/11
Key Points Comorbidities associated with overactive bladder may increase mortality, morbidity, impair quality of life (QOL) and economic costs These comorbidities include Falls and fractures Urinary tract and skin infections Sleep disturbances Depression Reference Brown JS, McGhan WF, Chokroverty S. Comorbidities associated with overactive bladder. Am J Manag Care . 2000;6(suppl 11):S574-S579. 09/28/11
Key Points Overactive bladder often negatively affects QOL Shown here is the percent decrease in the mean SF-36 score by domain for individuals with overactive bladder urge incontinence compared with controls Physical function and emotional role (role of emotional health in ability to carry out daily activities) were most affected at approximately 28% decrease and 25% decrease, respectively Additional Information Other study results indicate that men and women with overactive bladder complain of significantly more frequent sleep disturbances than do individuals without overactive bladder and are significantly more depressed (women more than men) than individuals without overactive bladder (particularly if they have overactive bladder with urge incontinence) Reference Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol . 2003;20:327-336. 09/28/11
Key Points Various treatment options are available for individuals who have overactive bladder Pharmacologic therapy includes Antimuscarinic drugs (eg, darifenacin) Drugs acting on membrane channels (eg, calcium antagonists) Antidepressants (eg, duloxetine) Alpha-adrenoreceptor antagonists (eg, alfuzosin) Beta-adrenoreceptor antagonists (eg, terbutaline) Phosphodiesterase type-5 inhibitors (in men) (eg, sildenafil) Cyclo-oxygenase (COX) inhibitors (eg, indomethacin) Hormones (eg, estrogen) Reference Thüroff JW, Abrams P, Andersson KE, et al. EAU guidelines on urinary incontinence. Eur Urol . 2011;59:387-400. 09/28/11
Key Points Effective pharmacologic therapy for overactive bladder relies on specificity of inhibition of M 3 (muscarinic) receptor Antimuscarinic agents that target the M 3 receptor block those located on the smooth muscle of the bladder M 1 and M 2 receptor inhibition affects other areas of the body that can result in changes in short-term memory recall and cognitive function, as well as heart rate M 3 receptor specificity allows for targeting of the affected tissue needing therapy Reference Abrams P, Andersson KE, Buccafusco JJ, et al. Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder. Br J Pharmacol . 2006;148:565-578. 09/28/11
Key Points Shown here are the various areas of the body where different muscarinic receptors are located As previously mentioned, agents that target the M 1 receptors on the cerebral cortex may have an impact on short-term memory and cognitive functions Agents that target the M 2 receptors on cardiac muscle may impact heart rate Inhibition of M 3 receptors on the smooth muscle of the bladder and bowel may favorably affect urinary bladder function References Abrams P, Andersson KE, Buccafusco JJ, et al. Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder. Br J Pharmacol . 2006;148:565-578. Sarria B, Naline E, Zhang Y, et al. Muscarinic M 2 receptors in acetylcholine-isoproterenol functional antagonism in human isolated bronchus. Am J Physiol Lung Cell Mol Physiol. 2002;283:L1125-L1132. 09/28/11
Key Points Antimuscarinic agents for the effective treatment of overactive bladder require 1-3 High affinity and specificity for the M 3 receptor High specificity for the receptors on the bladder; important to minimize leaks and accidents and minimize possible side effects of the central nervous system (CNS) and CV system No significant effects on memory have been observed between M 3 -selective antagonists and placebo; however, significant memory deterioration has been demonstrated with less-selective agents 3 References Abrams P, Andersson KE, Buccafusco JJ, et al. Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder. Br J Pharmacol . 2006;148:565-578. Lipton RB, Kolodner K, Wesnes K. Assessment of cognitive function of the elderly population: effects of darifenacin. J Urol . 2005;173:493-498. Kay G, Crook T, Rekeda L, et al. Differential effects of the antimuscarinic agents darifenacin and oxybutynin ER on memory in older subjects. Eur Urol. 2006;50:317-326. 09/28/11
Key Points ENABLEX ® is a selective M 3 receptor antagonist that works by inhibiting the receptors located on the detrusor smooth-muscle cells of the bladder M 3 receptors are also involved in gastrointestinal smooth-muscle contraction, saliva production, and iris sphincter function The relative affinity of ENABLEX ® for M 3 receptors over other muscarinic receptors is shown in the table 1 ENABLEX ® has a 9-fold greater affinity for M 3 receptors than M 1 receptors and a 59-fold greater affinity for M 3 receptors than M 2 receptors 1,2 Compared with the other M 3 receptor antagonists shown here, ENABLEX ® has the highest affinity for M 3 receptors and exhibits more selectivity for M 3 than for M 1 , M 2 , and M 4 receptors This potentially allows for specific targeting of the bladder, while minimizing effects on other organs, which can lead to side effects References Abrams P, Andersson KE, Buccafusco JJ, et al. Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder. Br J Pharmacol . 2006;148:565-578. ENABLEX ® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. Geriatric Consultant Resources, LLC. Overactive bladder in the elderly. http://www.gcrweb.com/OABdss/comprehensive/comp-02a-muscar.htm. Accessed March 25, 2011. 09/28/11
Key Points There is potential for all antimuscarinic agents to cross the blood-brain barrier (BBB); however, less-selective agents such as oxybutynin have been associated with more impairment of cognitive functions 1 Factors that determine the likelihood of BBB crossing include 2 Lipophilicity: more-lipophilic agents favor crossing the BBB Molecular weight: smaller molecules favor crossing the BBB Polarity: less-polar molecules favor crossing the BBB References Lipton RB, Kolodner K, Wesnes K. Assessment of cognitive function of the elderly population: effects of darifenacin. J Urol . 2005;173:493-498. Kay G, Granville L. Antimuscarinic agents: implications and concerns in the management of overactive bladder in the elderly. Clin Ther . 2005;27:127-138. 09/28/11
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Key Points Clinical studies have demonstrated that ENABLEX ® is an effective treatment for overactive bladder ENABLEX ® is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency 1 The efficacy of ENABLEX ® is well established in >1000 subjects 1 ENABLEX ® is easy to use, as it has a flexible, once-daily dosing of either 7.5- or 15-mg tablets 1 ENABLEX ® is a selective M 3 inhibitor and thus provides targeted treatment of overactive bladder while potentially minimizing side effects 1-3 ENABLEX ® is well studied (>6000 subjects and up to 2 years) 1 References ENABLEX ® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. Serra DB, Affrime MB, Bedigian MP, et al . QT and QTc interval with standard and supratherapeutic doses of darifenacin, a muscarinic M 3 selective receptor antagonist for the treatment of overactive bladder. J Clin Pharmacol . 2005;45:1038-1047. Haab F, Corcos J, Siami P, et al. Long-term treatment with darifenacin for overactive bladder: results of a 2-year, open-label extension study. BJU Int. 2006;98:1025-1032. 09/28/11
Key Points Pooled analysis of 3 phase 3, 12-week clinical trials; subjects on 7.5 mg, 15 mg Primary efficacy measure was median change in number of incontinence episodes per week Secondary efficacy measures were Number of significant leaks per week Voiding frequency Bladder capacity Frequency and severity of urgency Number of nocturnal awakenings Reference Chapple C, Steers W, Norton P, et al. A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M 3 selective receptor antagonist, in the treatment of overactive bladder. BJU Int. 2005;95:993-1001. 09/28/11
Key Points ENABLEX ® has been shown to be effective in significantly reducing incontinence Data from a pooled analysis of 3 phase 3, 12-week clinical trials showed that ENABLEX ® significantly reduced incontinence by 68% for subjects taking 7.5 mg of ENABLEX ® Reference Chapple C, Steers W, Norton P, et al. A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M 3 selective receptor antagonist, in the treatment of overactive bladder. BJU Int. 2005;95:993-1001. 09/28/11
Key Points ENABLEX ® has been shown to be effective in significantly reducing incontinence Data from a pooled analysis of 3 phase 3, 12-week clinical trials showed that ENABLEX ® significantly reduced incontinence episodes by 77% for subjects taking 15 mg of ENABLEX ® Reference Chapple C, Steers W, Norton P, et al. A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M 3 selective receptor antagonist, in the treatment of overactive bladder. BJU Int. 2005;95:993-1001. 09/28/11
Key Points ENABLEX ® has also been shown to be effective in significantly reducing the number of urgency episodes 48% of subjects taking 7.5 mg of ENABLEX ® had ≥30% reduction from baseline in urgency episodes at 12 weeks 31% of subjects taking 7.5 mg of ENABLEX ® had ≥50% reduction in urgency episodes Reference Chapple C, Steers W, Norton P, et al. A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M 3 selective receptor antagonist, in the treatment of overactive bladder. BJU Int. 2005;95:993-1001. 09/28/11
Key Points ENABLEX ® has also been shown to be effective in significantly reducing the number of urgency episodes 49% of subjects taking 15 mg of ENABLEX ® had ≥30% reduction from baseline in urgency episodes at 12 weeks 34% of subjects taking 15 mg of ENABLEX ® had ≥50% reduction in urgency episodes Reference Chapple C, Steers W, Norton P, et al. A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M 3 selective receptor antagonist, in the treatment of overactive bladder. BJU Int. 2005;95:993-1001. 09/28/11
Key Points Treatment-emergent AEs (TEAEs) at 1 year are shown in the table 1,2 The most common TEAEs reported by individuals in all groups were dry mouth and constipation 1,2 Approximately 20% of subjects taking 7.5 mg of ENABLEX ® and 35% of subjects taking 15 mg of ENABLEX ® had dry mouth compared with roughly 8% of patients receiving placebo Approximately 15% and 21% of subjects taking 7.5 mg and 15 mg of ENABLEX ® , respectively, reported constipation compared with 6% of subjects in the placebo group Other common TEAEs included dyspepsia, abdominal pain, nausea, and urinary tract infections References ENABLEX ® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. Chapple C, Steers W, Norton P, et al. A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M 3 selective receptor antagonist, in the treatment of overactive bladder. BJU Int. 2005;95:993-1001. 09/28/11
Key Points In the pooled analysis, rates of treatment discontinuation were low for individuals in the 7.5-mg and 15-mg treatment groups Discontinuation rates due to constipation and dry mouth were low for all treatment groups. Rates ranged from 0.3% to 1.2% for constipation and 0% to 0.9% for dry mouth Reference Chapple C, Steers W, Norton P, et al. A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M 3 selective receptor antagonist, in the treatment of overactive bladder. BJU Int. 2005;95:993-1001. 09/28/11
Key Points 1 This was a multicenter, noncomparative, open-label, 2-year extension study Subjects were recruited from 1 of 2 phase 3, randomized, double-blind pivotal studies in which they received 12 weeks of treatment with darifenacin 3.75 mg, 7.5 mg, or 15 mg or placebo 2,3 In this study, subjects received darifenacin 7.5 mg, irrespective of pivotal study treatment, for the first 2 weeks. Thereafter, they were permitted to increase their dose to 15 mg if additional efficacy was required. Doses could be increased from 7.5 mg to 15 mg or decreased from 15 mg to 7.5 mg, as needed, for the remainder of the extension study (24 months) Primary objective Assess long-term safety and tolerability Secondary objective Evaluate long-term efficacy Efficacy variables Number of incontinence episodes/week Daily frequency of voiding Volume of urine passed/voided Daily frequency and severity of urgency Number of overactive bladder–related nocturnal awakenings/week Number of significant leaks/week References Haab F, Corcos J, Siami P, et al. Long-term treatment with darifenacin for overactive bladder: results of a 2-year, open-label extension study. BJU Int. 2006;98:1025-1032. Steers W, Corcos J, Foote J, Kralidis G. An investigation of dose titration with darifenacin, an M 3 -selective receptor antagonist. BJU Int. 2005;95:580-586. Haab F, Stewart L, Dwyer P . Darifenacin, an M 3 selective receptor antagonist, is an effective and well-tolerated once-daily treatment for overactive bladder. Eur Urol . 2004;45:420-429. 09/28/11
Key Points Results from a 2-year extension study are shown here 1, 2 Subjects were enrolled from two, 12-week, phase 3, double-blind, placebo-controlled pivotal trials Over the treatment period of 24 months, subjects achieved a significant reduction in incontinence episodes Compared to baseline, subjects aged ≥65 years had a 63% median reduction in incontinence episodes at the end of 12 weeks and a further decrease to 80% after 3 months This reduction reached a plateau between months 6 and 24, with a median % reduction in incontinence episodes of about 84% References Haab F, Corcos J, Siami P, et al. Long-term treatment with darifenacin for overactive bladder: results of a 2-year, open-label extension study. BJU Int. 2006;98:1025-1032. Hill S, Elhilali M, Millard RJ, et al. Long-term darifenacin treatment for overactive bladder in patients aged 65 years and older: analysis of results from a 2-year, open-label extension study . Curr Med Res Opin . 2007;23:2697-2704. 09/28/11
Key Points Results through the 2-year extension study demonstrated low rates of discontinuation from TEAEs, with the 2 most common TEAEs being constipation and dry mouth 1-3 Discontinuation rate due to constipation was 2.4%, and for dry mouth, 1.3% 1 Other commonly reported TEAEs from these studies included dyspepsia and headache 1-3 References 1. Haab F, Corcos J, Siami P, et al. Long-term treatment with darifenacin for overactive bladder: results of a 2-year, open-label extension study. BJU Int. 2006;98:1025-1032. 2. Haab F, Stewart L, Dwyer P . Darifenacin, an M 3 selective receptor antagonist, is an effective and well-tolerated once-daily treatment for overactive bladder. Eur Urol . 2004;45:420-429. 3. Steers W, Corcos J, Foote J, Kralidis G. An investigation of dose titration with darifenacin, an M 3 -selective receptor antagonist. BJU Int. 2005;95:580-586. 09/28/11
Key Points 12-week, open-label, single-arm, multicenter study Conducted in ENABLEX ® -naïve subjects who had expressed dissatisfaction (lack of sufficient effect and/or AEs) with prior treatments with either oxybutynin or tolterodine Subjects underwent a 2- to 3-week prescreening/washout period followed by a week during which they were asked to complete a bladder diary for 5 consecutive days to establish baseline symptoms and overactive bladder severity Eligible subjects received darifenacin 7.5 mg QD for the first 2 weeks and were then given the option of up-titration to darifenacin 15 mg QD if additional efficacy was required and treatment was well tolerated (down titration was not permitted) Primary efficacy measured the change in Patient Perception of Bladder Condition (PPBC) score from baseline to end of study Secondary efficacy measures included micturition frequency, urgency, and urge urinary incontinence episodes after 2, 6, and 12 weeks of treatment compared with baseline Reference Zinner N, Kobashi KC, Ebinger U, et al. Darifenacin treatment for overactive bladder in patients who expressed dissatisfaction with prior extended-release antimuscarinic therapy. Int J Clin Pract . 2008;62:1664-1674 . 09/28/11
Key Points PPBC scores were subject self-reported from 6 options: No problems, very minor problems, some minor problems, some moderate problems, severe problems, or many severe problems PPBC scores showed that the majority of subjects had “some moderate” problems with bladder control at baseline At 12 weeks, statistically significant improvement was reported for these subjects, as well as patients across the spectrum of severity from “no problems” to “many severe problems” with bladder control Reference Zinner N, Kobashi KC, Ebinger U, et al. Darifenacin treatment for overactive bladder in patients who expressed dissatisfaction with prior extended-release antimuscarinic therapy. Int J Clin Pract . 2008;62:1664-1674 . 09/28/11
Key Points This was a multicenter, randomized, double-blind, double-dummy, placebo-controlled, 3-week study The primary end point was the effect on recent (delayed) memory as assessed using the Name-Face Association Test at week 3 Secondary end points included Recall on First-Last Name Association Test Misplaced Objects Test Delayed recall scores at weeks 1 and 2 Effects on immediate memory Visual attention Information processing Psychomotor/reaction time Additional information: First-Last Name Association Test: Subjects are presented with 4 pairs of first and last names and then are asked to recall corresponding first names as each last name is presented. Two separate tests were performed (first and second acquisition) Reference Kay G, Crook T, Rekeda L, et al. Differential effects of the antimuscarinic agents darifenacin and oxybutynin ER on memory in older subjects. Eur Urol. 2006;50:317-326. 09/28/11
Key Points Change in cognitive function (particularly memory) is a concern for elderly individuals taking antimuscarinic agents, as some of these muscarinic antagonists can cross the BBB In this study, 2 different antimuscarinic agents, darifenacin (ENABLEX ® ) and oxybutynin extended release (ER), were given to subjects ≥60 years of age Oxybutynin binds M 1 and M 3 receptors, whereas ENABLEX ® has higher specificity for M 3 receptors Results of a delayed recall on the First-Last Name Association Test showed that oxybutynin ER resulted in significant impairment vs placebo at weeks 1 and 2. In contrast, no significant differences were observed between ENABLEX ® and placebo at any time point Reference Kay G, Crook T, Rekeda L, et al. Differential effects of the antimuscarinic agents darifenacin and oxybutynin ER on memory in older subjects. Eur Urol. 2006;50:317-326. 09/28/11
Key Points This was a 7-day, single-center, randomized, parallel-group study in healthy volunteers Subjects received once-daily darifenacin at steady-state therapeutic (15 mg) and supratherapeutic (75 mg) doses, alongside controls receiving placebo or moxifloxacin (positive control, 400 mg) Blood samples were taken pre- and postdose, and plasma concentrations were determined using liquid chromatography and mass spectrometry Standard 12-lead ECGs, including three 10-second lead II rhythm strips, were digitally collected in triplicate pre- and postdose The primary end point measured change from mean baseline in Fridericia-corrected QT interval (QTcF) at T max , based on the ECG recording taken at the time corresponding to each subject’s C max Secondary end points included Mean change from baseline in QT/QTcF Maximum QT interval postdose change from baseline Reference Serra DB, Affrime MB, Bedigian MP, et al . QT and QTc interval with standard and supratherapeutic doses of darifenacin, a muscarinic M 3 selective receptor antagonist for the treatment of overactive bladder. J Clin Pharmacol . 2005;45:1038-1047. 09/28/11
Key Points The majority of patients with overactive bladder will need long-term treatment to manage their disease. Therefore, CV safety is an important concern for many individuals In this 7-day study, patients were given 15 mg ENABLEX ® , 75 mg ENABLEX ® , 400 mg moxifloxacin, or placebo Moxifloxacin, a fluoroquinolone antibacterial agent known to prolong QT interval by 5 to 10 milliseconds, was used as a positive control Results showed that there were no significant changes in the QTcF interval when ENABLEX ® was titrated up to 75 mg, beyond the highest therapeutic dose Note: The QT interval refers to the time period between the Q and T waves on ECG. Reference Serra DB, Affrime MB, Bedigian MP, et al . QT and QTc interval with standard and supratherapeutic doses of darifenacin, a muscarinic M 3 selective receptor antagonist for the treatment of overactive bladder. J Clin Pharmacol . 2005;45:1038-1047. 09/28/11
Key Points Data from clinical studies show that ENABLEX ® has established efficacy and safety showcasing the high specificity for the M 3 receptor 1-7 Efficacy data showed a significant reduction in the number of incontinence and urgency episodes per week from 3 randomized, multicenter, double-blind, 12-week studies 2 and significant improvement in overactive bladder symptoms in subjects who switched from previous overactive bladder therapy 3 Data support the selectivity for the M 3 receptor, 1 with effects comparable to placebo on delayed or immediate recall memory in older subjects 4 and no significant change in QTcF 5 A 2-year extension study demonstrated that ENABLEX ® has a favorable safety, tolerability, and efficacy profile 6 ; in subjects ≥65 years of age, it was well tolerated, with no overall differences in safety or efficacy observed 1,7 References ENABLEX ® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. Chapple C, Steers W, Norton P, et al. A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M 3 selective receptor antagonist, in the treatment of overactive bladder. BJU Int. 2005;95:993-1001. Zinner N, Kobashi KC, Ebinger U, et al. Darifenacin treatment for overactive bladder in patients who expressed dissatisfaction with prior extended-release antimuscarinic therapy. Int J Clin Pract. 2008;62:1664-1674 . Kay G, Crook T, Rekeda L, et al. Differential effects of the antimuscarinic agents darifenacin and oxybutynin ER on memory in older subjects. Eur Urol. 2006;50:317-326. Serra DB, Affrime MB, Bedigian MP, et al . QT and QTc interval with standard and supratherapeutic doses of darifenacin, a muscarinic M 3 selective receptor antagonist for the treatment of overactive bladder. J Clin Pharmacol . 2005;45:1038-1047. Haab F, Corcos J, Siami P, et al. Long-term treatment with darifenacin for overactive bladder: results of a 2-year, open-label extension study. BJU Int. 2006;98:1025-1032. Hill S, Elhilali M, Millard RJ, et al. Long-term darifenacin treatment for overactive bladder in patients aged 65 years and older: analysis of results from a 2-year, open-label extension study. Curr Med Res Opin . 2007;23:2697-2704. 09/28/11
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Key Point After considering Amy’s history and treatment options, what would be your next step? 09/28/11
Key Points After considering Amy’s history and treatment options, what would be your next step? ENABLEX ® as an Option In clinical studies, ENABLEX ® has demonstrated significant reductions in incontinence and urgency episodes Reference Chapple C, Steers W, Norton P, et al. A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M 3 selective receptor antagonist, in the treatment of overactive bladder. BJU Int. 2005;95:993-1001. 09/28/11
Key Points After considering Amy’s history and treatment options, what would be your next step? ENABLEX ® as an Option In clinical studies, ENABLEX ® has demonstrated significant reductions in incontinence and urgency episodes 1 Discontinuation rates from 3 phase 3 studies were minimal 1,2 Reference Chapple C, Steers W, Norton P, et al. A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M 3 selective receptor antagonist, in the treatment of overactive bladder. BJU Int. 2005;95:993-1001. 2. Serra DB, Affrime MB, Bedigian MP, et al . QT and QTc interval with standard and supratherapeutic doses of darifenacin, a muscarinic M 3 selective receptor antagonist for the treatment of overactive bladder. J Clin Pharmacol . 2005;45:1038-1047. 09/28/11
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Key Point After considering George’s medical history, what would be your next step? What would you prescribe? 09/28/11
Key Points After considering George’s medical history, what would be your next step? What would you prescribe? ENABLEX ® as an Option Antimuscarinics are currently the treatment of choice in elderly patients with overactive bladder Reference Chughtai B, Levin R, De E. Choice of antimuscarinic agents for overactive bladder in the older patient: focus on darifenacin. Clin Interv Aging. 2008;3:503-509. 09/28/11
Key Points After considering George’s medical history, what would be your next step? What would you prescribe? ENABLEX ® as an Option Antimuscarinics are currently the treatment of choice in elderly patients with overactive bladder 1 ENABLEX ® demonstrated significant improvements in PPBC scores at week 12 in patients switching from other overactive bladder treatments 2 References Chughtai B, Levin R, De E. Choice of antimuscarinic agents for overactive bladder in the older patient: focus on darifenacin. Clin Interv Aging. 2008;3:503-509. Zinner N, Kobashi KC, Ebinger U, et al. Darifenacin treatment for overactive bladder in patients who expressed dissatisfaction with prior extended-release antimuscarinic therapy. Int J Clin Pract . 2008;62:1664-1674 . 09/28/11
Key Points After considering George’s medical history, what would be your next step? What would you prescribe? ENABLEX ® as an Option Antimuscarinics are currently the treatment of choice in elderly patients with overactive bladder 1 ENABLEX ® demonstrated significant improvements in PPBC scores at week 12 in patients switching from other overactive bladder treatments 2 High M 3 specificity with no significant effect on memory 3,4 References Chughtai B, Levin R, De E. Choice of antimuscarinic agents for overactive bladder in the older patient: focus on darifenacin. Clin Interv Aging. 2008;3:503-509. Zinner N, Kobashi KC, Ebinger U, et al. Darifenacin treatment for overactive bladder in patients who expressed dissatisfaction with prior extended-release antimuscarinic therapy. Int J Clin Pract . 2008;62:1664-1674 . Lipton RB, Kolodner K, Wesnes K. Assessment of cognitive function of the elderly population: effects of darifenacin. J Urol . 2005;173:493-498. Kay G, Crook T, Rekeda L, et al. Differential effects of the antimuscarinic agents darifenacin and oxybutynin ER on memory in older subjects. Eur Urol. 2006;50:317-326. 09/28/11
Key Points After considering George’s medical history, what would be your next step? What would you prescribe? ENABLEX ® as an Option Antimuscarinics are currently the treatment of choice in elderly patients with overactive bladder 1 ENABLEX ® demonstrated significant improvements in PPBC scores at week 12 in patients switching from other overactive bladder treatments 2 High M 3 specificity with no significant effect on memory 3,4 ENABLEX ® has demonstrated consistent efficacy and safety in 12-week pivotal studies and a 2-year extension study 5-7 References Chughtai B, Levin R, De E. Choice of antimuscarinic agents for overactive bladder in the older patient: focus on darifenacin. Clin Interv Aging. 2008;3:503-509. Zinner N, Kobashi KC, Ebinger U, et al. Darifenacin treatment for overactive bladder in patients who expressed dissatisfaction with prior extended-release antimuscarinic therapy. Int J Clin Pract . 2008;62:1664-1674 . Lipton RB, Kolodner K, Wesnes K. Assessment of cognitive function of the elderly population: effects of darifenacin. J Urol . 2005;173:493-498. Kay G, Crook T, Rekeda L, et al. Differential effects of the antimuscarinic agents darifenacin and oxybutynin ER on memory in older subjects. Eur Urol. 2006;50:317-326. Haab F, Corcos J, Siami P, et al. Long-term treatment with darifenacin for overactive bladder: results of a 2-year, open-label extension study. BJU Int. 2006;98:1025-1032. Hill S, Elhilali M, Millard RJ, et al. Long-term darifenacin treatment for overactive bladder in patients aged 65 years and older: analysis of results from a 2-year, open-label extension study . Curr Med Res Opin . 2007;23:2697-2704. Steers W, Corcos J, Foote J, Kralidis G. An investigation of dose titration with darifenacin, an M 3 -selective receptor antagonist. BJU Int. 2005;95:580-586. 09/28/11
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Key Points After reviewing Joanne’s history and treatment concerns, what would be your next steps? What would you prescribe that would not adversely affect her memory? This presents as a unique case in that the patient’s symptoms of overactive bladder are now affecting family members 09/28/11
Key Points After reviewing Joanne’s history and treatment concerns, what would be your next steps? What would you prescribe that would not adversely affect her memory? This presents as a unique case in that the patient’s symptoms of overactive bladder are now affecting family members ENABLEX ® as an Option As bladder contractions are mediated primarily by M 3 receptors, antimuscarinics with high M 3 specificity are ideal for patients with overactive bladder Reference Chapple C, Steers W, Norton P, et al. A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M 3 selective receptor antagonist, in the treatment of overactive bladder. BJU Int. 2005;95:993-1001. 09/28/11
Key Points After reviewing Joanne’s history and treatment concerns, what would be your next steps? What would you prescribe that would not adversely affect her memory? This presents as a unique case in that the patient’s symptoms of overactive bladder are now affecting family members ENABLEX ® as an Option As bladder contractions are mediated primarily by M 3 receptors, antimuscarinics with high M 3 specificity are ideal for patients with overactive bladder 1 This is particularly important in elderly patients, who are more vulnerable to potential CNS and other safety concerns 2,3 References Chapple C, Steers W, Norton P, et al. A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M 3 selective receptor antagonist, in the treatment of overactive bladder. BJU Int. 2005;95:993-1001 Kay G, Crook T, Rekeda L, et al. Differential effects of the antimuscarinic agents darifenacin and oxybutynin ER on memory in older subjects. Eur Urol. 2006;50:317-326. Serra DB, Affrime MB, Bedigian MP, et al . QT and QTc interval with standard and supratherapeutic doses of darifenacin, a muscarinic M 3 selective receptor antagonist for the treatment of overactive bladder. J Clin Pharmacol . 2005;45:1038-1047. 09/28/11
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Key Points In conclusion, ENABLEX ® is an effective treatment for patients with overactive bladder. Clinical studies show a significant reduction in the number of incontinence and urgency episodes per week. 1 ENABLEX ® also produces significant improvement in overactive bladder symptoms in patients dissatisfied with previous therapy 2 ENABLEX ® has greater affinity for overactive bladder–specific M 3 receptors than other muscarinic, receptors and study results demonstrate that it targets overactive bladder while minimizing potential CNS- and CV-related side effects 3 A 2-year extension study demonstrated a favorable safety, tolerability, and efficacy profile 4 and showed that, in subjects ≥65 years of age, ENABLEX ® was well tolerated, and no overall differences in safety or efficacy were observed 3,7 No significant effects on delayed or immediate recall memory were noted in older subjects, 6 and no significant changes in QTcF were observed 7 References Chapple C, Steers W, Norton P, et al. A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M 3 selective receptor antagonist, in the treatment of overactive bladder. BJU Int. 2005;95:993-1001. Zinner N, Kobashi KC, Ebinger U, et al. Darifenacin treatment for overactive bladder in patients who expressed dissatisfaction with prior extended-release antimuscarinic therapy. Int J Clin Pract. 2008;62:1664-1674 . ENABLEX ® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. Haab F, Corcos J, Siami P, et al. Long-term treatment with darifenacin for overactive bladder: results of a 2-year, open-label extension study. BJU Int. 2006;98:1025-1032. Hill S, Elhilali M, Millard RJ, et al. Long-term darifenacin treatment for overactive bladder in patients aged 65 years and older: analysis of results from a 2-year, open-label extension study. Curr Med Res Opin . 2007;23:2697-2704. Kay G, Crook T, Rekeda L, et al. Differential effects of the antimuscarinic agents darifenacin and oxybutynin ER on memory in older subjects. Eur Urol. 2006;50:317-326. Serra DB, Affrime MB, Bedigian MP, et al . QT and QTc interval with standard and supratherapeutic doses of darifenacin, a muscarinic M 3 selective receptor antagonist for the treatment of overactive bladder. J Clin Pharmacol . 2005;45:1038-1047. 09/28/11
Key Points Case studies provide examples of ENABLEX ® as an effective overactive bladder treatment for a wide range of patients Data support the use of ENABLEX ® as first-line therapy for individuals such as Amy S, who has an active lifestyle; George R, who was previously been prescribed overactive bladder medications that they were dissatisfied with and for older patients, such as Joanne J, who are concerned with safety and AEs on memory Who is your patient, and is ENABLEX ® right for them? 09/28/11