Monthly Eblast

The rate of concurrent endometrial carcinoma among women with a biopsy proven diagnosis of atypical endometrial hyperplasia should help guide management decisions in these patients. 

  The Gynecologic Oncology Group (GOG) published a prospective multi-centered study of this issue in the journal Cancer Feb 15, 2006 Volume 106 number 4 pg 812-819.  Unfortunately, 7 years later many of our colleagues are unaware of this important study.  The most pertinent findings were as follows.

 1)  42.6% (123/289) of pts. undergoing primary surgical treatment were found to have concurrent invasive carcinoma in their hysterectomy specimens.

 2)  18.9% (14/74) of pts. who had expert gynecologic pathology 2nd opinion consultation "downgrade" their biopsy specimens to less that complex hyperplasia with atypia  still had endometrial carcinoma found in their hysterectomy specimens 

PRACTICAL IMPLICATIONS

A)  Pts. who are considering hormonal management in this setting should be aware that they have a significant likelihood of harboring a yet undiagnosed and potentially fatal endometrial cancer.

B)  Pts. undergoing hysterectomies for biopsy proven atypical endometrial hyperplasia have a clinically significant likelihood of having invasive endometrial carcinoma and should have their uterus sent for an intra-operative frozen section evaluation to  assess the need for formal surgical staging (a significant percentage of these pts. will be at risk for having extrauterine evidence of disease).

 Two recent reviews provide comprehensive updates of endometrial hyperplasia and endometrial cancer (see attached)

i) Endometrial Cancer - Obstetrics and Gynecology 120(2 Part 1): 383-397, August 2012

ii) Management of Endometrial Cancer Precursors- Obstetrics and Gynecology 120(5): 1160-1175, November 2012

 The Oklahoma Executive Board wishes to thank Dr. Mark Genesen, MD specializing in Gyn Oncology, for his assistance collating this information for our Oklahoma ACOG Members.

 

2013 February E-Blast - Update in Prenatal Testing for Aneuploidy

 Newest Non-Invasive Option for Prenatal Testing for Patients at Risk for Aneuploidy

The current method of prenatal screening for fetal aneuploidy utilizes serum biochemical markers in combination with ultrasound measurement of the nuchal translucency based on maternal and gestational age related background risks.  This screening results in a detection rate of 90-93% with a false positive rate of 2-3%.

 It has been found that fetal and maternal cell-free DNA (cfDNA) circulate in maternal plasma.  Fetal cfDNA is primarily derived from the placenta and is cleared from the maternal blood shortly after delivery.   A higher than expected percentage of a chromosome, such as chromosome 21, may indicate a trisomy of that chromosome.  This technique has been shown to detect trisomy 13, trisomy 18, and trisomy 21 as early as 10 weeks gestation.  No prospective studies are available, but the use of cfDNA has demonstrated detection rates for trisomy 13, trisomy 18, and trisomy 21 of approximately 98-99% with false positive rates of less than 0.5%. 

 Noninvasive prenatal testing using cfDNA became commercially available in late 2011.  Recent ACOG Committee Opinion from December 2012 suggested that cfDNA could be offered as a primary aneuploidy screening option for women at an increased risk of fetal aneuploidy.  This includes women 35 years of age or older, and increased risk of aneuploidy by first trimester of second trimester screening test, fetus with ultrasound markers of aneuploidy, a previous child with a trisomy, or a parent who is a carrier of a balanced translocation with increased risk of a trisomy. 

 It is important to remember that cfDNA testing detects only trisomy 13, 18, and 21 and at present does not offer other genetic information as diagnostic tests such as amniocentesis and chorionic villus sampling do.  The accuracy of cfDNA testing in twins and in the low risk population is not well established.  Women with positive results on cfDNA testing should be offered confirmation with diagnostic testing.   Prior to offering cfDNA testing, women should be counseled regarding limitations of the test and family history should be reviewed to determine if other screening or diagnostic options are more appropriate.  Maternal serum alpha-fetoprotein screening should still be offered.  Second trimester ultrasound should also be performed in high-risk pregnancies to evaluate closely for structural anomalies and to look for ultrasound markers of aneuploidy as a negative cfDNA test does not ensure an unaffected pregnancy.   

To access the ACOG 2012 Committee Opinion on Noninvasive Prenatal Testing for  Fetal  Aneuploidy visit:

acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Genetics/Noninvasive_Prenatal_Testing_for_Fetal_Aneuploidy

 The Oklahoma Executive Board wishes to thank Dr. John Stanley, MFM specializing in Maternal Fetal Medicine, for his assistance collating this information for our Oklahoma ACOG Members. 

 

2013 January E-Blast - 2012 Legislative Recap

As the new legislative session opens, we wanted to recap the 2012 session.  The Oklahoma legislative session ran from February through May 2012.  Eli Reshef, MD and Dana Stone, MD, are OBGYNs in our state that serve on the Women and Children’s Committee of the Oklahoma State Medical Association’s Legislative Council. They are able to closely follow bills of interest to obstetrician-gynecologists.  As you may remember, the major bills considered in 2012 that affected women’s health included:

I. The following bills passed and became law with the governor’s signature:
• Protect from liability when physicians render medical services at professional or amateur athletic events
• Prohibit abortions 20 weeks after fertilization because of the fetus’ ability to feel pain.
• Allow future tort damages over $100,000 to be paid in periodic payments.
• Reduce amount of damages in civil action for bodily injury to $350,000
• Mandate a physician must be present when RU-486 administered.
• Define medical care given at charitable clinics as covered by volunteer immunity act.
• Prohibit elective abortion coverage in any health exchanges.
• Mandate jury instructions that tort awards are not taxable.
• Require that abortion provider make fetal heartbeat audible before performing abortion.

II. Bills that were considered but did not pass, addressed the following issues:
• Prohibit research on human embryos
• Define “personhood” from the moment of conception
• Require medically accurate information in sex education classes
• Require that rape victims receive information about emergency contraception
• Require abortion clinics to conform to ambulatory surgery center standards
• Limit non-economic damages to $250,000 in tort cases
• Fund public cord blood bank by $5 fee on birth certificates
• Prevent use of state funds for any women’s health care where abortions are provided
• Prohibit compensation for egg donation
• Provide tax credit for any pregnancy after 24 weeks


November E-Blast - Long-Acting Reversible Contraception

Practice Bulletin #121: Long-Acting Reversible Contraception: Implants and Intrauterine Devices, updated in July 2011,  highlights many important points for us to incorporate into our practice.  Additionally two Committee Opinions attached (#539 and #450), also address adolescent usage of long-acting reversible contraceptives (LARC) and increasing LARC usage to decrease unintended pregnancy.  ACOG is much in favor of the two types intrauterine device and the contraceptive implants.  Some highlights of the Information is below:

 Intrauterine devices and contraceptive implants, also called long-acting reversible contraceptives (LARCs), are the most effective reversible contraceptives. 

  • Currently three LARC methods are available in the United States, two of which are intrauterine devices (IUDs), 1) the copper T380A IUD (ParaGard), 2) the levonorgestrel intrauterine system (Mirena), and 3) the etonogestrel single-rod contraceptive implant (Implanon / Nexplanon). 
  • LARCs are safe and appropriate contraceptive methods for most women and adolescents with pregnancy rates of less than 1% per year for perfect AND typical use.  
  • Return of fertility is rapid after the removal of the device.  
  • Nulliparous women and adolescents can be offered LARC methods, including IUDs
  • Insertion of an IUD can happen at any time in the menstrual cycle as long as pregnancy is excluded.  In postpartum women who are breastfeeding women, insertion is best 4 weeks after delivery.
  • For patients at high risk for a sexually transmitted infection (STI), it is reasonable to screen for STIs on the same day as IUD insertion and treat for any infection when results are available.
  • IUDs may be offered to women with a history of an ectopic
  • These contraceptives have the highest rates of satisfaction and continuation of all reversible contraceptives. 
  • LARC methods should be offered as first-line contraceptive methods and encouraged as options for most women. 

 

The Oklahoma Executive Board Wishes to thank Dr. Lydia D. Nightingale, Assistant Professor of Obstetrics and Gynecology, for her assistance in collating this information for Oklahoma ACOG members.

 Practice Bulletin 121:

acog.org/Resources_And_Publications/Practice_Bulletins/Committee_on_Practice_Bulletins_--_Gynecology/Long-Acting_Reversible_Contraception_--_Implants_and_Intrauterine_Devices

 Committee Opinion on LARC and Adolescents:

acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Adolescent_Health_Care/Adolescents_and_Long-Acting_Reversible_Contraception

 IUDs to Reduce Unintended Pregnancy:

acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Gynecologic_Practice/Increasing_Use_of_Contraceptive_Implants_and_Intrauterine_Devices_To_Reduce_Unintended_Pregnancy

 

October E-Blast- Compounded Hormone Therapy - NEWEST RECOMENDATIONS SUMMARIZED

In the August 2012 issue of Obstetrics and Gynecology, the American College of Obstetricians and Gynecologists (ACOG) and the American Society for Reproductive Medicine (ASRM) published a joint committee opinion entitled "Compounded Bioidentical Menopausal Hormone Therapy".

This committee opinion comprehensively discusses the multitude of issues with compounding and bioidentical, non-FDA approved medications as well as salivary hormone testing. It gives guidance to physicians and facts to patients. The following information summarizes the findings and recommendations from the committee opinion.

Current Evidence: The current evidence supports menopausal hormone therapy for short-term treatment of menopausal symptoms. The bad press of hormone replacement therapy from the Women's Health Initiative led consumers to search for safe and effective alternatives. The direct-to-consumer marketing for compounded bioidentical hormonal preparations as safe and effective alternatives to conventional menopausal hormone therapy have led to a recent increase in the popularity of compounded bioidentical hormones and hence physician questions.

Terminology: Compounding is the creation of an individualized preparation in response to a health care provider's prescription to create a medication tailored to the specialized needs of an individual patient. Bioidentical hormones are plant-derived hormones that are chemically similar or structurally identical to those produced by the body. The buzzwords of "individualized" treatment with "bioidentical hormones" seem appealing to both physicians and patients. Bioidentical hormones include commercially available products approved by the U.S.

FDA such as micronized progesterone and estradiol, as well as compounded preparation that are not regulated by the FDA. Many compounding pharmacies use the term bioidentical hormone to imply that these preparations are natural or the same as endogenous substances and, thus, are safe. The FDA has recognized the phrase bioidentical hormone therapy as a marketing term and not one based on scientific evidence.

Regulatory Issues: Compounded preparations are not regulated by the FDA. The Dietary Supplement Health and Education Act of 1994 exempted compounded preparations from regulation by the FDA. Therefore, dietary supplements are not required to prove safety or efficacy; hence, there is no major barrier to marketing them. Additionally, they are exempt from labeling requirements such as inclusion of contraindications and warnings. The lack of even rudimentary pharmacokinetic data for commonly prescribed bioidentical hormone preparations should cause considerable concern about the prudence of prescribing such medications.

Safety and Efficacy Issues: Because of a lack of FDA oversight, most compounded preparations have not undergone any rigorous clinical testing for either safety or efficacy, the purity, potency, and quality of compounded preparations are a concern. Because of variable bioavailablity and bioactivity, under-dosage and over-dosage are both possible which could mislead a patient into believing they are receiving endometrial protection or protection from osteoporosis.

Salivary Hormone Testing: Many advocates and compounders of bioidentical hormones recommend the use of salivary hormone level testing as a means of offering individualized therapy. There is no evidence that hormonal levels in saliva are biologically meaningful.

Salivary levels do not consistently provide a reasonable representation of endogenous circulating serum hormones. Salivary hormone levels vary depending on diet, time of testing, and the specific hormone being tested. Finally, saliva contains far lower concentrations of hormone than serum and is prone to contamination with blood, infectious agents, and epithelial cells--all of which may affect the level of hormone to be measured. If treatment is initiated for symptoms control of menopause, subjective improvement in symptoms is the therapeutic end point, and there is no need to assess hormone levels. Furthermore, hormone therapy should not be titrated to hormone levels by serum or saliva.

Patient Counseling: Physicians should exercise caution in prescribing compounded hormones when FDA-approved alternatives exist.

Conclusions and Recommendations by ACOG and ASRM:Evidence is lacking to support superiority claims of compounded bioidentical hormones over conventional menopausal hormone therapyCustomized compounded hormones pose additional risks. These preparations have variable purity and potency and lack efficacy and safety data.Because of variable bioavailability and bioactivity, both underdosage and overdosage are possibleConventional hormone therapy is preferred over compounded hormone therapy given the available data.Despite claims to the contrary, evidence is inadequate to support increased efficacy or safety for individualized hormone therapy regiments based on salivary, serum, or urinary testing.

Click Here to Link to the Committee Opinion acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Gynecologic_Practice/Compounded_Bioidentical_Menopausal_Hormone_Therapy

Another Useful Website Referenced in the Committee Opinion can be found HERE http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm183088.htm.

The Oklahoma Executive Board wishes to thank Dr. LaTasha B. Craig, specializing in Reproductive Endocrinology/Infertility, for her assistance collating this information for our Oklahoma ACOG Members

 

September E-Blast - The Importance of Yearly Well Women Visits

Dear Oklahoma Section,

With the attention being brought to the new pap guidelines, I wanted to highlight some of the efforts of the American College Of Obstetricians and Gynecologists to ensure that providers and patients realize the importance of yearly well woman visits. I have included a link for an excerpt published in the USA Today, recent news highlighting ACOG's efforts to decrease copays for preventive benefits as well as ensure contraceptive coverage and a link for ACOG Committee Opinion 534 on the Well Woman Visit. Furthermore, ACOG has suggested that this is an excellent time to consider immunizations for your patient and is working to improve the financial challenges often associated with immunization care.

Sincerely,

Grant Cox MD

Exhibit A

acog.org/~/media/Committee%20Opinions/Committee%20on%20Gynecologic%20Practice/co534.pdf

Exhibit B

http://www.usatoday.com/news/health/story/2012-08-01/gynocologist-guidelines/56665748/1

Exhibit C

August 1 Marks Beginning of No Co-Pay/No Deductible Preventive Care for Women ACOG worked with the Institute of Medicine (IOM), charged with advising HHS, encouraging inclusion of women’s preventive services specified in ACOG guidelines to ensure women’s health and well-being.

ACOG Executive Vice President Hal C. Lawrence, MD, told the IOM in January 2011: “The College’s clinical guidelines … offer an excellent resource … and encompass the entire field of women’s preventive care.

Our guidance is based on the best available evidence and is developed by committees with expertise reflecting the breadth of women’s health care and subject to a rigorous conflict of interest policy.” He further urged “the IOM to recommend coverage of the following services and products without cost-sharing:A. Well-woman visitsB. Preconception care visitsC. Counseling about and provision of family planning servicesD. HIV screening for women at average riskE. Screening for intimate partner violenceF. Testing for human papillomavirus (HPV) as a part of cervical cancer screening.”ACOG’s recommendations were accepted by the IOM and subsequently by HHS. As a result, all private health plans that began on or after September 30, 2010 are required to cover these services, at no out of pocket costs to patients, found here.On February 10, 2012, the White House proposed a religious exemption from the contraception mandate for certain group health plans. This “accommodation” exempts group health plans sponsored by certain religious employers, and group health insurance coverage in connection with these plans from the requirement to cover contraceptive services. An employer qualifies for this exemption if it

(i) has the inculcation of religious values as its purposes; (ii) primarily employs individuals who share its religious tenets; (iii) primarily serves individuals who share its religious tenets; and (iv) qualifies for non-profit status under the IRS rules. At the same time, the White House wanted to ensure that every woman would have free preventive care that includes contraceptive services no matter where she works. And so it requires insurers to offer group health plan coverage without contraceptive coverage to religious-affiliated organizations and to provide contraceptive coverage directly to individuals covered under the organization’s group health plan with no cost-sharing.

 

August E-Blast - Updates in Urogynecology

May and June 2012 represented an important milestone in the maturation of the Female Pelvic Medicine and Reconstructive Surgery (FPMRS) specialty.  The two NIH sponsored FPMRS networks, the Urinary Incontinence Treatment Network (UITN) and the Pelvic Floor Dysfunction Network (PFDN) both published the results of landmark studies in the New England Journal of Medicine.  

A randomized trial of urodynamic testing before stress incontinence surgery (NEJM 2012 366(21):1987-97.) reports on a multicenter trial in which 630 women with uncomplicated stress urinary incontinence were randomized to receive office evaluation only (including a cough stress test) or office evaluation and urodynamic testing before planned stress incontinence surgery.  Ninety-three percent of the women in both groups were treated with a midurethral sling.  The treatment success rates at one year were nearly equivalent in both groups; 77.2% in the office evaluation only group and 76.9% in the urodynamic-testing group.  The authors concluded that for women with uncomplicated stress urinary incontinence, preoperative office evaluation alone (positive cough stress test, normal post-voided residual and urinalysis with urethral hypermobility present) was not inferior to evaluation with urodynamic testing at one year.  Notably, this study did not address complicated populations such as those who have had previous incontinence surgery, urge-predominant urinary incontinence or patients with concurrent prolapse. 

A midurethral sling to reduce incontinence after vaginal prolapse repair(NEJM2012;366:2358-67.)  reports on a randomized-controlled trial in which 337 women undergoing vaginal prolapse repair were randomized to a retropubic midurethral sling (Gynecare TVT, Ethicon) or two suprapubic sham incisions.  Importantly, these women did not report urinary incontinence prior to surgery and Ethicon was not involved in the study in any way.  The women that were randomized to the sling procedure experienced significantly less de novo stress urinary incontinence at one year (27% vs. 43%).  The number of slings needed to prevent one new case of stress urinary incontinence at one year was six.  The women who were randomized to slings experienced more complications such as bladder perforation, bleeding and voiding dysfunction.  Experts may interpret the findings of this trial differently, but it emphasizes the critical aspects of shared decision making and establishing clear pre-operative expectations with patients. 

The Oklahoma Executive Board wishes to thank Dr. Mikio Nihira, specializing in FPMRS, for his assistance collating this information for our Oklahoma ACOG members.

 

July E-Blast - The New Pap Screening Guidelines and Implications

The significant new changes in cervical cancer screening guidelines has reaffirmed that change is hard. Many patients and practitioners are unsettled by these recommendations. The rationale, implications and benefits are succinctly reviewed in the most recent issue of the Green Journal, Obsetrics and Gynecology, Vol. 120, No 1, July 2012, P9-11. Please click here to access the full article.

 

We hope that you find this to be useful!

June E-Blast - Quick facts to promote optimal treatment for endometrial hyperplasia

This should be good to go, but I am waiting to first get a politically correct approval from David Miller who is the Chair of the GOG corpus committee.  The title is the next line.  

The rate of concurrent endometrial carcinoma among women with a biopsy proven diagnosis of atypical endometrial hyperplasia should help guide management decisions in these patients. 

 The Gynecologic Oncology Group (GOG) published a prospective multi-centered study of this issue in the journal Cancer Feb 15, 2006 Volume 106 number 4 pg 812-819.  Unfortunately, 5 years later many of our colleagues are unaware of this important study.  The most important findings were as follows.

1)  42.6% (123/289) of pts. undergoing primary surgical treatment were found to have concurrent invasive carcinoma in their hysterectomy specimens.

2)  18.9% (14/74) of pts. who had expert gynecologic pathology 2nd opinion consultation "downgrade" their biopsy specimens to less that complex hyperplasia with atypia     still had endometrial carcinoma found in their hysterectomy specimens 

PRACTICAL IMPLICATIONS

A)  Pts. who are considering hormonal management in this setting should be aware that they have a significant likelihood of harboring a yet undiagnosed and potentially fatal endometrial cancer.

 

B)  Pts. undergoing hysterectomies for biopsy proven atypical endometrial hyperplasia have a clinically significant likelihood of having invasive endometrial carcinoma and should have their uterus sent for an intra-operative frozen section evaluation to  assess the need for formal surgical staging (a significant percentage of these pts. will be at risk for having extrauterine

May E-Blast - 10 Diamonds

The February 2012 Green Journal included one of the best reviews I have seen for obstetricians in a long time--one that can truly be life-saving for our patients. These ten clinical "pearls" were given the upgrade to "diamonds" because of their importance in preventing maternal morbidity and mortality. In my hospital, we have shared this article with our L&D nurses, because nurses may recognize these situations first and must contact us quickly--and persistently.

Preventing Maternal Death: 10 Clinical Diamonds
Clark, Steven L.; Hankins, Gary D. V.
Obstetrics & Gynecology, February 2012,119(2, Part 1):360-364
Current Commentary

 

April E-Blast - What has ACOG done for you lately

Dear Oklahoma ACOG Member

 

The Executive Board of Oklahoma ACOG is actively working on behalf of all the OBGYNs and female patients in our state.  As a Section, the officers work as a conduit to national ACOG. If you ever wonder what national ACOG has done for you lately, know that they were instrumental in continuing to allow us to get reimbursed for OB ultrasounds in the office, and are on the forefront of legislative issues, such as IPAB (the Independent Payment Advisory Board organized by the federal government).  At a Section level, we have representatives on committees such as Oklahoma's Patient First committee (to ensure medical care is given only by appropriately trained providers) and Oklahoma's Obstetric Mortality Committee. Many members of ACOG OK were also integrally involved in ensuring tort reform was passed within our state, and Dana Stone is very active legislatively and with ACOG's national Political Action Committee (PAC).

 

We want to keep you aware of all that ACOG is doing.  Starting later this month, we will begin to send a monthly eblast to all Oklahoma ACOG members which will give a short synopsis about a sentinel piece of information recently published by ACOG that can have a dramatic impact on your practice. This is not meant to inundate you with another email or replace your general reading about changes in our field, but rather to allow for an easy manner to keep up with major events in OBGYN. We hope that you will enjoy them.

 

Other easy ways to stay aware of ACOGs activities include:

-Like us on Facebook!  District 7 has a new facebook page so check it out!

-Join ACOG's blog

-Make ACOG's website a link on your Google Page on your computer -Come to our Joint Section meeting at Big Cedar Lodge on June 8 and 9, 2012.

March 2012 E-Blast - OK Section Legislative Update

ATTACHMENTS:  We have grouped the bills according to their topics and subject matter.

 The 2011 Oklahoma state legislative session opened in February. There are many bills of interest to OB-Gyn's in the areas of tort reform, women's health, and embryonic stem cell research. There are also personhood bills that would consider a fertilized egg as a constitutionally-protected person. Please review the following bills and we strongly encourage you to contact your legislators to convey your personal views.  We have attached and group the subjects of the bills for your convenience.  Click on the link provided below then click on the Government Information bar on the left side of screen from there you will be able to find your legislator with all their contact information; http://tcmsok.org/

 The Bills are grouped accordingly please make copies for distribution so we may keep the patients informed and if they deem the bills of importance they will have the opportunity to contact their legislators.

 OKLAHOMAACOG SET TO LAUNCH SCOTT & WHITE WORTH THE WAIT PROGRAM FOR ADOLESCENTS:

The Oklahoma Section of the American College of Obstetricians and Gynecologists announced the organization has endorsed the Scott & White Worth the Wait program. The OKACOG Board will be meeting with Tulsa area school officials to introduce the Scott & White Worth the Wait Program in Oklahoma  The Board has invited Dr. Patricia Sulak from Temple, Texas who founded and directs the award winning Scott & White Sex Education Program to Tulsa to discuss the benefits of the program and answer questions.  The program has been adopted by numerous school districts in Texas and beyond.  The OKACOG Board is excited to make Scott & White Worth the Wait available to Oklahoma adolescents through the public school system.   For more information go to www.worththewait.org.

If you know any school administrators or educators we ask that you please send their contact information to joetta@tcmsok.org so that we may contact them about the program.  Please see the attached Flyer for the SWWTW meeting being held April 12th.

 Cesarean Section Quality Initiative:  March 2nd 2011, OSMA is meeting with Oklahoma Health Care Authority's legislators over this initiative and possible abuse of their power.  Wes Glinsmann has stated (The House Administrative Rules and Agency Oversight Committee has its regular meeting on Wednesday.  They have already passed our bill to require all agency rules to be approved by the Legislature, and we are using this as another example of agency abuse of their authority.  So the Committee has asked the Health Care Authority to come defend themselves at the Committee, and we will have representatives there to respond).  If you feel strongly about this initiative please contact Beverly Rupert, RN, BS, QualityEducation Specialistat 405-522-7239 or Beverly.rupert@okhca.org. and your legislators.

 

Contact:

Joetta Cunningham
Webmaster
joetta@tcmsok.org