FDA bans sales of transvaginal mesh

FDA takes action to protect women’s health, orders manufacturers of surgical mesh intended for transvaginal repair of pelvic organ prolapse to stop selling all devices

April 16, 2019 – The U.S. Food and Drug Administration today ordered the manufacturers of all remaining surgical mesh products indicated for the transvaginal repair of pelvic organ prolapse (POP) to stop selling and distributing their products in the U.S. immediately. The order is the latest in a series of escalating safety actions related to protecting the health of the thousands of women each year who undergo surgery transvaginally to repair POP.

The FDA has determined that the manufacturers, Boston Scientific and Coloplast, have not demonstrated a reasonable assurance of safety and effectiveness for these devices, which is the premarket review standard that now applies to them since the agency reclassified them in class III (high risk) in 2016. As part of the 2016 reclassification, manufacturers were required to submit and obtain approval of premarket approval (PMA) applications, the agency’s most stringent device review pathway, in order to continue marketing their devices in the U.S. The companies will have 10 days to submit their plan to withdraw these products from the market.

continue reading the FDA press announcement.
Read the meshCNN press release. Image credit leakylily.

In the UK

 

Developmental Origins of Endometriosis

a Swedish cohort study, Journal of epidemiology and community health, 2019

Abstract

Background
Endometriosis is a chronic condition affecting women of reproductive age and is associated with multiple health burdens. Yet, findings regarding its ‘developmental origins’ are inconsistent. We aimed to investigate the associations of birth characteristics with endometriosis. We also explored potential mediation by adult social and reproductive factors.

Methods
This cohort study consisted of 3406 women born in Uppsala, Sweden, between 1933 and 1972. We used data from archived birth records and endometriosis diagnoses at ages 15–50 recorded in the national patient registers. Socioeconomic and reproductive characteristics were obtained from routine registers. HRs were estimated from Cox regression.

Results
During the follow-up, 111 women have been diagnosed with endometriosis, and most cases are external endometriosis (ie, outside the uterus, n=91). Lower standardised birth weight for gestational age was associated with increased rate of endometriosis (HR 1.35 per standard deviation decrease; 95% CI 1.08 to 1.67). This increased rate was also detected among women with fewer number of live births (HR 2.38; 95% CI 1.40 to 4.07 for one child vs ≥2 children; HR 6.09; 95% CI 3.88 to 9.57 for no child vs ≥2 children) and diagnosed infertility problem (HR 2.00; 95% CI 1.10 to 3.61) prior to endometriosis diagnosis. All the observed associations were stronger for external endometriosis. However, no evidence was found that number of births was the mediator of the inverse association between standardised birth weight and endometriosis.

Conclusion
This study supports the developmental origins theory and suggests that exposure to growth restriction during the fetal period is associated with increased risk of endometriosis during reproductive years.
Image credit hellomagazine.

DES Exposure and Endometriosis

Vulvar Cancer is on the Rise in the UK, study shows

Relationship between vulvar symptoms and incidence of vulvar cancer in women referred to a rapid access clinic

Abstract

Objective
We performed a study to estimate incidence of vulvar cancer in women with vulvar symptoms (irritation, pain, bleeding +/− presence of lesion) referred to a secondary care, rapid‐access clinic.

Methods
Prospective data collection of all direct referrals from a primary to a secondary care gynecological oncology clinic from 2011 to 2016, for women with suspicious vulvar symptoms.

Results
32/393 (8.1%) women had vulvar cancer, and 24/393 (6.1%) had a premalignant lesion. Multivariate logistic regression showed that women referred without a specific lesion had considerably lower odds of a diagnosis of vulvar cancer than those with a lesion (OR=0.11, 95% CI: 0.03–0.49). In total, 30/234 (12.8%) women with a vulvar lesion (mass or ulcer), had vulvar cancer, compared with 2/159 (1.3%) of those referred without a lesion (these patients had vulvar irritation and bleeding but had a visible lesion on examination). None of the 140 women with irritation alone, in the absence of a visible lesion or bleeding, had pre‐invasive disease or cancer.

Conclusion
Presence of a vulvar lesion, especially if painful/bleeding, has a high positive predictive value for vulvar cancer and 12.8% of women presenting with any vulvar lesion to secondary care had cancer.

Discussion

Overall, 32/393 (8.1%) women referred with vulvar symptoms were diagnosed with a malignancy and a further 24/393 (6.1%) were diagnosed with a pre‐malignant lesion. The presence of a suspicious vulvar lesion, especially if symptomatic, was associated with a cancer diagnosis in 30/234 (12.8%) women. Unless the lesion is obviously benign (which in this series included: sebaceous inclusion cyst; urethral caruncle; inspissated sebaceous material trapped under the clitoral hood; and ecchymosis on a background of lichen sclerosus), a rapid‐access clinic referral is appropriate to exclude a malignancy in these women. A larger cohort would be required to stratify risk by age. However, as the incidence of vulvar cancer is increasing, especially in younger women, it would be important not to dismiss suspicious symptoms based on age alone.

Women without a visible lesion were extremely unlikely to have cancer, based on this cohort of patients (<1.3% depending on whether presence of lesion was defined by patient/primary care [0/159] vs secondary care (2/159). However, these findings would need to be applied to a larger population to test this hypothesis and with wider generalization to other healthcare populations. One strength of this dataset is that the population is well‐defined and relatively stable, so re‐referrals, subsequently diagnosed with a cancer, would have been referred back to the same clinic. In the present series, six women were re‐referred during the study period (one woman was seen three times and five women were seen twice). None of these women had a cancer diagnosis. Unfortunately, we were not able to define an average lead time from onset of symptoms to diagnosis from our data, since this was not reliably recorded.

Many women with symptoms of vulvar soreness and irritation, in the absence of a specific lesion, were diagnosed with an inflammatory condition; half had lichen sclerosus or lichen planus. Primary care physicians should be reassured that, in the absence of a suspicious lesion, a cancer diagnosis or a pre‐malignant condition was unlikely. As per dermatology guidelines, if there are classical signs of lichen sclerosis, a diagnostic biopsy is not needed if there is a response to high‐potency topical steroids. Women whose symptoms do not start to improve after 2–3 weeks of treatment, should be re‐assessed and referred if symptoms persist or a lesion develops.

The overall incidence of vulvar cancer in this series was slightly lower than in those in the literature. This is perhaps surprising, as the local population is relatively elderly; in the 2011 census 29.1% of West Somerset were aged 65 years or over compared with a UK average of 16.4%. However, this series is nearly 10‐fold larger than those previously published, so may reflect the increased statistical power of this study. It may also reflect a difference in local referral patterns and criteria, since women may be referred to a general gynecology clinic or a dermatologist in other areas. One study from an urban area in the South East of England looked at cancer diagnosis rates in women referred to a gynecologic fast‐track clinic. They included a total of 335 women referred to secondary care. Only 18 women had symptoms suggestive of vulvar cancer, of whom only two (11.1%) were diagnosed with vulvar cancer. A similar study, also from the South East of England, included only 13 women with vulvar symptoms and found a positive predictive value of a cancer diagnosis of 15.4% in this subset. A further series of women with suspected gynecologic malignancy, also from the South East of England, included 1105 women referred to secondary care. Forty‐four of these women were referred with suspected vulvo‐vaginal cancer and 13.6% were diagnosed with a malignancy.

These data help to differentiate between those who should be referred via a fast‐track clinic and those who could be treated more conservatively for vulvar symptoms, and could help to inform national guidance—including future updates of NICE guidelines. Further data would be required to determine whether these data had wider applicability in other, more diverse populations, and these data are limited by the secondary care focus of this study. It would be interesting to compare rates of women presenting with vulvar symptoms in a primary care population with secondary care referrals and cancer incidence in that population over the same time period to provide evidence for triage of those requiring rapid assessment. This is important in the face of the increasing incidence of vulvar cancer, due to changes in demographics and HPV prevalence.

Finally, many women delay presentation and may have significant symptoms for many months, due to fear, embarrassment or lack of awareness of vulvar conditions generally, and vulvar cancer in particular. Many women in our series had inappropriate treatment for vulvar skin conditions or suspicious lesions with low potency steroids, topical estrogens, anti‐fungal agents, antibiotics, or no treatment at all for prolonged periods. This may be due to ‘home remedy’ self‐treatment (possibly fueled by lack of knowledge and advertisements for ‘intimate itching’), avoidance of doctors, or reluctance to use adequate courses of high potency topical steroids, by both physicians and the women affected. Research is also needed to inform us about barriers to presentation, especially in older women, who are most at risk of vulvar cancers, and to improve health education for this under‐resourced area.
Feature image credit @DiggerGraham (see below).

The 30-year fight for breast implant safety

Breast implants are 60 years old, and we are still fighting about whether they are safe or not

Sybil Goldrich and Jamee Cook both suffered after getting breast implants, Sybil in 1983 and Jamee in 1998. Together, they are fighting regulators to get more information to people considering getting breast implants.

ICIJfights corruption with the world’s best cross-border watchdog journalism by over 160 investigative reporters in 60+ countries. The home of Offshore Leaks.”

L’agence du médicament retire du marché des implants mammaires

L’ANSM rappelle sa recommandation d’utiliser de préférence des implants mammaires lisses en chirurgie esthétique ou reconstructrice

Communiqué ANSM

Depuis l’apparition en 2011 des premiers cas de lymphomes anaplasiques à grandes cellules associés aux implants mammaires (LAGC-AIM), l’Agence nationale du médicament et des produits de santé (ANSM) a mené de nombreuses investigations afin d’étudier le lien entre la survenue de cas de LAGC et la texture des implants mammaires.

Au regard de l’ensemble des informations dont elle dispose, dont des avis d’experts indépendants, l’ANSM considère que la texturation de certains implants macrotexturés et implants à surface recouverte de polyuréthane constitue un facteur de risque dans l’apparition de LAGC-AIM.

Ainsi, l’ANSM prend la décision, par mesure de précaution, de retirer du marché ces implants afin de réduire l’exposition des femmes au risque de LAGC qui reste un risque rare mais grave.Compte tenu de la rareté de ce risque, l’ANSM ne recommande pas d’explantation préventive pour les femmes porteuses de ces implants.

L’ANSM met en place le numéro vert 0.800.71.02.35 pour répondre aux interrogations des patientes. Celles-ci sont également invitées à consulter un professionnel de santé en cas de questions complémentaires.

Compte tenu de la rareté du risque de survenue de LAGC-AIM et de l’avis du CSST, l’ANSM ne recommande pas d’explantation préventive des implants macrotexturés et des implants à surface recouverte de polyuréthane.

Liste des implants mammaires concernés par la décision de l’ANSM

En Savoir Plus

Primodos Drug Cover-Up : Yasmin Qureshi MP Talks, 2017

Yasmin Qureshi explains one possible reason for the Primodos cover-up

Yasmin Qureshi MP gives one reason Primodos drug problems that potentially deformed and killed babies might have been covered up.

More information

40 years after exposure, Pesticide linked to higher breast cancer risk

DDT and Breast Cancer: Prospective Study of Induction Time and Susceptibility Windows

According to a recent study, DDT exposure before puberty may have increased the breast cancer risk for women in their 50s. Study is the latest to suggest early-life exposures, even prior to birth, may hold the key to understanding who gets diseases, Environmental Health News reports.

2019 Study Abstract

Background
In a previous Child Health and Development Studies report, p, p’-DDT was associated with a fivefold increased risk of premenopausal (before age 50 years) breast cancer for women first exposed before puberty. Here we extend our observation to breast cancer diagnosed during early postmenopause (ages 50–54 years) to determine whether age at diagnosis modifies the interaction of DDT with age at exposure.

Methods
We conducted a second prospective, nested case-control study in the Child Health and Development Studies (153 incident breast cancer cases diagnosed at ages 50–54 years and 432 controls matched to cases on birth year). These were analyzed separately and pooled with our previous study (129 breast cancer cases diagnosed at ages 31–49 years and 129 controls matched on birth year). Blood samples were obtained during pregnancy (median age, 26 years), 1–3 days after delivery from 1959 to 1967 in Oakland, California. Serum was assayed for p, p’-DDT, o, p’-DDT, and p, p’-DDE. Odds ratios (ORs) below are given for doubling of serum p, p’-DDT. All statistical tests were two-sided.

Results
For early postmenopausal breast cancer, p, p’-DDT was associated with risk for all women (ORDDT 50–54 = 1.99, 95% CI = 1.48 to 2.67). This association was accounted for by women first exposed to DDT after infancy (ORDDT 50–54 for first exposure after infancy = 2.83, 95% CI = 1.96 to 4.10 vs ORDDT 50–54 for first exposure during infancy = 0.56, 95% CI = 0.26 to 1.19; Pinteraction DDT x age at first exposure = .01). In contrast, for premenopausal breast cancer, p, p’-DDT was associated with risk among women first exposed during infancy through puberty, but not after (ORDDT<50 for first exposure during infancy = 3.70, 95% CI = 1.22 to 11.26, Pinteraction DDT x age at first exposure x age at diagnosis = .03).

Conclusions
p, p’-DDT was associated with breast cancer through age 54 years. Risk depended on timing of first exposure and diagnosis age, suggesting susceptibility windows and an induction period beginning in early life. DDT appears to be an endocrine disruptor with responsive breast targets from in utero to menopause.

Detecting cervical precancer and reaching underscreened women by using HPV testing on self samples: updated meta-analyses

hrHPV testing with an appropriate assay offers a promising new strategy that could increase population coverage substantially

What is already known on this topic

  • Tests performed on self samples are less sensitive and less specific than tests performed on clinician samples when using a high-risk human papillomavirus (hrHPV) assay based on signal amplification
  • Response rates for hrHPV testing are higher for self sampling kits than for conventional invitations

What this study adds

  • Tests performed on self samples are similarly sensitive and slightly less specific than tests performed on clinician samples when using a hrHPV assay based on polymerase chain reaction
  • Response rates for hrHPV testing continue to be higher for self sampling kits than for conventional invitations

2018 Study Abstract

Objective
To evaluate the diagnostic accuracy of high-risk human papillomavirus (hrHPV) assays on self samples and the efficacy of self sampling strategies to reach underscreened women.

Design
Updated meta-analysis.

Data sources
Medline (PubMed), Embase, and CENTRAL from 1 January 2013 to 15 April 2018 (accuracy review), and 1 January 2014 to 15 April 2018 (participation review).

Review methods
Accuracy review: hrHPV assay on a vaginal self sample and a clinician sample; and verification of the presence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) by colposcopy and biopsy in all enrolled women or in women with positive tests. Participation review: study population included women who were irregularly or never screened; women in the self sampling arm (intervention arm) were invited to collect a self sample for hrHPV testing; women in the control arm were invited or reminded to undergo a screening test on a clinician sample; participation in both arms was documented; and a population minimum of 400 women.

Results
56 accuracy studies and 25 participation trials were included. hrHPV assays based on polymerase chain reaction were as sensitive on self samples as on clinician samples to detect CIN2+ or CIN3+ (pooled ratio 0.99, 95% confidence interval 0.97 to 1.02). However, hrHPV assays based on signal amplification were less sensitive on self samples (pooled ratio 0.85, 95% confidence interval 0.80 to 0.89). The specificity to exclude CIN2+ was 2% or 4% lower on self samples than on clinician samples, for hrHPV assays based on polymerase chain reaction or signal amplification, respectively. Mailing self sample kits to the woman’s home address generated higher response rates to have a sample taken by a clinician than invitation or reminder letters (pooled relative participation in intention-to-treat-analysis of 2.33, 95% confidence interval 1.86 to 2.91). Opt-in strategies where women had to request a self sampling kit were generally not more effective than invitation letters (relative participation of 1.22, 95% confidence interval 0.93 to 1.61). Direct offer of self sampling devices to women in communities that were underscreened generated high participation rates (>75%). Substantial interstudy heterogeneity was noted (I2>95%).

Conclusions
When used with hrHPV assays based on polymerase chain reaction, testing on self samples was similarly accurate as on clinician samples. Offering self sampling kits generally is more effective in reaching underscreened women than sending invitations. However, since response rates are highly variable among settings, pilots should be set up before regional or national roll out of self sampling strategies.

Whereas accuracy of new combinations of assays and self sampling devices can be evaluated in a diagnostic setting, acceptance and participation should be shown locally in a screening setting before general roll out.

Pas de glyphosate dans ma Teucha !!!

Les tampons et serviettes hygiéniques contiennent toujours des résidus chimiques

De nouvelles analyses mettent en évidence la présence récurrente de pesticides et de phtalates dans les protections périodiques féminines malgré les dernières recommandations officielles.

  • Le Billet de Sophia Aram, franceinter, 25 février 2019.
  • Tampons et serviettes : connaître la composition, c’est coton ! 60millions-mag, 2019/02/21.
  • Tampons et protections féminines : un rapport ni alarmant ni rassurant, 60millions-mag, 2018/07/20.
  • Tampons et protections féminines : une réglementation s’impose ! 60millions-mag, 2016/02/23.

US FDA Breast Implant Postapproval Studies

Largest-Ever Study Shows Silicone Breast Implants Associated with Rare Diseases

In the largest study of long-term safety outcomes for patients with breast implants, researchers at The University of Texas MD Anderson Cancer Center have found that silicone implants are associated with some rare diseases, autoimmune disorders and other conditions.

Abstract

Objective:
To analyze the long-term safety and efficacy outcomes of patients with breast implants.

Summary Background Data:
Research is ongoing regarding the safety of silicone breast implants. Despite the number of patients with breast implants followed by United States Food and Drug Administration large postapproval studies (LPAS), this database has not been thoroughly analyzed or reported.

Methods:
This is a multicentered, cohort study. LPAS prospectively monitor long-term implant-related outcomes and systemic harms for silicone/saline implants from 2 manufacturers (Allergan and Mentor) placed for primary/revision augmentation/reconstruction. Systemic harms, self-harm, and reproductive outcomes are compared with normative data. Implant-related complications are analyzed by implant composition and operative indication in the short and long terms.

Results:
LPAS data includes 99,993 patients, 56% of implants were silicone for primary augmentation. Long-term magnetic resonance imaging surveillance is under 5%. Compared with normative data, silicone implants are associated with higher rates of Sjogren syndrome (Standardized incidence ratio [SIR]8.14), scleroderma (SIR 7.00), rheumatoid arthritis (SIR5.96), stillbirth (SIR4.50), and melanoma (SIR3.71). One case of BI-ALCL is reported. There is no association with suicide. In the short term, rupture is higher for saline (2.5% vs. 0.5%, P < 0.001), and capsular contracture higher for silicone (5.0% vs. 2.8%, P < 0.001). At 7 years, reoperation rate is 11.7% for primary augmentation, and 25% for primary/revision reconstruction. Capsular contracture (III/IV) occurs in 7.2% of primary augmentations, 12.7% primary reconstructions, and is the most common reason for reoperation among augmentations.

Conclusions:
This is the largest study of breast implant outcomes. Silicone implants are associated with an increased risk of certain rare harms; associations need to be further analyzed with patient-level data to provide conclusive evidence. Long-term safety and implant-related outcomes should inform patient and surgeon decision-making when selecting implants.

Reference. Press release.