Pregnancy and rash: related or not related? Medscape

30-year-old, 34 weeks pregnant female, two healthy children. She complains of an increasing rash that has evolved over 4 weeks. It started on her limbs and then trunk, abdomen, including umbilicus, and neck, not compromising her face. The rash, which is very itchy, is urticariform, persistent in the same places, with confluent lesions especially on trunk, and some crusted papules on her extremities. Mucous membranes not involved. Abdomen US is normal. The biopsy revealed a perivascular and interstitial dermatitis with numerous eosinophils, without signs of PUPPP or Erythema Multiforme. There were no blisters and no signs of vasculitis or granulomas. DIF was negative for C3, IgA, IgG, IgM and fibrin. The dermato pathologist opined that the biopsy could be compatible with Adverse Drug Reaction, due to the large amount of eosinophils. The patient  felt better after she stopped the vitamins. After she had suspended the vitamins, and the rash had virtually disappeared in neck, upper limbs and abdomen, persisting some lesions on thighs. So a new biopsy was not necessary and the final diagnosis was "Adverse Drug Reaction" to the vitamins she had been taking.

Polycystic Ovary Syndrome: 5 Things You Might Not Know

More than 80 years ago, physician colleagues Irving Stein and Michael Leventhal noticed a pattern among some of the infertile women with menstrual irregularities they were seeing in their practice. They published their observations in a landmark report^[1] describing seven women who exhibited the triad of clinical symptoms — "polycystic" ovaries, hirsutism, and amenorrhea — associated with polycystic ovary syndrome (PCOS) to this day. Here are five key facts everyone should know about this common condition.

1. "Polycystic" is a misnomer.

PCOS isn't the first condition to be saddled with a name that is later found to be inaccurate or misleading. What Stein and Leventhal characterized as epithelial cysts are really immature antral follicles.^[2] The misnomer is unfortunate because it suggests that ovarian cysts are the defining feature of PCOS. Moreover, except in adolescents, the ovarian morphology isn't the most important feature used to diagnose the condition. Similarly, a woman with polycystic ovaries but no hormonal or metabolic aberrations does not have PCOS. But to date, experts haven't been able to agree on a new name for this syndrome that adequately represents its anatomic, clinical, and metabolic manifestations.^[3]

2. Far from rare, PCOS affects as many as 1 in 10 women.

Since the syndrome was first described by Stein and Leventhal, the diagnostic criteria for PCOS have changed, and it is now estimated that as many as 10% of women may be affected,^[4,5] although many remain undiagnosed. PCOS is also a diagnosis of exclusion. Other conditions with overlapping features (Cushing syndrome, androgen-producing tumors, medications with androgenic side effects, congenital adrenal hyperplasia) must first be ruled out.

Currently the most widely accepted criteria are the Rotterdam criteria, which state that PCOS can be diagnosed when two out of the following three criteria are met^[4]:

• Oligo- or anovulation
• Clinical or laboratory evidence of androgen excess
• Polycystic ovaries

Other diagnostic criteria put more emphasis on the hormonal and metabolic features and less on ultrasound findings (Table).

Table. Diagnostic Criteria for PCOS

Guideline Source	Diagnostic Criteria
National Institutes of Health	Anovulation Clinical or laboratory hyperandrogenism Both required
2003 Rotterdam criteria	Oligo-, anovulation Clinical or laboratory hyperandrogenism Polycystic ovaries 2 of 3 required
Androgen Excess and PCOS Society	Cinical or laboratory hyperandrogenism Oligo-, anovulation Polycystic ovaries 2 of 3 required; androgen excess must be present.

	Some patients with PCOS have regular menstrual cycles, but 85%-90% have more than 35 days between cycles or have fewer than nine cycles annually. Hyperandrogenemia (elevated free testosterone, free androgen index, or DHEA levels) and/or clinical evidence of androgen excess (hirsutism, acne, clitoromegaly, male body habitus) are present in up to 80% of affected women.[6] Polycystic ovaries are defined as having 12 or more small (2-9 mm) follicles per ovary, although some authors suggest a much higher number (> 25 per ovary).[6,7] Diagnosis becomes more challenging in teenagers and perimenopausal women. Among adolescents, cycle irregularity and acne are already common, and follicle counts tend to be high. Elevated serum androgen levels may be the most consistent marker for PCOS in teens, but all three Rotterdam criteria should be present to establish the diagnosis.[7] In perimenopausal years, cycles tend to become more regular and follicle counts lower in women with PCOS. Furthermore, age-related declines in ovarian and adrenal androgen secretion make the diagnosis challenging in menopausal women.[8] Although not diagnostic, certain findings are more common in women with PCOS, including obesity (at least 50%), elevated luteinizing hormone levels, insulin resistance, impaired glucose tolerance, type 2 diabetes, dyslipidemia, hypertension, endothelial dysfunction, hypercoagulability, and endometrial hyperplasia. Some affected women have expressed frustration with the process of evaluation and diagnosis that they underwent to find out what was wrong with them — why they couldn't lose weight or become pregnant, or why their menstrual periods were irregular, not to mention the acne and distressing growth of body hair. In recent crowdsourced data, 1 in 3 women reported that it took at least 2 years to be diagnosed with PCOS, and almost half saw three or more healthcare professionals along the way.[9] Nor were women satisfied with the information they received about their condition, giving particularly low marks to primary care providers, whom they judged as unqualified to manage PCOS. A mere 15% were satisfied with the information they received at the time of diagnosis.[9] 3. It's the most common cause of female infertility. The underlying cause of infertility among women with PCOS is oligo-ovulation or anovulation. In fact, 90% of women with oligo- or amenorrhea have PCOS.[7] The lack of ovulation isn't the only strike against fertility, because obesity, poorer oocyte quality, and an adverse endometrial environment can also impair a woman's chance of conceiving. In addition to the assessment of ovarian function, the couple should undergo a proper, full infertility evaluation (male factor infertility, tubal status, etc.). If the rest of the evaluation is normal, regular ovulation must be restored to improve fertility. Among women with a higher body mass index, weight loss should be the first-line treatment. The loss of as little as 5% of body weight can have a favorable effect on ovarian function. For women who do not conceive after lifestyle intervention, metformin (an insulin-sensitizing drug) has been shown to improve ovulation and live birth rates.[10] Clomiphene citrate is the recommended first choice for ovulation induction, successfully inducing ovulation in up to 80% of women with PCOS. The effect seems to be superior to metformin.[11,12] Combining the drug with metformin (especially in women who are resistant to clomiphene citrate) may further improve its efficacy.[10,12] As an alternative, aromatase inhibitors may induce ovulation without negative endometrial effects. Women who do not respond to oral agents can consider gonadotropin stimulation or laparoscopic ovarian drilling. Gonadotropins are typically started at a low dose with slow increases if needed in a step-up protocol. Gonadotropins are highly effective in inducing folliculogenesis but often lead to a multifollicular response, increasing the risk for ovarian hyperstimulation syndrome and multiple-gestation pregnancy. The use of in vitro fertilization with elective embryo cryopreservation and subsequent single embryo transfer may avoid these complications in women who are sensitive to stimulation.[13] Adding metformin can lower the risk for hyperstimulation.[14] The management of ovulatory infertility should begin with the least invasive approach (lifestyle intervention), moving stepwise toward more invasive (in vitro fertilization) treatments. Safety for the patient (avoiding ovarian hyperstimulation) and the pregnancy (avoiding multiple gestations) must be kept in mind, and in certain cases this may require moving on to a more invasive strategy sooner or even right away. 4. PCOS isn't just a reproductive disorder. The health consequences of PCOS traverse not only a woman's childbearing years but her entire lifespan. A meta-analysis based on 30 studies found the risk for insulin resistance to be increased 2.48-fold, the risk for diabetes 4.43-fold, and the risk for metabolic syndrome 2.88-fold.[15] It is therefore recommended to screen women with PCOS (especially those with high BMI) with an oral glucose tolerance test and lipid profile. Cardiovascular disease (CVD) risk factors (elevated LDL cholesterol/triglycerides, low HDL cholesterol, increased carotid intima thickness, increased coronary calcification, increased left ventricular volume, diastolic dysfunction, endothelial dysfunction) and obesity are significantly more common than in age-matched women without PCOS.[5,16] It is controversial whether these CVD risk factors translate into increased CVD morbidity or mortality, however. In a recent study, among reproductive-aged women diagnosed with PCOS, the risk for myocardial infarction, stroke, or CVD-related death was not increased.[17] The picture gets even more complicated as affected women enter menopause. The higher risks for glucose intolerance, diabetes, dyslipidemia, and metabolic syndrome persist into menopause in women with PCOS. The risk for hypertension, however, does not seem to be higher, and data are inconsistent on the risk for myocardial infarction, stroke, or CVD, with several studies finding no increased risk for CVD among menopausal women with PCOS.[17,18,19] The Endocrine Society recommends lifestyle changes to avoid the metabolic complications of PCOS that persist after a woman's reproductive years. For women who do not achieve health goals with diet and exercise, metformin is a key option.[16] Insulin resistance is undoubtedly involved in the pathomechanism of PCOS, but for a long time it was unclear what came first. Did insulin resistance cause the syndrome or did the endocrine abnormalities induce insulin resistance? Currently it is believed that insulin resistance is responsible for the endocrine and metabolic changes of PCOS. 5. A link with cancer is plausible. An association between PCOS and various cancers has long been studied. PCOS is accompanied by long-periods of unopposed estrogen exposure, which could induce endometrial hyperplasia and subsequent endometrial cancer. Recent data suggest a threefold increased risk for endometrial cancer among women with PCOS, as well as an increased risk for ovarian cancer.[20] Insulin might play a role in cancer risk as well, by increasing mitogenic activity of certain insulin binding sites in the endometrial stroma.[21] Furthermore, the hormonal regulation of endometrial cell death via apoptosis, influenced by the normal menstrual cycle, is shifted toward survival in women with PCOS, potentially providing cancer cells with a survival advantage.[21] These findings have led to studies to evaluate the role of insulin-sensitizing medications in the prevention or treatment of cancer. Preliminary findings suggest a protective role.[22]
	Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol. 1935;29:181-191. Source Khadilkar SS. Polycystic ovarian syndrome: is it time to rename PCOS to HA-PODS? J Obstet Gynaecol India. 2016;66:81-87. Source Rosenwaks Z. Polycystic ovary syndrome, an enigmatic syndrome begging for a name change. Fertil Steril. 2017;108:748-749. Source The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19:41-47. Source Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005;352:1223-1236. Source Anagnostis P, Tarlatzis BC, Kauffman RP. Polycystic ovary syndrome (PCOS): Long-term metabolic consequences. Metabolism. 2018;86:33-43. Source The Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS consensus Workshop Group. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS). Hum Reprod. 2012;27:14-24. Source Kudesia R, Neal-Perry GS. Menopausal implications of polycystic ovarian syndrome. Semin Reprod Med. 2014;32:222-229. Source Gibson-Helm, M, Teede H, Dunaif A, Dokras A. Delayed diagnosis and a lack of information associated with dissatisfaction in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2017;102:604-612. Source Morley LC, Tang T, Yasmin E, Norman RJ, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhea and subfertility. Cochrane Database Syst Rev. 2017;11:CD003053. Source Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007;356:551-566. Source Siebert TI, Viola MI, Steyn DW, Kruger TF. Is metformin indicated as primary ovulation induction agent in women with PCOS? A systematic review and meta-analysis. Gynecol Obstet Invest. 2012;73:304-313. Source Bosdou JK, Venetis CA, Tarlatzis BC, et al. Higher probability of live-birth in high, but not normal, responders after first frozen-embryo transfer in a freeze-only cycle strategy compared to fresh-embryo transfer: a meta-analysis. Hum Reprod. 2019;34:491-505. Source Palomba S, Falbo A, La Sala GB. Effects of metformin in women with polycystic ovary syndrome treated with gonadotrophins for in vitro fertilization and intracytoplasmic sperm injection cycles: a systematic review and meta-analysis of randomized controlled trials. BJOG. 2013;120:267-276. Source Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2010;16:347-363. Source Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, et al. Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2013;98:4565-4592. Source Cooney LG, Dokras A. Beyond fertility: polycystic ovary syndrome and long-term health. Fertil Steril. 2018;110:794-809. Source Meun C, Franco OH, Dhana K, et al. High androgens in postmenopausal women and the risk of atherosclerosis and cardiovascular disease: the Rotterdam study. J Clin Endocrinol Metab. 2018;103:1622-1630. Source Schmidt J, Landin-Wilhelmsen K, Brannstrom, et al. Cardiovascular disease and risk factors in PCOS women of postmenopausal; age: a 21-year controlled follow-up study. J Clin Endocrinol Metab. 2011;96:3794-3813. Source Chittenden BG, Fullerton G, Maheshwari A, Bhattacharya S. Polycystic ovary syndrome and the risk of gynaecological cancer: a systematic review. RBM Online. 2009;19:398-405. Source Palomba S, Falbo A, Zullo F, Orio Jr. F. Evidence-based and potential benefits of metformin in polycystic ovary syndrome: a comprehensive review. Endocr Rev. 2009;30:1-50. Source Sivalingam VN, Myers J, Nicholas S, Balen AH, Crosbie EJ. Metformin in reproductive health, pregnancy and gynaecological cancer: established and emerging indications. Hum Reprod Update. 2014;20:853-868. Source
	Peter Kovacs, MD, PhD August 02, 2019

High-Dose Vitamin D for Bone Health May Do More Harm Than Good.

 

  A study on Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength A Randomized Clinical Trial, by Lauren A. Burt, PhD; Emma O. Billington, MD, FRCPC¹; Marianne S. Rose, PhD; et al Duncan A. Raymond, MS; David A. Hanley, MD, FRCPC; Steven K. Boyd, PhD, published in JAMA. 2019;322(8):736-745. doi:10.1001/jama.2019.11889, indicates High-Dose Vitamin D for Bone Health May Do More Harm Than Good.

 

Results  Of 311 participants who were randomized (53% men; mean [SD] age, 62.2 [4.2] years), 287 (92%) completed the study. Baseline, 3-month, and 3-year levels of 25(OH)D were 76.3, 76.7, and 77.4 nmol/L for the 400-IU group; 81.3, 115.3, and 132.2 for the 4000-IU group; and 78.4, 188.0, and 144.4 for the 10 000-IU group. There were significant group × time interactions for volumetric BMD. At trial end, radial volumetric BMD was lower for the 4000 IU group (−3.9 mg HA/cm³ [95% CI, −6.5 to −1.3]) and 10 000 IU group (−7.5 mg HA/cm³ [95% CI, −10.1 to −5.0]) compared with the 400 IU group with mean percent change in volumetric BMD of −1.2% (400 IU group), −2.4% (4000 IU group), and −3.5% (10 000 IU group). Tibial volumetric BMD differences from the 400 IU group were −1.8 mg HA/cm³ (95% CI, −3.7 to 0.1) in the 4000 IU group and −4.1 mg HA/cm³ in the 10 000 IU group (95% CI, −6.0 to −2.2), with mean percent change values of −0.4% (400 IU), −1.0% (4000 IU), and −1.7% (10 000 IU). There were no significant differences for changes in failure load (radius, P = .06; tibia, P = .12).
Conclusions and Relevance  Among healthy adults, treatment with vitamin D for 3 years at a dose of 4000 IU per day or 10 000 IU per day, compared with 400 IU per day, resulted in statistically significant lower radial BMD; tibial BMD was significantly lower only with the 10 000 IU per day dose. There were no significant differences in bone strength at either the radius or tibia. These findings do not support a benefit of high-dose vitamin D supplementation for bone health; further research would be needed to determine whether it is harmful.

Slaughter-free beef: New beginning ??

Houston, we have a cultivated meat product ^!

The Delmonico brothers didn’t do it. Ronald McDonald didn’t do it. Neil Armstrong never even tried. Same goes for Julia Child.

None of these culinary giants or astronauts ever grew beef in space. That honor belongs to Aleph Farms of Rehovot, Israel. The company, a self-proclaimed “global leader in the cultivated meat industry,” collaborated with 3D Bioprinting Solutions of Moscow and others to produce slaughter-free beef in the Russian segment of the International Space Station in September.
The company released a press note "The actual process of growing a steak mimics natural “muscle-tissue regeneration occurring inside the cow’s body” and somehow uses a 3-D bioprinter to assemble “a small-scale muscle tissue.” We don’t really understand it, but the scientists and engineers here at LOTME Co. assure us it makes sense.
But why, you may ask, did they do it on the space station? Think of it as a stand-in for New York City. You know … if you can make it there, you can make it anywhere. We’ll let Didier Toubia, cofounder and CEO of Aleph Farms, explain: “In space, we don’t have 10,000 or 15,000 liter (3962.58 gallon) of water available to produce 1 kilogram (2.205 pounds) of beef.” It’s all about sustainable food production.

The next phase of the project, we think, is going to be even more interesting. For a proper fine dining experience in space, they’re going to grow a snooty French waiter to serve cultivated steak to the astronauts"

Watch this show

Time to conception after miscarriage: How long to wait?

An interpregnancy interval (IPI) of < 6 months following miscarriage is associated with an increased live birth rate in subsequent pregnancy, lower risks of preterm birth and subsequent miscarriage, and no difference in rates of stillbirth, pre-eclampsia, and low birth weight infants (strength of recommendation [SOR]: A, well-done meta-analysis). (IPI is defined as the time between the end of one pregnancy and the last menstrual period of a subsequent one.)

A very short IPI (< 3 months), when compared with an IPI of 6 to 18 months, is associated with the lowest rate of subsequent miscarriage (SOR: B, cohort study). However, for women who experience a pregnancy loss at 14 to 19 weeks’ gestation, an IPI < 3 months is associated with an increased risk of miscarriage or birth before 24 weeks’ gestation.

 

IPI shorter than 6 months carries fewer risks.

IPI shorter than 3 months following First trimester has lowest risk of all.  

But a short IPI after second-trimester loss increases risk of miscarriage

Short IPI may be linked to anxiety in first trimester of next pregnancy

RECOMMENDATIONS

The American College of Obstetricians and Gynecologists’ Practice Bulletin on Early Pregnancy Loss states that no quality data exist to support delaying conception after early pregnancy loss (defined as loss of an intrauterine pregnancy in the first trimester) to prevent subsequent pregnancy loss or other pregnancy complications.

WHO recommends a minimum IPI of at least 6 months after a spontaneous or elective abortion. This recommendation is based on a single multi-center cohort study in Latin America that included women with both spontaneous and induced abortions.

Source:  J Fam Pract. 2019 October;68(8):E12-E14

Toilet Sitting Position and Constipation, Sqiatting is Better,

Constipation  is one of the most common gastrointestinal disorders.

        It is refer to either very slow movement of food residues through the colon (slow transit constipation) or difficulty passing bowel movements after they reach the rectum (outlet dysfunction).

      The common symptoms of constipation are:

•Straining
•Hard or lumpy stools
•Feeling that there is a blockage in the rectum that prevents bowel movements from passing
•Having to press around the anal opening
•Less than three bowel movements per week

      In some circumstances, trouble passing stools can indicate a more serious health problem.

      Constipation regularly accompanying any of these 6 signs could probably indicate something more serious and you should consider consulting a doctor.

1. Ongoing cramps, bloating and intermittent diarrhea. (This could be a sign of Irritable Bowel Syndrome)

2. Lumps inside and around your bottom (anus)
(This could be signs of piles of hemorrhoids)

3. Constant abdominal pain (This could be a sign of diverticulitis disease)

4. Nausea, vomiting and fever (This could be a sign of diverticulitis)

5. Rectal Bleeding (This could be a sign of diverticulitis and bowel cancer)

6. Unintentional weight loss (This could indicate malabsorption issues or in rare cases colorectal cancer)

 

      These are just examples and not to be used a a diagnosis. Constipation could be corrected and prevented if given proper attention, lifestyle modification and medication. Among them are increasing dietary fiber in your diet, exercise to promote blood circulation and changing your toilet position.

Normal sitting position will choked your colon and make the release more difficult. When using Squatting toilet stool, the colon is released by changing the angle from 90 degrees to 35 degrees. It allows you an easier and more effective elimination, and relieve you from constipation, hemorrhoids, bladder, IBS & other Bowel disease.