RapidRx

Sept. 20, 2016 — New research seems to confirm that stress lowers a woman’s chances of becoming pregnant, particularly stress that occurs around the time of ovulation.

“If you are feeling more stress than you usually do [around ovulation time], you are 40 percent less likely to get pregnant that month,” said study author Kira Taylor. She is an assistant professor of epidemiology and population health at the University of Louisville School of Public Health and Information Sciences.

Taylor believes her team’s study is the first to look at stress at different time periods in a woman’s monthly cycle, to determine if there are different effects at different points.

In the study, the researchers evaluated 400 women, aged 40 and younger. All were sexually active and not using contraception.

“Only about a third were actively trying to get pregnant, but all were having unprotected sex, without birth control,” Taylor said.

On a daily basis, the women recorded their stress levels, from one (lowest) to four (highest). They did so for up to 20 cycles, or until pregnancy occurred. On average, the women recorded their stress for eight cycles.

Over the study period, 139 women became pregnant. There was a 46 percent reduction in conception for each one-unit rise in stress during the ovulation window, the researchers found. Day 14 of the cycle was estimated as the time of ovulation.

The impact on conceiving held even after the investigators took into account other factors, such as age, body mass index (a measurement based on weight and height), alcohol use and how often sex occurred.

The researchers looked at other times in the cycle as well, but “we did not find an effect of stress on implantation,” Taylor said. “Implantation generally occurs six to 10 days after ovulation, if you have conceived.”

While the study found a connection between stress and conception, it didn’t prove cause and effect.

In another finding, “women who did get pregnant had much higher levels [of stress] around the end of their cycle.” Taylor said that may be due to hormone levels, with increasing levels of estrogen and progesterone causing mood swings at that time.

Dr. Tomer Singer, director of reproductive endocrinology and infertility at Lenox Hill Hospital in New York City, said the new research pinpoints the time period most affected by stress.

“They were able to focus a light on the important time of being stress-free, and this is the first half of the [cycle],” he said.

Taylor’s team did not look at why stress affected conception at the time of ovulation. But, she speculated that “stress disrupts the signaling between the brain and the ovaries, and reduces the chances of ovulation.”

Singer agreed. He said when a woman has a high stress level, hormones responsible for ovulation can be disrupted.

This hormonal disruption can hamper the process, Taylor said, so “it could be nature’s way of saying ‘Don’t have a baby right now.’ ”

Singer suggested that women can reduce their stress levels by practicing yoga or mindfulness meditation, among other ways.

Moderate exercise, five times a week for 30 minutes, can also reduce stress, Taylor said. But exercising to extremes can reduce the likelihood of conceiving, she said.

She also suggested that using talk therapy and time-management skills could lower stress levels.

The study was published online recently in the Annals of Epidemiology.

The use of tenofovir disoproxil fumarate (TDF) during pregnancy resulted in lower rate of mother-to-child transmission of hepatitis B virus (HBV) compared with those who received usual care without antiviral therapy, a recent study finds.

To assess the efficacy of TDF use during pregnancy for the prevention of HBV transmission from mother to child, researchers randomized 197 mothers who were positive for hepatitis B e antigen (HBeAg) and who had an HBV DNA level higher than 200,000 IU per millilitre to receive usual care without antiviral therapy (n=100) or TDF (n=97; 300 mg/day) from 30 to 32 weeks of gestation until postpartum week 4. The participants were followed until postpartum week 28. All the infants received immunoprophylaxis.

The primary outcomes were the rates of mother-to-child transmission and birth defects. The secondary outcomes were the safety of TDF, the percentage of mothers with an HBV DNA level of less than 200,000 IU per milliliter at delivery, and loss or seroconversion of HBeAg or hepatitis B surface antigen at postpartum week 28.

At delivery, 68 percent of the mothers in the TDF group, as compared with 2 percent in the control group (2 of 100), had an HBV DNA level of less than 200,000 IU per milliliter (p<0.001). At postpartum week 28, the rate of mother-to-child transmission was significantly lower in the TDF group than in the control group, both in the intention-to-treat analysis (5 vs 18 percent; p=0.007) and the per-protocol analysis (0 vs 7 percent; p=0.01).

The maternal and infant safety profiles were similar in the TDF group and the control group, including birth-defect rates (2 and 1 percent, respectively; p=1), although more mothers in the TDF group had an increase in the creatine kinase level. After the discontinuation of TDF, alanine aminotransferase elevations above the normal range occurred more frequently in mothers in the TDF group than in those in the control group (45 vs 30 percent; p=0.03). The maternal HBV serologic outcomes did not differ significantly between the groups.

15 JUN 2016

An elevated level of urinary nephrin (nephrinuria) may be associated with an increased risk of preeclampsia (PE), according to a study, suggesting that a certain cut-off can facilitate identification of women with greater PE risk.

Researchers investigated the feasibility of nephrinuria use to assess the risk of PE by enrolling 89 pregnant women without hypertension or significant proteinuria in pregnancy (SPIP). The number of urine samples obtained was 31 during the first trimester, 125 during the second, and 93 during the third. Outcomes were changes in nephrin:creatinine ratio (NCR) and protein:creatinine ratio (PCR). SPIP was defined as PCR >0.27.

PE occurred in 14 of the women. In this group of women, NCR positively correlated with PCR (correlation coefficient, 0.862; p<0.0001).

However, there were no significant changes in NCR even with marked increases in PCR among 75 women with normotensive pregnancies. This shows that the increase in nephrinuria over the physiological range of proteinuria in pregnancy was small.

The risk of later PE development was greater among asymptomatic women with NCR >122 ng/mg (95th centile value for 75 women with normotensive pregnancies) than among those with NCR ≤122 during both the second trimester (relative risk [RR], 5.93; 95 percent CI, 2.59 to 13.6; 60 vs 10 percent) and third trimester (RR, 13.5; 3.31 to 55; 75 vs 5.5 percent).

Nephrin is a protein that is predominantly found at the glomerular slit diaphragm of podocytes. Previous studies have reported that nephrin expression is reduced in kidney biopsy specimens from women with PE and in autopsy specimens from women who died from PE. The reduced expression may be linked to increased shedding of nephrin from podocytes.

The findings suggest that NCR is unlikely to increase in normal pregnancy despite the gradual increases in PCR, whereas both NCR and PCR increase gradually with advancing gestation in PE pregnancies, researchers said. This indicates that urinary NCR may prove more useful in identifying women who are at higher risk of PE compared with urinary PCR.

11 Aug 2016

 

13 Aug 2016

Treatment with rivaroxaban appears to be associated with reduced incidences of hospitalisations and outpatient visits among patients with deep vein thrombosis (DVT) compared with low-molecular-weight heparin (LMWH) and warfarin, according to a study.

Researchers followed adult patients with DVT who initiated treatment with rivaroxaban (n=512) or LMWH/warfarin (n=512) immediately after diagnosis. The number of hospitalisations for all causes and for venous thromboembolism (VTE), healthcare resource utilisation (ER, outpatient, and other visits), as well as healthcare and pharmacy costs were assessed at 1, 2, 3, and 4 weeks after the diagnosis and compared between the two treatment arms.

The rivaroxaban treatment arm showed significantly lower mean all-cause hospitalisation numbers over 1 week (0.012 vs 0.032; p=0.044) and 2 weeks (0.022 vs 0.048; p=0.040) compared with the LMWH/warfarin arm. The mean VTE-related hospitalisation numbers were also significantly lower in the rivaroxaban arm over 1 week (0.008 vs 0.028; p=0.020), 2 weeks (0.016 vs 0.042; p=0.020), and 4 weeks (0.034 vs 0.068; p=0.036).

In terms of all-cause and VTE-related outpatient visits, the mean numbers were markedly lower among patients in the rivaroxaban arm than among those in the LMWH/warfarin arm over 1, 2, 3, and 4 weeks (p<0.001 for all).

Meanwhile, all-cause and VTE-related ER and other visits were comparable between the two treatment groups over the first 4 weeks.

Rivaroxaban users reported lower mean all-cause total healthcare costs than LMWH/warfarin users over the first 2 weeks (week 1: US$2,332 vs $3,428; p<0.001; week 2: $3,108 vs $4,524; p<0.001). Similarly, mean costs associated with all-cause hospitalisations (weeks 1 and 2) and pharmacy (weeks 1 to 4) were significantly lower among rivaroxaban users. Costs related to ER visits (weeks 1 to 4), outpatient visits (weeks 1 to 4), or other visits (with the exception of week 1) did not differ among patients between the two treatment arms.

The findings suggest that rivaroxaban is superior to LMWH/warfarin, with advantages such as simplified care facilitating less healthcare resource utilisation.

11 Aug 2016

Mesoblast Ltd has announced that data from a mid-stage trial for its experimental stem-cell therapy indicated that the therapy significantly alleviated symptoms and disease activity in rheumatoid arthritis (RA) patients who have stopped responding to commercially available biotech drugs. The findings hold numerous implications in the development of new, effective therapeutic approaches to rheumatoid arthritis.

A new method of combating RA

The symptoms and progression of RA are caused by pro-inflammatory white blood cells and activated T cells of the immune system. These trigger multiple pro-inflammatory cytokine pathways; that is, they activate many kinds of small proteins which signal to the cells to become inflamed. In other words, there is more than one way to transmit the message to the cells to get inflamed.

Existing therapies each target one way of transmitting the ‘inflammation message’ by inhibiting one type of protein, but none target more than one at the same time. Mesoblast’s treatment, on the other hand, inhibits multiple types of proteins that cause inflammation. Therefore, the patient experiences significant relief from the symptoms.

Hope for those who stopped responding to conventional drugs

Treatment with the Melbourne-based company involved the intravenous delivery of MPC-300-IV, a tier 1 product candidate consisting of 300 million Mesenchymal Precursor Cells (MPCs). The results of their 48-patient, 12-week Phase 2 trial have deemed the treatment to be well-tolerated with no serious side-effects nor any infusion-related accidents.

ACR is a scale to measure change in symptoms of RA. If patients experience a 20% relief of RA symptoms, the trial is said to have achieved ACR20. In patients who had previously been treated with at least one biologic drug, ACR20 was achieved by 55% of those who had received an infusion of 2 million cells per kilogram of their weight. In patients who had received treatment from at least one biologic drug without the infusion, only 33% achieved ACR20.

There is a term used to refer to a higher degree of improvement, ACR70, when patients report a 70% relief from RA. This was achieved by 36% after a single infusion of the Mesoblast treatment, compared to the placebo group which obviously showed no improvement. The biotechnology company also claims that the cell therapy improved patients’ physical function and reduced overall disease activity.

According to a statement made by Dr Allan Gibofsky, a rheumatologist at the Hospital for Special Surgery, New York, Mesoblast’s cell infusion therapy has ‘the potential to fill the major unmet medical need’ for patients that gain no benefit from popular biological treatments. The effects of new treatment methods for RA must be twofold – alleviating pain from RA and stopping the disease from getting worse simultaneously.

 

1 Aug 2016

 

5 Aug 2016

Initiation of opioid use in elderly patients with chronic obstructive pulmonary disease (COPD) more than doubled the risk of death from respiratory-related complications compared with non-opioid users, according to a retrospective population-based cohort study in Canada.

“The fact that incident opioids are frequently initiated in older adults with COPD makes these results particularly worrisome,” the researchers said. “Our findings suggest that a careful, individualized approach needs to be taken when administering opioids to older adults with COPD, given the potential for adverse respiratory outcomes.”

“These data raise concerns regarding the degree and manner with which opioids are used among vulnerable older adults with COPD,” said study authors Dr. Nicholas Vozoris from the Division of Respirology at the Department of Medicine of St. Michael’s Hospital in Ontario, Canada, and Dr. Denis O’Donnell of the Department of Medicine at Queen’s University in Ontario, Canada.

These findings showed that adverse outcomes could also develop in new lower-dose opioid users (≤30 mg morphine equivalents per day) and not limited to higher-dose opioid users as suggested in previous studies, the authors added.

When comparing the subgroup of patients using opioid-only medication with controls, new opioid users had a higher risk of outpatient exacerbations (p<0.0001).

The subgroup of new opioid-only users were also more likely to visit the emergency department or be hospitalized for COPD or pneumonia, or die from COPD or pneumonia or any other cause compared with controls (all p<0.0001).

Opioid-only agents usually contain more potent opioids like codeine and were indicated at a higher dose than opioid/non-opioid combination therapy, which might explain the difference in exacerbation risk in the subgroup analysis, the authors said.

“I almost never use opioids for my COPD patients. I would think that opioid-containing medication may be used to suppress cough or try to relieve the sensation of dyspnoea in these patients [in the study],” said Dr. Ong Kian Chung, a consultant respiratory specialist from the KC Ong Chest & Medical Clinic at Mount Elizabeth Medical Centre, Singapore, who was unaffiliated with the study.

“I would be cautious if the patients are very frail, elderly, already requiring oxygen supplementation and/or non-invasive ventilatory support,” he said.

For such vulnerable groups of patients, antihistamines, mucolytics or dextromethophan can be used to manage cough, while long-acting bronchodilators such as methylxanthines can be used for chronic dyspnoea, and steroids for COPD exacerbation, suggested Ong.