-
Human Reproduction (Oxford, England) Jun 2022How does hormonal contraceptive use and menstrual cycle phase affect the female microbiome across different body sites?
STUDY QUESTION
How does hormonal contraceptive use and menstrual cycle phase affect the female microbiome across different body sites?
SUMMARY ANSWER
The menstrual cycle phase, but not hormonal contraceptive use, is associated with the vaginal and oral but not the gut microbiome composition in healthy young women.
WHAT IS KNOWN ALREADY
Women with low vaginal levels of Lactobacillus crispatus are at increased risk of pre-term birth, fertility treatment failure, sexually transmitted infections and gynaecological cancers. Little is known about the effect of hormonal fluctuations on other body site's microbiomes as well as the interplay between them.
STUDY DESIGN, SIZE, DURATION
This study includes a cohort of 160 healthy young Danish women using three different contraceptive regimens: non-hormonal methods (n = 54), combined oral contraceptive (COC, n = 52) or levonorgestrel intrauterine system (LNG-IUS, n = 54). Samples were collected from four body sites during the menstrual cycle (menses, follicular and luteal phases) at Copenhagen University Hospital, Rigshospitalet, Denmark.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The oral, vaginal, rectal and faecal microbiomes were characterized by shotgun sequencing. Microbial diversity and community distance measures were compared between study groups, menstrual phase timepoints and body sites. All participants answered an extensive questionnaire on current health, lifestyle and sex life. Confounding factors such as smoking, BMI and diet were analysed by PERMANOVA. Plasma oestradiol and progesterone levels are correlated with microbiome composition.
MAIN RESULTS AND THE ROLE OF CHANCE
The use of COC and LNG-IUS was not associated with the microbiome composition or diversity. However, increased diversity in the vaginal microbiome was observed during menses, followed by a subsequent expansion of Lactobacillus spp. during the follicular and luteal phases which correlated with measured serum oestradiol levels (r = 0.11, P < 0.001). During menses, 89 women (58%) had a dysbiotic vaginal microbiome with <60% Lactobacillus spp. This declined to 49 (32%) in the follicular phase (P < 0.001) and 44 (29%) in the luteal phase (P < 0.001). During menses, bacterial richness and diversity in saliva reached its lowest point while no differences were observed in the faecal microbiome. The microbiome in different body sites was on average more similar within the same individual than between individuals, despite phase or hormonal treatment. Only the vagina presented a clear cluster structure with dominance of either L. crispatus, Lactobacillus iners, Gardnerella vaginalis or Prevotella spp.
LARGE SCALE DATA
The microbiome samples analysed in this study were submitted to the European Nucleotide Archive under project number PRJEB37731, samples ERS4421369-ERS4422941.
LIMITATIONS, REASONS FOR CAUTION
The cohort is homogenous which limits extrapolation of the effects of ethnicity and socio-economic status on the microbiome. We only present three defined timepoints across the menstrual phase and miss potential important day to day fluctuations.
WIDER IMPLICATIONS OF THE FINDINGS
The use of hormonal contraception did not significantly associate with the microbiome composition in the vagina, faeces, rectum or saliva in healthy young women. This is a welcome finding considering the widespread and prolonged use of these highly efficient contraceptive methods. The menstrual cycle is, however, a major confounding factor for the vaginal microbiome. As such, the time point in the menstrual cycle should be considered when analysing the microbiome of women of reproductive age, since stratifying by vaginal dysbiosis status during menstruation could be misleading. This is the first study to confirm by direct measurements of oestradiol, a correlation with the presence of L. crispatus, adding evidence of a possible hormonal mechanism for the maintenance of this desirable microbe.
STUDY FUNDING/COMPETING INTEREST(S)
This work was partly funded by the Ferring Pharmaceuticals through a research collaboration with The Centre for Translational Microbiome Research (CTMR) at the Karolinska Institutet (L.W.H., E.F., G.E. and I.S.-K.). Ferring Pharmaceuticals also funded the infrastructure to obtain the clinical samples at Copenhagen University Hospital ([#MiHSN01], M.C.K., Z.B., and H.S.N.). This work was also supported by funding from Rigshospitalet's Research Funds ([#E-22614-01 and #E-22614-02] to M.C.K.) and Oda and Hans Svenningsen's Foundation ([#F-22614-08] to H.S.N.). M.C.K., L.W.H., E.F., Z.B., G.E., L.E., I.S.-K. and H.S.N., are partially funded by Ferring Pharmaceuticals, which also provided funds for the collection and processing of the samples analysed in this study. H.S.N.'s research is further supported by Freya Biosciences and the BioInnovation Institute. H.S.N. has received honoraria from Ferring Pharmaceuticals, Merck A/S, Astra-Zeneca, Cook Medical and Ibsa Nordic. A.N.A. reports no competing interests.
Topics: Contraceptive Agents; Estradiol; Female; Humans; Menstrual Cycle; Microbiota; Pharmaceutical Preparations
PubMed: 35553675
DOI: 10.1093/humrep/deac094 -
Drug Delivery and Translational Research Mar 2022The field of nanomedicine has significantly influenced research areas such as drug delivery, diagnostics, theranostics, and regenerative medicine; however, the further... (Review)
Review
The field of nanomedicine has significantly influenced research areas such as drug delivery, diagnostics, theranostics, and regenerative medicine; however, the further development of this field will face significant challenges at the regulatory level if related guidance remains unclear and unconsolidated. This review describes those features and pathways crucial to the clinical translation of nanomedicine and highlights considerations for early-stage product development. These include identifying those critical quality attributes of the drug product essential for activity and safety, appropriate analytical methods (physical, chemical, biological) for characterization, important process parameters, and adequate pre-clinical models. Additional concerns include the evaluation of batch-to-batch consistency and considerations regarding scaling up that will ensure a successful reproducible manufacturing process. Furthermore, we advise close collaboration with regulatory agencies from the early stages of development to assure an aligned position to accelerate the development of future nanomedicines.
Topics: Drug Delivery Systems; Nanomedicine; Pharmaceutical Preparations; Regenerative Medicine; Research Design
PubMed: 34302274
DOI: 10.1007/s13346-021-01024-2 -
Breast Cancer Research : BCR May 2023Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship... (Review)
Review
Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting an essential role of P4. During the MC, P4 has a strong proliferative effect on normal breast epithelium, whereas estradiol (E2) has only a minimal effect. The origin of BC has been strongly linked to proliferation associated DNA replication errors, and the repeated stimulation of the breast epithelium by P4 with each MC is likely to impact the epithelial mutational burden. Long-lived cells, such as stem cells, present in the breast epithelium, can carry mutations forward for an extended period of time, and studies show that breast tumors tend to take decades to develop before detection. We therefore postulate that P4 is an important factor in a woman's lifetime risk of developing BC, and that breast tumors arising during hormonal contraception or after menopause, with or without menopausal hormone therapy, are the consequence of the outgrowth of pre-existing neoplastic lesions, eventually stimulated by estrogens and some progestins.
Topics: Female; Humans; Progesterone; Breast Neoplasms; Menstrual Cycle; Estrogens; Estradiol; Pharmaceutical Preparations
PubMed: 37254150
DOI: 10.1186/s13058-023-01661-0 -
Revista Brasileira de Enfermagem 2022to synthesize the evidence on intravenous device labeling used to identify medications administered to patients in Intensive Care Units, with a view to preventing... (Review)
Review
OBJECTIVES
to synthesize the evidence on intravenous device labeling used to identify medications administered to patients in Intensive Care Units, with a view to preventing medication errors.
METHODS
an integrative review, in the LILACS, IBECS, Embase, MEDLINE, Scopus, Web of Science and CINAHL databases, from November to December 2021, using descriptors and selection criteria. Data were collected in 11 articles and subsequently classified, summarized and aggregated.
RESULTS
pre-designed labels, with pre-defined colors and information, help to prevent medication identification errors. There is still a lack of standardization in the practice of labeling syringes, intravenous lines, infusion pumps and saline solution bags. There are errors related to the lack of labeling devices or to their performance with incomplete information.
CONCLUSIONS
device labeling is a barrier to defending the medication system safety and should be standardized.
Topics: Humans; Infusion Pumps; Intensive Care Units; Medication Errors; Saline Solution; Syringes
PubMed: 36197432
DOI: 10.1590/0034-7167-2022-0049 -
Nutrients Sep 2023Aronia melanocarpa berries are rich in antioxidants and possess a high antioxidant capacity. Aronia berries have shown potential in type 2 diabetes mellitus (T2DM)... (Randomized Controlled Trial)
Randomized Controlled Trial
Aronia melanocarpa berries are rich in antioxidants and possess a high antioxidant capacity. Aronia berries have shown potential in type 2 diabetes mellitus (T2DM) treatment, and previous studies indicate improvements in glycemia after supplementation. Unfortunately, the effectiveness of aronia berries is limited by the low bioavailability of aronia, which fermentation could potentially overcome. The objective of this study was to compare the effects of fermented or non-fermented aronia pulp with placebo in subjects with T2DM. This study was a triple-blinded, triple-crossover study with eight-week intervention periods with fermented aronia extract (FAE), non-fermented aronia extract (AE), and placebo. Extracts were incorporated in snack bars with 37% aronia (FAE or AE) or wheat bran (placebo) and 63% raisins and coconut oil. Pre- and post-treatment period, we did fasting blood samples, including hemoglobin A1c, fructosamine, insulin, glucose, glucagon-like peptide-1, glucose-dependent insulinotropic peptide (GIP) and glucagon, oral glucose tolerance tests, and anthropometric measurements. Of 36 randomized participants, 23 completed the trial. Aside from a higher increase in GIP after FAE supplementation compared to after placebo supplementation, aronia extracts had no effect. The increase in GIP levels after FAE supplementation may hold potential benefits, but the overall clinical impact remains unclear.
Topics: Humans; Diabetes Mellitus, Type 2; Photinia; Cross-Over Studies; Antioxidants; Insulin; Plant Extracts
PubMed: 37836472
DOI: 10.3390/nu15194188 -
The Journal of Maternal-fetal &... Dec 2023While medications for anxiety and depression are commonly used in the United States, it is unclear to what degree they are continued during pregnancy. We used a large...
While medications for anxiety and depression are commonly used in the United States, it is unclear to what degree they are continued during pregnancy. We used a large administrative database to determine whether psychiatric medications are continued during pregnancy and predictors of continued medication treatment. Of 2,672,656 women included in our analysis, 86,454 (3.1%) filled a pre-pregnancy prescription for an anxiolytic or antidepressant medication within 3 months of estimated conception. Of women who filled a pre-pregnancy prescription, 49.4%, 26.1%, and 20.1% filled subsequent prescriptions in the 1st, 2nd, and 3rd trimesters. Discontinuation rates ranged by pharmaceutical agent, from 16% for fluoxetine to 71% for alprazolam. White women and women over 25 were more likely to continue anxiolytic and antidepressant treatment during pregnancy. Because untreated and under-treated mental health conditions are linked to adverse maternal outcomes, high discontinuation rates may have important implications for maternal health.
Topics: Pregnancy; Female; Humans; United States; Depression; Anti-Anxiety Agents; Antidepressive Agents; Fluoxetine; Pharmaceutical Preparations; Pregnancy Complications
PubMed: 36710395
DOI: 10.1080/14767058.2023.2171288 -
Journal of Infection and Public Health Sep 2023Except for a few preventative Human Papillomavirus (HPV) vaccines, there is currently no cure for HPV infection. There are a number of cutting-edge strategies and potent... (Review)
Review
BACKGROUND
Except for a few preventative Human Papillomavirus (HPV) vaccines, there is currently no cure for HPV infection. There are a number of cutting-edge strategies and potent medications or herbal formulations that can be applied topically for early clearance of HPV infection before HPV DNA gets integrated into host cell genome. This is facilitated due to cervical cancer having distinct and well-recognized long precancerous stages.
OBJECTIVES
This review aims to outline every possible medication and formulation, both natural and synthetic, that can be applied topically as intravaginal application to help remove HPV infection at an early precancerous stage.
RESULTS
Several anti-HPV/HPV clearance compounds and formulations for high-grade lesions are undergoing clinical trials. However, the majority of compounds are still in the early stages of development and require additional research to become viable HPV clearance candidates. Synthetic drugs may be more promising because they may have a more targeted effect; however, they may also have significant adverse effects. On the other hand, natural medications are safer to use. They are less specific, but have minimal to no adverse effects.
CONCLUSIONS
This article may serve as a valuable resource of information for managing and preventing precancerous carcinogenic HPV infections. Research could be directed toward developing candidate drugs to make evidence-based decisions about advancing them to clinical trials and, eventually, to the market for potential use in the prevention and control of cervical cancer, which is almost always preventable or even curable if detected early.
Topics: Female; Humans; Uterine Cervical Neoplasms; Papillomavirus Infections; Synthetic Drugs; Papillomavirus Vaccines; Precancerous Conditions; Papillomaviridae
PubMed: 37535995
DOI: 10.1016/j.jiph.2023.06.016 -
MedEdPORTAL : the Journal of Teaching... Mar 2021The prevalence of opioid use disorder has increased steadily over the last decade (from 2.2 million in 2010 to 10.2 million in 2018) and with it, a surge in infectious...
INTRODUCTION
The prevalence of opioid use disorder has increased steadily over the last decade (from 2.2 million in 2010 to 10.2 million in 2018) and with it, a surge in infectious complications associated with injection drug use (IDU). Trainees in internal medicine routinely diagnose, manage, and treat patients experiencing these infections in the hospital setting as well as screen for and immunize against other comorbid infections in the ambulatory setting.
METHODS
This 90-minute, case-based, interactive workshop was led by two facilitators, an infectious diseases specialist and a senior internal medicine resident. To evaluate its effectiveness, we used a pre- and postsession survey administered at the beginning and end of the workshop. Learners were asked to rate comfort level in recognizing, managing, and counseling about various IDU-related infections, as well as to answer specific, content-level questions.
RESULT
Thirty of 42 participants who attended the workshop completed the evaluation. There was a statistically significant change in participants' comfort level with diagnosing and managing IDU-associated infections as well as ambulatory standards of care for people who inject drugs (PWID) from pre- to postworkshop.
DISCUSSION
Our workshop focused on the management and prevention of infections among PWID in both the inpatient and ambulatory settings. Learners demonstrated increased comfort in managing these conditions.
Topics: Hospitals; Humans; Infections; Inpatients; Pharmaceutical Preparations; Prevalence; Substance Abuse, Intravenous
PubMed: 33816787
DOI: 10.15766/mep_2374-8265.11124 -
Therapeutic Application, Phytoactives and Pharmacology of Tinospora cordifolia: An Evocative Review.Chinese Journal of Integrative Medicine Jun 2023Tinospora cordifolia (Guduchi or Gurjo), a herbaceous vine or climbing deciduous shrub, is consider as an important medicine in the Ayurvedic system of medication, which... (Review)
Review
Tinospora cordifolia (Guduchi or Gurjo), a herbaceous vine or climbing deciduous shrub, is consider as an important medicine in the Ayurvedic system of medication, which is available in India, China, Myanmar, Bangladesh and Srilanka. Menispermaceae is the family of this compound. T. cordifolia have a variety of properties to treat various ailments such as fevers, jaundice, diabetes, dysentery, urinary infections, and skin diseases. This compound has been subjected to many chemicals, pharmacological, pre-clinical, or clinical investigations and some new therapeutic potential effects have been indicated. This review aims to summarize the critical information concerning in areas of chemical constituents, chemical structure, and pharmacokinetic activities such as anti-diabetic, anticancer, immune-modulatory, antivirus (especially in silico study about COVID-19), antioxidant, antimicrobial, hepatoprotective and its effect on cardiovascular and neurological disorders as well as rheumatoid arthritis. This traditional herb needs more experimental study on the clinical, pre-clinical study, and clinical efficacy of these compounds for the prevention and treatment of COVID-19 and needs large-scale clinical studies to prove the clinical efficacy of this compound, especially in stress-related diseases and other neuronal disorders.
Topics: Humans; Tinospora; COVID-19; Plant Extracts; Antioxidants
PubMed: 37017881
DOI: 10.1007/s11655-023-3733-2 -
The Journal of Pharmacy Technology :... Apr 2022When medications dispensed from a hospital inpatient pharmacy aren't able to be found at their intended destination (ie, a missing dose), this can result in delayed...
When medications dispensed from a hospital inpatient pharmacy aren't able to be found at their intended destination (ie, a missing dose), this can result in delayed medication administration and rework to redispense the medication. Technology advancements in the medication use process have led to development of dose-tracking software that has the capability to track medication doses throughout the medication use cycle and document a medication's location to its destination. The primary objective of this study was to evaluate the impact of dose-tracking software on the number of inpatient pharmacy redispenses and nursing requests for missing medications. Secondary objectives included pharmacy staff satisfaction with dose-tracking software, its impact on workflow and patient safety, and compliance with dose-track scanning. The study design was a prospective, pre-post implementation to compare the requests for missing doses and associated dispenses of injectable medications during the set evaluation period. Dose-track scanning compliance data was collected and evaluated. A survey was also administered to staff to evaluate employee perception and satisfaction with usability and value of the software. During the preimplementation period, 40 021 injectable doses were dispensed, and 9841 (24.6%) were documented as redispensed doses. After dose-tracking implementation, 42 975 total injectable doses were dispensed with 9839 (22.9%) being redispensed. The count of medication messages was 10 661 in the preperiod and 11 475 in the postperiod. The data were normalized using case mix index (CMI) and patient days to account for variation in severity of illness. Implementation of dose-tracking software showed a decrease in the percentage of redispensed injectable medications.
PubMed: 35571343
DOI: 10.1177/87551225211069001