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Expert Opinion on Drug Delivery Nov 2020There is considerable interest in vaginal ring technology for sustained/controlled administration of drugs to the human vagina. Seven drug-releasing vaginal rings have... (Review)
Review
INTRODUCTION
There is considerable interest in vaginal ring technology for sustained/controlled administration of drugs to the human vagina. Seven drug-releasing vaginal rings have reached market and other experimental devices are in preclinical/clinical development. Although most women who have used rings are satisfied and find them acceptable, involuntary expulsions and voluntary removals are known to occur and are widely reported. There have been no previous efforts to review this topic and understand the factors contributing to expulsions.
AREAS COVERED
This article will help researchers, clinicians and product developers better understand the pertinent factors and issues around ring expulsions and removals, and inform new research aimed at optimizing ring product design. The review contains four sections: (i) introduction to vaginal ring technology; (ii) discussion of the anatomical, physiological, device, and user factors affecting ring expulsion; (iii) review of involuntary expulsions; (iv) review of voluntary removals; and (v) concluding remarks/opinions.
EXPERT OPINION
Further research is needed to better understand the factors contributing to involuntary ring expulsions and removals so that rings can be better designed to minimize rates of expulsion and to reduce removals. Determination of optimum ring dimensions and stiffness are likely key factors, alongside better counseling around removal and reinsertion.
Topics: Contraceptive Devices, Female; Female; Humans; Pharmaceutical Preparations
PubMed: 32684013
DOI: 10.1080/17425247.2020.1798927 -
Gynecological Endocrinology : the... Feb 2019Enhanced health care for patients with Down syndrome (DS) results in improved overall quality of life and longer life expectancy. The main gynecologic complaints of... (Review)
Review
Enhanced health care for patients with Down syndrome (DS) results in improved overall quality of life and longer life expectancy. The main gynecologic complaints of patients with DS and their caregivers relate to menstrual cycles, hygiene and reproductive issues. Certain aspects, such as age of menarche, menstrual cycles, internal genitalia, and hormone profile are similar to those observed in the general population. However, individuals with DS may have a higher incidence of other disorders related to menstruation, such as hypothyroidism, epilepsy and use of anticonvulsants. Contraceptive measures for individuals with DS can be used for both contraception and control of menstrual symptoms. The physician must be to make an individualized recommendation aimed at offering the most efficient and least invasive method with the fewest side effects. Among medical options are oral contraceptives, quarterly injectable medroxyprogesterone acetate, oral progesterone, a levonorgestrel-releasing intrauterine system, transdermal patch and vaginal rings. Surgical methods, including hysterectomy, endometrial ablation, or tubal ligation, are rarely considered because they raise ethical and legal questions. This article reviews the literature and basic guidelines to assist physicians who attend adolescent girls and women with DS to provide guidance on the appropriate management of the main gynecologic complaints of this population.
Topics: Contraception; Contraceptive Agents, Female; Contraceptive Devices, Female; Contraceptives, Oral, Hormonal; Down Syndrome; Female; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Medroxyprogesterone Acetate; Menstruation Disturbances; Progesterone; Transdermal Patch
PubMed: 30324830
DOI: 10.1080/09513590.2018.1501017 -
Acta Physiologica (Oxford, England) May 2024Mechanical ventilation (MV) results in diminished diaphragm size and strength, termed ventilator-induced diaphragm dysfunction (VIDD). VID increases dependence, prolongs...
AIM
Mechanical ventilation (MV) results in diminished diaphragm size and strength, termed ventilator-induced diaphragm dysfunction (VIDD). VID increases dependence, prolongs weaning, and increases discharge mortality rates. The Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is implicated in VIDD, upregulated following MV. JAK/STAT inhibition alleviates chronic muscle wasting conditions. This study aimed to explore the therapeutic potential of Ruxolitinib, an FDA approved JAK1/2 inhibitor (JI) for the treatment of VIDD.
METHODS
Rats were subjected to 5 days controlled MV (CMV) with and without daily Ruxolitinib gavage. Muscle fiber size and function were assessed. RNAseq, mitochondrial morphology, respirometry, and mass spectrometry were determined.
RESULTS
CMV significantly reduced diaphragm size and specific force by 45% (p < 0.01), associated with a two-fold P-STAT3 upregulation (p < 0.001). CMV disrupted mitochondrial content and reduced the oxygen consumption rate (p < 0.01). Expression of the motor protein myosin was unaffected, however CMV alters myosin function via post-translational modifications (PTMs). Daily administration of JI increased animal survival (40% vs. 87%; p < 0.05), restricted P-STAT3 (p < 0.001), and preserved diaphragm size and specific force. JI was associated with preserved mitochondrial content and respiratory function (p < 0.01), and the reversal or augmentation of myosin deamidation PTMs of the rod and head region.
CONCLUSION
JI preserved diaphragm function, leading to increased survival in an experimental model of VIDD. Functional enhancement was associated with maintenance of mitochondrial content and respiration and the reversal of ventilator-induced PTMs of myosin. These results demonstrate the potential of repurposing Ruxolitinib for treatment of VIDD.
Topics: Animals; Diaphragm; Pyrimidines; Nitriles; Rats; Respiration, Artificial; Male; Pyrazoles; Rats, Sprague-Dawley
PubMed: 38551103
DOI: 10.1111/apha.14128 -
Fertility and Sterility Mar 2021
Topics: Diaphragm; Endometriosis; Female; Humans; Laparoscopy; Reference Standards
PubMed: 33509631
DOI: 10.1016/j.fertnstert.2020.12.034 -
Expert Opinion on Pharmacotherapy Oct 2018Contraceptive vaginal rings (CVRs) are good contraceptive options because they do not require skilled providers, are self-administered, and show a higher stability of... (Review)
Review
INTRODUCTION
Contraceptive vaginal rings (CVRs) are good contraceptive options because they do not require skilled providers, are self-administered, and show a higher stability of drug diffusion.
AREAS COVERED
This article provides a review of the developments made with CVRs over the past number of years, while giving focus to the latest CVRs that have gone through clinical development. The author of the article also provides an expert perspective on the future of these useful therapeutic options.
EXPERT OPINION
Pharmacokinetic studies have shown that segesterone, an absorbable progestin that is used alone or in combination with ethinyl estradiol (EE) or E is the CVR of choice at this present time. Indeed, segesterone has demonstrated safety and efficacy as a CVR and is also an appropriate option for lactating women, as they are not absorbed orally. However, good cycle control is important for improved CVR adherence. CVRs that allow the combination of more than one drug may unravel another multi-purpose use when combined with microbicides and could provide combined protection to women who wish to protect themselves from pregnancy and sexually transmitted infection.
Topics: Contraceptive Agents, Female; Contraceptive Devices, Female; Female; Humans
PubMed: 30286682
DOI: 10.1080/14656566.2018.1519549 -
Muscle & Nerve Jan 2017Diaphragm excursion measured via ultrasound may be an important imaging outcome measure of respiratory function. We developed a new method for measuring diaphragm...
INTRODUCTION
Diaphragm excursion measured via ultrasound may be an important imaging outcome measure of respiratory function. We developed a new method for measuring diaphragm movement and compared it to the more traditional M-mode method.
METHODS
Ultrasound images of the right and left hemidiaphragms were collected to compare speckle tracking and M-mode measurements of diaphragm excursion. Speckle tracking was performed using EchoInsight (Epsilon Imaging, Ann Arbor, Michigan).
RESULTS
Six healthy subjects without a history of pulmonary diseases were included in this proof-of-concept study. Speckle tracking of the diaphragm is technically possible. Unlike M-mode, speckle tracking carries the advantage of reliable visualization and measurement of the left hemidiaphragm.
CONCLUSIONS
Speckle tracking accounted for diaphragm movement simultaneously in the cephalocaudad and mediolateral directions, unlike M-mode, which is 1-dimensional. Diaphragm speckle tracking may represent a novel, more robust method for measuring diaphragm excursion, especially for the left hemidiaphragm. Muscle Nerve 55: 125-127, 2017.
Topics: Aged; Diaphragm; Female; Functional Laterality; Healthy Volunteers; Humans; Male; Middle Aged; Ultrasonography
PubMed: 27533320
DOI: 10.1002/mus.25380 -
Korean Journal of Radiology 2018To evaluate the technical feasibility of four-dimensional (4D) CT for the functional evaluation of the pediatric diaphragm.
OBJECTIVE
To evaluate the technical feasibility of four-dimensional (4D) CT for the functional evaluation of the pediatric diaphragm.
MATERIALS AND METHODS
In 22 consecutive children (median age 3.5 months, age range 3 days-3 years), 4D CT was performed to assess diaphragm motion. Diaphragm abnormalities were qualitatively evaluated and diaphragm motion was quantitatively measured on 4D CT. Lung density changes between peak inspiration and expiration were measured in the basal lung parenchyma. The diaphragm motions and lung density changes measured on 4D CT were compared between various diaphragm conditions. In 11 of the 22 children, chest sonography was available for comparison.
RESULTS
Four-dimensional CT demonstrated normal diaphragm (n = 8), paralysis (n = 10), eventration (n = 3), and diffusely decreased motion (n = 1). Chest sonography demonstrated normal diaphragm (n = 2), paralysis (n = 6), eventration (n = 2), and right pleural effusion (n = 1). The sonographic findings were concordant with the 4D CT findings in 90.9% (10/11) of the patients. In diaphragm paralysis, the affected diaphragm motion was significantly decreased compared with the contralateral normal diaphragm motion (-1.1 ± 2.2 mm vs. 7.6 ± 3.8 mm, = 0.005). The normal diaphragms showed significantly greater motion than the paralyzed diaphragms (4.5 ± 2.1 mm vs. -1.1 ± 2.2 mm, < 0.0001), while the normal diaphragm motion was significantly smaller than the motion of the contralateral normal diaphragm in paralysis (4.5 ± 2.1 mm vs. 7.6 ± 3.8 mm, = 0.01). Basal lung density change of the affected side was significantly smaller than that of the contralateral side in diaphragm paralysis (89 ± 73 Hounsfield units [HU] vs. 180 ± 71 HU, = 0.03), while no significant differences were found between the normal diaphragms and the paralyzed diaphragms (136 ± 66 HU vs. 89 ± 73 HU, = 0.1) or between the normal diaphragms and the contralateral normal diaphragms in paralysis (136 ± 66 HU vs. 180 ± 71 HU, = 0.1).
CONCLUSION
The functional evaluation of the pediatric diaphragm is feasible with 4D CT in select children.
Topics: Diaphragm; Diaphragmatic Eventration; Female; Four-Dimensional Computed Tomography; Humans; Infant; Infant, Newborn; Lung; Male; Respiratory Paralysis; Retrospective Studies; Ultrasonography
PubMed: 29354007
DOI: 10.3348/kjr.2018.19.1.111 -
Nursing For Women's Health Apr 2023To examine the relationship between intrauterine devices (IUDs) and bacterial vaginosis (BV) through an integrative review of the current literature. (Review)
Review
OBJECTIVE
To examine the relationship between intrauterine devices (IUDs) and bacterial vaginosis (BV) through an integrative review of the current literature.
DATA SOURCES
CINAHL, MEDLINE, Health Source, Evidence-Based Medicine's Cochrane Central Registry of Controlled Trials, Embase, and Web of Science databases were searched.
STUDY SELECTION
Cross-sectional, case-control, cohort, quasi-experimental, and randomized controlled trials examining copper (Cu-IUD) and levonorgestrel (LNG-IUD) use in reproductive- age users with BV occurrence confirmed with Amsel's criteria or Nugent scoring were included. Articles included were published in the past 10 years.
DATA EXTRACTION
Fifteen studies met criteria, after an initial search identified 1,140 potential titles, and two reviewers assessed 62 full-text articles for inclusion.
DATA SYNTHESIS
Data were categorized into three groups: retrospective descriptive cross-sectional studies identifying point prevalence of BV among IUD users; prospective analytic studies examining BV incidence and prevalence among Cu-IUD users; and prospective analytic studies examining BV incidence and prevalence among LNG-IUD users.
CONCLUSION
Synthesis and comparison of studies were difficult because of disparate study designs, sample sizes, comparator groups, and inclusion criteria for individual studies. Synthesis of data from cross-sectional studies showed that all IUD users combined may have an increased point prevalence of BV compared with non-IUD users. These studies did not delineate LNG-IUDs from Cu-IUDs. Findings from cohort and experimental studies suggest a possible increase in BV occurrence among Cu-IUD users. Evidence is lacking to show an association between LNG-IUD use and BV.
Topics: Female; Humans; Retrospective Studies; Prospective Studies; Vaginosis, Bacterial; Cross-Sectional Studies; Levonorgestrel; Intrauterine Devices; Intrauterine Devices, Copper; Intrauterine Devices, Medicated; Contraceptive Agents, Female
PubMed: 36803608
DOI: 10.1016/j.nwh.2023.01.007 -
Respiratory Care Apr 2021Diaphragmatic respiratory effort during mechanical ventilation is an important determinant of patient outcome, but direct measurement of diaphragmatic contractility...
BACKGROUND
Diaphragmatic respiratory effort during mechanical ventilation is an important determinant of patient outcome, but direct measurement of diaphragmatic contractility requires specialized instrumentation and technical expertise. We sought to determine whether routinely collected clinical variables can predict diaphragmatic contractility and stratify the risk of diaphragm atrophy.
METHODS
We conducted a secondary analysis of a prospective cohort study on diaphragm ultrasound in mechanically ventilated subjects. Clinical variables, such as breathing frequency, ventilator settings, and blood gases, were recorded longitudinally. Machine learning techniques were used to identify variables predicting diaphragm contractility and stratifying the risk of diaphragm atrophy (> 10% decrease in thickness from baseline). Performance of the variables was evaluated in mixed-effects logistic regression and random-effects tree models using the area under the receiver operating characteristic curve.
RESULTS
Measurements were available for 761 study days in 191 subjects, of whom 73 (38%) developed diaphragm atrophy. No routinely collected clinical variable, alone or in combination, could accurately predict either diaphragm contractility or the development of diaphragm atrophy (model area under the receiver operating characteristic curve 0.63-0.75). The risk of diaphragm atrophy was not significantly different according to the presence or absence of patient-triggered breaths (38.3% vs 38.6%; odds ratio 1.01, 95% CI 0.05-2.03). Diaphragm thickening fraction < 15% during either of the first 2 d of the study was associated with a higher risk of atrophy (44.6% vs 26.1%; odds ratio 2.28, 95% CI 1.05-4.95).
CONCLUSIONS
Diaphragmatic contractility and the risk of diaphragm atrophy could not be reliably determined from routinely collected clinical variables and ventilator settings. A single measurement of diaphragm thickening fraction measured within 48 h of initiating mechanical ventilation can be used to stratify the risk of diaphragm atrophy during mechanical ventilation.
Topics: Atrophy; Diaphragm; Humans; Prospective Studies; Respiration, Artificial; Ultrasonography
PubMed: 33293364
DOI: 10.4187/respcare.08223 -
Medicine and Science in Sports and... Oct 2016Previous investigations have identified impaired trunk and postural stability in individuals with chronic ankle instability (CAI). The diaphragm muscle contributes to...
INTRODUCTION/PURPOSE
Previous investigations have identified impaired trunk and postural stability in individuals with chronic ankle instability (CAI). The diaphragm muscle contributes to trunk and postural stability by modulating the intra-abdominal pressure. A potential mechanism that could help to explain trunk and postural stability deficits may be related to altered diaphragm function due to supraspinal sensorimotor changes with CAI. The purpose of this study was to examine the diaphragm contractility in individuals with CAI and healthy controls.
METHODS
Twenty-seven participants with self-reported CAI and 28 healthy control participants volunteered. A portable ultrasound unit was used to visualize and measure the right and left hemidiaphragm thickness at the end of resting inspiration and expiration in supine while breathing quietly. The diaphragm movement was imaged and recorded on B-mode ultrasonography. The degree of diaphragm contractility was calculated from the mean of three images from the end of resting inspiration and expiration. Independent t-tests were used to compare the degree of diaphragm thickness of right and left sides between the CAI and the control groups.
RESULTS
The CAI group had a smaller degree of left hemidiaphragm contractility compared with the control group (P = 0.03). There was no between-group difference in other diaphragm variables.
CONCLUSION
Individuals with CAI appear to have altered diaphragm contractility, which may be an illustration of diaphragm dysfunction and central nervous system changes in CAI population. The association between CAI and altered diaphragm contractility provides clinicians a more comprehensive awareness of proximal impairments associated with CAI. Future investigation is needed to determine whether altered contractility of the diaphragm contributes to functional impairments, activity limitations, and participant restrictions commonly observed in patients with CAI.
Topics: Ankle Joint; Biomechanical Phenomena; Case-Control Studies; Diaphragm; Female; Humans; Joint Instability; Male; Muscle Contraction; Postural Balance; Retrospective Studies; Ultrasonography; Young Adult
PubMed: 27232242
DOI: 10.1249/MSS.0000000000000994