Placebo Pills Research Articles

The effects of vitamin D on sleep quality and pregnancy symptoms in pregnant women: a randomized, tripled-blinded and placebo-controlled clinical trial

PurposeBecause of the importance of having enough sleep in life and health, this study aims to determine the effect of vitamin D supplementation on sleep quality and pregnancy symptoms (primary outcomes) and side effects (secondary outcome).Design/methodology/approachIn this triple-blind randomized controlled clinical trial, 88 pregnant women with gestational age of 8–10 weeks and serum vitamin D concentration less than 30 ng/ml were allocated into vitamin D (n = 44) and control (n = 44) groups by blocked randomization method. The vitamin D group received a 4,000 IU vitamin D pill, and the control group received a placebo pill daily for 18 weeks. Independent t-, Mann–Whitney U and ANCOVA tests were used to analyze the data.FindingsThe post-intervention mean (SD: standard deviation) of total sleep quality score in the vitamin D and placebo group were 1.94 (2.1) and 4.62 (1.71), respectively. According to the Mann–Whitney U test, this difference between the two groups was statistically significant (p < 0.001). The mean (SD) of pregnancy symptoms in the vitamin D and placebo groups was 23.95 (16.07) and 26.62 (13.84), respectively, and there was no significant difference between the two groups based on ANCOVA test (p = 0.56). Considerable side effects were not observed in any groups.Originality/valueThis study was conducted due to the contradictory results of the effect of vitamin D on sleep quality and the high prevalence of sleep disorders and pregnancy symptoms.

Omega-3 enriched chick diet reduces the foraging areas of breeders in two closely related shearwaters from contrasting marine environments.

Seabirds have evolved several life-history characteristics to help buffer environmental stochasticity. However, particularly during the breeding season, seabirds may be affected by reductions in prey availability and localised oceanographic conditions caused by variations in the environment. The increase in sea surface temperature, triggered by accelerated global warming, is impairing phytoplankton production of omega-3 fatty acids (FAs). Here, we assessed the ecological role of omega-3 FAs on chick development and subsequently on breeder foraging behaviour in two closely related shearwater species foraging in contrasting marine environments. We supplemented chicks with omega-3 FA pills or with control placebo pills and monitored chick growth, chick health status and breeder at-sea foraging behaviour using global positioning system devices. We found that omega-3 chick supplementation reduced the 95% kernel utilization distribution of short trips of Cape Verde shearwaters, but overall, breeders kept a similar foraging pattern between treatments, potentially influenced by predictable prey patches off the West African coast. In contrast, for Cory's shearwaters, the parents of the omega-3 group greatly reduced the foraging effort. This suggests that the proximity to productive prey patches around the colony may help birds to adjust their effort and, therefore, energy expenditure, to changes in the development of their offspring, as driven by their nutritional status. Overall, our results suggest a link between a chick diet enriched in omega-3 FAs and parental foraging effort, providing insight into their ability to cope with a changing and increasingly stochastic marine environment.

(083) Baseline Characteristics of Participants in a Multicenter Randomized Clinical Trial of Vestibulodynia: Understanding Pathophysiology and Determining Appropriate Treatments (Vestibulodynia: UPDATe)

Abstract Introduction Vestibulodynia (VBD) is a common cause of sexual pain that affects ~14 million women in the United States. Many different therapies are used on a trial-and-error basis which can delay effective care. Two distinct VBD subtypes may benefit from different types of treatment: 1) VBD peripheral (VBD-p) - pain localized to the vulvar vestibule and 2) VBD central (VBD-c) - VBD and &amp;gt;1 chronic overlapping pain condition(s) affecting remote body regions. Thus, we are evaluating the efficacy of peripheral, central, and combined treatments for VBD-p vs VBD-c. We will also evaluate cytokine and microRNA biomarkers to help determine pathophysiology and predict treatment response. Objective To describe the design and present baseline participant characteristics of our ongoing RCT for VBD. Methods This is a multi-site randomized, double-blind trial that will enroll participants to one of four parallel arms: 1) peripheral treatment with 5% lidocaine/0.5 mg/ml 0.02% estradiol compound cream and placebo pills, 2) central treatment with tricyclic antidepressant nortriptyline pills and placebo cream, 3) lidocaine/estrogen cream and nortriptyline pills, or 4) placebo cream and placebo pills. The treatment phase will last 16 weeks, with clinical outcome measures and biomarkers assessed at 4 time points (0, 8, 16, and 24 weeks). We will enroll 400 women 18-50 years who report tenderness at the vulvar vestibule and report &amp;gt;3/10 pain with tampon insertion on a numeric rating scale (NRS). Primary outcome is pain with tampon test. Secondary outcomes include self-reported pain on the McGill Pain Questionnaire, psychosocial measures, pressure pain thresholds (PPTs) measured at the vaginal vestibule, levator ani muscles, and remote body sites, and levels of cytokines and microRNAs in local vaginal and circulating blood samples using multiplex assays and RNA sequencing to determine the ability of these biomarkers to predict treatment response. Results So far 135 subjects have enrolled and 78 of these have completed the study. Enrollment remains open, with 27 subjects active and 30 subjects discontinued. Mean (range) age is 26.9 (18-48) years and body mass index is 23.7 (16-37). Self-disclosed racial identity of subjects is: White (67.4%), Asian (14.1%), Multiracial (9.6%), Black (8.9%), with 14.8% of subjects identifying as Hispanic or Latino. Of the enrolled subjects, 94/135 (69.6%) subjects are categorized VBD-c, and 41/135 (30.4%) are categorized VBD-p. Of those categorized as VBD-c, fibromyalgia syndrome (39.3%), endometriosis (34.1%), back pain (25.20%), irritable bowel syndrome (19.3%), chronic headaches (16.3%), temporomandibular disorder (11.1%), interstitial cystitis (10.4%) and chronic fatigue syndrome (1.5%) have been reported. At baseline visit, subjects report an average tampon test score of 4.2 (□ 2.11) and 93.3% of subjects report pain during vaginal intercourse. Conclusions We have launched a multicenter randomized trial to evaluate the efficacy of peripherally and centrally acting medications used for treating unique VBD subtypes based on distinct clinical and biological signatures. We hope to advance our knowledge of the pathophysiologic mechanisms underlying VBD-p and VBD-c, determine the efficacy of peripheral, central, and combined therapies in alleviating pain in women with VBD-p and VBD-c, and identify biomarkers that predict treatment response. Disclosure No

Ursodeoxycholic Acid Use After Bariatric Surgery: Effects on Metabolic and Inflammatory Blood Markers

BackgroundIn addition to the reduction of symptomatic gallstone disease, ursodeoxycholic acid (UDCA) might also have beneficial metabolic effects after bariatric surgery. We examined the impact of UDCA on liver enzymes, hemoglobin A1c (HbA1c), lipids, and inflammation markers.MethodsPatients in the UPGRADE trial (placebo-controlled, double-blind) were randomized between UDCA 900 mg daily or placebo pills for 6 months after bariatric surgery. Patients without blood measurements pre- or 6 months postoperatively were excluded. The change in liver enzymes, Hba1c, lipids, and inflammation markers after surgery were compared between the UDCA and placebo group, followed by a postoperative cross-sectional comparison.ResultsIn total, 513 patients were included (age [mean ± SD] 45.6 ± 10.7 years; 79% female). Preoperative blood values did not differ between UDCA (n = 266) and placebo (n = 247) groups. Increase of alkaline phosphatase (ALP) was greater in the UDCA group (mean difference 3.81 U/l [95%CI 0.50 7.12]). Change in other liver enzymes, HbA1c, lipids, and CRP levels did not differ. Postoperative cross-sectional comparison in 316 adherent patients also revealed a higher total cholesterol (mean difference 0.25 mg/dl [95%CI 0.07–0.42]), lower aspartate aminotransferase (mean difference −3.12 U/l [−5.16 – −1.08]), and lower alanine aminotransferase level (mean difference −5.89 U/l [−9.41 – −2.37]) in the UDCA group.ConclusionUDCA treatment leads to a higher, but clinically irrelevant increase in ALP level in patients 6 months after bariatric surgery. No other changes in metabolic or inflammatory markers were observed. Except for the reduction of gallstone formation, UDCA has no effects after bariatric surgery.Graphical

Effectiveness of Conditioned Open-label Placebo With Methadone in Treatment of Opioid Use Disorder

Methadone treatment is the most effective evidence-based treatment for opioid use disorder (OUD), but challenges related to dosing and premature treatment dropout argue for adjunct interventions to improve outcomes. One potential behavioral intervention with low risk involves harnessing placebo effects. To determine the effect of a pharmacologically conditioned open-label placebo (C-OLP) on 90-day methadone dose, retention, drug use, withdrawal, craving, quality of life, and sleep. This 2-arm, open-label, single-blind randomized clinical trial was conducted between December 5, 2017, and August 2, 2019, in an academically affiliated community opioid treatment program. Analyses were conducted between October 1, 2019, and April 30, 2020. A total of 320 newly enrolled adults seeking treatment for moderate to severe OUD were assessed for study eligibility; 131 met eligibility criteria, provided informed consent, and were randomized to either C-OLP or treatment as usual (TAU) in an unequal-block (3:2) manner. Exclusion criteria were pregnancy, hospital/program transfers, and court-ordered treatment. Participants randomized to C-OLP received pharmacologic conditioning and a placebo pill and methadone, and participants randomized to TAU were given methadone only. Participants met with the study team 5 times: at baseline (treatment intake) and 2, 4, 8, and 12 weeks postbaseline. Interactions were balanced between the 2 groups. Outcomes included 90-day methadone dose (primary) and treatment retention, drug use, withdrawal, craving, quality of life, and sleep quality (secondary). Analyses were conducted as intention-to-treat. Of the 131 people enrolled in the study, 54 were randomized to TAU and 77 to C-OLP. Mean (SD) age was 45.9 (11.2) years; most of the participants were Black or African American (83 [63.4%]) and male (84 [64.1%]). No significant group differences were observed in the mean (SD) 90-day methadone dose (83.1 [25.1] mg for group TAU, 79.4 [19.6] mg for group C-OLP; t = 0.621991; P = .43), but the groups differed significantly in their retention rates: 33 (61.1%) for TAU and 60 (77.9%) for C-OLP (χ21 = 4.356; P = .04; number needed to treat for the beneficial outcome of 3-month treatment retention, 6; 95% CI, 4-119). C-OLP participants also reported significantly better sleep quality. In this randomized clinical trial, C-OLP had no effect on the primary outcome of 90-day methadone dose. However, C-OLP participants were significantly more likely to remain in treatment. These findings support the use of C-OLP as a methadone treatment adjunct, but larger trials are needed to further examine the use of C-OLP. ClinicalTrials.gov Identifier: NCT02941809.

Memantine May Reduce Hair-Pulling, Skin Picking

Memantine May Reduce Hair-Pulling, Skin Picking

377 Randomized Placebo-controlled Trial to Test the Efficacy of genetically informed biomarker Nicotine Metabolite Ratio (NMR), and transdermal nicotine replacement therapy (NRT) versus varenicline

OBJECTIVES/GOALS: The overall aim of the proposed study is to evaluate the effectiveness and clinical utility of the NMR as a biomarker of response to placebo, transdermal nicotine, and varenicline to be utilized within the clinical practice as a point-of-care predictor to tailor an individual’s smoking cessation treatment. METHODS/STUDY POPULATION: A 12-week phase II, stratified multicenter, randomized, placebo-controlled trial of 3 treatment groups to measure treatment-seeking smokers (n-900:150 slow metabolizers; 150 normal metabolizers), randomized to 12-weeks of nicotine patch (active patch + placebo pill), varenicline (active pill + placebo patch), or placebo (placebo pill + patch). At the end of treatment, patients will be followed for 12 months. Study Population: Adult smokers 18–65 years old reported smoking≥10 cigarettes/day for≥6 months (verified by carbon monoxide (CO) &gt;10 ppm). Drug and route of administration: RESULTS/ANTICIPATED RESULTS: The study would conclude the effectiveness of the interventions well defined. DISCUSSION/SIGNIFICANCE: The report will provide robust evidence to support the effectiveness of NRT intervention on smoking cessation.

Individual Differences in Corticostriatal White-matter Tracts Predict Successful Daily-life Routine Formation.

Despite good intentions, people often fail to cross the "intention-behavior gap," especially when goal achievement requires repeated action. To bridge this gap, the formation of automatized routines may be crucial. However, people may differ in the tendency to switch from goal-directed toward habitual control. To shed light on why some people succeed in forming routines while others struggle, the present study related the automatization of a novel, daily routine to individual differences in white-matter connectivity in corticostriatal networks that have been implicated in goal-directed and habitual control. Seventy-seven participants underwent diffusion-weighted imaging and formed the daily routine of taking a (placebo) pill for 3 weeks. Pill intake was measured by electronic pill boxes, and participants filled out a daily on-line questionnaire on the subjective automaticity of this behavior. Automatization of pill intake was negatively related to striatal (mainly caudate) connectivity with frontal goal-directed and cognitive control regions, namely, ventromedial pFC and anterior cingulate gyrus. Furthermore, daily pill intake was positively related to individual differences in striatal (mainly caudate) connectivity with cognitive control regions, including dorsolateral and anterior pFC. Therefore, strong control networks may be relevant for implementing a new routine but may not benefit its automatization. We also show that habit tendency (assessed with an outcome-devaluation task), conscientiousness, and daily life regularity were positively related to routine automatization. This translational study moves the field of habit research forward by relating self-reported routine automatization to individual differences in performance on an experimental habit measure and to brain connectivity.

Effects of Ginger on Disgust, Sexual Arousal, and Sexual Engagement: A Placebo-Controlled Experiment

ABSTRACT Sexual problems are common complaints across countries and cultures, and behavioral immune system theory suggests disgust plays an essential role in sexual functioning. The current study investigated 1) if disgust induced by sexual body fluids would reduce sexual arousal, reduce the likelihood of sexual engagement, and enhance disgust toward subsequent erotic stimuli, and 2) if the administration of ginger would affect these reactions. We administered either ginger or placebo pills to a sample of 247 participants (M age = 21.59, SD = 2.52; 122 women) and asked them to complete either behavioral approach tasks with sexual body fluids or with neutral fluids. Next, participants viewed and responded to questions concerning erotic stimuli (nude and seminude pictures of opposite-sex models). As expected, the sexual body fluids tasks induced disgust. The elevated disgust induced by sexual body fluids tasks resulted in lower sexual arousal in women, whereas ginger consumption counteracted this inhibiting effect of disgust on sexual arousal. Disgust elicited by sexual body fluids also increased disgust toward the subsequent erotic stimuli. Ginger increased sexual arousal toward the erotic stimuli in both men and women who had completed the neutral fluids tasks. Findings provide further evidence of the role of disgust in sexual problems, and, importantly, that ginger may improve the sexual function of individuals via its sexual arousal-enhancing effect.

Teenagers’ and parental attitudes towards the use of placebo pills

The placebo response a significant therapeutic improvement after a placebo intervention — can be high in children. The question arises of how optimal advantages of placebo treatment in pediatric clinical care be achieved. In this era of shared-decision making, it is important to be aware of patients’ and parental attitudes. Therefore, the aim of the current study was to assess teenagers’ and parental views on the use of placebo pills in pediatric clinical care. All patients (aged 12–18 years) and parents of children (aged 0–18 years), visiting the pediatric outpatient clinic between March 2020 through December 2020, were invited to participate in this study multicenter survey study. Of 1644 distributed questionnaires: 200/478 (47%) teenagers and 456/1166 (45%) parents filled out the complete survey. More parents were positive towards prescribing placebo medication than teenagers (80% vs. 71%, p = .019), especially when the clinician disclosed the use of a placebo to parents and teenagers, respectively (76% vs. 55%, p = .019). Increasing age of teenagers was positively associated with the willingness for placebo interventions (OR 0.803, 95%CI 0.659–0.979), as was a higher level of parental education (OR 0.706, 95%CI 0.526–0.949). Conclusion: This study emphasizes the willingness of teenagers and parents to receive placebo medication. Placebo medication becoming more acceptable and integrated into daily care may contribute to a decrease in medication use.What is Known:• A placebo is a treatment without inherent power to produce any therapeutic effect, but can result in significant therapeutic improvement, the so-called placebo response.• Treatment response rates after placebo interventions in children can be high, ranging from 41 to 46% in pediatric trials.What is New:• Most teenagers (71%) and parents (80%) find it appropriate for healthcare professionals to prescribe placebo medication.• Compared to adult care, pediatrics has a unique feature to disclose placebo treatment to parents while concealing it for the young patient: the majority of teenagers (85%) and parents (91%) agree to disclose placebo treatment to parents exclusively.

Oral contraceptive use and menstrual cycle influence acute cerebrovascular response to standing.

To determine if the menstrual cycle and oral contraceptives (OC) influence responses to acute orthostatic stress and if these factors are clinically relevant to the diagnosis of initial orthostatic hypotension (iOH). Young, healthy women were recruited, including OC users (n=12) and non-users (NOC; n=9). Women were tested during the low hormone (LH; placebo pills; days 2-5 natural cycle) and high hormone (HH; active dose; days 18-24 natural cycle) menstrual phases. Changes in mean arterial pressure, cardiac output, heart rate, the 30:15 heart rate ratio and cerebrovascular resistance indices within 30s of standing were examined. There were no effects of OC or menstrual cycle on hemodynamic responses during standing (all p>0.05). In the LH phase, OC users had a greater fall in mean middle cerebral artery blood velocity (MCAV) compared to NOC (p<0.05). However, this was reversed in the HH phase, where OC users had a reduced fall in mean MCAV (p<0.05). Interestingly, 8 women (OC and NOC) had drops in systolic/diastolic blood pressure meeting the criteria for iOH, and 7 of those 8 women displayed this drop in a single phase of the menstrual cycle. Our results indicate that chronic versus acute OC use (i.e., long-term use observed via LH phase versus short-term use observed via HH phase) have opposing effects on cerebral blood velocity during standing. Further, our results highlight that multiple assessments across the cycle may be necessary to accurately diagnose iOH, as most women met the diagnostic criteria during a single menstrual phase.

Evaluation and comparison of therapeutic effects of probiotics and colloidal bismuth subcitrate on abdominal bloating.

Functional abdominal bloating is one of the functional gastrointestinal disorders (FGIDs). Here, we aimed to investigate and compare the effects of probiotics and colloidal bismuth subcitrate on abdominal bloating. This was a double-blinded randomized clinical trial performed on 125 patients with functional abdominal bloating in Isfahan in 2020-2021. At the beginning of the study, information on the frequency of abdominal bloating, its severity, the occurrence of early satiety, frequency of borborygmus, frequency of belching, and the frequency of defecation per week was collected. Patients were divided into 3 groups receiving familact probiotic pills that contained 7 bacterial strains, colloidal bismuth subcitrate tablets, and placebo pills for 4 weeks. Afterwards, the frequency and severity of abdominal bloating and other symptoms were compared. After 2 weeks, patients in the probiotic group had a significantly lower frequency of abdominal bloating compared to other groups (P= 0.006). After 4 and 8 weeks, patients in the probiotic group and bismuth group had a lower frequency of bloating )3.18±3.02, 4.11±3.34) compared to placebo (5.10±3.54) (P= 0.001 and P= 0.037, respectively). During the study, patients in the probiotic group had a significantly lower bloating severity (41.90% had no symptom) compared to bismuth and placebo groups (12.50 ,12.00% had no symptom) (p< 0.05). The frequency of borborygmus was significantly lower in the probiotic group after 2 and 4 weeks during the study compared to other groups (1.62±0.2 Vs 2.69±0.3, 2.45±0.3 ) (P= 0.010 and P= 0.013, respectively). According to our data, consumption of probiotics improves the frequency and severity of abdominal bloating and reduces borborygmus. Colloidal bismuth subcitrate also has significant effects.

Mixing properties of bi-disperse ellipsoid assemblies: mean-field behaviour in a granular matter experiment.

The structure and spatial statistical properties of amorphous ellipsoid assemblies have profound scientific and industrial significance in many systems, from cell assays to granular materials. This paper uses a fundamental theoretical relationship for mixture distributions to explain the observations of an extensive X-ray computed tomography study of granular ellipsoidal packings. We study a size-bi-disperse mixture of two types of ellipsoids of revolutions that have the same aspect ratio of α ≈ 0.57 and differ in size, by about 10% in linear dimension, and compare these to mono-disperse systems of ellipsoids with the same aspect ratio. Jammed configurations with a range of packing densities are achieved by employing different tapping protocols. We numerically interrogate the final packing configurations by analyses of the local packing fraction distributions calculated from the Voronoi diagrams. Our main finding is that the bi-disperse ellipsoidal packings studied here can be interpreted as a mixture of two uncorrelated mono-disperse packings, insensitive to the compaction protocol. Our results are consolidated by showing that the local packing fraction shows no correlation beyond their first shell of neighbours in the binary mixtures. We propose a model of uncorrelated binary mixture distribution that describes the observed experimental data with high accuracy. This analysis framework will enable future studies to test whether the observed mean-field behaviour is specific to the particular granular system or the specific parameter values studied here or if it is observed more broadly in other bi-disperse non-spherical particle systems.

Melatonin for prevention of acute kidney injury in patients treated with intravenous polymyxin B: a double-blind, placebo-controlled randomized clinical trial

ObjectivesTo evaluate the effect of melatonin versus placebo on the incidence of acute kidney injury (AKI) in patients treated with polymyxin B. MethodsWe performed a single-centre, double-blind, randomized clinical trial (NCT03725267) of 30-mg oral melatonin versus placebo for patients treated with intravenous polymyxin B. Patients aged ≥18 years receiving polymyxin B for ≤48 hours were eligible. Melatonin or placebo pills were administered until the end of polymyxin B treatment or for a maximum of 14 days. The main outcome was any level of AKI. ResultsEighty-eight patients were randomized: 44 in the melatonin group and 44 in the placebo group. The study ended prematurely because of polymyxin B shortage during the COVID-19 pandemic. The patients' mean age was 63.6 ± 17.3 years, and 60.2% of the patients were men. Forty-six (52.3%, 23 in each group) patients developed AKI during the follow-up period. The incidence rate of AKI was 81.9/1000 and 77.4/1000 patients per day in melatonin and placebo groups, respectively (hazard ratio, 1.09; 95% CI, 0.61–1.94; p 0.78). Renal failure and 30-day mortality were similar between the groups. Moreover, the incidence of AKI was not different in pre-specified sub-groups. DiscussionMelatonin initiated in the first 48 hours of therapy did not reduce the incidence of AKI in patients treated with polymyxin B.

The Efficacy and Safety of Zaoren Anshen Capsule in Combination with Zolpidem for Insomnia: A Multicentre, Randomized, Double-Blinded, Placebo-Controlled Trial.

Insomnia is the most common sleep disorder with high rate of prevalence, persistence, and leads to negative consequences. The mainstays of insomnia treatment have limitations due to either the side effects of hypnotics or limited accessibility to cognitive behavioral therapy. This study aims to compare the efficacy and safety of the traditional Chinese medicine (TCM) Zaoren Anshen capsule alone or as an adjunct treatment with different doses of the nonbenzodiazepine medication zolpidem tartrate in treating insomnia. This randomized, double-blind, multicentre placebo control trial was conducted in 131 patients with chronic insomnia. The patients were randomly assigned to one of the following four regimen groups: Group ZA + Z5 : Zaoren Anshen capsule and 5 mg zolpidem tartrate (n = 32); Group Z5: 5 mg zolpidem tartrate and placebo capsule (n = 35); Group Z10 : 10 mg zolpidem tartrate and placebo capsule (n = 32); Group ZA : Zaoren Anshen capsule and placebo pill (n = 32). The drugs were administered for 4 weeks. All patients were evaluated by the Insomnia Severity Index (ISI) at 0, 2, 4, 5, and 6 weeks, and adverse events were recorded. There are significant differences in the comparison between the four groups at each treatment stage (P < 0.05). Repeated measurement analysis of variance (ANOVA) of ISI scores in each treatment stage of the four groups exhibits significant differences in time effect, intergroup effect, and interaction effect (P < 0.05). After four weeks of drug administration, the treatment efficacy is similar in Groups ZA + Z5 and Z10 (93%) and in Groups Z5 and ZA (62% and 65%, respectively). Groups ZA + Z5 and Z10 present significantly lower ISI scores compared with Groups Z5 and ZA (P < 0.05), which indicates better treatment response of Groups ZA + Z5 and Z10. No significant difference was observed in the incidence of adverse events between the groups. Zaoren Anshen capsule can effectively treat insomnia disorder either alone or in combination with zolpidem tartrate. A preferred combination of TCM Zaoren Anshen capsule with zolpidem can provide a magnified therapeutic efficacy with fewer side effects than zolpidem-only management, clinical trial registration number: Chinese Clinical Trial Registry ChiCTR-IPR-1600969.

RF32 | PSUN65 Effect of Oral Contraceptive Medication on Blood Pressure, Plasma Renin, and Aldosterone Levels

Abstract Background Combination oral contraceptive medications may cause elevations of plasma renin activity and aldosterone levels. Clinical Case A 20-year-old female with a past medical history of chronic migraines and allergic rhinitis was referred to endocrinology for evaluation of secondary hypertension after she was found to have elevated renin levels by her primary care physician. The patient was noted to be hypertensive during a tonsillectomy 4 months prior and had also experienced an increased frequency of headaches prompting an evaluation for secondary hypertension and the initiation of lisinopril 10 mg daily. Her other medications included levocetirizine, biotin, and the combined oral contraceptive pill (OCP) norgestimate-ethinyl estradiol (0.25 mg/0.035 mg). Physical examination was remarkable for blood pressure 130/85mmHg, Pulse rate 77, BMI 30 kg/m2, pale striae on upper arms, lower back and abdomen, and a slight fat pad on the posterior nape of her neck. Initial lab results revealed normal plasma sodium, potassium, metanephrines and normetanephrines, plasma renin activity (PRA) 70.657 ng/mL/h (0.167-5.380 ng/mL/h), aldosterone 18.9 ng/dL (0.0-30.0 ng/dL), and 8: 00 amcortisol 30.3 mcg/dL (6.2-19.4mcg/dL). Doppler ultrasound and magnetic resonance angiography excluded renal artery stenosis and abdominal renin-secreting tumors. Owing to concern about OCP interference with the measurements of PRA and aldosterone levels, these tests were repeated at the end of a seven-day OCP placebo pills and biotin withdrawal. Lab results revealed: PRA &amp;gt;178 ng/mL/h, aldosterone 15.3 ng/dL, 1 mg overnight dexamethasone suppression test cortisol 1.1 mcg/dL, and 24-hour urinary cortisol 22.4 mcg/L (normal value &amp;lt;24mcg/L). Subsequently, the patient agreed to discontinue OCP and biotin and have labs redrawn 6 weeks later, which revealed PRA of 0.9 ng/mL/h and aldosterone of 5.9 ng/dL. Her blood pressure also normalized off the oral contraceptive and lisinopril was successfully discontinued. Conclusion This case report demonstrates the clinically significant impact of oral contraceptive medication on blood pressure, plasma renin activity and aldosterone levels. It's well known that oral contraceptives may cause elevations in PRA and aldosterone1 likely due to an upregulation of angiotensin mediated by the effect of ethinyl estradiol on the hepatocytes1, albeit not previously reported of the magnitude found in our patient. The extreme elevations of PRA and aldosterone in our patient suggested a diagnosis of either renovascular hypertension, renin secreting neoplasm or coarctation of aorta all of which were excluded. The subsequent normalization of blood pressure, PRA and Aldosterone off oral contraception×6 weeks confirmed that the OCP was the source of her hypertension and lab abnormalities. This case highlights the importance of identifying and omitting interfering medications when evaluating patients for secondary causes of hypertension. References Oelkers WK. Effects of estrogens and progestogens on the renin- aldosterone system and blood pressure. Steroids 1996;61: 166–71. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:36 p.m. - 12:41 p.m.

Associations between pituitary-ovarian hormones and cognition in recently menopausal women independent of type of hormone therapy

ObjectivesTo examine associations of pituitary-ovarian hormone levels with cognition before and after different formulations of hormone therapy (HT) or placebo independent of treatment group. MethodsRecently menopausal, healthy women were randomized to 0.45 mg/day oral conjugated equine estrogens (o-CEE, n = 109), 50 μg/day transdermal 17β (tE2, n = 107) or placebo pills and patches (n = 146); women on active treatment received oral 200 mg/day micronized progesterone for 12 days per month. Levels of estrone, 17β-estradiol, follicle stimulating hormone, luteinizing hormone, androstenedione, and testosterone were determined prior to and after 48 months of study participation. Neuropsychological testing was administered at baseline, and months 18, 36 and 48. Latent growth curve models controlling for education level, age, APOE allele status, waist circumference, and treatment examined the trajectories of each cognitive domain after accounting for the effect of hormone levels at baseline and months 18, 36 and 48. A linear multivariate mixed model examined the effect of changes in hormone levels on changes in trajectories of complex attention tasks with varying degrees of difficulty. ResultsAll women were adherent to treatment at month 48. Higher baseline estrone levels were associated with poorer global cognition, auditory attention and working memory, visual attention, and executive function, but not working memory. Higher levels of baseline 17β-E2 were associated with poorer cognitive performance, with marginal significance at baseline in speeded language and mental flexibility (p = 0.013). Other hormone levels were not associated with cognition. Controlling for all treatments, hormone levels at baseline and at month 48 did not have any significant correlation with cognitive trajectories over time. SummaryIn healthy, recently menopausal women, baseline estrone levels were inversely associated with selected cognitive factors independent of two types of HT or placebo during 4 years of follow-up. Baseline levels of the other pituitary-ovarian hormones studied were not associated with baseline cognition, nor were changes in any hormones associated with changes in cognition during the study. The marginal association between estradiol levels and cognitive factors warrants further investigation. ClinicalTrials.gov numbersNCT00154180, NCT00623311.

Comparing the efficacy of lycopene &amp; lycopene with hyaluronidase in management of oral sub mucous fibrosis-A clinical study

Oral submucous fibrosis (OSMF) is a scarring disease of the oral cavity that develops over time. Lycopene is a potent antioxidant found in tomatoes that has the best singlet oxygen quenching capability and a strong capacity to quench other free radicals in vitro of all the dietary carotenoids. A protein called hyaluronidase, which is found in mammalian sperm and testes, hydrolyzes hyaluronic acid to alter the permeability of connective tissue.To determine the effectiveness of lycopene and lycopenehyaluronidase in treating OSMF, as well as a comparison of their effectiveness.: 45 people with OSMF were enrolled in the study and divided into three groups. Patients in Group A received two evenly divided doses of Lycored 16 mg twice daily for three months. Patients in Group B received LycoRed and a 1500 IU intralesional injection of hyaluronidase twice a week for three months. Patients in Group C received placebo pills. The patients were evaluated at the end of three months. We observed the opening of the mouth, visual examination, palpatory findings, and burning sensation.For lycopene and lycopene–hyaluronidase combination, there was a statistically significant difference in mouth opening and burning sensation compared to placebo.

Placebo Effect in Randomized Trials of Major Depressive Disorder With Psychotic Features: A Systematic Review and Descriptive Meta-Analysis.

In the 1980s, the response rate of major depressive disorder with psychotic features (MDD-Psy) to placebo pills was reported to be close to 0%. To our knowledge, this placebo response rate has not been systematically reassessed. We undertook a systematic review of randomized controlled trials (RCTs) that have used a placebo or sham control group for MDD-Psy. We searched MEDLINE and identified 9 relevant publications reporting on 10 studies comparing a placebo or sham interventions versus an active intervention. We extracted reported rates of response or of dropout for all causes associated with placebo versus active intervention(s) and aggregated response and dropout rates across trials. Two sham-controlled electroconvulsive therapy (ECT) trials did not provide response rates. In the 3 pharmacotherapy studies published in the 1980s, 0 of 12 participants (0%) responded to placebo versus 13 of 38 (34.2%) responding to the active interventions. In contrast, 5 RCTs published in the 2000s, 114 of 339 participants (33.6%) randomized to placebo responded versus 149 of 373 participants (39.9%) randomized to active interventions; dropout rates were 71/236 (30.1%) for placebo versus 84/282 (29.8%) for the active interventions. As expected, response rates to placebo pills in RCTs for MDD-Psy increased markedly from the 1980s to the 2000s. Methodological issues in the design and conduct of more recent RCTs may have contributed to the high placebo response. However, one needs to consider this placebo response rate when interpreting the result of recent trials of MDD-Psy, which typically have not included a "pure" placebo condition.

Fluoxetine for non-arteritic anterior ischemic optic neuropathy: A double-blind, randomized clinical trial

Introduction: Fluoxetine raises the levels of BDNF (brain-derived neurotrophic factor). BDNF is known to improve neurogenesis and plasticity, so it seems to improve Anterior Ischemic Optic Neuropathy (AION). The goal of this study was to find out how Fluoxetine affects the clinical outlook of people with AION. Methods: In this double-blind, placebo-controlled, randomized clinical trial, patients with AION split into two groups: the fluoxetine group (n=50), which took 20 mg of Fluoxetine every day, and the control group (n=50), which took a placebo pill instead. Both groups were followed for six months. Before and after the trial, patients were given clinical and non-clinical evaluations. Results: 100 people took part in this study and were evaluated. Subjects in the Fluoxetine group had better visual acuity than those in the placebo group. They had lower scores on the LogMAR scale (P: 0.008 and 0.002), better MD parameters of perimetry (P: 0.003 and 0.002), and shorter VEP latencies (P (in 1st minute): 0.001 and 0.001, P (in 15th minute): 0.038 and 0.011. After the trial of Fluoxetine therapy, there were no changes in color vision, Rnfl in all dimensions, PSD parameter of perimetry, or VEP amplitudes (Ps&gt; 0.05. Conclusion: Fluoxetine showed promise as a therapy for people with AION, and it was safe to use as a treatment option in addition to corticosteroids