Participants in the active group received the 'pharmacist standard counseling' plus the 'pharmaceutical care service' designed by the research group. Both services were delivered by one female clinical pharmacist who has a Master's degree in pharmaceutical sciences, 5-year work experience in community pharmacies, and comprehensive knowledge of PCOS. The time it took to deliver the counseling and education to each participant in the active group was formally assessed. This time assessment excluded data collection and questionnaire filling time (which was planned to take around 15 min).
Participants in the active group received the usual care delivered at the community pharmacies plus the pharmaceutical care service designed by the research group and provided by the clinical pharmacist. The intervention was delivered via oral advice and recommendations, and written material, with a special focus on diet and exercise.

Participants in the control group received the usual care only which is the 'pharmacist standard counseling' involved dispensing the prescribed medication (delivered by the pharmacist in charge), counseling on how to take the dispensed medications, and a brief reply to questions if asked by the participants. The 'pharmacist standard counseling' followed what was normally delivered to females with PCOS by pharmacists working at community pharmacies in both countries. This 'pharmacist standard counseling' was established based on what was observed and reported by the project research team after viewing the usual pharmacists' interaction with females with PCOS for two weeks in each country before the start of the study.
Participants in the control group were informed that the educational intervention (the pharmaceutical care service) will be delivered to them after the end of the study (for ethical reasons).

Participants in the active group received the usual care delivered at the community pharmacies plus the pharmaceutical care service designed by the research group and provided by the clinical pharmacist. The intervention was delivered via oral advice and recommendations, and written material, with a special focus on diet and exercise.

Polycystic Ovary Syndrome

The intervention was provided in the format of oral plus written information. The information provided included the importance of exercise and motivational messages to exercise more at home or in the gym.
The 2nd part was about the importance of decreasing the stress levels. Participants were informed to perform a simple breathing exercise on daily basis twice a day.
The 3rd part aimed at improving participants' diets. They were informed to follow specific diet recommendations and to avoid certain types of food, explaining to them how it may negatively affect their PCOS condition.
The 4th part was about the PCOS treatment that was discussed with the participants. Females were advised on the importance of using their correct treatment. They were informed of the importance of adhering to their prescribed medications, accepting that it was a long-term treatment plan, and to consult with their specialist if their treatment was not effective, or in the case of medication side effects.

The PCOS pharmaceutical care service

Five branches of Pharmacy 1

Almazra pharmacy

Alwafaa pharmacy

Kinda Pharmacy

The Impact of a Pharmaceutical Care Model on Improving Polycystic Ovary Syndrome

The Impact of a Pharmaceutical Care Model on Improving Polycystic Ovary Syndrome Associated Factors Amongst Females in Jordan and Syria

Anxiety prevalence assessment using the Beck Anxiety Inventory. The BAI scale, consisted of 21-multiple-choice questions, with 4-point scale indicating the degree of anxiety severity (0-3; all questions were scored positively). Points were summed to produce a total measure score, indicating four levels of anxiety severity: 0-7 reflecting minimal level of anxiety, 8-15 reflecting mild level of anxiety, 16-25 reflecting moderate level of anxiety and 26-63 reflecting severe level of anxiety. The possible score for each participant ranged from 0 to 63. Lower scores indicated better anxiety symptoms.

Depression prevalence assessment using the Beck Depression Inventory. The BDI is a 4-point scale (0-3) indicating the level of depression severity, with the score referring to six levels: 0-10 indicating the ups and downs reported by the participant were normal, 11-16 reflecting mild mood disturbances, 17-20 reflecting borderline clinical depression, 21-30 reflecting moderate depression, 31-40 reflecting severe depression, and over 40 reflecting extreme depression. The possible score for each participant ranged from 0 to 63. The BDI Questionnaire evaluates pessimistic attitude, loss of appetite, sad mood and feelings of guilt. Lower scores indicated better depression symptoms.

Levels of Anxiety severity and mean score assessment were done by the Beck Anxiety Inventory.
The BAI scale, consisted of 21-multiple-choice questions, with 4-point scale indicating the degree of anxiety severity (0-3; all questions were scored positively). Points were summed to produce a total measure score, indicating four levels of anxiety severity: 0-7 reflecting minimal level of anxiety, 8-15 reflecting mild level of anxiety, 16-25 reflecting moderate level of anxiety and 26-63 reflecting severe level of anxiety. The possible score for each participant ranged from 0 to 63. Lower scores indicated better anxiety symptoms.

Levels of Depression severity and mean score assessment were done by the Beck Depression Inventory.
The BDI is a 4-point scale (0-3) indicating the level of depression severity, with the score referring to six levels: 0-10 indicating the ups and downs reported by the participant were normal, 11-16 reflecting mild mood disturbances, 17-20 reflecting borderline clinical depression, 21-30 reflecting moderate depression, 31-40 reflecting severe depression, and over 40 reflecting extreme depression. The possible score for each participant ranged from 0 to 63. The BDI Questionnaire evaluates pessimistic attitude, loss of appetite, sad mood and feelings of guilt. Lower scores indicated better depression symptoms.

Quality of Life assessment using the polycystic ovary syndrome health-related QOL questionnaire (PCOSQ).
It has a 30 questions about symptoms related to menstruation and mood. It can identify seven factors affecting the QOL in PCOS women including: emotional disturbance, hirsutism, weight concerns, infertility, menstrual symptoms, menstrual predictability and acne. The QOL was analyzed individually as a continuous scale out of seven to assess the QOL in patients (the higher the score is, the better the QOL is). After that, each question of the 30 questions included in the PCOSQ questionnaire was analyzed, and the mean score within each question was obtained and compared between baseline and follow-up. After that, each domain included in the QOL questionnaire was analyzed individually. Mean score of each domain was obtained and compared between baseline and follow-u to assess the impact of lifestyle modifications on that domain.

Systolic and diastolic blood pressure measurements were measured using the right arm, twice after a 10-min rest and averaged by using the gold standard, mercury sphygmomanometers

Blood Glucose levels assessment using the Multi-parametric device.

Blood Cholesterol levels assessment using the Multi-parametric device.

Blood Triglycerides levels assessment using the Multi-parametric device.

the Body Mass Index was calculated for each participant depending on their weight and hight.

smokers participants recorded the number of cigarettes smoked per day.

Applied Science Private University

Participants in the active group received the usual care delivered at the community pharmacies at both countries plus the pharmaceutical care service designed by the research group and provided by the clinical pharmacist, an experienced female with extensive knowledge on PCOS. The intervention was delivered via oral advice and recommendations, and written material, with a special focus on diet and exercise. Participants in the control group received the usual care only and did not receive the pharmaceutical care service.
Following the intervention, both groups were followed up for four months and re-interviewed at the community pharmacy.

The study is a single-blinded randomized controlled trial. The patients 'study groups were only known for the clinical pharmacist.

Following baseline microcirculatory and blood pressure measurements, as well as the collection of urine and saliva samples, participants on the "beetroot" group were asked to consume 140ml beetroot juice (James White Drinks Company, Suffolk, UK). The 140 ml of beetroot juice equate to approximately 8.4 mmol of NO3- .

Following baseline microcirculatory and blood pressure measurements, as well as the collection of urine and saliva samples, participants on the "placebo" group were asked to consume 140 ml nitrate-depleted beetroot juice (James White Drinks Company, Suffolk, UK).

Aging

Drink consumption was followed by regular BP measurements and collection of saliva samples every 30 minutes for four hours. Microcirculatory measurements were then repeated and saliva and urine samples were collected again.
After the last measurement subjects were provided with a standardized meal with a very low nitrate intake to eat within 30minutes. Participant then left the research centre and they were asked to collect a saliva sample after two hours from the completion of the meal. This was immediately followed a dose of labelled nitrate (4mg in 100ml of distilled water) to drink within one minute. Subjects were then asked to collect six additional saliva samples until the next morning (four before going to bed and two in the morning), accompanied by measurements of resting BP.
Cross-over assessments were then repeated in the same order at Visit 3, followed a wash-out period of at least one week before entering the second arm of the study.

Crossover intervention

Exploring the Effect of Inorganic Nitrates on the Human Microvascular Physiology - a Pilot Study.

Non-invasive laser Doppler flowmetry (LDF) measurements (Periflux 5000 System, Perimed, Sweden) will be used as an index of cutaneous (microcirculatory) function and red blood cell flux. To obtain a measure of microcirculatory, NO-dependent, endothelial-function (26) measurements will be taken once at Visit 1 and twice (prior to and 3 hrs. after beverage ingestion) on Visits 2 and 3, using thermal hyperaemia. For this, four 7-point integrating probes (Model 413, Perimed) housed within local heating units (Model 455, Perimed) will be placed on the ventral aspect of the left forearm. The heating units will be initially set at 33 °C. After a 10-min baseline recording, the temperature of the heating unit will then be increased to 42 °C at a rate of 1 °C every 10 seconds to obtain maximum skin blood flow; this (i.e., a stable plateau in skin blood flow) is usually observed after approx. 25 minutes of localised heating.

Resting BP sure will be recorded intermittently throughout the test using an automated system (Dinamap Dash 2500, GE Healthcare. Duplicate measurements of BP wil be performed covertly and only showed to the participant at the end of the study visit. Before each measurement participants will be invited to rest in a sitting position for at least 15 minutes.

Nitrate reductase activity will be investigated by evaluating the differences in salivary nitrite concentrations according to a validated method. Briefly, ten millilitres of a solution of potassium nitrate in distilled water will be held in the mouth for 5 min and then collected. Background levels of nitrate reduction were estimated by subtracting values obtained from holding distilled water alone in the mouth. NO3- and NO2- concentrations will be measured by chemiluminescence.

A non-invasive stable isotopic method will be used to assess whole-body NO production (ONT Method). Subjects will receive an oral dose of labelled sodium nitrate in 100ml of distilled water (4mg Na15NO3) and the isotopic decay of the tracer in saliva samples will be used to derive estimates of NO production. Nitrate concentrations will be measured by chemiluminescence. Nitrate enrichments will be measured using Gas Chromatography Mass Spectrometry (GCMS).

Mid-stream urine samples will be collected into sterile containers and an aliquot and will stored at -80 ⁰C until analysis at a later date. Saliva will be collected into sterile eppendorfs and stored at -80 ⁰C until analysis at a later date. Both salivary and urinary samples will be used for NO3- and NO2- measurements. Saliva samples will also be used to assess isotopic enrichment of labelled NO3- as previously described. Sodium hydroxide will be added to urine and saliva samples to avoid nitrate degradation.

Due to ethical approval restrictions there were no plans for IPD available to other researchers.

Sheffield Hallam University

University of Sheffield

University of Nottingham

Patients switch from taking warfarin in the evening to taking warfarin in the morning.

Patients continue taking warfarin in the evening as per their usual routine.

Atrial Fibrillation

Thrombus Due to Heart Valve Prosthesis

Deep Venous Thrombosis

Thromboembolism

Warfarin

University of Alberta

Vancouver Coastal Health Research Institute

The Effect of Medication Timing on Anticoagulation Stability in Users of Warfarin: The "INRange" RCT

Our primary outcome, percentage change in time spent OUTSIDE of therapeutic range is chosen because we believe this is a measure more likely to be shared by patients across a wide range of TTR (i.e. a patient with high baseline TTR and a patient with low baseline TTR may still share a similar % change in time outside of therapeutic range as a response to our intervention). This would not be true for change in TTR itself. It is also the time spent outside of range which contributes more directly to risk of thrombosis and hemorrhage and hence the change in this measure is more clinically meaningful than the change in TTR itself.

The percentage of patients with TTR > 75% provides the percentage of patients considered to have excellent control.

The percentage of patients with TTR < 60% provides the percentage of patients for whom other anticoagulation strategies may be indicated.

Includes all-cause mortality, hospitalization for stroke, hospitalization for GI bleeding, and deep venous thrombosis / pulmonary embolism.

For those patients with at least one INR value above the therapeutic range, the maximum INR observed.

For those patients with at least one INR value below the therapeutic range, the minimum INR value observed.

Includes non-hemorrhagic stroke, deep vein thrombosis, pulmonary embolus and acute arterial occlusion

Includes all bleeding events requiring hospitalization such as hemorrhagic stroke and GI bleeding

Patient self-reports of adherence to their allocated intervention during telephone follow-up occurring at 1 week, 1 month and upon study completion

Upon publication of all planned manuscripts stemming from this work, anonymized patient level trial data will be posted on www.PragmaticTrials.ca

spinacia oleracea/heilablóðfall

The Impact of a Pharmaceutical Care Model on Improving Polycystic Ovary Syndrome

Exploring the Effect of Inorganic Nitrates on the Human Microvascular Physiology - a Pilot Study.

The Effect of Medication Timing on Anticoagulation Stability in Users of Warfarin: The "INRange" RCT

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