Sunday, January 19, 2020

Influence of Physical Activity on the Quality of of Breast Cancer Patients

Influence of Physical Activity on the Quality of of Breast Cancer Patients 

Abstract

Introduction: Breast cancer is the most common neoplasm among women. As a consequence of the increased number of cancer diagnoses, and concomitant mortality reductions for most types of cancer many patients live with physical and psychosocial problems associated with the disease and its treatment that may compromise their quality of life (QoL). Exercise has been recommended as part of standard care for patients with cancer to help prevent and manage physical and psychosocial problems and improve QoL. The objective of the current study was to compare the impact of physical activity practice in women with breast cancer, through indicators of quality of life.
Methodology: This is a randomized study with breast cancer patients in a large general hospital in southeastern Brazil. The questionnaires were applied regarding function and quality of life (EORTC QLQ-C30 and BR-23). Patients were randomly allocated into two groups: control, without intervention and treatment group, with the practice of physical exercises and nutritional orientation. Physical activity was performed for 3 hours/ week through active-assisted exercises of flexion, abduction, extension, and rotation of upper limbs and treadmill walking at speed tolerated by the patient. After six months of participation, all patients were reassessed, with blindness of the investigator. Results: The study did not reveal statistical difference in the constructs cited (p> 0.05) between the control group and the treatment group regarding "Global Health Status” " Functional Scale” and " Scale of Symptoms ", however the patients in physical activity presented better mood and confidence being more adapted to face the challenge of the disease.
Discussion: The practice of physical activity showed no benefit in improving quality of life and functional capacity in patients with breast cancer in the evaluation by questionnaires in a short period established, however, showed favorable trends for improvement in successive evaluations.

Introduction

Worldwide, there will be about 2.1 million newly diagnosed female breast cancer cases in 2018, accounting for almost 1 in 4 cancer cases among women. The disease is the most frequently diagnosed cancer in the vast majority of the countries [1]. Longterm survival rates after a diagnosis of breast cancer are steadily rising. This is good news, but clinicians must also recognize that this brings new challenges. Survivors of breast cancer represent a unique group who must be cognizant of the long-term side effects of their treatment protocols and be given information to encourage a proactive approach to their overall health [2]. The treatment can lead to changes in a woman's self-image and functional loss as well as psychological, emotional and social alterations. Such alterations in women that have undergone treatment for carcinoma of the breast can be quantified on a quality of life scale. Quality of life assessment is considered to be an important patient reported outcome reflecting treatment, effectiveness, success. The patient experiences represent one of the most important therapeutic goals and a primary end point in many modern clinical studies [3]. It is believed that determination, fortitude, and optimism can override the biologic effects of a malignant disease and can improve survival [4,5].
Some valid studies by responsible investigators clearly show an enhanced survival among subsets of patients with breast cancer who attended a weekly group support program in contrast with persons with similar prognoses who acted as the control group. Although, few consistent studies definitely verify that a positive attitude will affect the overall course of malignant disease, quality of life can be meaningfully enhanced when patients are appropriately optimistic and realistic about their illness [6]. Breast cancer has been recognized as a chronic disease. This reflects efforts about the early diagnosis and improvement of the proposed treatments. Breast cancer survivors represent a unique and extremely complex group of patients, who experience the side effects of the proposed treatment protocols, which are aggravated by pre-existing comorbidities at the onset of breast cancer treatment [2]. The survival rate of women with breast cancer has increased in the last two decades due to improved early diagnosis and increased possibilities for more effective treatment. This treatment success, however, increases the risk of cardiovascular disease that depends on the therapies, the stage of the disease and the time of diagnosis [2].
A protective effect of physical activity in the pathogenesis of breast cancer is well established [7]. The protective mechanisms of physical activity in breast cancer survival are, however, less documented; the evidence indicates that survival is improved by promotion of cardiovascular health and preventing over- weight [8]. Until very recently the specialists discouraged oncological patients to practice physical activity, believing that this is not a safe practice considering the health condition of these patients. In 2009, the American Cancer Society (ACS) convened a panel of experts and created a Guideline for the practice of physical activity in cancer patients, among these women with breast cancer. ACS has shown to be safe the practice of physical activity in women with breast cancer, even in the presence of chemotherapy, radiotherapy and hormonal therapy [9].
The Guideline states that exercise training should improve physical function, bone mineral density, homolateral shoulder mobility to surgery, hemoglobin levels, psychological effects such as self-esteem and mood. Exercises should decrease the symptoms and side effects of chemotherapy and radiation therapy. The exercise should be prescribed respecting the capacity of each woman, staging of the disease and the time of evolution of the disease. It should be performed 150 minutes of moderate activity or 75 minutes of vigorous or intense activity per week [9]. Studies that demonstrate the efficacy of physical activity are heterogeneous and are inconclusive about the type of exercise, whether stretching, aerobic exercises, or resistance exercises. [10]. Directly receiving an orientation regarding physical activity does not imply a change of habit or even adherence to the practice of exercises. The exercise prescription must respect the disabilities presented by each woman. It must be individualized, within the functional capacity of each patient, observing muscular strength, cardiovascular capacity, loss of range of motion and presence of comorbidities. Adherence to the exercises is not always satisfactory and depends on a qualified professional who accompanies and encourages these women to practice exercises. The objective of the current study was to compare the impact of physical activity practice in women with breast cancer, through indicators of quality of life.

Patients and Methods

This is a randomized study with breast cancer patients in a large general hospital in southeastern Brazil. Patients were randomly allocated into two groups: 26 in control, without intervention and 24 in treatment group, with practice of physical exercises. Physical activity was performed for 3 hours / week through active-assisted exercises of flexion, abduction, extension and rotation of upper limbs and treadmill walking. Physical activity was individualized within the functional capacity of each patient, observing muscular strength, cardiovascular capacity, loss of range of motion and presence of comorbidities. The study was approved by the research ethics committee. Written informed consent was obtained from the patients, and they were assured that their treatment would not differ in any way from the pre-existing standard of care in the institution. The questionnaires were applied regarding Quality of Life Questionnaire (EORTC QLQ-C30 and BR-23). The EORTC QLQ-C30 (hereafter, QLQ-C30) is a popular instrument for measuring the general cancer quality of life, and it is used internationally.
The QLQ-C30 includes 30 items and is composed of 15 multiitem scales or quality of life domains that evaluate functioning, symptoms and overall health (2 items). The functioning scales include physical (5 items), emotional (4 items), cognitive (2 items), role (2 items) and social functioning (2 items). The symptom scales measure nausea and vomiting (2 items), fatigue (3 items) and pain (2 items) and 6 single items assessing financial impact and various physical symptoms. Most of the 30 items have 4 response levels (not at all, a little, quite a bit and very much), with 2 questions that address overall health with 7 response levels (on a scale from very poor to excellent). All of the scales and single-item measures were scored according to the standard scoring rules identified in the EORTC QLQ-C30 Scoring Manual. The principles for scoring these scales are the same in all cases. First, we estimate the average of the items that contribute to the scale; this is the raw score. Second, we use a linear transformation to standardize the raw score, so that the scores range from 0 to 100. Higher functional scale scores represent better functioning, but higher symptom scores indicate worse symptoms [11].
The EORTC QLQ-BR23 (hereafter, QLQ-BR23) [12] is a breast cancer module of the EORTC QLQ and is developed for use among breast cancer patients varying in disease stage and treatment modality (i.e., surgery, chemotherapy, radio- therapy and endocrine treatment). When employed in conjunction with the QLQ-C30, the use of the QLQ supplementary modules, including QLQ-BR23, can provide more detailed information relevant to evaluating the QOL in specific patient populations. It includes 23 items composed of 4 functioning scales [i.e., body image (4 items), sexual functioning (2 items), sexual enjoyment (1 item) and future perspective (1 item)] and 4 symptom scales [systemic therapy side effects (7 items), breast symptoms (4 items), arm symptoms (3 items) and upset by hair loss (1 item)] The scoring approach is identical in principle to that for the function and symptom scales and the single items of the QLQ- C 30. After 6 months of participation, all patients were reassessed, with blindness of the investigator.

Results

The study did not reveal statistical difference in the constructs cited (p> 0.05) between the control group and the treatment group regarding "Global Health Status " and functional scales however the patients in physical activity presented better mood and confidence being more adapted to face the challenge of the disease. The practice of physical activity didn't show benefit in improving quality of life in patients with breast cancer in the evaluation by questionnaires in a short period established, however showed favorable trends for an improvement in successive evaluations. There was no statistical difference in the construct symptom scale in the treatment group (p = 0.065) but there was a slight difference in the control group over time (p = 0.048). Table 1. Regarding the instrument of QOL BR- 23, in both control and treatment groups, there was no difference in functional scale from time 1 to time 2 (After 6 months). On the symptom scale, there was no statistical difference in the treatment group, but there was a difference in the control group (p = 0.037). Within the symptom scale, the highest score has more symptoms, means worse health status.
Through the generic instrument of QLQ-C30, in the treatment group the symptoms improved over time. On the QLQ BR-23 specific instrument, the symptoms worsened over time. There was therefore no difference between the control and treatment groups, but the specific symptoms of breast cancer, such as Systemic therapy side effects, Arm Symptoms, Upset by hair loss remained over time and were statistically relevant.

Discussion

The practice of physical activity has been advocated by the academic community as an essential practice in the survival of women with breast cancer. The benefits of exercise reduce the deleterious effects of proposed treatments, such as cardiotoxicity and even have a positive effect on comorbidities. We have to think not in the woman with breast cancer, but in the woman, who survived breast cancer [2]. Patients were invited to participate in a group of exercises once a week supervised by physical therapy and are encouraged to exercise for at least two more hours throughout the week, totaling 150 minutes of aerobic physical activity as recommended per the American Cancer Society guidelines [13]. Guiding and trying to include the practice of physical activity in the lives of these women is not an easy task, it requires a lifestyle change, which is mediated not only by environmental factors or linked to illness, but also to personal factors. Barriers to physical activity practice need to be assessed and discussed, and a qualified professional for the prescription and orientation of the exercise is still required, which should be individualized [14].
The literature has shown that physical activity plays a fundamental post-treatment role in breast cancer, decreasing mortality rates and recurrence of the disease in these women. The autonomy of the subject is constantly encouraged [15,16]. The results of present study did not show benefit in improving quality of life in patients with breast cancer in the evaluation by questionnaires in a short period established. Bjoneklett, (2012) also did not found no difference between the support group and the control group regarding quality of life. A total of 392 patients were divided into two groups: one control group and another intervention group. This intervention group received orientation, relaxation training and mental visualization exercises. However, both groups showed improvement of symptoms and fatigue over time [17]. In this study it was possible found favorable trends for an improvement in successive evaluations because the team realized that the patient who has adherence, participation in the support group, shows more safety, acceptance and more serenity throughout her treatment, equal the results found in other researches that reinforces the difficulty that health professionals have to demonstrate the beneficial effect of the support group over time (Table 2) [17].
Many women with breast cancer will not die from cancer but from comorbidities such as obesity, hypertension, hyperlipidemia and diabetes mellitus, diseases that will affect the disease-free survival of these women. Breast cancer survivors should be instructed to recognize the long-term side effects of the treatments.They are subjected to be encouraged to healthy lifestyle habits and lifestyle changes that have as pillars the practice of physical activity and healthy eating [2]. The change in lifestyle and the participation and responsibility opens the hope for a new concept of health. Health is not just absence of disease and have normal tests. Be health calls for a deepening of philosophy, self-knowledge, psychology and the attitude of being open to new ways of perceiving reality. It is important to set goals in life, to have time in addition to working, doing physical activity, playing, laughing, having fun, finding friends and get emotional support, allowing situations that give pleasure, seeking a true meaning for life.
However, how to do it is a difficult task, sensitizing these women to healthy lifestyle habits like exercising or eating healthy, is a challenge to be overcome. Healer is a total-health approach to wellness that includes treating the mind, body, and spirit of a patient with breast cancer. Our long-term goal is to help patients with breast cancer under-stand the importance of energy balance. By helping patients with breast cancer achieve healthy weight and healthy biometrics, we can maximize their chances for long-term survival [2]. The practice of physical activity has been advocated by the academic community as an essential practice in the survival of women with breast cancer. The benefits of exercise reduce the deleterious effects of proposed treatments, such as cardiotoxicity and even have a positive effect on comorbidities. We have to think not in the woman with breast cancer, but in the woman, who survived breast cancer.

Powder Injection Molding - An Excellent Micromanufacturing Process to Produce Low-Cost Zirconia Dental Implants and Abutments https://biomedres01.blogspot.com/2020/01/journals-on-biomedical-engineering_16.html

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Effect of Light Emitting Diodes (LED) with 430-480 nm Wavelength Upon Tooth Movement

Effect of Light Emitting Diodes (LED) with 430-480 nm Wavelength Upon Tooth Movement 

Abstract

Objective: To evaluate whether light emitting diodes (LED) curing light had any effect upon orthodontic tooth movement.1
Material and Methods: Randomization, split mouth technique and double-blind trial was performed in 20 adults, Angle's Class I or II, patients. Canine retraction into upper first premolar extraction using Niti coil spring was performed. Either LED (3M Elipar S10 with intensity of 1200 mW/ cm2 wavelength range 430-480 nm) was applied every 3 weeks or placebo on control side. Three digital panorex were taken with calibrated wire at the start of retraction and after retraction every 9 weeks interval. Measurement of canine tooth movement was done by synapse program on digital panorex and rate of canine tooth movement was gathered at the end of phase 1, phase 2 and total time (18 weeks). Rate of tooth movement, canine angulation changes and score of pain level were contrasted using matched paired T test.
Results: Average rate of canine tooth movement for LED VS. control group; in phase I was 0.32 and 0.33 mm/week, in phase 2 was 0.25 and 0. 22 mm/week, and in total time was 0.28 and 0.27 mm/week respectively. In all 3 phases there were no statistical difference in the rate of canine movement or canine angulation change between the LED and control groups. VAS pain score revealed that patients were more sensitive on the LED side than control side.
Conclusion: LED light with 430-480 nm wavelength could not accelerate the rate of canine tooth movement into extraction site.
Keywords: Randomized Clinical Trial; Light Emitting Diodes; Led Curing Light; Accelerated Tooth Movement; Orthodontics

Introduction

Two basic ways to reduce the orthodontic treatment duration or accelerating orthodontic tooth movement (AOTM) could be classified into 2 categories;
    a) Surgical invasive method and
    b) Non-surgical invasive method [1] The invasive procedures were associated with postoperative morbidity and harmful effects on periodontal tissues; thus the patient's acceptance of the procedure was low.
Non-invasive method seems to be a more promising technique because it provided many advantages, for example, easy access, better experience for patients, without surgical complications. These techniques include; electrical currents [2] resonance vibration [3] pulsed electromagnetic fields [4] pharmacological approaches [5] and Photo biomodulation [6, 7]. photo biomodulation is a system using various light sources either lasers or light emitting diodes (LED) with different parameters (wavelength, output power, continuous wave or pulsed operation modes, pulse parameters) to stimulate natural biological processes in order to reduce treatment time [8]. Light in the red to near infrared wavelengths around 6301000 nm have been found to be the best penetration into tissue and activates intra-cellular signaling mechanisms [9] The mechanisms may include
    a) Activation of mitochondrial photo acceptor molecule; cytochrome c oxidase to increase ATP production, nitric oxide and very low levels of reactive oxygen species [9-11] or
    b) Capillary dilatation to increase blood flow and osteoclastic activity [12]
Compared to lasers, LEDs are non-coherent, safer, and less expensive. So far, there were only a few clinical studies about LEDs inducing AOTM. Most of them used LED devices developed by Biolux research, Canada. There were mainly 2 types of devices
    a) Extra-oral type [7, 11, 13] and 2) Intra-oral type [14] Wave length of 850 nm with the energy intensity ranging from 6.92 J/cm2 to 24 J/cm2 was used by 3 studies who used extraoral device [7, 11, 13] and 9.3 J/cm2 using intra-oral device [14] AOTM by LED light is non-invasive treatment and less aggressive than Laser. If this method can really accelerate OTM, it might be recommended for orthodontic practices. However, the results of AOTM of these reports were contradicting. Three studies reported significant positive results [7, 11, 14] while Chung et al [13] found no significant result for AOTM in retraction phase using extra-oral device. However, equipment to generate the light in red to near infrared range (630-1000 nm) was not practically used in dental clinic due to high cost and evidence is still insufficient. Recently, the situation was even more confusing because there were some dentists talking about using LED curing light to accelerate OTM. So far, there was no study reported about using low wave length of the blue light for AOTM. Our research question was related to the effect of LED curing light upon orthodontic tooth movement. The objective of this randomized controlled trial study was to compare the rate of canine tooth movement into upper first premolar extraction case between the intraoral LED curing light with 430-480 nm wavelength and the control groups.

Materials and Methods

Prior to participant recruitment, this trial was reviewed and approved by institutional Review Board (IRB). Certificate of approval was granted by Faculty of Dentistry/ Faculty of Pharmacy, ### University: COA.No.MU-DT/PY-IRB 2016/011.1102. Our clinical study comprised 2 parts as follows.
    LED heat test: In order to ensure patient safety, LED light curing unit (3M Elipar S10) with intensity of 1200 mW/cm2, wavelength range of 430-480 nm was tested for heat generated at specific distance of 0, 3, 5 mm and at duration of 5, 10, 15, 20 seconds by using digital thermometer ( Thomas Scientific Inc, USA) The changing temperature was measured 3 times per distance and average values were calculated.

Canine Movement Randomized Clinical Trial

Clinical Registry: Our research was granted clinical registry reference number: ISRCTN96521746 by the International Standard Randomised Controlled Trial Number. Twenty-one volunteers were recruited from the Orthodontic clinic of ### University according to IRB protocol.
a) Inclusion criteria
Adult patients age ≥18 years old
Angle's Class I or II, with upper anterior teeth proclination and protrusion
Crowding less than 2 mm.
Treatment required full fixed edgewise appliance therapy of all permanent teeth, with bilateral symmetrical extraction of upper first premolar teeth.
    b) Exclusion criteria
    i. Presence of systemic illnesses or bone diseases.
    ii. Current exposure to any medical or dental condition that could potentially affect study results such as using of bisphosphonates
    iii. Pregnancy
    iv. Patients planning to relocate or move during the treatment period
Participants were informed of the study design and were also asked to provide written consent.

Sample Size Calculation

Based on results of previous study by Ekizer et al. 11using the following data
Group 1: Mean (M): 1.37 / Standard deviation (s):0.79 / Sample size (n):20
Group 2: Mean (M): 1.13/ Standard deviation (s):1.11 Sample size (n):20
The effect size: Cohen's d = (1.13 - 1.37) / 0.963379 = 0.25
Standard Deviation of the CHANGE in the outcome S(Δ) = 0.4
(calculated from standard deviation =0.79/ within-subject correlation of the outcome = 0.87) The sample size was determined by two dependent means (σ=0.25, Δ =0.4, α=0.05, P=0.2)
Group size N calculated for paired T-test is equal to 20

Randomization

Randomization using random number table and split mouth technique were used to allocate the side of the maxillary teeth (left and right sides) to be the LED or the placebo sides. The protocol is presented in CONSORT diagram (Figure 1). Double trial-blind method was used. One researcher (CU) controlled the assignment of the LED and placebo and the allocation concealment of the LED and placebo side. The LED probe was covered with a foil sheath in placebo side, however the foil sheath at the end of probe was left exposed in LED side. The operator (NV) used LED protective eye-glasses to prevent identification of the method used.

Orthodontics Protocol

The full arch set-up using pre-adjusted edgewise appliances 0.022 x 0.028 slot (MBT™, 3M Unitek, USA) was the same on both the LED and placebo sides. Four weeks after initial aligning and leveling, bilateral first premolars were extracted. Anchorage was prepared by ligation of second premolar, first and second molars. The maxillary canines were retracted distally 0.016 x 0.022 SS. A light NiTi closed coil spring ligating between canine and first molar was used to retract each canine posteriorly to give an initial force of 200 grams as measured by orthodontic tension gauge (Figure 2). The force was activated every 6 weeks by reactivating the spring tension to 200 g setting.
Figure 2: Canine retraction using NiTi closed coil spring.
A. LED application on buccal side.
B. LED application on palatal side.

LED Protocol

Canine on 1 side was subjected to LED intervention while the other side (No LED) was used as placebo control. The LED dental curing light device (Elipar™ S10, 3M ESPE, USA) with energy output 1200 mW/cm2, Energy intensity 6 J/cm2, wavelength range 430- 480 nm was used. Dental curing lights was tested using radiometer for determining the light intensity prior to light application. LED application was made around canine root 6 points buccally and 6 points lingually, 5 seconds per point at distance 3 mm from gingiva (Figure 2). LED was applied every 3 weeks for 7 times. LED curing light characteristics are presented in Table 1.

Radiographs Protocol

At the first Orthodontic record and treatment plan, participants had x-ray panoramic, lateral cephalometric and full mouth parallel radiographs taken. During research, digital panoramic radiographs was recorded 3 times. First time, at the start of canine retraction and then every 9 weeks later. Calibrated measuring wires of 15 mm. in length were ligated to brackets on both sides prior to radiographs taken. These calibrated measuring wires would be used to adjust for magnification distortion inherent in panoramic films. The rate of canine tooth movement was gathered for 3 intervals; phase 1 (3-12 weeks), phase 2 (12-21 weeks and total time (3-21 weeks). Operator performed blinded assessment of canine tooth movement, not knowing the side of LED nor Placebo. Digital measurements was carried out using the Synapse program (PACSDTMU, version 1.0, Fujifilm, Tokyo). The measurements included
    a) Distance between distal aspect of canine bracket to mesial aspect of first molar bracket.
    b) Canine tooth axis angulation to palatal plane was measured in order to determine type of canine tooth movement. Calibrated measuring wires was used to adjust for the actual distance of canine movement from digital panoramic radiograph. Rate of canine tooth movement per week was then calculated using the below formula (Figure 3).
Figure 3: Measurement of canine tooth movement and tooth angulation from digital panoramic radiograph using Synapse program.

Complications of Treatment

Parallel films and Electric pulp vitality testing (EPT) were taken before and after treatment to identify root resorption and pulp vitality [15] Classification of root resorption was based on the method used by Levander and Malmgren classification in 1988 [16] The grading of root resorption could be classified as
Grade 1 = minimal resorption (irregular apical contour), Grade 2 = moderate (< 2 mm), Grade 3 = severe resorption (> 2 mm < 1/3 root) and Grade 4 = extreme resorption (> 1/3 root).

Pain Assessment

Every visit, after application of LED curing light for 7 times, the volunteers were asked to rate their pain level in LED side and control side by using numerical rating scale (NRS) sheet with scores 1-10 (0 = no pain, 1-3 = mild pain, 4-6 = moderate pain, 7-10 = severe pain). Summary of overall treatment protocol and method of data collection are presented in Table 2.

Complications

Apical root resorption of retracted canine and tooth vitality was evaluated before and after treatment. Results found that there was no canine root resorption in all teeth except two teeth (one in LED side, the other in control side) which showed Grade 1: minimal resorption and all teeth were vital (positive to EPT test).

Pain Assessment

Pain score of LED group was significantly higher than placebo group. LED side had significant mean NRS pain score (3.29±1.8) more than control side (0.59±0.61). In LED side, participants gave high pain score at 1-3 visits of LED application. In control side participants mostly gave higher score at first visit of LED application and decreased gradually after that.

Power of Test Calculation

Using the following values for paired data sample type in the online website [18]
Sample size = 20
Effect size was assessed as:
μ1 = mean of total time LED group
μ2 = mean of total time Control group
σ2 = common error variance = 0.01
2 sided test
Significance level = 0.05 The power achieved was 0.98

Reliability Test

    a) Excellent agreement (95% CI) was demonstrated for all groups as follows calibrated measuring wires with ICC = 0.875
    b) Distance of tooth movement with ICC = 0.893 and
    c) Angulation measurement with ICC = 0.948

Discussion

This study utilized the application of intra-oral LED curing unit (430-480 nm wavelength, 1,200 mW/cm2, 6 J/cm2) over gingival tissue of upper canine retracted into first premolar extraction site. The protocol of this LED application was 5 seconds per spot, 12 spots per tooth with frequency of once every 3 weeks. The results showed that this LED application did not have any effect upon the rate of canine movement. The methodology of our study was unlike other LED studies in several aspects (Table 4). Firstly, the wave length was shorter (430-480 nm) compared to other studies (618-850 nm). Our LED was in the range of blue light while other studies was in the range of red light [7,11,13,14]. The blue light has a shorter wave length, with higher energy but scatters more easily than other visible light [19]. This fact could be demonstrated by the energy output of LED used in our study was 1200 mW/cm2 while the LED of other study using the red light had a lower energy output of 20-150 mW/cm2 [7,11,13,14].
Other differences of our LED protocol compared to previous studies were as follows.
    a) Our study applied less frequent LED exposure (7 times in 4 month) while other studies demanded daily application by patients.
    b) We used shorter exposure time of only 5 seconds while other studies required exposure of 20 - 60 minutes per day The reason of shorter exposure time was due to the greater heat generated by our LED device. It should be noted that Shaughnessy et al [14] who used intra-oral device of red-light LED had the application time of only 5 minutes per arch per day
    c) LED exposure in our study was intra-orally while most other studies used extra-oral device and applied LED via soft tissue cheeks [7, 11] It might be interesting to note that the intra-alveolar energy intensity (0.92- 6.9 J/cm2) as reported by manufacturer of extra-oral device LED was reduced remarkably when compared with the original values [13] One possible reasons was that the thickness of the cheek had interfered LED light penetration into the alveolar tissue resulting which may result in inadequate energy intensity.
Another different characteristic of blue light and red light was the penetration capacity. Barolet [20] explained that different wavelengths had different chromophores such as blue (400-470 nm), red (630-700 nm) and infrared light (700-1200). The longer the wavelength, the deeper the penetration into tissues. The penetration depth was less than 1 mm at wavelength of 400 nm and 1- 6 mm at wavelength of 630 nm. So, the red light could penetrate deeper in gingiva than blue light and may reach more organism such as mitochondria. Kolte et al [21] demonstrated that the thickness of buccal gingiva in maxillary arch was 1.60 (±0.43) mm in 16-24 years and Ramesh et al [22] said that thickness of palatal gingiva was 2.39 (0.99) in 14-21 years. Therefore, the blue light LED used in our study was presumably had less penetration capacity than other red-light LED studies.
LED light activated cytochrome c oxidase in mitochondrial electron transport chain. Horie and Morrison [23] stated that cytochrome c oxidase contains two hemes, cytochrome a and cytochrome a3. Proper absorbed spectrum of cytochrome a was 605-630 nm and cytochrome a3 was 445-460 nm. Although the wave length in our study could hypothetically activated cytochrome a3. There were many other factors why our study did not show statistical difference in the rate of canine tooth movement. For example, specific wavelength range, intensity, penetration capacity, frequency of exposure, timing of exposure [9] So that our blue light LED intervention was not able to penetrate tissue and activated underlying organism that control tooth movement.
The LED protocol in our study did not show any adverse effects. The heat increase of 1.33 degree was considered safe for pulp and periodontal tissue.
Kwon SJ et al [24]. reviewed that damage to the tooth- supporting tissues (cementum, periodontal ligament and alveolar bone) could be induced by temperature more than 10 degrees. X-ray using parallel technique after 4-month retraction by NiTi coil spring (150-200g) found no canine root resorption in all teeth but 2 teeth (one in LED side, other in control side) which showed minimal resorption. This root resorption could occur in normal orthodontic tooth movement [25] Regarding Pain test, NRS was one of the best methods available for pain studies. Results of this research showed that the highest pain intensity peak took place both with the LED and placebo side at the first LED exposure. There was slightly pain reduction after that. Participants did not complain about any discomfort, gingival irritation or pain at next appointment visit. Although control side was not exposed to LED light, participants felt some mild pain. The most common theories used to explain this situation was the placebo effect from person's expectations [26].

Strength

This study used randomization method. It prevents the selection bias and insures against the accidental bias. It also produced the comparable groups and eliminates the source of bias in treatment assignments. Our RCT, split mouth study met the criteria of randomization, allocation concealment, intent to treat analysis, operator blinded assessment and power calculation. However, patient could not be blinded due to heat generated on the LED side.

Limitations

Our study measured distance of canine tooth movement from panoramic radiographs. Panoramic technique was quite sensitive to magnification and geometric distortion. Catic et al [27] mentioned that panoramic radiography was an effective method for measuring the liner measurement of vertical, horizontal, oblique and angular variables if it was on only one side of the mandible and if knowing the magnification factor. However, this study tried to resolve this problem by using calibrated measuring wires on both sides to calculate magnification values in each radiograph and measure distances nearest the reference wire for minimal magnification error. Further investigations were warranted to analyze whether the duration, frequency or method of LED exposure would have any effect on the rate of orthodontic tooth movement.

Conclusion

Intraoral LED light (430-480 nm wavelength, 6 J/cm2) exposer over gingival tissue had no bio-stimulatory effect to accelerate canine retraction into first premolar extraction site.


Serious Adverse Events: What to Expect in Clinical Trials with Participation of Multiple Sclerosis Patients?https://biomedres01.blogspot.com/2020/01/serious-adverse-events-what-to-expect.html

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Friday, January 17, 2020

Serious Adverse Events: What to Expect in Clinical Trials with Participation of Multiple Sclerosis Patients?

Serious Adverse Events: What to Expect in Clinical Trials with Participation of Multiple Sclerosis Patients? 

 

Abstract

Abbreviations: SAE: Serious Adverse Event; MedDRA: Medical Dictionary for Regulatory Activities; SOC: System Organ Class; IMP: Investigational Medicinal Product; AEs: Adverse Events

Introduction

Multiple Sclerosis

Multiple sclerosis is an inflammatory disease attacking myelinated axons in the central nervous system, destroying the myelin and the axon in variable degrees. It causes significant physical disability within 20-25 years in more than 30% of patients. The cause of multiple sclerosis is still unknown; it can be triggered or perpetuated by an as-yet-unidentified environmental factor in a genetically predisposed person. MS is considered an autoimmune disease; the immune system attacks the myelin sheets in the brain or spinal cord. Multiple sclerosis is most commonly diagnosed in people in their 20s and 30s. It is a life-time condition; average life-expectancy is slightly reduced. Worldwide, approximately 2.1 million people are affected, with prevalence in women [1].

Clinical Trials

According to the definition in ICH GCP, in clinical trials only those adverse events (AEs) are assessed as serious (SAEs) that occurred after any dose of the Investigational Medicinal Product (IMP) and resulted in death, were life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or caused a congenital anomaly/birth defect. [2] Some of SAEs, which are assessed by investigators as related to the IMP, and also unexpected from regulatory standpoint - never registered before with the IMP - were accounted separately as they require expedited reporting to Regulatory Authorities, Ethics Committees, and Investigators participating in the studies with this IMP [2]. Pregnancies, which are actually not SAEs but require expedited reporting by the investigators and close follow-up until delivery and perinatal period of the baby were also included into account. A great deal of publications discusses the safety findings of clinical trials, but they do not specify serious events in detail. [3-6] This retrospective analysis provides an overview on the number and type of serious AEs in clinical trials with general multiple sclerosis patient population and is independent on the study drug or treatment arm.

Retrospective SAE Analysis

Retrospective analysis of SAEs was performed from data of 11 completed Phase II and III clinical trials completed with multiple sclerosis patients within the period of 2008-2018. A total of 4463 subjects in the age of 18 and 55, from Europe, Australia, North America and South Africa were enrolled in the studies (Table 1).
During the analyzed trials 1361 SAEs were registered in 14.5% of treated subjects. One fourth of these SAEs were assessed as related to the investigational drug and unexpected (SARs), affecting almost 5% of the patients. A high amount of pregnancies was reported, 250 cases in 4.1% of all study subjects, in female subjects and female partners of male subjects. The most common seriousness criterion observed was hospitalization or prolongation of existing hospitalization. The most common disease groups according to System Organ Class (SOC) analysis using the Medical Dictionary for Regulatory Activities (MedDRA) were Infections and infestations and Nervous systems disorders. 10% of the reported SAEs were due to different sorts of infections: Pneumonia, Herpes zoster, Sepsis, Urinary tract infection, Cellulitis, Gastroenteritis and Appendicitis.





biomedres-openaccess-journal-bjstr

Note:
14.5% of all patients
23.8% of all SAEs
4.5% of all patients
0.3% of all patients
4.1% of all patients
The high occurrence of any kind of infection in MS patients is likely due to the fact that the drugs used for treatment have the common side effect of reducing white blood cell count. 8% of all SAEs (excluding cases of MS relapse) were connected to various illnesses of the nervous system. The explanation to their high occurrence can be either because of the inefficacy of the study drug or randomization into the placebo treatment arm. 13 subjects were died while in the trial, representing 0.35% of all treated patients.
The main reasons for death were due to Infections and infestations in 25% of the death cases. The rest of the cases belonged to the following disease groups: Blood and lymphatic system disorders; Neoplasms benign, malignant and unspecified; Nervous system disorders; Psychiatric disorders and Respiratory, thoracic and mediastinal disorders.

Conclusion

This retrospective analysis of SAEs in clinical trials with multiple sclerosis, an inflammatory disease attacking the central nervous system, aimed to provide safety data from 11 clinical trials. SAEs were registered in 14.5% of treated patients, and quarter of them assessed as related to the study therapy. Most common SAE causes were Infections and infestations and Nervous systems disorders. 0.35% of treated patients died and the main reason was again Infections and infestations. The high prevalence of infections could be accounted for the side-effects of MS treatment.



Fermentation of Pretreated Herbaceous Cellulosic Wastes to Ethanol by Anaerobic Cellulolytic and Saccharolytic Thermophilic Clostridiahttps://biomedres01.blogspot.com/2020/01/journals-on-medical-informatics-bjstr_16.html

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Thursday, January 16, 2020

Journals on Medical Informatics - BJSTR Journal

Abstract

#Lignocellulosic waste streams from agriculture, paper and wood industry are renewable, plentiful and low-cost raw materials that can be used for large-scale production of liquid and gaseous biofuels. As opposed to prevailing multi-stage biotechnological processes developed for #bioconversion of cellulosic substrates to ethanol where high cost cellulase preparations are used, consolidated #Bioprocessing (CBP) offers to accomplish cellulose and xylan hydrolysis followed by fermentation of both C6 and C5 sugars to ethanol in a single-stage process. Syntrophic microbial consortium comprising of anaerobic, #thermophilic, cellulolytic, and saccharolytic bacteria in the genus Clostridia with improved ethanol productivity and high tolerance to fermentation end-products had been proposed for achieving CBP. 65 new strains of anaerobic #thermophilic cellulolytic and saccharolytic Clostridia were isolated from different wetlands and hot springs in Georgia.

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Journals on Biomedical Engineering - BJSTR Journal

Abstract

Micro Powder #Injection Molding (μPIM) has being the elected process for large series production of near net shape metal/ceramic parts with complex geometries and high series. The present study demonstrates the feasibility of Yttrium-Stabilized Zirconia dental implants and abutments production by μPIM giving rise to cheap devices. Coatings of #nanocrystalline ZrxOy contributes to an asset due the improvement of #osseointegration. Nowadays the teeth loss is increasingly a reality which can affect people either physical and psychologically. A high number of patients have one or more missing tooth and it is estimated that one in four Americans over the age of 74 have lost all their natural teeth. Many options exist to replace missing teeth, but dental implants have become one of the most functional #biomaterials to replace one (or more) missing tooth over the last decades. The most used materials in dental implants are titanium and its alloys (historically) and #zirconia (more recently) [1], because of their excellent #biocompatibility with the hard tissues. Ceramic implants, partially stabilized zirconia implants, are gradually becoming an excellent option for implantologists arousing the interest of the biggest dental implant companies worldwide, due to factors such as biocompatibility [2], non-release of metal ions (contrary to titanium implants).

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Journals on Regenerative Diseases - BJSTR Journal

Abstract

To determine of the parameters of the systolic (SBPV) and diastolic (DBPV) blood pressure variability dependent on the level of the athletes' health (H) "#Spiroarteriocardiorhythmograph” was used. 104 male athletes, at the age of 20.6 ± 0.9, who were engaged in various sports, were analyzed. Taking into account the level H, they were divided into 3 groups: the first group with a high-level H was 39 people ("high”), the second group was 46 ("average”), the third group was 19 ("low”). This report analyzes the #differences in the ranks of the parameters of the SBPV and DBPV - TPSBP (mmHg2), VLFSBP (mmHg2), LFSBP (mmHg2), HFSBP (mmHg2), LF/HFSBP (mmHg2/mmHg2), TPDBP (mmHg2), VLFDBP (mmHg2), LFDBP (mmHg2), HFDBP (mmHg2), LF/HFDBP (mmHg2/mmHg2). There were no possible differences in any registered SBPV values. We can speak about the reducing tendency in regulatory influences in all frequency grades, with the exception of high-frequency ones (HFSBP mmHg2), which is invalid tendency. After #analyzing the DBPV data it becomes clear that in terms of VLFDBP (mmHg2) possible differences between "high” and "low” are quite pronounced.

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Influence of Physical Activity on the Quality of of Breast Cancer Patients

Influence of Physical Activity on the Quality of of Breast Cancer Patients  Abstract Introduction: Breast cancer is t...