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| ID | Type | Description | Link |
|---|---|---|---|
| 5U01FD005240 | U.S. FDA Grant/Contract | View source |
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| Name | Class |
|---|---|
| Food and Drug Administration (FDA) | FED |
| Center for Psychiatry And Behavioral Medicine Inc. | INDUSTRY |
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The purpose of this study is to evaluate the association between blood drug levels and the corresponding scores of commonly used behavioral instruments based upon data collected following administration of three different methylphenidate hydrochloride extended-release drug products in children with ADHD.
This is a randomized, double-blind, 4-treatment and 4-period crossover study conducted in a school laboratory environment to evaluate the hour-by-hour behavioral instrument scores and hour-by-hour PK of 3 different extended-release MPH formulations as well as placebo in children with ADHD. The complete study consists of three periods: Screening, Dose Titration and Double-Blind Crossover in a Laboratory Classroom.
The double-blind phase will consist of four periods (or four weeks): each week will consist of blinded administration with one of the three active methylphenidate hydrochloride treatments or placebo from Sunday through Saturday. On the last day of each period (Saturday), study participants will be evaluated in a laboratory classroom setting. On Saturdays, the blinded doses of each study drug will be administered at the school site by study staff on the morning of the test laboratory classroom day. On the other days, the medication will be taken in the morning at home.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Methylphenidate HCl ER tablets 1 | Active Comparator | During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase |
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| Placebo | Placebo Comparator | During the double-blind period, in one of the 4 study weeks, the study participant will take a blinded placebo instead of one of the the 3 active comparators. |
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| Methylphenidate HCl ER tablets 2 | Active Comparator | During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase |
|
| Methylphenidate HCl ER for suspension | Active Comparator | During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methylphenidate HCl ER tablets 1 | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Permanent Product Measure of Performance (PERMP) for Three Methylphenidate Hydrochloride Extended-release Drug Products | The Permanent Product Measure of Performance (PERMP) involves objective individualized mathematics tests. Scores will be obtained ten times on each classroom day at pre-dose, and at approximately 0.5, 1.5, 2.5, 4, 5, 6, 8, 10 and 12 hours post-dose. PERMP Attempted is reported here. Scale ranges 0 math questions answered to 400 math questions answered. The more number of questions answered (better score), the higher the PERMP Attempted score is. | 0.5, 1.5, 2.5, 4, 5, 6, 8, 10 and 12 hours post-dose on each classroom day |
| Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale for Three Methylphenidate Hydrochloride Extended-release Drug Products | The Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) scale is a validated, 13-item rating of subjective impairment of classroom behaviors (0 = normal/no impairment; 1 = slight impairment; 2 = mild impairment; 3 = moderate impairment; 4 = severe impairment; 5 = very severe impairment; 6 = maximal impairment). The SKAMP consists of four subscales: SKAMP-Attention, SKAMP-Deportment, SKAMP-Quality of Work, and SKAMP-Compliance, in addition to SKAMP-Total (reported here). SKAMP-Total is a sum of the four sub-scales and has a range of 0-78. The higher the score, the higher the impairment. Scores will be obtained during each classroom cycle during each full laboratory classroom day at pre-dose, and at 0.5, 1.5, 2.5, 4, 5, 6, 8, 10, and 12 hours post-dose. The scores will be based on the child's behavior during 20 minutes of each cycle. | 0.5, 1.5, 2.5, 4, 5, 6, 8, 10 and 12 hours post-dose on each classroom day |
| Maximum Drug Concentration Observed (Cmax) for Three Methylphenidate Hydrochloride Extended-release Drug Products | PK samples will be taken eight times on each classroom day at approximately 0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose, and Cmax will be measured. The objectives of this measure is to estimate PK metrics, including Cmax, appropriate for characterizing rate and extent of absorption in each phase of the drug release and the evaluate the disposition and eliminating processes for each medication studied. The minimum value is pg/mL and there is was no maximum defined prior to the interventions. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Spencer, MD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States | ||
| Center for Psychiatry and Behavioral Medicine |
88 individuals signed consent. 82 individuals were eligible for the study. 80 individuals were exposed to the open-label phase (Methylphenidate HCL ER Tablets 1). 76 individuals entered the double-blind phase. 72 individuals completed the entire study. Since this is a crossover study, these were the same individuals (88 consented, not 301).
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| ID | Title | Description |
|---|---|---|
| FG000 | All Participants | Participants received 4 different medications at the following 5 time points.
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| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Concerta Open Label |
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| Placebo |
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| Methylphenidate HCl ER Tablet 1 |
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| Methylphenidate HCl ER Tablet 2 |
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| Methylphenidate HCl ER Suspension |
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80 individuals were exposed in the open-label phase of the study which involved Methylphenidate HCl ER Tablets 1 (Concerta).
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| ID | Title | Description |
|---|---|---|
| BG000 | Open-Label: Methylphenidate HCl ER Tablets 1 | During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. Methylphenidate HCl ER tablets 1 |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Permanent Product Measure of Performance (PERMP) for Three Methylphenidate Hydrochloride Extended-release Drug Products | The Permanent Product Measure of Performance (PERMP) involves objective individualized mathematics tests. Scores will be obtained ten times on each classroom day at pre-dose, and at approximately 0.5, 1.5, 2.5, 4, 5, 6, 8, 10 and 12 hours post-dose. PERMP Attempted is reported here. Scale ranges 0 math questions answered to 400 math questions answered. The more number of questions answered (better score), the higher the PERMP Attempted score is. | Note that not all participants who entered the study completed all arms and all time points, hence the discrepancy in number of participants analyzed between arms and different time points. | Posted | Mean | Standard Deviation | score on a scale | 0.5, 1.5, 2.5, 4, 5, 6, 8, 10 and 12 hours post-dose on each classroom day |
|
Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit
Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Methylphenidate HCl ER Tablets 1 | During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER tablets 1 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Insomnia | Psychiatric disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Thomas Spencer | Massachusetts General Hospital | 617-724-5600 | spencer@helix.mgh.harvard.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 30, 2017 | Sep 2, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D013535 | Suspensions |
| ID | Term |
|---|---|
| D003102 | Colloids |
| D045424 | Complex Mixtures |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
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| Drug |
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| Methylphenidate HCl ER tablets 2 | Drug |
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| Methylphenidate HCl ER for suspension | Drug |
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| 0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose on each classroom day |
| Time to Reach Cmax (Tmax) for Three Methylphenidate Hydrochloride Extended-release Drug Products | PK samples will be taken eight times on each classroom day at approximately 0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose, and Tmax will be measured | 0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose on each classroom day |
| Las Vegas |
| Nevada |
| 89128 |
| United States |
| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase
Methylphenidate HCl ER tablets 1
| OG001 | Placebo | During the double-blind period, in one of the 4 study weeks, the study participant will take a blinded placebo instead of one of the the 3 active comparators. Placebo |
| OG002 | Methylphenidate HCl ER Tablets 2 | During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER tablets 2 |
| OG003 | Methylphenidate HCl ER for Suspension | During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER for suspension |
|
|
| Primary | Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale for Three Methylphenidate Hydrochloride Extended-release Drug Products | The Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) scale is a validated, 13-item rating of subjective impairment of classroom behaviors (0 = normal/no impairment; 1 = slight impairment; 2 = mild impairment; 3 = moderate impairment; 4 = severe impairment; 5 = very severe impairment; 6 = maximal impairment). The SKAMP consists of four subscales: SKAMP-Attention, SKAMP-Deportment, SKAMP-Quality of Work, and SKAMP-Compliance, in addition to SKAMP-Total (reported here). SKAMP-Total is a sum of the four sub-scales and has a range of 0-78. The higher the score, the higher the impairment. Scores will be obtained during each classroom cycle during each full laboratory classroom day at pre-dose, and at 0.5, 1.5, 2.5, 4, 5, 6, 8, 10, and 12 hours post-dose. The scores will be based on the child's behavior during 20 minutes of each cycle. | Note that not all participants who entered the study completed all arms. Thus, the number differs between the arms to reflect the number of participants who provided data for that arm. N=67 for all MPH HCl ER tab 1 time points. N=72 for all placebo time points. N=66 for all MPH HCl tab 2 time points. N=68 for all MPH Hcl ER susp timepoints. | Posted | Mean | Standard Deviation | units on a scale | 0.5, 1.5, 2.5, 4, 5, 6, 8, 10 and 12 hours post-dose on each classroom day |
|
|
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| Primary | Maximum Drug Concentration Observed (Cmax) for Three Methylphenidate Hydrochloride Extended-release Drug Products | PK samples will be taken eight times on each classroom day at approximately 0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose, and Cmax will be measured. The objectives of this measure is to estimate PK metrics, including Cmax, appropriate for characterizing rate and extent of absorption in each phase of the drug release and the evaluate the disposition and eliminating processes for each medication studied. The minimum value is pg/mL and there is was no maximum defined prior to the interventions. | 76 participants entered the double-blind randomization phase and each participant provided at least one data point for these analyses. | Posted | Mean | Standard Deviation | pg/mL | 0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose on each classroom day |
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|
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| Primary | Time to Reach Cmax (Tmax) for Three Methylphenidate Hydrochloride Extended-release Drug Products | PK samples will be taken eight times on each classroom day at approximately 0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose, and Tmax will be measured | 76 participants entered the double-blind randomization phase and each participant provided at least one data point for these analyses. | Posted | Mean | Standard Deviation | Hours | 0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose on each classroom day |
|
|
|
| 0 |
| 80 |
| 0 |
| 80 |
| 69 |
| 80 |
| EG001 | Placebo | During the double-blind period, in one of the 4 study weeks, the study participant will take a blinded placebo instead of one of the the 3 active comparators. Placebo | 0 | 74 | 0 | 74 | 12 | 74 |
| EG002 | Methylphenidate HCl ER Tablets 2 | During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER tablets 2 | 0 | 73 | 0 | 73 | 20 | 73 |
| EG003 | Methylphenidate HCl ER for Suspension | During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER for suspension | 0 | 74 | 0 | 74 | 23 | 74 |
| Low Appetite | Gastrointestinal disorders | Non-systematic Assessment |
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| Emotional Lability | Psychiatric disorders | Non-systematic Assessment | Emotional Lability, Moodiness, Irritability |
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| Upper Respiratory Infection | Infections and infestations | Non-systematic Assessment |
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| GI Distress | Gastrointestinal disorders | Non-systematic Assessment |
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| Abdominal Pain | Gastrointestinal disorders | Non-systematic Assessment |
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| Vomited | Gastrointestinal disorders | Non-systematic Assessment |
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| Headache | Nervous system disorders | Non-systematic Assessment |
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| Anger/Aggression/Oppositional Behavior | Psychiatric disorders | Non-systematic Assessment |
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| Dysphoria/Anxiety | Psychiatric disorders | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
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| Epistaxis | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Ankle Pain/Strain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Strep Throat/Sore Throat | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Influenza | Immune system disorders | Non-systematic Assessment |
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| Motor Tics | Nervous system disorders | Non-systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Bug Bites/Bee Stings | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Otitis Media/Ear Pain | Ear and labyrinth disorders | Non-systematic Assessment |
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| Carious Teeth | Immune system disorders | Non-systematic Assessment |
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| Growth Hormone Deficiency | Endocrine disorders | Non-systematic Assessment |
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| Muscle Strain/Pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Cellulitis | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Mouth Ulcers/Bad Breath | Infections and infestations | Non-systematic Assessment |
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| Dry Mouth | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Eye Pain | Eye disorders | Non-systematic Assessment |
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| Sunburn | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Weight Loss | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Foreign Body Swallowed | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Finger Laceration | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Flat Affect | Social circumstances | Non-systematic Assessment |
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| Urinary Tract Infection | Renal and urinary disorders | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | Non-systematic Assessment |
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| Toe Fracture | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Heart Palpitations | Cardiac disorders | Non-systematic Assessment |
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| Staring Episodes | Psychiatric disorders | Non-systematic Assessment |
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