Caries
Conditions
Keywords
Caries, Cavity
Brief summary
The purpose of this study is to compare standard fillings and silver diamine fluoride (SDF) for treatment of cavities in baby teeth. The investigators will compare the effectiveness of stopping the cavity, cost of the treatments and the opinions of the families and the dental providers.
Detailed description
To determine the effectiveness of the application of silver diamine fluoride (SDF) in comparison to conventional restorative treatments in International Caries Detection and Assessment System criteria (ICDAS) 5 and 6, one and two surface carious lesions in primary molars which will be assessed based on major and minor failure criteria when followed for one year. Additionally, parents'/children's and providers' perceptions will be assessed as well as the cost of both regimens, to include both chair time spent and materials' costs.
Interventions
DEVICESilver Diamine Fluoride
No caries removal will take place. The tooth will be dried and Silver Diamine Fluoride will be placed on the carious dentin until saturated. Excess will be blotted dry with a cotton pellet.
PROCEDUREConventional Caries Management
These children will receive restorative dental care in alignment with the American Academy of Pediatric Dentistry guidelines, within the confines of the Mott Children's Health Center clinic. This treatment typically includes administration of local anesthesia, placement of rubber dam, caries removal with rotary and hand instruments, and placement of a final restoration.
Sponsors
Mott Children's Health Center
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 10 Years
Healthy volunteers
No
Inclusion criteria
* Presence of at least one active (soft) cavitated carious lesions in the primary dentition, extending into dentin (ICDAS 5 or 6) * The selected tooth must have a one or two surface lesion (more than 1/3 of the crown of the tooth must be remaining) and must allow for direct application of SDF * Study teeth will not have any spontaneous or elicited pain due to caries, tooth mobility, or signs of pulpal infection * Selected primary teeth must have an anticipated exfoliation date greater than 12 months away
Exclusion criteria
* Hereditary developmental defects such as Amelogenesis Imperfecta and Dentinogenesis Imperfecta * Severe medical conditions that do not allow the child to be managed in the clinic * Known allergy /sensitivity to dental materials being used, including SDF * Inability of the child to cooperate for treatment, recall examinations, or periapical radiographs * Wards of the State, for consenting reasons
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Caries Arrest of Teeth in the SDF Group Measured by Dentin Color (Yellow, Brown, Black) | 12 Months | Color of the cavity at the end of the trial |
| Caries Arrest of Teeth in the SDF Group Measured by Change in Size | 12 Months | Number of participants in the SDF arm that had an increase in lesion size at any point in the 12 months of the trial, as this is a treatment failure. Treatment failures were assessed throughout the 12 month duration of the trial, and children with treatment failures were then removed from the trial for further clinical treatment. |
| Caries Arrest of Teeth in the SDF Group Measured by Dentin Texture (Soft, Hard) | 12 Months | Texture of the cavity's dentin of soft means the cavity is still an active infection. If the cavity is hard, the cavity is no longer an active infection (has been arrested). Please note dentin texture cannot be assessed for the Conventional group as the dentin is no longer accessible following baseline treatment. |
| Restoration Integrity for Teeth in Control Group (Secondary Caries, Lost Restoration, Restoration Needing Repair) | 12 Months | Secondary caries, lost restorations, or restorations needing repair are treatment failures. Treatment failures were assessed throughout the 12 month duration of the trial, and children with treatment failures were removed from the trial for further clinical treatment. |
| Signs of Pulpal Pathology (Lesion Reaching the Pulp Requiring Pulpular Treatment-pulpotomy and/or Pulpectomy-, Reversible Pulpitis, Irreversible Pulpitis, Abscess) | 12 Months | Signs of pulpal pathology are treatment failures. Treatment failures were assessed throughout the 12 month duration of the trial, and children with treatment failures were removed from the trial for further clinical treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Child Assessment of Appearance of Teeth (Very Happy, Not Happy or Sad, Very Sad) | 12 Months | — |
| Child Assessment of Experience During Dental Visit (Didn't Hurt, Hurt a Little, Hurt a Lot) | 12 Months | — |
| Number of Providers Who Find Treatment With SDF More Favorable in Time for Treatment (More, Same, Less) | Baseline | Data collected at baseline only. |
| Time of Treatment Procedures (Duration of Time in Minutes) | Baseline | — |
| Costs of Treatment (Dollars) | Baseline | Cost of one application of SDF and one 1-2 surface conventional restoration. Cost was calculated by taking the average Medicaid reimbursement across all U.S. states. |
| Number of Providers Who Find Treatment With SDF More Favorable in Ease of Treatment (Easier, Harder, Same Difficulty) | Baseline | — |
| Number of Providers Who Find Treatment With SDF More Favorable in Preference of Treatment Modality (More Preferable, no Preference, Less Preferable) | Baseline | — |
| Parent Assessment of Appearance of Child's Teeth | 12 Months | Parents were asked Are you concerned with the appearance of your child's teeth? |
| Parent Assessment of Treatment Provided | 12 Months | Parents were asked If your child had another cavity, would you be willing to have that tooth treated with the same treatment option provided to your child in this study? |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Silver Diamine Fluoride This arm will receive Silver Diamine Fluoride applied to their carious lesion, at baseline and 6 months, in lieu of restoration placement, with the goal of arresting caries.
Silver Diamine Fluoride: No caries removal will take place. The tooth will be dried and Silver Diamine Fluoride will be placed on the carious dentin until saturated. Excess will be blotted dry with a cotton pellet. | 56 |
| Conventional Caries Management Restorative dental care according to American Academy of Pediatric Dentistry guidelines. This treatment typically includes administration of local anesthesia, placement of rubber dam, caries removal with rotary and hand instruments, and placement of a final restoration.
Conventional Caries Management: These children will receive restorative dental care in alignment with the American Academy of Pediatric Dentistry guidelines, within the confines of the Mott Children's Health Center clinic and the University of Michigan School of Dentistry. | 42 |
| Total | 98 |
Baseline characteristics
| Characteristic | Silver Diamine Fluoride | Conventional Caries Management | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 56 Participants | 42 Participants | 98 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 4.7 years STANDARD_DEVIATION 1.9 | 4.8 years STANDARD_DEVIATION 1.7 | 4.8 years STANDARD_DEVIATION 1.8 |
| dmft | 5.6 dmft STANDARD_DEVIATION 3.7 | 7.2 dmft STANDARD_DEVIATION 3.8 | 6.3 dmft STANDARD_DEVIATION 3.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants | 40 Participants | 91 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants | 22 Participants | 54 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 14 Participants | 16 Participants | 30 Participants |
| Region of Enrollment United States | 56 participants | 42 participants | 98 participants |
| Sex: Female, Male Female | 29 Participants | 16 Participants | 45 Participants |
| Sex: Female, Male Male | 27 Participants | 26 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 56 | 0 / 42 |
| other Total, other adverse events | 36 / 56 | 3 / 42 |
| serious Total, serious adverse events | 0 / 56 | 0 / 42 |
Outcome results
Primary
Caries Arrest of Teeth in the SDF Group Measured by Change in Size
Number of participants in the SDF arm that had an increase in lesion size at any point in the 12 months of the trial, as this is a treatment failure. Treatment failures were assessed throughout the 12 month duration of the trial, and children with treatment failures were then removed from the trial for further clinical treatment.
Time frame: 12 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Silver Diamine Fluoride | Caries Arrest of Teeth in the SDF Group Measured by Change in Size | 10 Participants |
Primary
Caries Arrest of Teeth in the SDF Group Measured by Dentin Color (Yellow, Brown, Black)
Color of the cavity at the end of the trial
Time frame: 12 Months
Population: Only 39 of the 40 children who attended the 12 month visit in the SDF arm had cavities available for assessment. One child's tooth exfoliated (fell out) normally one week prior to the 12 month appointment.~Please note dentin color cannot be assessed for the Conventional group as the dentin is no longer accessible following baseline treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Silver Diamine Fluoride | Caries Arrest of Teeth in the SDF Group Measured by Dentin Color (Yellow, Brown, Black) | Black | 37 Participants |
| Silver Diamine Fluoride | Caries Arrest of Teeth in the SDF Group Measured by Dentin Color (Yellow, Brown, Black) | Brown | 0 Participants |
| Silver Diamine Fluoride | Caries Arrest of Teeth in the SDF Group Measured by Dentin Color (Yellow, Brown, Black) | Yellow | 2 Participants |
Primary
Caries Arrest of Teeth in the SDF Group Measured by Dentin Texture (Soft, Hard)
Texture of the cavity's dentin of soft means the cavity is still an active infection. If the cavity is hard, the cavity is no longer an active infection (has been arrested). Please note dentin texture cannot be assessed for the Conventional group as the dentin is no longer accessible following baseline treatment.
Time frame: 12 Months
Population: Only 39 of the 40 children who attended the 12 month visit in the SDF arm had cavities available for assessment. One child's tooth exfoliated (fell out) normally one week prior to the 12 month appointment.~Dentin texture cannot be assessed for the Conventional group as the dentin is no longer accessible following baseline treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Silver Diamine Fluoride | Caries Arrest of Teeth in the SDF Group Measured by Dentin Texture (Soft, Hard) | Soft Dentin | 10 Participants |
| Silver Diamine Fluoride | Caries Arrest of Teeth in the SDF Group Measured by Dentin Texture (Soft, Hard) | Hard Dentin | 29 Participants |
Primary
Restoration Integrity for Teeth in Control Group (Secondary Caries, Lost Restoration, Restoration Needing Repair)
Secondary caries, lost restorations, or restorations needing repair are treatment failures. Treatment failures were assessed throughout the 12 month duration of the trial, and children with treatment failures were removed from the trial for further clinical treatment.
Time frame: 12 Months
Population: Please note restoration integrity cannot be assessed for the SDF group as this group does not receive a restoration.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Silver Diamine Fluoride | Restoration Integrity for Teeth in Control Group (Secondary Caries, Lost Restoration, Restoration Needing Repair) | Missing restoration | 1 Participants |
| Silver Diamine Fluoride | Restoration Integrity for Teeth in Control Group (Secondary Caries, Lost Restoration, Restoration Needing Repair) | Secondary caries and lesion progression | 1 Participants |
| Silver Diamine Fluoride | Restoration Integrity for Teeth in Control Group (Secondary Caries, Lost Restoration, Restoration Needing Repair) | Intact restoration | 40 Participants |
Primary
Signs of Pulpal Pathology (Lesion Reaching the Pulp Requiring Pulpular Treatment-pulpotomy and/or Pulpectomy-, Reversible Pulpitis, Irreversible Pulpitis, Abscess)
Signs of pulpal pathology are treatment failures. Treatment failures were assessed throughout the 12 month duration of the trial, and children with treatment failures were removed from the trial for further clinical treatment.
Time frame: 12 Months
Population: All children were assessed for signs of pulpal pathology throughout the trial.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Silver Diamine Fluoride | Signs of Pulpal Pathology (Lesion Reaching the Pulp Requiring Pulpular Treatment-pulpotomy and/or Pulpectomy-, Reversible Pulpitis, Irreversible Pulpitis, Abscess) | Reversible Pulpitis | 1 Participants |
| Silver Diamine Fluoride | Signs of Pulpal Pathology (Lesion Reaching the Pulp Requiring Pulpular Treatment-pulpotomy and/or Pulpectomy-, Reversible Pulpitis, Irreversible Pulpitis, Abscess) | Reversible Pulpitis and Later Periapical Infection | 2 Participants |
| Silver Diamine Fluoride | Signs of Pulpal Pathology (Lesion Reaching the Pulp Requiring Pulpular Treatment-pulpotomy and/or Pulpectomy-, Reversible Pulpitis, Irreversible Pulpitis, Abscess) | Periapical Infection | 2 Participants |
| Silver Diamine Fluoride | Signs of Pulpal Pathology (Lesion Reaching the Pulp Requiring Pulpular Treatment-pulpotomy and/or Pulpectomy-, Reversible Pulpitis, Irreversible Pulpitis, Abscess) | No Sign of Pulpal Pathology | 51 Participants |
| Conventional Caries Management | Signs of Pulpal Pathology (Lesion Reaching the Pulp Requiring Pulpular Treatment-pulpotomy and/or Pulpectomy-, Reversible Pulpitis, Irreversible Pulpitis, Abscess) | No Sign of Pulpal Pathology | 41 Participants |
| Conventional Caries Management | Signs of Pulpal Pathology (Lesion Reaching the Pulp Requiring Pulpular Treatment-pulpotomy and/or Pulpectomy-, Reversible Pulpitis, Irreversible Pulpitis, Abscess) | Reversible Pulpitis | 1 Participants |
| Conventional Caries Management | Signs of Pulpal Pathology (Lesion Reaching the Pulp Requiring Pulpular Treatment-pulpotomy and/or Pulpectomy-, Reversible Pulpitis, Irreversible Pulpitis, Abscess) | Periapical Infection | 0 Participants |
| Conventional Caries Management | Signs of Pulpal Pathology (Lesion Reaching the Pulp Requiring Pulpular Treatment-pulpotomy and/or Pulpectomy-, Reversible Pulpitis, Irreversible Pulpitis, Abscess) | Reversible Pulpitis and Later Periapical Infection | 0 Participants |
Secondary
Child Assessment of Appearance of Teeth (Very Happy, Not Happy or Sad, Very Sad)
Time frame: 12 Months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Silver Diamine Fluoride | Child Assessment of Appearance of Teeth (Very Happy, Not Happy or Sad, Very Sad) | Very Happy | 29 Participants |
| Silver Diamine Fluoride | Child Assessment of Appearance of Teeth (Very Happy, Not Happy or Sad, Very Sad) | Not Happy or Sad | 7 Participants |
| Silver Diamine Fluoride | Child Assessment of Appearance of Teeth (Very Happy, Not Happy or Sad, Very Sad) | Very Sad | 4 Participants |
| Conventional Caries Management | Child Assessment of Appearance of Teeth (Very Happy, Not Happy or Sad, Very Sad) | Very Happy | 26 Participants |
| Conventional Caries Management | Child Assessment of Appearance of Teeth (Very Happy, Not Happy or Sad, Very Sad) | Not Happy or Sad | 3 Participants |
| Conventional Caries Management | Child Assessment of Appearance of Teeth (Very Happy, Not Happy or Sad, Very Sad) | Very Sad | 0 Participants |
Secondary
Child Assessment of Experience During Dental Visit (Didn't Hurt, Hurt a Little, Hurt a Lot)
Time frame: 12 Months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Silver Diamine Fluoride | Child Assessment of Experience During Dental Visit (Didn't Hurt, Hurt a Little, Hurt a Lot) | Hurt a Lot | 3 Participants |
| Silver Diamine Fluoride | Child Assessment of Experience During Dental Visit (Didn't Hurt, Hurt a Little, Hurt a Lot) | Didn't Hurt at All | 27 Participants |
| Silver Diamine Fluoride | Child Assessment of Experience During Dental Visit (Didn't Hurt, Hurt a Little, Hurt a Lot) | Hurt a Little | 10 Participants |
| Conventional Caries Management | Child Assessment of Experience During Dental Visit (Didn't Hurt, Hurt a Little, Hurt a Lot) | Hurt a Little | 4 Participants |
| Conventional Caries Management | Child Assessment of Experience During Dental Visit (Didn't Hurt, Hurt a Little, Hurt a Lot) | Hurt a Lot | 0 Participants |
| Conventional Caries Management | Child Assessment of Experience During Dental Visit (Didn't Hurt, Hurt a Little, Hurt a Lot) | Didn't Hurt at All | 25 Participants |
Secondary
Costs of Treatment (Dollars)
Cost of one application of SDF and one 1-2 surface conventional restoration. Cost was calculated by taking the average Medicaid reimbursement across all U.S. states.
Time frame: Baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Silver Diamine Fluoride | Costs of Treatment (Dollars) | 20.62 Dollars |
| Conventional Caries Management | Costs of Treatment (Dollars) | 79.68 Dollars |
Secondary
Number of Providers Who Find Treatment With SDF More Favorable in Ease of Treatment (Easier, Harder, Same Difficulty)
Time frame: Baseline
Population: The 98 instances of treatment below were given by about 15 providers. The provider stated the ease of treatment for each treatment instance.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Silver Diamine Fluoride | Number of Providers Who Find Treatment With SDF More Favorable in Ease of Treatment (Easier, Harder, Same Difficulty) | Harder for the provider | 0 Participants |
| Silver Diamine Fluoride | Number of Providers Who Find Treatment With SDF More Favorable in Ease of Treatment (Easier, Harder, Same Difficulty) | Easier for the provider | 46 Participants |
| Silver Diamine Fluoride | Number of Providers Who Find Treatment With SDF More Favorable in Ease of Treatment (Easier, Harder, Same Difficulty) | The same level of difficulty for provider | 10 Participants |
| Conventional Caries Management | Number of Providers Who Find Treatment With SDF More Favorable in Ease of Treatment (Easier, Harder, Same Difficulty) | Harder for the provider | 9 Participants |
| Conventional Caries Management | Number of Providers Who Find Treatment With SDF More Favorable in Ease of Treatment (Easier, Harder, Same Difficulty) | Easier for the provider | 2 Participants |
| Conventional Caries Management | Number of Providers Who Find Treatment With SDF More Favorable in Ease of Treatment (Easier, Harder, Same Difficulty) | The same level of difficulty for provider | 31 Participants |
Secondary
Number of Providers Who Find Treatment With SDF More Favorable in Preference of Treatment Modality (More Preferable, no Preference, Less Preferable)
Time frame: Baseline
Population: The 98 instances of treatment below were given by about 15 providers. The provider stated their treatment preference for each treatment instance.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Silver Diamine Fluoride | Number of Providers Who Find Treatment With SDF More Favorable in Preference of Treatment Modality (More Preferable, no Preference, Less Preferable) | More preferable treatment for provider | 21 Participants |
| Silver Diamine Fluoride | Number of Providers Who Find Treatment With SDF More Favorable in Preference of Treatment Modality (More Preferable, no Preference, Less Preferable) | No preference in treatment for provider | 35 Participants |
| Silver Diamine Fluoride | Number of Providers Who Find Treatment With SDF More Favorable in Preference of Treatment Modality (More Preferable, no Preference, Less Preferable) | Less preferable treatment for provider | 0 Participants |
| Conventional Caries Management | Number of Providers Who Find Treatment With SDF More Favorable in Preference of Treatment Modality (More Preferable, no Preference, Less Preferable) | More preferable treatment for provider | 0 Participants |
| Conventional Caries Management | Number of Providers Who Find Treatment With SDF More Favorable in Preference of Treatment Modality (More Preferable, no Preference, Less Preferable) | No preference in treatment for provider | 41 Participants |
| Conventional Caries Management | Number of Providers Who Find Treatment With SDF More Favorable in Preference of Treatment Modality (More Preferable, no Preference, Less Preferable) | Less preferable treatment for provider | 1 Participants |
Secondary
Number of Providers Who Find Treatment With SDF More Favorable in Time for Treatment (More, Same, Less)
Data collected at baseline only.
Time frame: Baseline
Population: The 98 instances of treatment below were given by about 15 providers. The provider stated how much time each treatment instance took compared to the alternate arm.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Silver Diamine Fluoride | Number of Providers Who Find Treatment With SDF More Favorable in Time for Treatment (More, Same, Less) | More time | 0 Participants |
| Silver Diamine Fluoride | Number of Providers Who Find Treatment With SDF More Favorable in Time for Treatment (More, Same, Less) | Same amount of time | 1 Participants |
| Silver Diamine Fluoride | Number of Providers Who Find Treatment With SDF More Favorable in Time for Treatment (More, Same, Less) | Less time | 55 Participants |
| Conventional Caries Management | Number of Providers Who Find Treatment With SDF More Favorable in Time for Treatment (More, Same, Less) | More time | 12 Participants |
| Conventional Caries Management | Number of Providers Who Find Treatment With SDF More Favorable in Time for Treatment (More, Same, Less) | Same amount of time | 27 Participants |
| Conventional Caries Management | Number of Providers Who Find Treatment With SDF More Favorable in Time for Treatment (More, Same, Less) | Less time | 3 Participants |
Secondary
Parent Assessment of Appearance of Child's Teeth
Parents were asked Are you concerned with the appearance of your child's teeth?
Time frame: 12 Months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Silver Diamine Fluoride | Parent Assessment of Appearance of Child's Teeth | No | 33 Participants |
| Silver Diamine Fluoride | Parent Assessment of Appearance of Child's Teeth | Yes | 7 Participants |
| Conventional Caries Management | Parent Assessment of Appearance of Child's Teeth | No | 26 Participants |
| Conventional Caries Management | Parent Assessment of Appearance of Child's Teeth | Yes | 3 Participants |
Secondary
Parent Assessment of Treatment Provided
Parents were asked If your child had another cavity, would you be willing to have that tooth treated with the same treatment option provided to your child in this study?
Time frame: 12 Months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Silver Diamine Fluoride | Parent Assessment of Treatment Provided | No | 7 Participants |
| Silver Diamine Fluoride | Parent Assessment of Treatment Provided | Yes | 33 Participants |
| Conventional Caries Management | Parent Assessment of Treatment Provided | No | 3 Participants |
| Conventional Caries Management | Parent Assessment of Treatment Provided | Yes | 26 Participants |
Secondary
Time of Treatment Procedures (Duration of Time in Minutes)
Time frame: Baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Silver Diamine Fluoride | Time of Treatment Procedures (Duration of Time in Minutes) | 5 Time in Minutes |
| Conventional Caries Management | Time of Treatment Procedures (Duration of Time in Minutes) | 30 Time in Minutes |