To determine whether the oral administration of calcium aluminosilicate clay (CASAD) reduces the rate of grade 3 diarrhea associated with irinotecan administration in patients with colorectal cancer

Patients were provided with CASAD or placebo capsules. The treatment arm received capsules containing 500 mg of the active compound taken as two tablets four times daily. Treatment lasted for six weeks or until treatment criteria were met. After six weeks, all patients were offered off-label CASAD for an additional six weeks. Patients who developed diarrhea were provided standard-of-care antidiarrheal medication. Patients completed baseline assessments of bowel statuses and additional assessments at three, five, and six weeks. Daily bowel logs were completed by patients and reviewed at the third, fifth, and sixth provider visits.

• N = 100
• AGE RANGE = 20–83 years
• MALES: 54%, FEMALES: 46%
• KEY DISEASE CHARACTERISTICS: Metastatic colorectal cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Scheduled to receive irinotecan alone or with other agents: Eastern Cooperative Oncology Group status ≤ 2

• SITE: Multi-site
• SETTING TYPE: Outpatient
• LOCATION: MD Anderson and affiliates

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care

This was a phase II, randomized, double-blinded, multicenter study. Patients were randomized on a 1:1 ratio to receive CASAD or a placebo. Patients were stratified according to irinotecan therapy, no concurrent therapy, or concurrent therapy in addition to irinotecan.

• MD Anderson Symptom Inventory (MDASI)
• Patient completed bowel/ostomy assessment
• Daily diary

There were no differences between groups. In the CASAD arm, seven out of 49 patients in the CASAD arm versus three out of 46 patients in the placebo arm developed grade 3 diarrhea during the first six weeks (PR = 0.10). The incidence of any grade of diarrhea was similar in both arms. There was no difference in gastrointestinal (GI) toxicities between the two groups.

CASAD was ineffective in preventing diarrhea in this patient population. There were no issues with GI toxicities, indicating that CASAD was clinically safe.

• Subject withdrawals ≥ 10%
• Other limitations/explanation: Weak science on which study it was based on

CASAD is not indicated as a preventive measure for diarrhea associated with irinotecan administration.

To systematically review the currently available high-quality evidence evaluating treatments for moist desquamation in patients receiving radiotherapy

Databases used were AMED, BIOMED, BIOSIS, BNI, British Library Integrated Catalogue, CINAHL, Cochrane, Current Controlled Trials, DARE, Dissertation Abstracts, DoH Research Findings Register, EMBASE, HSRProj, IBSS, Index to Theses, ISI Wok, Medline, National Cancer Research Network, National Register of Cancer Trials, National Research Register, PROQUEST, and ZETOC. Keywords searched were radiotherapy, radiation therapy, deep x-ray therapy, irradiation, wounds, moist desquamation, desquamation burns, radiation burns, radiotherapy burns, broken skin, ulcers, wound healing, skin care, wound care, and epithelial. Studies were included if they

• Were randomized controlled trials or controlled clinical trials
• Investigated the impact of one or more interventions for moist desquamation in patients of any diagnosis receiving radiation therapy
• Included measurements of wound healing time or other skin integrity measures and some form of patient comfort or acceptability measure.

Studies were excluded if they

• Were not in a language where translation was available to the author
• Were published before 1990
• Did not have a control
• Investigated prophylactic agents or preventive interventions only.

The search returned 166 articles. Of these, 20 were relevant. Only 10 were included in the review. Studies were evaluated for quality using the CASP guidelines for clinical trials. Of the 10 studies that met inclusion criteria, none were judged to be of very poor quality, so all were included in the review. Studies were not homogenous in interventions or variables examined, so no meta-analysis was undertaken. A qualitative overview of results is presented.

• The total sample size across 10 studies was approximately 575.
• Some studies did not specify the number of patients in a control group.
• Most studies did not find a significant difference associated with interventions; two studies showed a statistically significant reduction in healing time in their intervention group (studies using gentian violet), and one study showed a significantly increased healing time in their intervention group (hydrogel).
• All studies examined the use of some type of topical skin treatment.

• Hydrogel and hydrocolloid dressings have been recommended by professional groups and are founded on moist wound healing principles; however, this review found conflicting evidence to support the use of either of these. It was noted that these can be very expensive and can leak.
• Limited evidence supports the effectiveness of other types of dressing.
• Limited evidence supports creams and other topical agents.
• Gentian violet was the most frequently used control substance. It was noted that this is no longer recommended by the department of health in the UK because of its carcinogenic potential.

No convincing evidence for any intervention was found. Evidence was mixed concerning the use of hydrogel and hydrocolloid dressings; however, improved patient comfort was sometimes seen with these. Other dressings studied did not show positive results and comparison dry dressings may cause injury of granulating tissue with daily removal for treatment. A number of other types of dressings that might be useful were briefly identified, but there are no reports of research using these yet. Limited evidence supports other interventions. Most findings with topical agents were equivocal. In one study, hydrocortisone cream appeared to reduce healing time (abstract only).

Although the author states that the 10 studies included were all of sufficient quality for use according to the guidelines used, results reported per study indicate that one study may have reported information that was untrue, one study was identified as being poorly reported with insufficient information, and one study was identified as fairly low quality.

Well-designed research in this area is urgently needed.

To examine differences in incidence and risk of chemotherapy-induced nausea and vomiting (CINV) among patients receiving low emetogenic chemotherapy (LEC) with or without prophylactic granisetron 

The first cohort of patients received 8 mg IV bolus dexamethasone or 10 mg metachloepramide. The second cohort also was given 3 mg IV bolus of granisetron.  Both groups were given dexamethasone (2-4 mg twice daily) or metochlopramide (10 mg three times daily) tablets to be taken for three days after chemotherapy. CINV was evaluated for 120 hours, days 1–5 after chemotherapy.

• The study consisted of 94 patients.
• Mean age of patients was 53.4 years.
• The sample was 51% male and 48% female.
• Disease types were not described.
• Drugs used in chemotherapy were gemcitabine, vinorelbine, fluorouracil, and docetaxel.
• The percentage of patients who were chemotherapy naïve was 19% in both groups.

The study was conducted at a single outpatient site in Malaysia.

All patients were in active, antitumor treatment.

This was a two-group cohort, observational trial.

• Patients recorded emesis in diaries using a rating system adapted from the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool.
• Complete control was defined as no nausea or vomiting and no use of rescue medication.

Those who received granisetron had lower rates of acute and delayed nausea and emesis. The only significant difference between groups was in the prevalence of acute emesis; 3.9% of those who received granisetron experienced acute emesis versus 19% of those who did not receive granisetron (p = 0.017). No differences were found between groups in complete control rates in either the acute or delayed phases. With analysis controlling for covariates influencing CINV, those receiving granisetron had a lower risk of CINV (overall response [OR] = 0.1, 95% confidence interval [CI] = 0.02–0.85, p = 0.034).

Patients receiving granisetron in addition to antiemtic regimens recommended for LEC had a lower incidence of acute emesis, but no effect was found on delayed phase symptoms or acute nausea.

• The sample size was small with fewer than 100 patients.
• A risk of bias exists because no blinding or random assignment was used.

Common recommendations for CINV prophylaxis with LEC do not include the use of neurokinin 1 (NK1) or 5-HT₃ medications but, rather, rely primarily on the use of increased dexamethasone dosage for control. This study examined the addition of a 5-HT₃ to an LEC antiemetic regimen and demonstrated a significant improvement in acute emesis. Granisetron is more costly than a single-agent antiemetic regimen such as dexamethasone, so additional antiemetic use is seen as controversial or “overtreatment.” Nurses can advocate for consideration of aggressive prevention of CINV to minimize the adverse patient experience with chemotherapy, balanced with recognition of potential cost burdens to the patient. As shown in many other studies, control of nausea (rather than emesis) remains challenging. The strength of findings in this study are limited by the study design. Further well-designed research in this area is warranted.

To evaluate the impact of a nursing intervention incorporating structured symptom assessment and management of the chemotherapy-related symptoms of nausea, vomiting, fatigue, and mucositis.

A consecutive sample of 249 patients, who were scheduled to receive first-line chemotherapy, received structured symptom assessment and management, facilitated by WISECARE+, an information technology–based program. Symptom data was self-report by patients using a paper questionnaire for 14 consecutive days following each cycle of chemotherapy, starting on the first day of treatment.

• In total, 249 patients (22.9% male, 77.1% female) were included.
• Age was 15 to 85+ years.
• Patients had breast, lung, ovarian, or colorectal cancer; osteosarcoma; acute myeloid leukemia (AML); acute lymphoblastic leukemia (ALL); or lymphoma.
• Patients were chemotherapy-naïve, physically and psychologically fit adults.

• Multisite
• Inpatient and outpatient
• Pan-European:  eight clinical sites in Belgium, Denmark, England, Ireland, and Scotland

Patients were undergoing the active treatment phase of care.

The study used a pre- and postintervention design.

• The Chemotherapy Symptom Assessment Scale (C-SAS) rigorously tested for criterion validity, construct validity, test-retest reliability, and internal consistency (a = 0.75).   
• WISE Tool (electronic patient and symptom record/database):  No validity or reliability data were provided.

Patients experienced less nausea postintervention, but pre/post differences were only significant at days 0 to 4 (p = 0.025). Similarly, patients had less vomiting after the intervention but pre and post differences were only significant at days 0 to 4 (p < 0.001). Although changes in oral problems varied at different time points in the study, overall repeated measures analysis showed reduction in oral problems over the course of the study (p = 0.016). There was no effect of the intervention on fatigue.

Structured nursing symptom assessment and management of chemotherapy-related symptoms improved the symptoms of nausea, vomiting, and oral problems (mucositis) related to chemotherapy.

• No appropriate control group was used.
• The study sample was extremely heterogeneous, and the study was possibly underpowered.
• The study did not evaluate interventions specific to mucositis but, rather, the format or structuring of interventions. The study was not designed to specify if the oral problems were strictly mucositis.

The study used patient-assessed symptom data that was collected in real time. The data measured the incidence, severity, and associated distress of the symptoms. Additional research is needed to evaluate the effectiveness of the structured symptom assessment and management of chemotherapy-related symptoms.

To evaluate the efficacy of benzydamine oral rinse for prevention of radiation-induced mucositis

Patients rinsed for 2 minutes four times a day with 15 mL study medication (0.15% benzydamine oral rinse) or identical placebo (in appearance and taste) from the first day of radiation therapy (RT) to the end of treatment. Patients were encouraged to brush their teeth at least twice daily and rinse as necessary with normal saline or sodium bicarbonate. Commercial mouthwashes were prohibited.

• The study reported on a sample of 81 patients with a mean age 56.
• There were 54 females and 27 males.
• All patients had been diagnosed with head and neck cancer and were scheduled to receive a total external beam RT dose of at least 50 Gy in standard fractions and at least 2 oral or oropharyngeal sites were included in the planned RT treatment volume.

The study was conducted at the Radiation Oncology Department of the Cancer Institute at Tehran University of Medical Sciences in 2004-2005.

This was a double-blind, randomized, placebo-controlled trial.

• Patients oral hygiene before and during RT (number of tooth brushing per day) was recorded.
• The Radiation Therapy Oncology Group (RTOG) grading system was used.
• Patients were visited once.

• The statistical analysis revealed that three variables significantly affected the grade of mucositis at the end of the treatment: smoking before and during RT (p = 0.008), chemoradiation (p = 0.002), and receiving benzydamine (p = 0.001).
• Benzydamine produced a statistically significant reduction in mucositis during RT (p < 0.001).
• An increase in the grade of mucositis in the first three weeks of treatment was found in both groups, but, after that time, a remarkable difference was found in this parameter in the two groups. Overall, mucositis scores increased rapidly in severity between the third and seventh week of treatment, with a plateau occurring near the end of RT in the placebo group. In the benzydamine group, the plateau appeared from the third week to the end of therapy.

Benzydamine 0.15% oral rinse was safe and well tolerated. It significantly reduced RT-induced mucositis, which also decreased the interruption of treatment.

• The study was conducted at a single institution.
• The sample size was small, with fewer than 100 patients.
• The authors did not address who conducted the mucositis assessment, opening up the possibility for discrepancy between the evaluators.

Nurses will need to know how to effectively teach patients to use the oral rinse. This study also highlights the importance of daily oral hygiene, which is another good teaching point.

To assess the preventive effects of single and repeat treatment with dexamethasone on delayed nausea and vomiting in patients receiving carboplatin-based chemotherapy

• The study was carried out using the Ehime University Hospital electronic health record.
• It consisted of 64 patients with various malignancies who had been treated with carboplatin-based combination chemotherapy. 
• Chemotherapy-induced nausea and vomiting (CINV) assessment was conducted three times a day for the first five days after the chemotherapy cycle began, using the nausea and emesis score and food intake score.  
• The frequency of need for rescue antiemetics also was assessed.

• The study consisted of 64 patients.
• The mean age was 59 years for the Repeat Treatment group and 62 years for the Single Treatment group. 
• Race was not included in the sample description.
• Just over half of the patients were male (57%).
• Patients were diagnosed primarily with lung and ovarian cancers.
• Patients were excluded if they had complications such as brain metastases that might induce nausea or vomiting, hepatic failure, or ulcerative diseases; were receiving drugs that affect nausea and vomiting (e.g., major or minor tranquilizers, corticosteroids given for other reasons than prevention of CINV); were receiving concomitant radiation therapy; or were receiving total parenteral nutrition (TPN).

This was a single-site study conducted at an inpatient setting in Ehime, Japan.

• All patients were in active treatment.
• The study has applications for late effects and survivorship.

This was a retrospective, observational study.

• Nausea and emesis was rated on a five-point scale (1 = absent,  3 = nausea, 5 = emesis).
• Food intake was rated on a five-point scale (5 = complete intake, 3 = partial meal, 1 = missed meal because of nausea and vomiting).
• Frequency of need for rescue antiemetics was recorded.

• Demographic data was very different for the two groups. The Repeat Treatment Group was comprised of all women with gynecologic cancers. The Single Treatment group was mostly lung cancer, and 71% of the group were male. Data from both groups demonstrated that nausea and vomiting was well controlled on Day 1. The Single Treatment group received almost all placlitaxel, while the Repeat Treatment Group received docetaxel. No patients in the Single Treatment group experienced emesis, and only two subjects experienced emesis in the Repeat Treatment group.
• A significant negative correlation was found between the total nausea and vomiting scores and food intake scores on days 2–5.
• Almost half of the patients (45%) required antiemetics. The frequency of need for rescue antiemetics overall was significantly less in the Repeat Treatment group (26.9%) compared to the Single Treatment group (57.9%).
• Overall response was 0.268 (CI = 0.091–0.789, p = 0.015).

• The authors stated that repeat treatment of dexamethasone may be more effective than single-dose dexamethasone for prevention of delayed CINV (after 24 hours) for patients treated with carboplatin-based combination chemotherapy.
• The Repeat Treatment Group, which consisted of all women treated with multiple doses of dexamethasone, experienced less delayed CINV, as defined by the need for rescue antiemetics.
• Results would need to be confirmed in a larger, prospective clinical trial.

• This retrospective study design relied on the accurate documentation of events by others.
• This study had a small sample size of 64 subjects, with even smaller groups for comparison study.
• The groups were not heterogenous, making comparison difficult. The only constant was the use of carboplatin-based combination chemotherapy.
• All patients were not chemotherapy naïve. History of previous CINV, smoking history, or motion sickness was not described.
• Measurement scales combining nausea and vomiting are not precise enough to know magnitude of nausea.

Patients treated with carboplatin-based combination chemotherapy may benefit from a daily dose of dexamethasone for three days following initiation of chemotherapy.

To evaluate the effectiveness of implementing the new methicillin-resistant Staphylococcus aureus (MRSA) control measures in a tertiary care unit in Japan

The study was conducted in Japan, where the rate of MRSA was the second highest in the Asia-Pacific region—69.5%—in 2002. Although Japan was following infection control practices, the rate was not going down because its survey for the incidence of MRSA was not standardized. In 2003, according to the Society for Healthcare Epidemiology of America (SHEA), Japan started to strictly follow the evidence-based infection control guidelines, which included wearing gowns, masks, and gloves, in addition to implementing contact isolation in a separate room and conducting nasal swab cultures for colonization before discontinuing isolation. Two basic metrics also have been included to conduct surveys on the basis of SHEA and the Infection Control Practices Advisory Committee. To conduct this study, the authors have reviewed patients' data from January 2003–December 2010.

• N = 1,000
• AGE: No specific age noted
• MALES, FEMALES: Not noted
• KEY DISEASE CHARACTERISTICS: MRSA

• SITE: Single site           
• SETTING TYPE: Inpatient           
• LOCATION: Tertiary care center in Japan

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Elder care

• Quasi-experimental cohort study conducted to evaluate the changes of MRSA incidence and MRSA bloodstream infection (BSI) incidence after implementation of the infection control practices in the tertiary care center

•  SAS (version 9.2)

The study showed a significant reduction in MRSA infection or colonization and MRSA BSI (p < .0001) after strongly implementing the new infection control practices in the tertiary setting.

This was the first study conducted at a tertiary level in Japan. It was based on the evidence based-practice showing a significant reduction in MRSA spread and MRSA infection burden, which was proved after strictly following the new practices of MRSA control, including isolating the patient. Through this study, the authors also standardized in discontinuing the isolation of MRSA patients based on SHEA and the Infection Control Practices Advisory Committee.

• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: This study implemented multifaceted interventions, and defining the relative effect of each intervention is impossible. The test used is only able to detect the outcomes and cannot detect changes in trends.

Nurses play an important role in implementing infection control practices, as nurses are the one who come into contact with patients first. Nurses can follow these guidelines and also advise other healthcare workers to do the same.

The objective of this study was to evaluate the efficacy of injectable form of oxycodone on pain and dyspnea in terminally ill patients with cancer.

• Medical records of patients who received continuous subcutaneous oxycodone for pain relief were analyzed. 
• Patients' verbal ratings that were documented were used for analysis. 
• Changes in ratings and use of rescue doses were analyzed.

• The study reported on a sample of 95 patients.
• The mean age was 71.7 years, with a range of 47–92 years.
• Of the sample, 56% were males and 44% were females.
• Tumor types varied; the most common were lung and colon.
• All patients were in inpatient hospice care.

This single-site study was conducted in an inpatient setting in Japan.

• Patients were receiving end-of-life care.
• The study has clinical applicability for palliative care.

The study was a retrospective, descriptive trial.

A three-point symptom severity verbal rating was used.

• The most frequent reason for initiating subcutaneous oxycodone was patient difficulty taking oral medication. 
• Duration of administration ranged from 2.08–111.2 days, with an average of 14.4 days. 
• Initial base dosages used ranged from 4.8–84.6 mg per day, and final base doses averaged 61.8 mg per day, with a range of 3.8–192 mg per day. 
• Most patients were previously receiving parenteral morphine, oral oxycodone, or transdermal fentanyl.
• Effect on pain was rated as moderate in 50% of patients and as high in 41.7%.
• Effect on dyspnea was moderate in 36.5% and high in 4.2%. 
• The most common side effect was drowsiness/somnolence.

Subcutaneous oxycodone administration was effective for reduction of pain and dyspnea in some patients.

• The study had a small sample size of less than 100 patients.
• The study had a risk of bias (no control group, no blinding, and no random assignment).
• Measurement validity/reliability is questionable.
• Data were extracted retrospectively from medical records.

• This study describes the experience of one group in using subcutaneous oxycodone in end-of-life palliative care. 
• The study has many limitations, so the strength of this evidence is low. 
• Subcutaneous oxycodone administration may be a useful alternative for pain and dyspnea management in some patients.

To study the effects of low-level laser therapy (LLLT) in postmastectomy lymphedema

Patients were randomly assigned to either a laser or sham group. Patients in the laser group were treated with GA-As laser device wavelength 890 nm over the arm and axillary areas. Therapy was administered three times a week for three weeks. Then, after an eight-week interval, the same treatment protocol was repeated. Patients received a total of 18 treatments.

• The study involved 11 female patients; eight patients completed the therapy (four in each group).
• The patients were all diagnosed with unilateral postmastectomy lymphedema.

This was a double blind controlled trial.

Investigators measured changes in patients’ limb circumferences, pain scores, range of motion (ROM), heaviness of the affected limb, and desire to continue the treatment. Measurements were taken before and during the treatment at 3, 9, 12, 18, and 22 weeks.

• Eight patients completed the study.
• Reduction in limb circumference occurred in both groups but was greatest in the treatment group.
• Greater pain reduction occurred in the treatment group and desire to continue the therapy was greater in the treatment group. The other two parameters had no difference.

The study reported that LLLT may be effective in reducing arm circumference and pain. Researchers encouraged further studies with larger samples and more therapy. The study used a good design and excellent blinding.

• The study size was very small.
• The design had some similarities to Carati et al. (2003) but did not use same means of objective assessment.

STUDY PURPOSE: To complete a systematic review of palliative care interventions in randomized, controlled trials (RCTs) involving adults with life-limiting illness and meta-analysis to identify the relationship of those intervention with quality of life, symptom burden, and survival of those adults and their caregivers

TYPE OF STUDY: Systematic review of palliative care RCTs

• FINAL NUMBER STUDIES INCLUDED = 56 (30 with cancer)
• TOTAL PATIENTS INCLUDED IN REVIEW = 12,731 patients, 2,479 caregivers 
• SAMPLE RANGE ACROSS STUDIES: The mean patient age was 67 years; no caregiver age data were available. Sample sizes ranged from 27–434 participants.
• KEY SAMPLE CHARACTERISTICS: All patients had life-limiting illnesses. Patients were in hospital, home, and ambulatory settings. Subjective outcomes: Half of reviewed trials had a high level of bias (55.8%), and 16% had a low level of bias; the rest was unknown. Objective outcomes: 44% had a high level of bias, and 6.9% had a low level of bias; the rest was unknown or not measured. Study interventions included physical and psychological aspects of care, with cultural sensitivity underused and underrepresented. Interventions addressed a median of five of eight palliative care components.

PHASE OF CARE: Active cancer care
 
APPLICATIONS: Palliative care

The reviewers looked at nine domains: patient quality of life, physical symptoms, survival, patient mood, advanced care planning, site of death, resource utilization and expenditures, satisfaction with care, and caregiver outcomes resulting from patient symptom burden, survival, and quality of life. Patient quality of life was assessed in 24 studies (4,576 patients). Twelve of those studies had high risk of bias and seven were low risk of bias (five were unknown). Of the seven low-risk-of-bias studies, five reported improved quality of life. In fifteen trials, quality of care was associated with a statistically significant improvement in quality of life. High bias and heterogeneity were significant issues in the analysis. Physical symptoms were reviewed in 29 trials (10,105 people). Seventeen of 29 trials looked at physical symptoms. Of the seven that were low risk bias, after sensitivity analyses, palliative care was not associated with change in symptom burden in four trials at the 1- to 3-month follow-up because of heterogeneity. The reviewers went on to describe that, because of high risk of bias and heterogeneity, no association existed between palliative care and improved survival, patient mood, advanced care planning, site of death, and resource use.

In this review, the evidence suggests that palliative care intervention improves symptom burden and patient quality of life in those who have been diagnosed with an advanced cancer or with a serious illness. The review was not able to establish if palliative care improved caregiver quality of life. Significant issues existed with assessing the association of palliative care with quality of life, symptom burden, and adult survival because of the problematic quality and rigor of RCTs used in the systematic review and meta-analysis.

• Mostly low quality/high risk of bias studies
• High heterogeneity
• The authors reported multiple limitations of this review, including the wide spectrum and diversity in palliative care interventions. This diversity contributed to heterogeneity to the meta-analysis. Missing data, the exclusion of quasiexperimental studies, and trial statistical analysis may have contributed to underpowered studies in the meta-analysis. Across trials, clinical trial data were not uniformly reported, and information about points in time when patient and caregiver may have received palliative care was lacking. The risk of study bias (a subjective interpretation) and use of the Cochrane Risk of Bias tool may not have defined specifics of behavioral interventions found in many of the trial studies used in the meta-analysis and systematic review.
• No specific information provided on evaluation rating forms
• No caregiver-only studies included in meta-analysis to measure caregiver outcomes
• No trial focused on influence of culture on intervention assessment or effect.

Multiple RCTs have established that palliative care improves patient experience and quality of care. Insufficient evidence exists to assess whether that is true for patient and caregiver dyads or for caregivers assessed separately from patients. More studies reflecting methodological rigor, cultural sensitivity, and quality to identify aspects of effective palliative care for both patients and caregivers remain a priority.