PHASE OF CARE: Multiple phases of care
 
APPLICATIONS: Pediatrics, elder care, palliative care

Various psychosocial interventions, including educational interventions, cognitive behavioral therapy, relaxation training, and supportive group therapy, were found to reduce the length of patients’ hospital stays, decrease the number of days to proficiency in self-care for stoma, decrease levels hospital anxiety and depression, and increase quality of life.

Various forms of psychosocial interventions were used to improve outcomes, but no clear winner was found. All forms seemed to improve patient outcomes.

• A limited number of studies met the inclusion criteria.

Evaluate the wound healing effects of RhEGF in patients with radiation-induced oral mucositis.

RhEGF 25 mcg/day was applied topically to the oral cavity twice daily for seven days.

The study was comprised of 11 patients, with an age range of 34-70 years.

Females: 2, Males: 9

Diagnosis Information: Nine patients with head and neck cancer, two patients with lymphoma

Other Key Characteristics: Concurrent chemo/RT five patients. Patients had severe mucositis at the point of study entry.

Single site: Seoul, Korea

Prospective trial--pilot study

Unaided oral and soft palate evaluation was done on day seven.

Oral mucositis was scored according to RTOG criteria.

All patients showed improvements in oral mucositis, with decreased mean RTOG grades. Two patients with grade 4 improved to grade 3; two patients with grade 4 improved to grade 2; five patients with grade 3 improved to grade 2; and two patients with grade 3 improved to grade 1. None of the patients had to interrupt RT because of acute mucositis.

Topical treatment with RhEGF has a therapeutic effect on RT-induced oral mucositis.

Small sample size (pilot study). Mucositis evaluated by unaided eye and restricted or oral and soft palate-may have not been consistent grading if done by different individuals. Sample was too varied, including nasopharyngeal tumors, oropharynx tumors, and hypopharynx tumors and lymphoma. These all differ greatly in the treatment techniques, amount of radiation given, and severity of reaction.

More data are needed to determine effectiveness. Topical applications have limitations as far as adherence to the intended amount of drug and effective coverage of mucosa with medication. Topical application may be easier to apply, but not for everyone, and depending on the taste, an aversion to the taste may occur over time.

To compare the efficacy, side effects, and use of rescue medication associated with two two-hour sustained-release morphine preparations: SR1 (MS Contin, Purdue Frederick Co., CN) and SR2 (Oramorph SR, Roxane Laboratories, Columbus, Ohio)

Patients' pain had been stabilized prior to treatment-group random assignment. Stabilization was defined as pain requiring fewer than four rescue doses in the previous 24 hours and pain rated as moderate or less for 48 consecutive hours. Patients were randomly assigned to SR1 or SR2 medication every 12 hours for five days. Investigators gathered data about side effects and compliance by means of daily telephone calls. Investigators assessed the acceptability of the medications at the end of the study, by asking patients if they wanted to continue taking the drug they were receiving.

• The sample was composed of 32 patients.
• Mean patient age was 63.5 years. The age range was 27–79 years.
• Of all patients, the percentage of females was 44% and the percentage of males was 56%.
• Most frequent cancer types were lung cancer and gynecologic and colorectal cancers. The majority of patients had metastatic disease.

• Single site
• Outpatient
• Cleveland Clinic, Cleveland, Ohio, United States

Randomized open-label, parallel-group trial

Five-point rating scale (0 = none, 4 = severe), to measure pain

Authors noted an overall trend toward lower pain rating scores in the SR2 group. This difference was statistically significant (p = 0.05)  on day 3 only. The total accumulative rescue dose over the study period was significantly higher for SR1 (p = 0.03). Authors noted no significant differences in side effects between the two groups. All patients taking SR2 elected to remain on that medication; 75% of patients preferred to continue taking SR1. Median morphine dose overall was higher in the SR1 group. The sample size was determined by power analysis.

The study suggests that, compared to SR1, SR2 may provide better analgesic efficacy, resulting in less overall need for rescue medication.

• The study had a small sample size, with fewer than 100 participants.
• The study used only one measure of pain intensity.
• The study duration was very short, just five days.

Findings suggest that the efficacy of various formulations of controlled- and sustained-release oral morphine preparations can be different. Nurses should be aware of this in the context of managing chronic pain. Researchers should undertake long-term studies to provide clinically relevant data in this regard.

A phase II study of methylphenidate for depression in patients with advanced cancer

Patients who were identified as being depressed by a palliative medicine attending physician were treated with methylphenidate twice daily. Doses were titrated per regimen until response was obtained. Patients were assessed during a telephone call or bedside interview. The study timeframe was seven days.

• N = 30
• MALES: 50%, FEMALES: 50%
• KEY DISEASE CHARACTERISTICS: Primary cancer sites: breast (5), esophagus (4), head and neck (4), lung (4), pancreas (4), colorectal (2), and other (7)
• OTHER KEY SAMPLE CHARACTERISTICS: Inclusion criterion was the answer of “yes” to the question, “Are you depressed?” with no current or previous antidepressant use.

• SITE: One center was included.
• SETTING TYPE: Inpatients and outpatients were enrolled in the palliative care program.

• Question, “Are you depressed?”
• Other symptoms (anorexia, concentration problems, fatigue, and sedation) were assessed by a categorical rating (none, mild, moderate, or severe) before starting methylphenidate and daily thereafter.
• Pain was assessed using a 0–10 scale.
• Known side effects of methylphenidate also were assessed.
• Satisfaction question: ”Are you satisfied with the way the drug affected your mood?” was asked at the end of the study on day seven.

Depression was resolved in all patients, most on day three. The maximum daily dose needed was 20 mg. Other symptoms also improved, mean pain scores significantly decreased, and all who responded to treatment were satisfied with therapy.

• Small sample with no randomization
• Long-term efficacy and side effect data are needed.
• Single-site data are less transferable than multi-site data.

To measure the long- and short-term effects of a group family cancer caregiver psychoeducational intervention delivered in palliative home care settings on caregiver preparedness, health perception, anxiety, reward, burden, and depression

Study caregivers meeting inclusion criteria received random assignments to the psychoeducational or control group, which received standard care support. The former group participated in theoretically based, weekly afternoon group sessions delivered by an interdisciplinary team in a palliative care setting to increase caregiver preparedness for family member palliative care needs. Each session lasted two hours per week over a three-week period. The use of a session manual ensured consistent structure and content presentation to all groups. Content included patient symptom management, daily nutritional care, caregiver support, and existential issues related to family member diagnoses. Both control and intervention groups received standard care from patient palliative care settings. Data collection occurred for both groups at baseline, the end of the intervention, and two months after the intervention.

• N = 194    
• AVERAGE AGE = 61.5 years
• MALES: 34%, FEMALES: 66%
• KEY DISEASE CHARACTERISTICS: Overall, 90% of the patient sample had cancer with a life expectancy of at least five weeks to allow intervention completion.
• OTHER KEY SAMPLE CHARACTERISTICS: In total, 90% of caregivers attended two or three sessions, 74% were married, almost half were employed or retired, and more than half lived with the patient. Spouses were the recipients of the caregiver intervention in 48% of study participants.

• SITE: Multi-site    
• SETTING TYPE: Home    
• LOCATION: Ten specialized palliative home care settings in metropolitan Sweden

• PHASE OF CARE: End of life care
• APPLICATIONS: Palliative care 

Randomized, unblided, controlled trial consistent with the Consolidated Standards of Reporting Trials

• Preparedness for Caregiving Scale (PCS): Assesses degree of caregiver-perceived ability to provide family member with palliative care; good validity, reliability and internal consistency
• Caregiver Competence Scale (CCS): Assesses caregiver-perceived degree of competency; reflects high internal consistency
• Rewards of Caregiving Scale (RCS): Measures caregiver degree of perceived rewards of caregiving; reflects high internal consistency
• Caregiver Burden Scale (CBS): Measures five aspects of strain, isolation, emotional response and context of care; reflects high internal consistency
• Health Index: Measures degree of caregiver perceived health; high internal consistency
• Hospital Anxiety and Depression Scale (HADS): Measures degree of experiencing those concepts in palliative care; high Cronbach’s alpha scores on two subscales

The study had 21 intervention sessions programs with an average of four caregivers per session. The mean age of the 175 patients in the study was 72 years, and greater than half of the sample was female and enrolled in Swedish palliative homecare for a median time of four months. In the first caregiver follow-up, the intervention group had significant increases in preparedness (p = 0.041) and caregiving competency (p = 0.001) from baseline as compared to control group (p = 0.041 by simple linear regression analysis). The second follow-up showed significantly higher intervention group scores on caregiver preparedness as compared to the control group (p = 0.12). No other significant findings for caregiving competency, rewards, burden, health, anxiety, or depression were found.

This study’s psychoeducational intervention showed significant improvements in caregivers’ preparedness in short- and long-term measurements and in caregivers’ perceived competency in the short-term. The nature of the intervention (three weeks) may have minimized significant effects on caregiver preparedness, competence, and rewards of caregiving compared to longer, previously published, six-session interventions that found such effects. No negative intervention effects occurred although other caregiver variables did not improve under investigation. Baseline data indicated that caregivers had low to moderate levels of burden, depression, and anxiety, and they had positive health perceptions that may have indicated that a short-term intervention would have a limited effect.

• Risk of bias (no blinding)
• Subject withdrawals ≥ 10% 
• Other limitations/explanation: Possible inconsistency with standard care delivery across settings

There is a need for diverse cultural randomized, controlled studies defining successful interventions that improve caregiver quality of life during palliative care. This Swedish study reflected high rates of caregiver attrition because of patient deaths or health deterioration. This suggests a critical need for innovative, personalized, short-term interdisciplinary healthcare interventions housed within the context of healthcare systems to meet caregiver needs.

The purpose of the study was to investigate the efficacy, safety, and pharmacokinetics of various single doses of pegfilgrastim per chemotherapy cycle in women receiving chemotherapy with doxorubicin and docetaxel.

On day 2 of each chemotherapy cycle, 24 hours after chemotherapy completion, patients either received a single subcutaneous injection of pegfilgrastim or began daily injections of filgrastim for 14 days or until absolute neutrophil count (ANC) recovery to 10 x 10⁹/L after nadir. Within the pegfilgrastim group, patients received 30, 60 or 100 mcg/kg. Filgastrim was given at 5 mcg/kg per day. Patients were randomly assigned to treatment group. Treatment was repeated for each cycle, up to four cycles. Blood samples were collected at screening, before each chemotherapy cycle, and once weekly during cycle 1. Findings were evaluated regarding duration of grade 4 neutropenia and rates of febrile neutropenia.

• 137 participants
• The mean age was 50 years (SD = 9)
• Women made up 100% of the sample.
• All had breast cancer and were receiving the same type of chemotherapy regimen.  
• About 33% had stage II disease, 33%had stage III, and about 33% had stage IV disease.

Multiple sites in the United States

Active antitumor treatment

Randomized dose finding phase II. Analysis also included open-label phase data.

• Grade 4 neutropenia defined as ANC less than 0.5 x 10⁹/L
• Febrile neutropenia was defined as grade 4 neutropenia plus an oral temperature of 38.2ºC or higher.

Mean duration of grade 4 neutropenia in patients on filgastrim during cycle 1 was 2.5, and was 2.0 in patients receiving 30 mcg/kg pegfilgastrim (95% CI [0.35,1.93]). There was not a statistically significant difference in cycle 1 with the other pegfilgastrim dosage groups. Mean time to ANC recovery for cycle 1 was 9.4 days with filgastrim, 9.5 with 100 mcg pegfilgastrim (p = 0.05), 10.3 with 60 mcg (p = 0.05) pegfilgastrim,  and 11 with 30 mcg doses (not significant). There were no significant differences across groups in any other outcome measure. There were no significant differences in adverse events. A single dose of pegilfrastim produced a sustained serum concentration, with maximum concentration at about 24 hours, and was sustained until ANC nadir.

Pegfilgastrim at a single dose per chemotherapy cycle was similar to daily filgastrim in efficacy and adverse effects.

• Risk of bias (no blinding)
• Selective outcomes reporting
• Measurement/methods not well described
• Results reporting is somewhat confusing, as the sample sizes per measure vary throughout.  
• Only data from cycle 1 was fully analyzed.  
• Authors state that they pooled results from the open-label phase and randomized study phase, but it is not clear which data are which.

Findings suggest that single dose of pegfilgastrim per chemotherapy cycle is similar to daily filgastrim dosing in terms of safety and efficacy. The need for fewer subcutaneous injections with single dosing may be beneficial to patients.

To investigate the effects of rye bread and cultured buttermilk on bowel function, colon metabolism, and gastrointestinal symptoms in adults with constipation.

For three weeks before the beginning of the study, participants were instructed not to use products containing Lactobacillus rhamnosus GG (LGG). At the end of the baseline period, participants were randomized into one of five groups.

1. Rye bread: minimum of 240 g per day of whole-grain rye bread
2. LGG: 400 g per day of cultured buttermilk with LGG
3. Rye bread plus LGG: minimum 240 g per day of whole-grain rye bread and 400 g per day cultured buttermilk with LGG 
4. Laxative: laxative use as usual and maximum of 192 g per day of white wheat bread 
5. Control: maximum of 192 g per day of white wheat bread

Foods considered to have laxative effects (e.g., prunes, flax, fiber products) were only allowed for the laxative group. All participants were permitted laxative use as necessary after first contacting the principal investigator. Participants were to exclude products containing other lactic acid bacteria.

Participants collected all feces for five days during the baseline week, one day during week 1, and five days during week 3. The samples were kept frozen until taken to the study center. Sitzmarks^® Radiopaque capsules were used to determine total intestinal transit time (TITT) measurements.

• The study reported on a sample of 51 patients.
• Mean patient age was 46 years (range 22–78).
• The sample comprised 47 women and four men.
• Patients self-reported constipation and laxative use.

A metropolitan area in Helsinki, Finland

This study had a randomized, unblended, 2 x 2 factorial design (LGG given, LGG not given, rye bread given, rye bread not given).

Patients self-reported the following.

• Stool consistency (-1 = loose, 0 = normal, 1 = hard)
• Ease of defecation (-1 = easy, 0 = normal, 1 = straining)
• Rank of abdominal symptoms (i.e., abdominal pain, flatulence, borborygmi, abdominal bloating, constipation, diarrhea) (0 = no symptoms, 1 = mild, 2 = moderate, 3 = severe)

• Rye bread, compared with white wheat bread, shortened TITT by 23% (p = 0.04), increased weekly defecations by 1.4 (p = 0.014), softened feces (odds ratio [OR] = 3.98, p = 0.037), eased defecation (OR = 5.08, p = 0.018), increased fecal acetic acid by 24% (p = 0.044), increased fecal butyric acid by 63% (p < 0.001), and reduced fecal enzyme (β-glucuronidase) activity by 23% (p = 0.014).
• Rye bread, compared with laxatives, reduced TITT by 41% (p = 0.006), reduced fecal enzyme (β-glucuronidase) activity by 38% (p = 0.033), and reduced fecal pH by 0.31 units (p = 0.006).
• LGG did not significantly improve bowel function or affect colonic metabolism.
• Adverse abdominal symptoms did not significantly differ among the study groups.

In adults with constipation, bowel function and colonic metabolism may improve more with rye bread consumption than with wheat bread consumption or common laxative use without causing adverse abdominal symptoms. Cultured buttermilk with LGG did not significantly improve bowel function or affect colonic metabolism in this population.

• The sample size was small (fewer than 100). In addition, the study design was 2 x 2 factorial with a control, so five groups existed. Therefore, the already small total sample size (N = 51) was distributed into very small study groups of only 8 to 12 participants each. 
• The study was not blinded.
• The ratio of women to men was not balanced.

Rye bread consumption may be more effective in relieving constipation than wheat bread or commonly used laxatives in adults. However, the convenience sample of volunteers was small, comprised predominately men, and did not include patients with cancer. Additional study is warranted in a larger population that includes patients with cancer, as well as a balanced number of women and men.

The 10-day study had two arms: alprazolam 0.5 mg three times a day or progressive muscle relaxation three times a day.

• The study reported on a sample of 147 patients.
• Sample age range was 18–70 years.
• Patients were receiving active cancer treatment at three centers.
• Patients had Karnofsky scores greater than 60.

A randomized controlled trial (nonblinded) design was used.

• Covi Anxiety Scale
• Raskin Depression Scale
• Hamilton Anxiety Rating Scale (HARS)
• Symptom Checklist–90 (SCL-90)
• Patient’s Global Impression Scale
• Physiologic measures: Pulse and blood pressure

There was significant decrease in anxiety (HARS, ABS, SCL-90 subscale) and depression (SCL-90 subscale) in both treatment arms (p < 0.001). There was minimal change in pulse and blood pressure.

• The study yielded equivocal findings regarding alprazolam and progressive relaxation. 
• The study had no long-term follow-up, only a 10-day period.
• The sample was largely white (87%) and female (64%).
• Older study

• FINAL NUMBER STUDIES INCLUDED = 11 (nine randomized, controlled trials and two quasiexperimental designs)
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,033
• SAMPLE RANGE ACROSS STUDIES: 9–385 patients
• KEY SAMPLE CHARACTERISTICS: All had advanced cancer

PHASE OF CARE: End of life care
 
APPLICATIONS: Palliative care

Interventions included massage or aromatherapy massage (five studies), physical therapy and massage (one study), transcutaneous electrical nerve stimulation (TENS, one study), acupuncture (one study), reflexology (one study), warm water footbath (one study), biofeedback-assisted relaxation (one study), and varied strategies of relaxation and imagery with nature sounds (one study). The effectiveness of massage was mixed, TENS had the potential to reduce pain on movement, acupuncture reduced pain immediately after the intervention but the benefit was transient, reflexology showed no effect, relaxation with biofeedback was beneficial, and psychoeducational and behavior strategies had only a short-term effect. Most studies were found to have a relatively high risk of bias.

There was insufficient evidence to draw firm conclusions about the effectiveness of nonpharmacologic interventions to reduce pain among patients with advanced cancer.

• Very few studies included for most of the specific interventions
• High risk of bias of studies were included

Treating pain is a high priority among patients with advanced cancer receiving palliative care. The effectiveness of many nonpharmacologic interventions is unclear and warrants additional well-designed research. Most of the evidence involved studies in inpatient settings. Additional research among outpatients and those receiving palliative care in the home is needed. Nonpharmacologic interventions are generally low-risk. The identification of approaches than can facilitate reductions in pain would be beneficial for patients with cancer-related pain.

To review current knowledge and provide guidance to clinicians regarding care for the prevention of mucositis, particularly pediatric patients

The databases searched and search keywords were not stated.

This study has clinical applicability to pediatrics.

Experts generally agree that oral care is important and that oral care instructions should include brushing teeth 2–3 times per day, flossing, rinsing with a bland agent such as sterile water, using fluoride therapy, and using mouth moisturizers. These measures are recommended regardless of hematologic status. Experts recommend changing toothbrushes frequently. Dental assessments should be performed at initial diagnosis. This report provides a summary of the oral care guidelines of four organizations.

This report provides general recommendations for oral hygiene but no specific review of evidence or evidence quality.

This report provides a general overview and supports the development and implementation of specific protocols based on evidence for oral care.