To evaluate effects of nurse navigation on depression among patients newly diagnosed with cancer

The nurse navigation intervention was designed to address care delays, care coordination, information needs, and help in patient decision-making and lack of emotional and social supports for patients. Patients randomized to receive the intervention had weekly nurse navigator contacts for 16 weeks. Nurses used a distress thermometer to identify problems and monitor progress. Those with high distress scores and suspected to have depression were referred for further assessment and treatment. Outcomes were evaluated in a four month follow-up telephone interview.

• N = 248  
• MEAN AGE: 61.3 years
• MALES: 11.3%, FEMALES: 88.7%
• KEY DISEASE CHARACTERISTICS: Breast, colorectal, and lung cancers, mostly stage I and II
• OTHER KEY SAMPLE CHARACTERISTICS: Most had at least some college education, they were predominantly Caucasian, and the majority were married.

• SITE: Multi-site  
• SETTING TYPE: Not specified    
• LOCATION: Seattle, WA

PHASE OF CARE: Active antitumor treatment

• Randomized cohort controlled study
• Secondary analysis

• Patient Health Questionnaire-9 (PHQ-9)
• Distress Thermometer (DT)
• Patient Assessment of Chronic Illness Care (PACIC)

Most patients did not have depression at baseline. For those with higher baseline PHQ-9 scores, nurse navigation patients had higher PACIC scores; however, differences were not statistically significant.

Findings did not show that nurse navigation was of greater benefit for patients with depressive symptoms or had an impact on depression scores.

• Risk of bias (no appropriate attentional control condition)

Findings of this study did not show that nurse navigation affected depressive symptoms or was of greater benefit to patients with depression among those newly diagnosed with cancer.

• FINAL NUMBER STUDIES INCLUDED = 17 (10 experimental and seven descriptive)
• SAMPLE RANGE ACROSS STUDIES: 6–64 patients (experimental), 5–100 patients (descriptive)
• KEY SAMPLE CHARACTERISTICS: Age range was 6–84 years; only one study reported on patients with cancer (n = 23)

PHASE OF CARE: Late effects and survivorship

Improvements were noted in fatigue in eight of 17 studies, and improvement was noted in cognition in 14 of the 17 studies reviewed. Neurofeedback interventions were well tolerated with only three studies reporting any side effects.

Insufficient evidence was presented to suggest that these complementary and alternative medicine therapies (neurofeedback) are useful in the management of cancer-related fatigue or cognition.

• Only one of the 17 studies included a population of cancer survivors (BCS, n = 23)
• Heterogeneity of other samples; majority non-clinical samples
• Majority of studies were low-quality

Additional research needs to be done before this type of therapy can be recommended.

To study the efficacy of palifermin for prophylaxis of OM in pediatric patients undergoing hematopoetic cell transplant (HCT)

Patients were randomly assigned to receive either IV palifermin 60 mcg/kg per day starting three days prior to transplant conditioning chemotherapy or placebo. All patients received basic oral hygiene and invasive nutrition as needed. All other aspects of care were essentially the same between groups. OM was assessed daily from 7 days prior to transplantation to 28 days after transplantation. Assessment was conducted by the same clinician.

• N = 54
• MEDIAN AGE = 11 years
• AGE RANGE = 7–16 years
• MALES: 48%, FEMALES: 52%
• KEY DISEASE CHARACTERISTICS: All had lymphoblastic leukemia and were undergoing HCT.

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Italy

• PHASE OF CARE: Active antitumor treatment

• Placebo-controlled randomized controlled trial

• Oral Mucositis Daily Questionnaire (OMDQ)
• World Health Organization (WHO) Oral Mucositis Toxicity Scale

Significantly fewer patients in the palifermin group developed grade 2 (p = 0.038) and grade 4 (p = 0.006) mucositis compared to the placebo group. Grade 4 was seen in 11% of patients in the palifermin group and 59% of patients in the control group. Fewer patients in the palifermin group had any grade mucositis, but not all differences in grades were statistically significant. The duration of grade 3 and 4 OM in patients in the palifermin group was three days compared to eight days in the control group (p < 0.001). The only adverse reactions reported were rashes and altered taste, lasting for 48–72 hours. The cumulative morphine daily dose per body weight was lower in the palifermin group (p = 0.04).

Palifermin was shown to effectively reduce the severity, prevalence, and duration of OM among pediatric patients undergoing HCT and was not associated with any significant adverse effects.

• Small sample (< 100)
• Risk of bias (no blinding)

Palifermin was shown to be beneficial to pediatric patients undergoing HCT for primary prophylaxis for OM. OM is one of the most painful and debilitating effects of high-dose myeloablative chemotherapy. Nurses can advocate for the consideration of palifermin in these patients. Additional research in support of these findings is warranted, and research regarding the potential role of palifermin in other types of chemotherapy regimens associated with OM is needed.

The purpose of the study is to investigate the use of acupuncture during chemotherapy on white blood cell count, absolute neutrophil count, and endogenous G-CSF level.

Patients were randomly assigned to receive acupuncture or sham acupuncture sessions 2–3 times weekly beginning one week prior to chemotherapy cycle 2 and ending at the beginning of cycle 3 of chemotherapy.  A standard acupuncture protocol was administered by five different experienced providers. An electroacupuncture machine was connected to needles and a heat lamp was placed above the feet of the patient. Lab work was obtained at baseline, the nadir of cycle 1 and then every seven days during the study period.

• The sample consisted of 20 participants with a mean age of 50.4 years.
• All participants were female.
• All had newly diagnosed ovarian cancer and were receiving myelosuppressive therapy.

Multiple sites in New England

Active antitumor treatment

 Double-blind, randomized, placebo-controlled trial

• Complete blood counts
• NCI Common Terminology Criteria for Adverse Events (version 3)
   

Five patients withdrew from the trial due to disease progression, side effects of chemotherapy, or time commitment. After patients received six acupuncture sessions, there was a significant different in white blood cell counts between groups in favor of acupuncture (p = 0.04). These differences remained at nadir and the second recovery day. Average absolute neutrophil counts (ANCs) were higher in the acupuncture group at several time points, but this difference was not statistically significant. G-CSF levels in the acupuncture group were about four times higher; however, this difference between groups was not statistically significant.

Acupuncture may be helpful in  in patients receiving myelosuppressive chemotherapy in reducing neutropenia and associated problems. More definitive study in this area is needed to better evaluate the clinical efficacy of acupuncture in this area

• Small sample size (less than 30 participants)
• Intervention was expensive, impractical, or training was needed
• Recruitment was done over 24 months; however, few patients out of a large pool were successfully enrolled. The dropout rate in the study was high. These factors raise the question of practicality to provide this type of intervention. 
• The authors noted that patient travel to receive the acupuncture treatments was a barrier encountered.

Study findings suggest some promise for use of acupuncture among strategies for the prevention of infection; however, due to the very small sample size, no firm conclusions can be drawn. Issues seen in this study point to the problem of time and frequent travel for patients involved in cancer treatment to participate in this type of intervention. Further research in the use of acupuncture with larger trials is needed for further evaluation of efficacy.

To test the feasibility, cultural sensitivity, and effect of an expressive writing intervention.

Patients completed baseline assessments by mail and received three envelopes that were to be opened according to labels for study week. They were asked to write about their deepest feelings about having cancer and about the strategies they used for coping. They were to write for 20 minutes each week. After the last writing assignment and three and six months later they completed study questionnaires by mail. Focus group interviews were also conducted.

• The sample was comprised of 19 women.   
• Mean age was 54 years (range 31–83).
• Patients had stage I and II breast cancer. 
• Mean time since diagnosis was two years.
• Patients has been in the United States an average of 19 years.
• Most patients had a household income of less than $15,000, and more than 90% had a high school education.

 The study used a quasiexperimental, pre-/post repeated measures design.

• Functional Assessment of Cancer Therapy–Breast (FACT-B)
• Physical symptoms checklist
• Positive and Negative Affect Score (PANAS)
• Posttraumatic Growth Inventory (PTGI)
   

At three months, the change in fatigue showed a partial eta² of 0.066, and eta² for posttraumatic stress was 0.208. There was 100% compliance in completing writing assignments. Patients commented that the activity was meaningful for Chinese women.

 Findings suggested that expressive writing is a feasible and acceptable intervention for Chinese American women.

• The study had a small sample size, with less than 30 patients.
• The study had risks of bias due to no control group, no blinding, no random assignment, and the sample characteristics.*
• Unintended interventions or applicable interventions not described would have influenced the results.
• Outcomes reporting was selective.
• Patient withdrawals were 10% or greater.
• * The activity may not be acceptable to other cultural groups or to men. There was a 15% drop-out rate, suggesting that not all women appreciated the approach. The authors provided no confidence intervals for the statistics reported. Repeated measures may have given testing threat to validity.

Expressive writing appeared to be an acceptable intervention for these women. The study design and sample size did not allow for any firm conclusions about effects to be drawn.

To test the effect of emotionally expressive writing in a randomized, controlled trial of patients with metastatic breast cancer (MBC) and to determine whether the effects of the intervention varied as a function of perceived social support or time since metastatic diagnosis.

The sample was recruited from several sources; all contact occurred via telephone, mail, or email. Patients were randomized to either an emotional or control writing condition and were mailed a packet of sealed envelopes. Trained research assistants telephoned women at the beginning of each of the four writing sessions within a three-week interval to read instructions and called back 20 minutes later to ask the women to stop writing. The women mailed the essays to the research office at the end of each session for analysis. Outcomes were measured three months after the final writing.

• The sample was comprised of 62 women.
• Mean age was 53.8 years (standard deviation = 10.3 years; range 29–78).
• Patients had stage IV MBC.
• Patients could be on or off treatment.

• Single site
• Home
• California

• Patients were undergoing the long-term follow-up phase of care.
• The study has clinical applicability for end of life and palliative care.

The study was a randomized, controlled trial.

• Center for Epidemiologic Studies Depression Scale (CESD)    
• 7-Item Intrusion Scale
• Impact of Events Scale (IES)
• Negative Somatic Symptoms (Pennebaker 1982)
• Pittsburgh Sleep Quality Index (PSQI)
• Demographic/medical variables
• Questionnaire reactions to participation at three months

No significant differences existed between the two experimental conditions on demographic/medical variables, depression, intrusive thoughts, or sleep disturbances. There were no main effects for the experimental condition to predict intrusive thoughts. Perceived emotional support at study entry interacted with the experimental condition to predict IES-Intrusion (F [1, 56] = 11.61; p = 0.001). For women with a decreased level of emotional support at entry, the effect of the experimental condition was significant (p = 0.002). There was no effect on sleep in newly diagnosed patients but increased sleep disturbances for women who had been diagnosed more than 4.7 years.

Contrary to the hypothesis, expressive writing did not reduce psychological distress or improve physical health as quantified by fewer sleep disturbances and somatic symptoms.

• The study had a small sample size, with less than 100 patients.
• The study lacked heterogeneity and was white.
• Physical health measures relied on self-reports.
• The study was underpowered to detect an effect in the subset of women who had not previously participated in a cancer support group or talked with a mental health professional about cancer.

Expressive writing may be helpful for a subset of patients with MBC (those with low levels of social support and recently diagnosed) and contraindicated for others (those living longer with the diagnosis). Further studies should explore alternative writing topics, such as perceived benefits of the cancer experience.

To test the effects of emotionally expressive writing versus disease-related writing on patients with metastatic breast cancer; to determine whether the effects of expressive writing vary as a function of perceived social support or time since diagnosis of metastasis   

Investigators used three sources of recruitment: a larger study, flyers, and advertising on a website and Listserv. All contact with patients was via telephone, postal mail, or email. Participants completed baseline assessments, which gathered data about demographics and emotional support. Investigators collected saliva samples. Patients were randomized to either the emotional or control writing condition, and patients received information about the exercises. Patients were scheduled to participate in four 20-minute sessions that occurred at patients' convenience within a three-week interval. A research assistant monitored compliance. After each session, a patient mailed her writing to the research office. At study entry and three months after the final writing session, a by-mail questionnaire measured outcomes according to stated instruments.

• The sample was composed of 62 participants, 31 were in the expressive writing group and 31 were in the control group.
• Mean patient age was 53.8 years (SD = 10.3 years). The age range was 29–78 years.
• All participants were female.
• All patients had stage IV metastatic breast cancer.
• Participants were eligible for the study if they could complete the writing exercises and assessments in English and if they were undergoing any medical treatment for cancer.
• Of all participants, 74% were college-educated, 71% were married or partnered, 87% were white, and 78% were not working outside the home. On average, participants had been diagnosed with breast cancer 7.9 years ago. Most had received the diagnosis of stage IV cancer 3.3 years ago. The cancer of most participants had metastasized to the bone.
• Of all participants, 72% had had experience with support groups, 63% were working on cancer-related issues with a mental health professional, and 63% had journaled about their cancer experience.
   

• Multisite.
• Home.
• California (October 2006–April 2009); however, information was posted online and on a Listserv.

• Phases of care: multiple phases of care
• Clinical applications: supportive care (end-of-life and palliative care), late effects and survivorship
   

Randomized controlled trial

• Center for Epidemiologic Studies Depression Scale (CESD), a 20-item scale to assess the frequency of depression symptoms in the past week.
• Seven-item intrusions subscale of the Impact of Event Scale (IES), to measure the extent of distress caused by cancer-related intrusive thoughts over the past week.
• Instrument, developed by Pennebaker (1982), to measure negative somatic symptoms. The instrument, shown to be responsive to the expressive writing intervention, asks respondents to report the number of days in the past month on which they experienced each of nine somatic symptoms.
• Pittsburgh Sleep Quality Index (PSQI), to assess sleep quality over the past month and yield a total sleep disturbance score. Scores of 5 and above indicate clinically significant sleep disruptions. This scale has been used as an outcome measure in previous trials of expressive writing as practiced by patients with advanced cancer.
• Items adapted from a tool by Alferi et al. (2001), to measure perceived emotional support.
• Questionnaire, to gather demographic data.
   

• Investigators observed no significant main effects of the experimental condition, with respect to demographic or cancer-related variables or experience with cancer, support groups, psychotherapy, or journaling. 
• Investigators reported no significant group differences, at study entry, regarding symptoms of depression, intrusive thoughts, sleep disturbance, somatic symptoms, or perceived emotional support.
• A significant condition, correlated with social support interaction, emerged regarding intrusive thoughts: Expressive writing was associated with reduced intrusive thoughts in women reporting low emotional support. The significant condition correlated with time, because investigators also observed an interaction between the measure of metastatic diagnosis and the measures of somatic symptoms and sleep disturbance. Relative to the control, participants in the intervention who were more recently diagnosed had fewer somatic symptoms. Intervention participants with longer diagnosis duration exhibited increases in sleep disturbance.
• Among outcome variables, only scores reflecting depression symptoms correlated significantly with intrusive thoughts (r = 0.56, p < 0.001), sleep disturbance (r = 0.30, p = 0.019), and somatic symptoms (r = 0.53, p < 0.001). None of the correlations between the other three outcome variables was significant.

Expressive writing did not produce reduction in psychological distress or improvement in physical health. The intervention may be beneficial for a subset of patients with metastasis and contraindicated for other patients.

• The study had a small sample size, with fewer than 100 participants.
• Participants were predominantly white and well educated.
• Outcome measures related to physical health relied on self-reporting.
• The study was underpowered in regard to detection of main effects. Study design should have included alternative writing topics or a control topic unrelated to cancer.
   

Expressive writing may be of benefit to a certain subset of patients. The intervention is cost-effective and an activity that patients with low levels of social support can do. Future study should apply the expressive-writing approach to vulnerable, underserved, and understudied populations and offer broader topics for expressive writing (e.g., benefits of the cancer experience, a topic unrelated to cancer). Investigators should provide writing supplies. Future research should consider privacy protections (possibly from family members), especially in cultures that place great value on the privacy of written material.

To test the hypothesis that d-methylphenidate (d-MPH) would produce a significant reduction in fatigue compared to placebo.

Patients were randomized to receive the study drug or an identical appearing placebo; packaging and labeling were done by a pharmacist not involved in other aspects of the study. Patients received 5 mg of the drug twice daily by mouth. Measures were performed at baseline and at weeks 1 and 8, which was the end of the double-blind treatment phase. Weekly dose modifications were performed at the investigators' discretion based on the magnitude and duration of response assessed weekly by Clinical Global Improvement–Impression (CGI-I) scores. The maximum allowable total daily dosage was 50 mg/day in two to three doses per day.

• In total, 154 patients (94.1% women) with cancer who met the proposed International Classification of Diseases, 10th Revision (ICD-10) criteria for a diagnosis of cancer-related fatigue were included. 
• Mean age was 52.8 years (standard deviation = 9.3 years) (range 18–70).
• Patients had multiple types of cancer, excluding primary or metastatic brain tumors. The highest proportion of patients had breast or ovarian cancer.
• Patients were included if they
  • Were treated with at least four cycles of chemotherapy concluded at least two months prior to study entry
  • Had no concurrent cancer treatment, history of major psychiatric illness, learning or attentional deficitis, or prior treatment with the study drug. 
  • Were nonpregnant and nonlactating women.
• Additional screening and criteria were established for depression and cognitive function. 

• Multisite
• Twenty-four academic or community-based cancer treatment centers in the United States

This was a double-blind, randomized, controlled study.

• CGI-I scale
• Functional Assessment of Chronic Illness Therapy–Fatigue subscale (FACIT-F)
• Swanson, Nelson, and Pelham Attention Deficit/Hyperactivity Scale (SNAP)
• High Sensitivity Cognitive Screen (HSCS)
• Eastern Cooperative Oncology Group (ECOG) performance status
• Mini-Mental State Exam (MMSE)

D-MPH–treated patients had lower ECOG performance status scores than placebo-treated patients (p = 0.03), indicating better performance. The mean highest dose achieved in d-MPH–treated patients was 27.7 mg/day (range 10–70). A significantly greater improvement in FACIT scores from baseline was seen in patients who received d-MPH compared to placebo at week 8 (p = 0.02). In the study group, there was a mean 10.5-point score reduction in the d-MPH group. Reduction in fatigue was seen at an average dose of 27.7 mg/day of the study drug. All patients had reduction in CGI scores, indicating decreased severity of symptoms from baseline to week 8. Improvement in these scores was seen in a significantly greater percentage of those given d-MPH (p = 0.02). The most frequent adverse events were headache, nausea, and dry mouth in the treatment group and headache, diarrhea, and insomnia in the placebo group. There was a higher rate of adverse events in the d-MPH group. Eleven percent of the treatment group experienced serious adverse events that led to study discontinuation. Events that led to discontinuation were nausea, vomiting, feeling jittery, and abnormal electrocardiogram.

D-MPH treatment in an individualized dosing regimen based on therapeutic response and side effects was associated with a significant improvement in fatigue.

• There was a predominance of breast and ovarian cancers in the sample, suggesting that findings may not be generalizable to broader populations of patients.
• Baseline performance status was better in the experimental group than in the placebo group. The potential effect of this difference was not analyzed or addressed.
• The sample did not include patients in active treatment, so the findings are not readily applicable in that situation.
• The study duration was only eight weeks, so the effect of this intervention over the longer term is not clear from these findings.

Future studies need to be performed that address a broader range of patient types. The effectiveness of d-MPH in combination with other interventions, such as exercise, should be examined.

The study's primary aim was to evaluate the potential therapeutic effect and safety of dexmethylphenidate (d-MPH) in the treatment of patients with chemotherapy-related fatigue. Its secondary aim was to examine the impact of d-MPH on cognitive functioning.

Participants were randomized to a placebo group or an intervention group receiving 5 mg of d-MPH twice daily (10 mg/day total).

• The total number of participants was 154.
• There were 76 participants in the intervention group and 78 in the placebo group.
• The average participant age was 52.8 ± 9.3 years.
• 94.7% of the participants were female and 5.3% were male.
• The majority of participants had breast or ovarian cancer. 

The study took place across 24 academic and community-based cancer centers.

This was a randomized, double-blind, placebo-controlled, parallel-group study.

Cognitive measures were taken with the

• Mini-Mental State Examination (MMSE) for global cognitive functioning
• High Sensitivity Cognitive Screen (HSCS) for memory, language, attention, concentration, visual motor, spatial awareness, and self-regulation
• Modified Swanson, Nelson and Pelham Attention Deficit/Hyperactivity Scale (SNAP).

Other measures were taken with the

• ICD-10 Criteria for fatigue
• Beck Depression Inventory (BDI) for depression
• Clinical Global Impression Scale (CGI-S) for severity of illness
• Functional Assessment of Chronic Illness Therapy - Fatigue Subscale (FACIT-F) for chronic illness and quality of life specific to fatigue symptoms
• ECOG performance status for general well-being. Scores range from 0 (indicating perfect health with no restriction of activities) to 5 (indicating death).

The primary outcome of focus was fatigue. Participants treated with d-MPH had significant improvement in fatigue symptoms at week 8 on the FACIT-F (p = 0.02) and on the CGI-S (p = 0.02). The d-MPH treatment group had higher drug-related events (63% vs. 28%) and greater discontinuation of medication (11% vs. 1.3%) than the placebo group. Cognitive function was not significantly improved.

d-MPH can be of benefit in the treatment of fatigue. However, results do not support d-MPH-mediated reduction in cognitive impairment in adult patients with cancer after chemotherapy.

• The study was underpowered to determine an effect on cognitive functioning.
• HSCS has been reported to be susceptible to practice effects and therefore may have underestimated the level of cognitive impairment in participants.
• The small number of men and the fact that most participants had diagnoses of breast or ovarian cancer limit generalizability.

To show the addition of naloxone improves constipation symptoms in patients with non-malignant pain receiving high-dose oxycodone prolonged release (PR).

Patients were randomized to receive either oxycodone PR and naloxone PR or oxycodone PR plus matched oxycodone PR/naloxone placebo. Patients had oxycodone PR titrated to an effective analgesic dose over a 7- to 28-day period and were converted to the study laxative, bisacodyl. Oxycodone immediate release was used as pain rescue medication. Patients were eligible to participate in a 52-week open-label extension. Mean pain over the past 24 hours and bowel function were measured at each study visit and in patient diaries on a daily basis.

• The study reported on a sample of 222 patients (81.5% female and 18.5% male).
• Mean age was 56.2 to 57.5 years (SD = 10.5) across both study groups.
• Patients with cancer-related pain were excluded.
• Predominant problems were musculoskeletal and connective tissue disorders.
• Patients required 60 to 80 mg oxycodone PR equivalent per day and had constipation.

• Multi-site
• Outpatient
• Germany

This was a double-blind, placebo-controlled, randomized study with an extension phase.

• Bowel Function Index (BFI)
• Pain Intensity Scale (numeric rating 0-10)
• Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYMN)
• Subjective Opioid Withdrawal Scale (SOWS)
• Patient diary

• During the first four weeks of the study in the double-blind phase, the difference in mean BFI scores was significantly different (PR = -14.9, p < 0.0001, 95% confidence interval [-17.9, -11.9]) in favor of the oxycodone-PR/naloxone-PR group.
• There were no differences between groups in mean pain measures.
• There were no substantial differences between groups in supplemental analgesic use.
• Significantly fewer patients in the oxycodone-PR/naloxone-PR group took laxatives (p = 0.0009).
• Most common events were nausea, pain, and headache in both groups.
• Withdrawal scores were stable, low, and similar between groups.

Oxycodone PR/naloxone PR was superior to oxycodone PR at improving bowel function and symptoms of constipation. That improvement was achieved without affecting the analgesic efficacy of the oxycodone component.

• The study period of 12 weeks is limited in the setting of much longer-term opioid use.
• Although the study design specified a maximum number of laxative rescue doses, actual rescue laxatives taken were not described and were not analyzed between the two groups.
• Patients with cancer-related pain were specifically excluded; therefore, application to that group is not clear.

The combination of oxycodone PR/naloxone PR in patients with cancer warrants investigation to determine potential benefits in reducing opioid-induced constipation in this population.