Carnitine is hypothesized to be key in the energy metabolism and regulation of adenosine triphosphate (ATP) promotion and a protective effect of mitochondrial metabolism. Carnitine deficits are common in cancer patients and other chronically ill persons.
 

L-carnitine supplementation was given in dose levels of 250 mg/day. Dose levels were planned to increase by 500 mg until the target dose of 3000 mg/day was reached.

Of 645 adult patients, 13% met following inclusion criteria:

• Age of at least 18 years
• Greater than 3 month life expectancy
• Self-reported fatigue was moderate to severe for at least one week
• Carnitine deficiency
• Karnofsky Performance Status (KPS) of 50% or greater.

Patients were excluded from the study if they had severe disease, brain tumor, or stroke; were unable to complete the assessment tools; had started erythropoietin within less than 3 months; had received radiotherapy or chemotherapy within one week prior to the study; or were unable to consent.

Hospice and Cancer Center

The study used an open-label, dose-finding, safety design, with dose cohorts of three.

• Brief Fatigue Inventory (BFI)
• Center for Epidemiological Studies Depression Scale (CESD)
• Quality of sleep
• Epworth Sleepiness Scale (ESS)
• KPS

• Of the patients, 83% reported fatigue with a significant decrease in BFI score after one week (p = .009).
• CESD decreased (p = 0.028).
• ESS decreased (p = 0.015).
• No significant change occurred in KPS.
• Dose was safely escalated to 1750 mg/d.

• The study had a small sample size.
• Hospice patients often have multiple medical problems. 
• Three higher dose levels were not reached.
• Treatment length was short (one week). 
• The effect of prolonged use is unknown.
• No monitoring of dietary carnitine was performed.
• It is unknown if L-carnitine supplementation accelerates cancer or interferes with the effects of certain agents.

Cost of supplements and monitoring levels of L-carnitine is unknown.

To determine the efficacy of L-carnitine supplementation for fatigue in patients with cancer.

Patients were randomized to receive 1 g of L-carnitine liquid twice daily for four weeks or placebo.  For weeks five to eight, all patients received L-carnitine in an open-label extension. Outcome measures were assessed at baseline and at weeks four and eight.

• In total, 237 patients (42% male, 58% female) were included.
• Age was not reported.
• Disease types were not reported.
• About 80% of patients were currently receiving chemotherapy and 18% were receiving radiotherapy. Slightly less than one-third were receiving antidepressants. 

• Multisite 
• Outpatient 
• United States

Patients were undergoing the active antitumor treatment phase of care.

The study was a randomized, double-blind, placebo-controlled, phase III trial followed by a four-week open-label extension.

• Brief Fatigue Inventory (BFI)
• Center for Epidemiologic Studies Depression Scale (CESD)
• Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)
• Eastern Cooperative Oncology Group (ECOG) performance status
• Blood sample analysis for plasma carnitine and acylcarnitine
   

The group receiving L-carnitine had a greater increase in plasma carnitine levels. At week four, one-third of those on placebo were carnitine-deficient, compared to 11% of those who were receiving carnitine (p ≤ 0.001). BFI scores improved significantly in both groups by approximately one point (p < 0.001). There were no differences between groups in fatigue, depression, or pain. Over time, there was a significant decrease in the proportion of patients with severe fatigue, pain, and depression; however, there were no significant differences between groups. There were few high-grade toxicities. In one patient, the cause of death was possibly related to treatment.

Supplementation of 1 g of L-carnitine did not improve fatigue, pain, or depression in these patients.

Of the patients, 25% to 30% had missing outcome data; however, power analysis showed that the sample size was sufficient.

The findings showed that dietary supplementation with L-carnitine did not improve fatigue, depression, or pain in patients with cancer. Nurses can advise patients that this approach has not been shown to be helpful, as these results provide strong evidence that L-carnitine is not effective for these symptoms.

To explore how bereaved relatives experienced early intervention with soft tissue massage during the first four months since the death of a family member who received palliative cancer care

Study data resulted from two interactions with Swedish-speaking relatives of deceased patients with cancer who had received care in a large palliative care unit. Demographic and baseline data were collected in an initial 60-minute visit to the relative. Hand or foot soft tissue massage, which is defined as a gentle but firm movement of the skin that activates touch receptors, was done in slow strokes, light pressure, and circling movement using lightly scented vegetable oil.

One week after an eight-week intervention involving either protocol-driven or relative election of either hand or foot soft tissue massage, the first author audiotaped hour-long interviews with the 18 study participants. Open-ended interviews focused on the experience of receiving the massages via a dialectical validation approach to ensure understanding of relatives’ experience. The authors supported trustworthiness and qualitative credibility factors during interviews and data analysis processes based on interview transcriptions and close attention text. An additional follow-up telephone call six to eight months after the interview was intended to encourage participants to reflect on their current life situation in relation to the grieving process.

• The sample (N = 18) was comprised of 14 females (78%) and 4 males (22%) who were bereaved relatives of deceased patients with cancer.
• The age range of participants was 34–78 years (mean age = 56.2 years).
• Diagnoses of the deceased patients were not noted.
• The relationship to the patient was widow (9), widower (4), daughter (3), and sister (2).
• The type of massage chosen was foot (9), hand (8), and hand and foot (1).
• The working status of participants was sick leave (7), retired (6), and working full- or part-time (5).
• Three relatives had previous experience with deep body massage.
• The study authors provided no other information, such as educational status, about the sample. This status may help to interpret the rich textual findings presented by the authors.
• Of the sample, 14 expressed interest in participating the first few weeks of their relative’s death, although the authors planned to contact relatives within three to six weeks of the relative’s death.
• Seven relatives chose not to participate due to living too far away or a lack of interest in study participation.
• Most chose to receive massages in their home, and most massages occurred in a silent environment.

• Single site
• Home or palliative care center
• Stockholm, Sweden

A prospective, descriptive, qualitative design was used.

• Private interviews were audiotaped in which bereaved relatives narrated freely about their experience of receiving soft tissue massage over eight weeks.
• Follow-up telephone conversations were initiated six to eight months postinterview “to see how the relative was doing.”

A qualitative content analysis allowed various levels of interpretation and abstraction to support one predominant theme: Bereaved relatives felt “feelings of consolation and help in learning to restructure everyday life.” The theme derived from four categories: (a) a helping hand at the right time, (b) something to rely on, (c) moments of rest, and (d) moments of retaining energy. Overall, soft tissue massage supported relatives’ need for comfort, as well as hope during a difficult transition time for relatives who sought a balance of grieving and moving on with their lives after the death of a loved one. No analysis of the follow-up telephone conversations appeared in the article.

Early interventions for relatives who grieve the loss of a family member’s death, including sequential soft tissue hand or foot massage, may facilitate relatives’ feelings of belonging, human connection to healthcare staff who cared for their family member before death, sense of self, and energy to structure life after a family member’s death. Too often, delayed interventions cause unnecessary worry and suffering of bereaving relatives. The offering of soft tissue massage to those relatives at a desired time may constitute a cost-effective way to support bereaved relatives early in their grieving process.

• The sample was small, with less than 30 participants.
• Although the sample size appears adequate for qualitative studies, further replication of the study across cultures and healthcare units would expand application of the findings to multiple relatives who experience the death of a family member. For example, in some cultures, there may be limited acceptance of personal touching by a person that is not family.
• Recruitment for this qualitative study occurred in one specialized palliative care unit, thus limiting generalizability of the study findings. The study also occurred in Sweden, and this may influence access and acceptance of soft tissue massage as a culturally-sensitive intervention in the United States. Scope of practice issues in the United States and other countries may influence nurses’ use of massage therapy with population groups, as well as nurses’ continued contact with families following a family member’s death. In this study, it appeared that at least one of the study authors served as a massage therapist, a behavior that may “cross the line” in the United States of inappropriately meshing two distinct healthcare provider roles.
• The authors did not address “member checking,” a common process in qualitative research in which data findings gain support from a person experiencing the topic under study. The input of a grieving caregiver once the study data resulted would have addressed validation of the findings and expanded interpretation of those.

Early support, including that inherent in the delivery of soft tissue massage, to grieving relatives of a family member who died from cancer or other chronic illnesses, offers a cost-effective intervention that may improve the health of those relatives. This intervention needs further testing to determine its efficacy but does highlight the importance of grieving relatives reconnecting with the healthcare professional, physical touch, and getting needed support. Further research with diverse populations in other global communities may extend understanding and acceptance of this potentially future intervention to add quality-of-life care to relatives and other family members. Testing of a soft tissue massage intervention could support evidence for the effectiveness of this intervention and nurses’ referral of caregivers to this intervention for improved quality of life.

STUDY PURPOSE: To determine if prophylactic or treatment transfusion of platelets is required, and answer questions of optimal prophylactic platelet dose, platelet threshold to be used, and whether a therapeutic only strategy is as safe and effective as prophylaxis

TYPE OF STUDY: Meta-analysis and systematic review

PHASE OF CARE: Active antitumor treatment

Studies compared therapeutic only versus prophylactic platelet transfusion or placebo. The incidence of severe or life-threatening bleeding as many as 30 days from study entry was significantly different (RR = 4.91, 95% CI [0.86, 28.12]) in favor of prophylactic transfusion. Differences in other outcomes such as bleeding episodes, duration, etc., could not be estimated. There was no evidence of differences in adverse events. Patients in the therapeutic-only arm had less platelet transfusions and a shorter time to first bleeding episode. Findings regarding an appropriate platelet threshold are not provided.

Patients receiving therapeutic platelet transfusion may be at greater risk for bleeding than those given platelets prophylactically. There may not be an increased risk of adverse events or death if platelet transfusions are given only therapeutically.

• Limited number of studies included
• Mostly low quality/high risk of bias studies
• High heterogeneity
• Methods for grading of bleeding and recording of bleeding varied across studies.
• Extremely wide confidence interval

Results of this review need to be viewed with caution, as the quality of studies included was low to moderate and there was insufficient evidence to answer many questions regarding differences in outcomes. Further research would be helpful—while prophylactic platelet transfusion is the usual standard of care, and somewhat reduces risk of bleeding, there is no evidence to show any effect in terms of mortality and other disease-related outcomes. Transfusions are not risk free. Overall, there is very limited evidence for interventions to prevent bleeding.

G-CSF 230 mcg/m² given days 4–17 unless the post-nadir neutrophil count exceeded 10x10⁹/1 after day 12. Treatment repeated every 21 days for up to six cycles of chemotherapy (cyclophosphamide, doxorubicin, and etoposide).
Control was placebo injection.
Patients in the placebo group crossed over to G-CSF after episode of febrile neutropenia.

The study was comprised of 199 patients, of the 211 patients who had enrolled.
G-CSF = 95
Placebo = 101
Small-cell lung cancer

Multicenter

Randomized, prospective, control phase III trial

Febrile neutropenia was the primary endpoint. Also looked at infectious complications and oral mucositis.
WHO scale
Oral candidiasis included as mucositis incidence, severity, and time to onset.
Duration of mucositis was determined by a combination of patient reporting and clinical examination findings.
 

54% versus 72% episode of mucositis in G-CSF versus placebo group. Most episodes were grade I–II. Median duration of mucositis was the same for both groups (eight days).
First-cycle mucositis: 28% versus 47% (p = 0.041)
 

Difficult to determine some results because of cross-over nature of study. Also allowed dose reduction in treatment group, which decreased mucositis; confounding results.

Trials with nonmyelosuppressive therapy are needed to determine effect.

• Eighteen citations listed: No evaluative summary of sources or levels of evidence 
• Note provided by authors on levels of evidence (I-V) and grades of recommendation (A-D) as used by the American Society of Clinical Oncology provided in the tables of recommendations
• Statements within the guidelines without grading were considered standard clinical practice as recommended by the expert authors and the ESMO faculty

• Definition: Incidence of FN, complications, and mortality rates
• Regimens: Risk of FN > 20%
• Indication: FN primary prophylaxis with ​hematopoietic growth factors (hGFs)
• Special situations: hGFs and standard therapy
• Dose schedule: Administration of granulocyte-colony stimulating factor (G-CSF) and pegfilgrastim
• Indications: Use G-CSF and pegfilgrastim; high-risk situations
• G-CSF after autologous stem-cell transplant or allogeneic transplant
• Mobilization of peripheral blood stem cell autologous or allogeneic settings
• G-CSF treatment for radiation injury

• Data sources before 2010 may be outdated.
• Not all tumor types and treatments were represented.
• No process was provided for how these guidelines were developed.
• The inclusive resources cited were not evaluated separately with a table of evidence.
• These guidelines were established on expert opinion, consensus of ESMO faculty, and the adoption of ASCO levels of evidence and grades of recommendations.

Identifying patients at-risk for FN and the appropriate use of hGFs is critical to improve patient outcomes. Nurses must consider the strength of evidence for and the process of guideline development of treatments before using clinical practice guidelines in patient care.

To evaluate the rate of uncontrolled chemotherapy-induced nausea and vomiting (CINV) after initiation of antiemetic prophylaxis with palonosetron as compared to all other 5-HT₃ antagonists in patients diagnosed with hematologic malignancies and receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC)

Subjects who were 18 or older, were identified from eight million cancer discharges that are part of the Premier Perspective Database, which includes data from more than 600 hospital systems. After establishing the correct diagnosis and pharmacologic treatment, data were retrospectively extracted from the database from initiation of chemotherapy to the end of eight rounds of chemotherapy treatment or for six months. 

• This study reported on 971 patients with a mean age of 61.9 years.
• The sample was 48% male and 52% female.
• Primary hematologic malignancies were defined as lymphoma (79%), myeloma (6.4%), and leukemia  (AML , CML, ALL, CLL, and other leukemia, 14%).   
• Patients were chemotherapy naïve, with no prior evidence of nausea or vomiting.
• Patients had hematologic malignancies and were initiated with single or multiday chemotherapy and antiemetic prophylaxis with palonosetron (group 1) or all other 5-HT₃ antagonists (group 2). The sample was 71.2 % white. Patients who received palonosetron represented 22% of the sample.

This was a multisite, outpatient study based on the Premier Perspective Database containing data from more than 600 hospitals.

• All patients were in active treatment.
• This study has application to late effects and survivorship.

This was a longitudinal, retrospective observational study.

The primary study outcome was rate of uncontrolled CINV events in the study follow-up period of eight cycles of chemotherapy or six months, with events operationally defined by either the need for rescue antiemetics on day two or by any of the ICD-9 codes for nausea, vomiting or volume depletion, dehydration, or hypovolemia. The unit of analysis was one cycle, defined as number of treatments in seven days.

• Of 971 subjects for whom data were extracted, 211 subjects were treated initially with palonosetron and 760 subjects were treated with other 5-HT₃ antagonists.  The groups were comparable in most aspects, including the Charlson Comorbidity Index (mean CCI = 0.2); however, group 1 had a higher percentage of patients who received HEC.
• After adjusting for baseline differences in the two groups, multivariate analysis results predicted a 20.4% lower CINV event rate per chemotherapy cycle in patients with hematologic malignancies treated with palonosetron. This difference was slightly more than one episode per cycle. No significant differences were found in the actual event rate from analysis. 
• Females were shown to have a higher CINV rate, but it was not statistically significant.
• Cycle length (total days within week) also was found to be associated with CINV, with increased days leading to more CINV.

Patients treated with palonosetron in the outpatient setting had significantly lower CINV event rates (decrease of 20%) versus patients treated with other 5-HT₃ antagonists after adjusting for baseline differences.  However, because this study did not look at the contribution of other antiemetics (e.g., aprepitant, dexamethasone), we may only conclude that in a fairly large sample of patients from the Premier Perspective Database, the group of patients who were given palonosetron on the initiation of HEC or MEC experienced less CINV.

• A retrospective study design relies on the accurate documentation of events by others; however the large sample size is definitely a plus.  
• Using a combined data set pulls patients from many practices, the researchers cannot control for variation in clinical practices. We do not know why palonosetron was chosen originally.
• The use of other antiemetics were not considered, including corticosteroids and the neurokin 1 (NK1) receptor antagonist aprepitant, which may have an impact on the study results.
• We do not know the patients' histories of previous nausea and vomiting, motion sickness, smoking history, or how much medication was given.

Palonosetron should be considered for the prevention of CINV in patients with hematologic malignancies being treated with HEC or MEC. 

The objective of the study is to determine whether the administration of oxygen therapy alleviated dyspnea in adults with chronic end-stage disease versus breathing room air or placebo air in a non-acute care setting.

Databases searched were Cochrane reviews, OVID MEDLINE, CENTRAL, CINAHL (1982-2006), Cancer Lit (1975-2006), ACP Journal Club (1991-2006), Turning Research Into Practice (TRIP) (1997-2006), Dissertation Abstracts (ProQuest Digital Dissertations) (1985-2004), LILACS (1994-2006), Australasian Medical Index (National Library of Australia) (1990-2006) via Informit, LOCATOR plus (U.S. National Library of Medicine), EMBASE (1987-2006), PubMed (1950s-2006) (National Library of Medicine).

Search keywords oxygen, dyspnea, dyspnea, palliative, terminal, breathless, end-stage, and adult as either text words or mesh headings were used to search EMBASE Excerpta Medica, Australasian Medical Index, Latin American and Caribbean Health Sciences Literature (LILACS), and American College of Physicians (ACP) Journal Club and Dissertation Abstracts.

The Cochrane Library was searched using the terms oxygen and dyspnea or dyspnea and palliative or terminal.

Studies were included if they

• Were a randomized controlled trial (blinded or unblinded) performed in a non-acute care setting
• Included participants with chronic terminal illness (excluding chronic obstructive pulmonary disease) and breathlessness at rest or on mild exertion with or without hypoxemia
• Compared usual active treatment plus palliative oxygen therapy with a control groups
• Compared mean levels of dyspnea experienced by participants with a chronic terminal illness before and after administration of oxygen gas or room air/placebo
• Used a valid instrument to measure dyspnea.

Four hundred forty-six initial articles were retrieved. Only randomized controlled trials were considered for this review, with inclusion of unblended studies. Electronic databases were searched for predefined search terms. All studies were assessed for methodologic quality using a 0-5 scale based on the Oxford Quality Scale, and Quality of Concealment of allocation was rated.

Eight studies met inclusion criteria, for a final total sample of 144. Sample sizes across studies ranged from 12-45. Oxygen for dyspnea was evaluated in four studies among patients with cancer, three studies among patients with cardiac failure (CHF), and one study among patients with kyphoscoliosis. Of the sample, 99 were males and 46 were females. All were adults with listed comorbidities, some with or without domiciliary oxygen, with moderate to severe dyspnea.

Overall oxygen was not associated with reduction in the symptom of dyspnea.

Due to small number of research studies, variation in study methodologies, and small sample sizes among studies, evidence is still inconclusive regarding the short-term or long-term benefit of oxygen therapy over air inhalation in patients with cancer with dyspnea due to end-stage malignancy.

Newer, larger, well designed, controlled, randomized studies are needed with adequate power to detect variations in breathlessness with sufficient “washout” time between test gas inhalation times. Therefore, immense caution is suggested regarding the benefits of short-term oxygen inhalation over air inhalation for dyspnea relief in terminal care patients.

• Study Design: Both randomized and nonrandomized studies were considered to acquire a complete understanding of the topic area. The key inclusion criterion was that all studies, regardless of design, had to include some form of physical exercise training for patients surgically treated for NSCLC. This review intended to include quantitative, qualitative, and mixed-method study designs.
• Participants: Studies that included participants diagnosed with resectable NSCLC were included in this review. Exercise interventions were defined as supervised or unsupervised inpatient, outpatient, community- or home-based interventions that included any type of exercise training applied to patients surgically treated for NSCLC. Some studies included additional components. Four studies included education, four included smoking cessation, and three used phone calls.
• Outcome measures: All outcomes measured were recorded in this review. 

• Study Design: All poster abstracts and non-English full-text articles were excluded.  
• Participants: Studies with < 65% of the patient population were excluded to ensure a consistent sample.

PHASE OF CARE: Multiple phases of care

• Fatigue increase was noted in studies presurgery to immediately postsurgery, yet the authors did not cite which studies.  
• Fatigue reduction was found from baseline to postintervention in three out of five studies. The authors note that in two studies, fatigue severity from baseline to postintervention was not reduced and that each of these studies were of a different type of exercise (resistance) with different intervention timing (preoperative).
• Fatigue reduction was noted to be sustained in two participants who did not receive adjuvant therapy as compared to those who underwent adjuvant treatment.

Preliminary findings from the review suggest that intervention via exercise compared with usual care pre- and postsurgery may reduce fatigue. The results from the systematic review show the infancy of this particular field of study with very few studies included for analysis, with the majority of studies being of observational methodology. In addition, studies included a wide range of exercise prescriptions.

The field of treatment for fatigue in the surgical NSCLC population is in its infancy. In one study of the reviewer’s expertise, it is noted that the article was labeled as an unsupervised intervention when the article discusses the actual supervision of subjects participating in the exercise intervention.

Additional study of the best exercise prescription for fatigue management is needed related to patients undergoing surgery. The best timing for such interventions is not clear.

To evaluate the effect of exercise on cancer-related fatigue during and after cancer treatment. This was an update of a study from 2008. A secondary objective, subject to available data, was to explore the effect of exercise in different types of cancer populations.

Databases searched were the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), CINAHL (1982 to March 2011), British Nursing Index (January 1984 to March 2011), AMED (1985 to March 2011), SIGLE (1980 to March 2011), and Dissertation Abstracts International (1861 to March 2011).  The authors also searched references of all articles; hand searched the following journals up to April 2011: Cancer, Journal of Clinical Oncology, Psycho-Oncology, Cancer Practice, Oncology Nursing Forum; and searched unpublished literature through searches of conference proceedings up to June 2011.

Appendix 1 details the keywords searched, including expanded neoplasms, leukemia, lymphoma radiation therapy, bone marrow transplantation, exercise, movement, and fatigue.

Studies were included in the review if 

• They evaluated and reported the effect of physical exercise on cancer-related fatigue
• They compared exercise with no exercise, a usual care group (i.e., no specific exercise program prescribed), or an alternative treatment or exercise regime for fatigue associated with cancer
• The intervention took place in any setting and was delivered to a group or individual participant
• Any type of physical exercise, including aerobic exercise, strength training, and flexibility exercises, was performed
• They investigated an exercise program accompanied by attempts to promote participant engagement.

Studies were excluded if they explored multidimensional programs in which the effects of exercise alone could not be determined and if a specific exercise program was not described and participants were only given advice or education about the potential benefits of exercise.

Fifty-eight new references plus 28 from the original review were retrieved.

Two independent reviewers reached 100% consensus; they assessed the methodological quality of the studies from the previous review.

• Fifty-six total studies were included in the final review (28 new plus 28 from the original review).
• The sample sizes ranged from 10 to 242 participants; the total number of participants was 4,068.
• Participants had various cancer diagnoses and various timing since diagnosis.
• The majority of participants had breast cancer.
• There was a mix of female and male patients; however, 29 of 56 studies included only females.
• Mean age ranged from 39 to 70 years (mostly in the 50s).

Patients were undergoing multiple phases of care.

Statistically significant improvements in fatigue were identified following an exercise program performed either during cancer therapy (standardized mean difference [SMD] = -0.23; 95% confidence interval [CI] [-0.23, -0.33]) or following cancer therapy (SMD = -0.44; 95% CI [-0.79, -0.09]). Statistically significant beneficial effects were identified specific to breast cancer (n = 672) and prostate cancer (n = 239) populations, but not for those with hematological malignancies (n = 114). Statistically beneficial effects were identified following aerobic training but not following resistance training or low-intensity mind-body interventions.

Sufficient evidence exists to support the recommendation of aerobic exercise during and after treatment for patients with breast or prostate cancer. Insufficient evidence exists to support the recommendation of hematological malignancies or other solid tumors. Exercise modalities other than aerobic exercise do not have sufficient evidence to support their recommendation.

Most studies

• Had small sample sizes
• Did not blind the intervention
• Provided little information about those who refused to participate
• Included self-reports
• Had exercise programs that did not reach the current recommended amounts for adults.

Aerobic exercise is recommended for appropriate patients during and after treatment for breast or prostate cancer. Consider recommending exercise for other solid tumors. Research is needed for various cancer types and stages, including palliative care and for types and duration of exercise.