The intervention consisted of individual muscle relaxation training over three sessions plus instructions for home practice twice daily. Patients were either in the relaxation (n = 15) or usual care (n = 15) group. The outcome was sleep.

• The sample was comprised of 30 patients (11 men, 19 women).
• Mean age was 56 years (range 21–80).
• Patients had various cancers.

• Quiet office in the hospital, patient’s home, or patient’s hospital room
• Southeastern United States

Patients were undergoing the active treatment and long-term follow-up phases of care.

The study was a randomized, controlled trial.

Daily diary and questionnaire pertaining to sleep behavior the previous night, for a total of nine nights

Sleep-onset latency was reduced in the relaxation group compared with the usual care group; differences in sleep latency were maintained at the three-month follow-up. No differences were found in other sleep variables.

• Sleep was measured by self-reports.
• Training is needed in delivering muscle relaxation.

No cost issues existed.

To compare the effectiveness of two psychotropic medications, mirtazapine and imipramine, on distressing somatic symptoms (i.e., pain, nausea, vomiting, decreased appetite, and sleep disturbance) of cancer as well as symptoms of depression and anxiety.

Patients self-selected to receive psychotropic medication and supportive psychotherapy (intervention group) or supportive psychotherapy only. Those who elected to take medication were randomly enrolled to receive mirtazapine or imipramine. Mean dosage of mirtazapine ranged from 5 to 30 mg/day, depending on the visit. Mean dosage of imipramine ranged from 5 to 100 mg/day, depending on the visit. Each group was then assessed at three visits:  baseline and three and six weeks after therapy had begun.

• The sample was comprised of 53 patients with cancer (35%–38.5% male, 61.5%–65% female).
• Median age was 43 to 47.5 years (range 26–56).
• All cancer types were included; no information about cancer stage was provided. 
• In each group, median time since diagnosis ranged from 6.5 to 8 months.
• All patients had an additional psychiatric diagnosis. All had cancer; were undergoing chemotherapy; and had been diagnosed with major depressive disorder, adjustment disorder, and/or anxiety disorder.

• Single site
• Outpatient
• Large oncology research and training hospital in Turkey

Patients were undergoing the active treatment phase of care.

The study used a prospective, repeated measures design.

• Patient sociodemographic information    
• Pain, nausea, and vomiting (evaluated by single-symptom scale)
• Weight
• Appetite (evaluated by single item)
• Hamilton Rating Scale for Depression (HRSD) (three items to assess sleep disturbance)
• Hospital Anxiety and Depression Scale (HADS), Turkish version

• Among the three visits, no significant differences were observed with regard to the degree of pain, nausea, vomiting, or appetite in the mirtazapine, imipramine, and control groups, and nor did differences exist in terms of the scores relating to the degree of pain, nausea, vomiting, appetite, weight, or insomnia, among the mirtazapine, imipramine, and control groups.
• In the mirtazapine group, the initial, middle, and late insomnia scores improved between the first and second and first and third visits. In the control and imipramine groups, no significant change occurred in insomnia scores between visits.
• In the imipramine group, a significant difference was seen in weight at the three visits. Median weight decreased from the second to third visit.
• In the mirtazapine group, statistically significant differences were noted in the mean total, anxiety, and depression HADS scores at each visit. Especially notable were score changes between the first and second visit. In the imipramine and control groups, no differences were found in the total, anxiety, and depression HADS scores across visits. 

Mirtazapine is effective in resolving insomnia and in reducing the symptoms of anxiety and depression in patients with cancer who have depression, anxiety, or adjustment disorders.

• The study had a small, heterogeneous sample, with less than 100 patients.
• The study had a high drop-out rate; by six weeks, 10 of 20 patients had dropped out of the control group, 4 of 20 had dropped out of the mirtazapine group, and 4 of 13 had dropped out of the imipramine group.
• The study had no control group or random assignment and presented no information about confounding factors. 
• Patients were not controlled for use of concomitant medications to treat the somatic symptoms being evaluated.

Mirtazapine may be useful in treating anxiety, depression, and insomnia in patients undergoing chemotherapy for cancer who have clinically relevant anxiety or depression. More systematic research, such as placebo-controlled studies, is required.

To evaluate the efficacy of oral branched-chain amino acids versus placebo on anorexia and food intake in patients with cancer

A mixture of 4.8 g branched-chain amino acids was administered three times daily versus placebo powder three times daily for 60 minutes before each meal for seven consecutive days.

• The initial sample included 28 patients; attrition of 3 patients occurred secondary to early surgery not related to study (treatment arm = 13,  placebo arm = 12).
• Groups were equivalent in sex, age, and tumor origin.
• Patients were included in the study if they were newly diagnosed with cancer, undergoing surgical resection, experiencing anorexia, and not losing weight.
• None of the patients received radiotherapy or chemotherapy during the study or four weeks prior.

Multiple institutions in Italy that were not listed or further described

A double-blinded, placebo-controlled, randomized trial design was used.

• Nutritional status prior to and at end of study using biochemical indices
• Daily caloric intake measured by weighing food before and after each meal
• Presence of anorexia measured using questionnaire not described in the article
• Blood tests on days 0, 3, and 7 to measure levels of plasma amino acids and tryptophan

Nutritional status was within normal limits for both groups prior to and at the end of study. Daily caloric intake was significantly increased in the treatment arm. There was no change in the placebo group. Incidence of anorexia was significantly decreased in the treatment arm (100% prior to and 45% at the end of study). There was no significant change in the placebo arm (100% prior to and 84% at the end of study). Blood tests showed a significant increase in plasma amino acid levels and a decrease in free tryptophan levels in the treatment arm and no change in levels noted in the placebo arm.

• The study had a small sample size.
• Inclusion criteria was fairly narrow, including newly diagnosed, resectable patients who were not losing weight. Whether results can be applied to patients with cancer not meeting these criteria is questionable.
• The study had a short treatment time of seven days, leading to questions regarding long-term effects.
• The measurement tool used for anorexia was a questionnaire not described in this paper but rather referenced from a previous article.
• Anorexia was not defined.
• The study sites were not listed or described.

To update the information available on the effectiveness of laxatives and methylnaltrexone for constipation management in palliative care patients.

Databases searched were MEDLINE and the Cochrane Central Register of ControlLed Trials (Central).

Search keywords were laxatives, methylnaltrexone, and palliative care.

Studies were included in the review if

• They reported on adults receiving palliative care.
• Patients used laxatives or methylnaltrexone for constipation.

Studies were excluded if they reported on healthy volunteers, drug misuse–related constipation, or bowel obstruction.

A total of 186 references were retrieved. If citation screening did not identify whether a study was eligible, the full text was reviewed for acceptability. Two authors independently screened studies and discussed differences of opinion. Randomized controlled clinical trials were evaluated for inclusion.

• Seven studies comprising a total of 616 patients were included.
• Key characteristics were use of lactulose, senna, co-danthramer, misrakasneham,  and magnesium hydroxide with liquid paraffin.

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

• The best laxative for this patient population is unclear.
• Methylnaltrexone is effective in patients with opioid-induced constipation.

Well-designed clinical trials are needed to help identify which laxatives are most effective for palliative care patients with constipation.

Very few clinical trials effectively evaluated the use of laxatives in this patient population.

To determine whether more precise guidance can be given regarding use of osmotic laxatives, and to assess the evidence for their use in children with constipation.

Databases searched were PubMed, Embase, the Cochrane Library, and Google Scholar. Reference lists were also hand searched.

Search keywords were polyethylene glycols, lactulose, senna, bisacodyl, picosulphate, constipation, defecation, cathartics, infant, child, preschool, adolescent, and clinical trial.

Studies were included in the review if they

• Were a randomized clinical trial of osmotic laxative versus placebo or an active comparison
• Reported on patients aged younger than 18 years with a diagnosis of constipation of more than three months in absence of structural, endocrine, or metabolic disease
• Recorded a quantitative effect on constipation
• Were published in a peer-reviewed journal.

Initial searching provided 100 clinical trials and 71 review articles. A final group of seven trials was identified for consideration in this review.

The seven final studies encompassed data on 594 patients.

• A consensus appears to exist among studies that PEG is more effective than lactulose.
• One systematic review in 2006 found no evidence to support use of stimulant laxatives or bulk-forming agents among children.
• One study compared PEG 3550 with milk of magnesia. No difference existed between groups regarding bowel movements; however, more children refused treatment with milk of magnesia than with PEG (35% versus 5%, p < 0.001).

The review highlights the necessity of considering what treatment children will accept in managing symptoms.

This review was done in children with functional constipation, so findings may not be clearly applicable in children with constipation related to cancer treatment. PEG may be helpful and more effective than lactulose in the management of constipation in children with cancer, and may be more accepted than milk of magnesia.

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

No difference in effectiveness was demonstrated in lactulose compared with senna; senna plus lactulose compared with magnesium hydroxide plus liquid paraffin; misrakasneham compared with senna; and docusate plus senna compared with placebo plus senna.

The best laxatives for this patient population is unclear.

Very few clinical trials effectively evaluated the use of laxatives in this patient population.

More RCTs are needed to help evaluate the effectiveness and improve the quality of care of patients in palliative care.

STUDY PURPOSE: To assess the effects of support interventions on the psychological and physical health of informal caregivers of patients in the terminal stage of disease

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 11, 8 in meta-analysis
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,836
• SAMPLE RANGE ACROSS STUDIES: 30–363
• KEY SAMPLE CHARACTERISTICS: In eight trials, care recipients had terminal stage cancers; varied ethnic groups

PHASE OF CARE: End-of-life care

APPLICATIONS: Palliative care

Nine studies used interventions aimed to directly support the caregiver, and in five of these, the intervention was also aimed at the patient. In two trials, the aim was to indirectly support the caregiver via patient support. A meta-analysis of eight studies aimed at direct caregiver support to reduce psychological distress, in favor of the intervention (SMD = –0.15, 95% confidence interval [–0.28, –0.02], p = 0.02). Studies measuring improvement in coping or quality of life did not show any significant effect of the intervention. Two trials showed improved access to health services with the intervention, and one did not show any difference between groups in physical health outcomes of the caregivers.

Support interventions aimed directly at the caregiver reduced short-term psychological distress, with a small effect size, and resulted in marginal and insignificant improvements in coping and quality of life.

• Mostly low quality/high risk of bias studies
• High heterogeneity

Supportive interventions provided directly to informal caregivers had small but significant positive effects on caregiver psychological outcomes.

To determine the effectiveness of kefir in preventing treatment-related gastrointestinal complaints and to determine the effects of kefir on quality of life (QOL) among patients receiving chemotherapy treatment for colorectal cancer.

Patients were included if they had stage II, III, or IV colorectal cancer; were 18 years or older; had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2; and were receiving standard treatment with 5 FU or oral fluoropyrimidine. Patients were randomized to either the control group or the experimental (kefir) group. Kefir (500 mL) was industrially prepared by Altinkilic Company in Istanbul. Patients were instructed to use 250 mL of kefir two times per day for one week during chemotherapy treatment. Side effects of treatment were evaluated in both groups one week after each chemotherapy cycle. QOL was evaluated after the third and sixth cycles of treatment.

• The sample was comprised of 37 patients (65% male, 35% female).  
• Mean age was 54.32 years (standard deviation = 12.77 years).
• Patients had colorectal cancer stage II to IV.
• Of the patients, 29 (78%) were married.

• Single site 
• Istanbul University Oncology Institute

Patients were undergoing the active treatment phase of care.

The study was a randomized, controlled trial.

• Memorial Symptom Assessment Scale (MSAS)    
• Functional Assessment of Cancer Therapy–General (FACT-G):  A Turkish version of the FACT-G was validated in this study by the authors. Cronbach's alpha values for subscales varied from 0.69 to 0.76, with a value of 0.9 for the total scale.

There were no statistically significant differences between groups in patients’ disease-related complaints before the intervention. No statistically significant changes were observed between pre- or posttreatment for the control group for the MSAS-GDI subscale scores; however, statistically significant increases in symptom distress (p < 0.05) were observed in the experimental (kefir) group from pre- to posttreatment. For the MSAS-PHYS subscale, the control group experienced a significant increase in symptoms over pretreatment scores (p < 0.05); however, a significant increase occurred in physical symptoms after each treatment cycle (p < 0.05) in the experimental group, with physical scores significantly higher (p = 0.03) in the experimental group after the fifth cycle compared to the control group. Scores for the MSAS-PSYCH were also significantly higher (p = 0.01) in the experimental group compared to the control group after the sixth treatment cycle. Total MSAS scores were significantly higher for each treatment cycle compared to pretreatment for the experimental group (p < 0.05) and were significantly higher than the control group after the fifth treatment cycle (p = 0.02). The experimental group reported significantly fewer problems sleeping than the control group after all rounds of chemotherapy (p = 0.05). No significant differences were observed between groups for QOL (p > 0.05).

The kefir intervention did not affect QOL. Patients receiving kefir reported increased physical and psychological systems and increased symptom distress compared to patients not receiving kefir but reported fewer problems sleeping.

• The study had a small sample size, with less than 100 patients.
• The approach to sleep measurement was limited.

Kefir may increase physical complaints, including gastrointestinal complaints, in patients with colorectal cancer receiving chemotherapy. Kefir does not have a significant effect on QOL. Further study is needed to determine the effects of kefir on sleep problems in this population.

To determine the kind of nonpharmacological interventions used by Turkish patients with cancer for symptom management during chemotherapy, whether a relationship exists between symptom experience and nonpharmacological intervention use, and what personal and illness-related variables predict the symptom experience and nonpharmacological interventions use in this population

Patients completed the following. If patients were unable to complete the tools themselves, a friend or relative verbally asked the patient the questions.

• Patient Characteristics Form
• Eastern Cooperative Oncology Group (ECOG) Performance Status scale
• Nightingale Symptom Assessment Scale (N-SAS)
• Use and perceived effectiveness of nonpharmacological interventions used during chemotherapy using dichotomous responses (0 = not effective, 1 = yes, effective)

• The study reported on 202 pages with a mean age of 48.82 years (SD = 1.44 years).
• The sample was 41.6% male and 58.4% female.
• Cancer diagnoses were breast (27.2%), colorectal (16.8%), gynecologic (14.4%), lung (13.4%), lymphoma (7.4%), urologic (6.4%), gastric (5.4%), bone (4.5%), head and neck (2.5%), skin and sarcomas (2.0%).
• Other key sample characteristics include that 66.8% of patients had primary disease and 33.2% had metastatic disease; 58.4% had ECOG performance status of 0 (fully active), 29.7% had ECOG performance status of 1, and 11.9 % had ECOG performance state of 2.

The study was conducted at a single site, outpatient setting at the Istanbul University Institute of Oncology in Turkey.

Patients were undergoing the active phase of treatment care.

This was a descriptive study.

• The Patient Characteristics Form had 17 items that addressed demographic, disease, and treatment characteristics at the time of initial diagnosis. 
• The Eastern Cooperative Oncology Group (ECOG) Performance Status assesses performance status of patients with cancer using six possible number responses.
• The Nightingale Symptom Assessment Scale (N-SAS) is a Likert -type, quality-of-life scale that includes 38 items addressing symptom experience of patients with cancer during chemotherapy. Three subscales (psychological well-being, social well-being, and physical well-being) are used. The original study using this author-developed scale reported that the subscales have high internal reliability and Cronbach’s alpha values between 0.81 and 0.87 and 0.93 for the overall tool. This study reported Cronbach’s alpha reliability for the subscales as follows.
  • Psychological, 0.88
  • Social, 0.80
  • Physical, 0.85
• Effective nonpharmacological interventions were identified from the literature and grouped into three subgroups based on the scale’s subgroups of psychological, social, and physical.

• Physical symptom distress was higher than psychological and social symptom distress.  The most frequent symptoms reported were fatigue (85.1%), nausea (70.8%), alopecia (68.3%), dry mouth (64.4%), and impaired sleep habits (62.9%).  Nonpharmacological interventions used to relieve physical distress included resting (38.2%) and sleeping (12.9%) for fatigue; drinking liquids (9%) and oral care (15.9%) for dry mouth; and exercise (8%) and massage (5.5%) for other physical symptoms. Most subjects (72.5%) preferred pharmacological interventions for physical symptoms.
• Psychological symptom distress was most frequently addressed by support (7.5%), resting (6.5%), and exercise (1.5%). Only 3% of patients preferred pharmacological interventions for psychological symptoms. Social interventions included pomades for skin and nail changes (19.4%) and berets, scarves and wigs for alopecia (6.5%).  An increase in symptoms “enhanced” the use of the physical and all nonpharmacological interventions in general.  The well-being of women and younger patients and patients who had metastatic disease, surgery, and high ECOG performance scores were low for all subgroups and overall (p < 0.05).
• Social well-being was lower in patients with breast cancer, patients who received taxane-based therapy, and those who were housewives. Social interventions were more frequently used by university graduates (p = 0.024). Psychological interventions were more often used by students compared to housewives, retired, self-employed people, and working people (p = 0.028). Patients below the age of 50 preferred to use psychological interventions using logistic regression (overall response [OR] = 3.06 [95% confidence interval (CI) = 1.17–7.96]).

Most patients with cancer in Turkey preferred pharmacologic interventions for symptom management.  Exercise, as a recognized evidence-based intervention, was only reported to be used by a few patients. The authors recommended that oncology nurses teach patients more about the side effects of chemotherapy and associated nonpharmacological interventions. Although other studies have produced such evidence-based recommendations, they were not developed from this study of self-reported symptoms and interventions of Turkish people receiving chemotherapy. The authors did not report if or how teaching occurred from the perspective of the nurse or the patient or family.

• No appropriate control group was included.
• Only patient survey data was used.
• Data was exclusively from a Turkish patient population at one point in time (which differed among patients) and with various diagnoses and treatments . 
• No discussion was included comparing these results to results from similar symptom and intervention surveys in other countries and cultures.

An individualized assessment of each patient's knowledge and preferences is important to all cultures and practices.

To investigate if the addition of acetyl-L-carnitine (ALC) to sagopilone (SAG) in patients with ovarian cancer (OC) and castration-resistant prostate cancer (CRPC) reduced the overall incidence of SAG-induced peripheral neuropathy (PN) compared to SAG and placebo, and to evaluate the safety and efficacy of ALC-SAG compared to SAG-placebo

Patients were randomized to treatment and placebo-controlled arms. All patients received a three-hour infusion every three weeks of SAG 16 mg/m² either with oral ALC (1000 mg) three times a day or oral placebo three times a day for six treatment cycles. ALC or placebo was continued for 30–33 days after the last SAG treatment. Patients with CRPC received oral prednisone 5 mg every two days as standard of care for quality of life.

• N = 111 completed study (n = 53 [ALC-SAG arm], n = 58 [SAG-placebo arm]) 
• MEDIAN AGE = 62 years
• AGE RANGE = 29–82 years
• MALES 35%, FEMALES 65% (out of total N = 150 enrolled) 
• KEY DISEASE CHARACTERISTICS: Metastatic/advanced Disease; OC and CRPC patients had no evidence of PN at enrollment.
• OTHER KEY SAMPLE CHARACTERISTICS: Ovarian cancer International Federation of Gynecology and Obstetrics (FIGO) grades IV (18%), III (69%), II (6%), I (7%); the CRPC median Gleason total score was 8; patients with CRPC taking prednisone 5 mg

• SITE: Multi-site    
• SETTING TYPE: Unknown  
• LOCATION: Europe

• PHASE OF CARE: Active treatment
• APPLICATIONS: Elder care, palliative care

Phase-II, prospective, placebo-controlled, double-blind, randomized trial

• PN was evaluated for time to incidence, time to recovery, and grade of neuropathy within six or fewer cycles.
• Measurement tools/instruments for evaluation of PN not described
• Modified Response Evaluation Criteria in Solid Tumors was used to evaluate tumor size.
• CA-125 blood test
• Prostate-specific antigen (PSA) blood test

No difference in the incidence or median duration of PN existed in either arm. No difference existed in best overall response, tumor markers, time-to-event variables (progression free survival or time to progression), or discontinuations because of adverse events in either arm. Slightly more serious adverse events and grade 3–4 adverse events were reported in the SAG-placebo arm. ALC reduced the incidence of grade 3–4 PN in patients in the SAG-ALC arm compared to patients in the the SAG-placebo arm; however, actual statistical results were not reported.

ALC given concurrently with SAG in patients with advanced OC was reported to reduce the incidence of grade 3–4 PN after six cycles of treatment; however, no results showing statistical significance were provided.

• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Subject withdrawals ≥ 10% (26%)
• Study methods poorly described
• PN evaluation tool not provided
• Number of cycles and types of prior regimens in sample not described
• Inclusion/exclusion criteria not described
• Statistical methods for analysis of data and significance not described but depicted in tables
• Patient with CRPC on prednisone could potentially confound results
• No report of grades or types/frequencies of adverse events in either group
• No information on what was used as the placebo

ALC concurrently with SAG after six cycles reduced the incidence of grade 3–4 PN in patients with advanced OC. No benefit was observed in patients with CRPC or in reducing the incidence of grade 1–2 for either patients with OC or CRPC. Further randomized, controlled trials are needed to determine the benefits, duration of benefits, and quality of life for ALC-SAG or other neurotoxic regimens in diverse tumor types.