To measure the efficacy of lactulose as a treatment for vincristine-induced intractable constipation or for the prevention of vincristine-associated constipation in patients with cancer.

Patients received lactulose 20 ml BID to 25 ml TID.

• The study reported on a sample of eight patients with lymphoma or leukemia.
• Patients were aged 22 to 67 years.
• Six patients (five women and one man) had protracted problems with constipation.
• Two men received prophylactic treatment with lactulose immediately after vincristine therapy was initiated.

• Inpatient
• Royal Perth Hospital in Western Australia

This was a descriptive study.

Time-to-first bowel movement after vincristine treatment and initiation of lactulose therapy.

All patients obtained relief of constipation within two days of initiating lactulose.

• The sample size was small.
• Patients were not randomized.
• Side effects and duration of use were not reported.

To investigate the effect of a short-acting intranasal benzodiazepine on dyspnea, which is extremely common in those with life-limiting disease and negatively impacts quality of life (QOL)

Participants were given six identical bottles of nasal spray, three of which contained a placebo and three of which contained midazolam (benzodiazepine being studied) with the concentration of 0.5 mg per spray. The bottles were numbered one through six  in random sequence. Patients were instructed to inhale a total of three times on each occasion of use with the total dose of active drug delivered being 1.5 mg. The participants were asked to use bottle number 1 on the first day, number 2 on the second day, and so on, using no single nasal spray for more than 24 hours. The dosages were not to be delivered more frequently than every four hours, and if participants did not experience dyspnea on a certain day, they were not required to use a nasal spray that day. The participants were formally assessed by investigators at baseline, day 7, and day 14. The participants were also contacted by phone throughout the study on specific days to ensure compliance. The participants formally scored the first dose administered each day, and at the end of each study day, participants documented how many times they used the nasal spray and if there was any benefit using a variety of tools and surveys.

• N = 62
• MEDIAN AGE = 70 years
• AGE RANGE = 62–78 years
• MALES: 48%, FEMALES: 52%
• CURRENT TREATMENT: Not applicable. Patients were instructed to continue baseline medications and treatment of underlying condition, and no further information on this matter was collected.
• KEY DISEASE CHARACTERISTICS: Participants were from two different countries—participants in New Zealand had a greater proportion of participants with cancer, and participants in Austrailia had a larger proportion of participants with respiratory diseases. 
• OTHER KEY CHARACTERISTICS: All participants had dyspnea related to either a life-limiting disease or the treatment of the disease with the average score being > 3/10 on a scale of 1–10 with 10 being the worst breathlessness. All participants had an adequate performance status and were able to operate the nasal spray independently. Study participants were in or outpatients recruited across four sites in Australia and New Zealand. Any participants receiving sustained-release opioids were to continue to take these medications throughout the study period and any of those on dependent supplemental oxygen were also instructed to continue at the same flow rate for the duration of the study.

• SITE: Multi-site
• SETTING TYPE: Blend of inpatients and outpatients
• LOCATION: The participants were recruited from an oncology/palliative care department in a hospital in Australia and from three palliative care services in New Zealand.

• PHASE OF CARE: Symptom management, palliation, end of life
• APPLICATIONS: Palliative care

• Randomized, double-blind, placebo-controlled crossover design with participants taking both placebo or the trial medication at various times

The Covi Anxiety Scale (CAS) and the Cancer Dyspnea Scale (CDS) were completed by clinicians and examined verbal reports, patient behaviors, and somatic symptoms of anxiety. Participants documented how many times they had used the nasal spray in 24 hours and if they found any benefit in a daily log. Participants rated dyspnea, anxiety, and drowsiness on an 11-point numerical rating scale (NRS).

No significant benefit of the intranasal midazolam on anxiety scores was noted. No difference at any time point of investigation existed between the midazolam and the control group, and no difference in the dyspnea scores or positive change in dyspnea existed between the control bottles of nasal spray and the midazolam when looking closer into age, gender, baseline anxiety, depression, and disease. The greatest benefit was seen at 30 minutes after the use of both the control spray and the midazolam, with no difference between the two groups. When questioned about adverse events, participants revealed that side effects worse than they were at baseline were low grade and most likely from the use of the nasal spray, with the most common being nasal cavity irritation and sinus reactions.

The study failed to demonstrate a meaningful benefit of intranasal midazolam on dyspnea or anxiety. Though the nasal cavity is thought to be a good way to deliver the effects of medications quickly, intranasal midazolam did not effectively relieve the participants’ dyspnea.

• Small sample (< 100)
• Baseline sample/group differences of import: The sample contained patients with a variety of diseases, with the majority having cancer or respiratory diseases. Further studies should target a single disease type because of the differences in characteristics and presentations of dyspnea.
• The sample size was limited because participants had to be able to operate the nasal spray device and have an adequate performance status; this is unfortunate since many terminally ill patients needed to be excluded from the study. 
• The study participants had low anxiety scores at baseline, which may have affected the study results of the intervention in question, and measures may have been subject to floor effects.
• Many of the older adult patients in the study found the nasal sprays difficult to use, and several of the bottles were faulty and did not delivery a reliable spray, which may have resulted in a less-than-planned dose delivered.

The study findings demonstrated that intranasal midazolam was not effective in relieving dyspnea. This study magnified the importance of finding ways to better control dyspnea in terminally ill patients and the impact on quality of life if not done. The effectiveness of benzodiazepines on dyspnea needs further investigation, and nurses should continue with the administration of low-dose opioids to treat patient dyspnea, as this remains the evidence-based medication of choice.

To identify a dose of methylphenidate to test formally in a subsequent N-of-one trial of fatigue.

Patients with fatigue 4/10 or more at baseline received titrated doses of methylphenidate beginning at 5 mg/day up to 15 mg twice daily (BID) at three-day intervals.

• In total, nine patients (20% male, 80% female) were included.   
• Age ranged from 56 to 86 years.
• Patients had breast, ovarian, and other cancers.
• No demographic information was available.

• Single site  
• Outpatient  
• Queensland, Australia

Patients were undergoing the transition phase on “stable treatment,” not on chemotherapy.

The study was a prospective trial.

• Wu Cancer Fatigue Scale
• Functional Assessment of Cancer Treatment–Fatigue (FACT-F)
• Edinburgh Depression Scale
• Daily toxicity and symptom diaries
• Karnofsky Performance Status (KPS)
• Global Impression of Change
   

• Nine patients began taking 5 mg of methylphenidate daily; seven patients increased to 5 mg BID; six patients increased to 10 mg BID; five patients received the maximum dose of 15 mg BID, and three patients were unwilling to increase the dose to the maximum because they were satisfied with the response at a lower dose.
• No statistical information was provided; overall, fatigue and depression improved until day 9 of the study (5 mg BID dose of methylphenidate) after which the rate of improvement was slower.
• There was little correlation between performance status and maximum tolerated dose.
• Although toxicity was difficult to measure due to small numbers and side effects at baseline, no patient discontinued due to toxicity.
   

Methylphenidate 5 mg BID was chosen as the ideal dose to test against placebo.

• The study had a small sample size, with less than 100 patients.
• The study lacked a control group.
• There was significant attrition.
• There was one treatment site in one country.
• The study lacked racial/ethnic diversity.
• The aim of the study was not to determine if methylphenidate was effective in managing fatigue but rather to find an ideal dose to use for a future randomized, controlled trial.

Nurses in research can use a 5-mg BID dose of methylphenidate to test against placebo.

To determine whether ketamine, delivered subcutaneously with dose titration over five days, has greater clinical benefit than placebo when used in conjunction with opioids and standard adjuvant therapy in the management of cancer pain

• Patients received either a continuous subcutaneous infusion of ketamine on a five-day, escalating-dose schedule (100 mg, 300 mg, and 500 mg over 24 hours) or placebo (normal saline) given over five days. 
• Patients were assessed every 24 hours for pain (least, average or best)  using the Brief Pain Inventory (BPI). No dose change occurred if 80% of ketamine was delivered, pain improvement was greater than 2, and no more than four breakthrough pain doses were needed.
• Dose reductions occurred if toxicity was unacceptable. The drug was discontinued at 500 mg if no response to pain occurred or toxicity became intolerable.

• The study reported on 149 patients with a mean age of 63.
• The sample was 55% male and 45% female.
• Patients had refractory pain secondary to cancer or its treatment.
• For 48 hours prior to beginning the study, participants could have no change in baseline opioid dosing. 
• Patients were excluded if they had received ketamine within the past six months, had radiotherapy to a site of pain within two weeks, or received any other procedure that may affect pain.

This was a multisite, inpatient study conducted in Australia.

• Patients were in the late effects and survivorship phase of care.
• This study has clinical applicability for palliative care.

This was a randomized, double-blinded, placebo-control study.

• The Common Terminology Criteria for Adverse Events v 3.0, Clinician-Administered Dissociative States Scale, and BPI were used.
• A positive response was defined as a clinically relevant improvement in pain.

• Findings showed no significant differences between study groups. Pain declined somewhat over time in both groups. The decline in worst pain ratings was lower in the ketamine group (p = 0.034). No differences were found between groups in use of rescue medication.
• More patients withdrew from the ketamine arm. The incidence of adverse events was higher with ketamine.
• The most common events were light headedness, hypoxia, and somnolence. Psychotoxicity significantly increased each day, and, by day 3, the odds of psychotoxicity development were significantly higher in the ketamine group (OR = 2.53; 95% CI [1.11, 5.78]; p = 0.027).

Ketamine was only associated with improvement in worse pain compared to placebo, and it was associated with more adverse events and psychotoxicity.

• A risk of bias exists because of the sample characteristics.
• The findings are not generalizable.
• Entry inclusion criteria included an average pain score of 3 or more on BPI. This may not reflect clinically acceptable pain of 3 or 4. 
• Concerns exist regarding the aggressive dosing and short duration of the study. The short duration of the study over five days with rapid escalation of ketamine may have been overly aggressive. A question exists around whether more careful titration of ketamine may have altered results.

Ketamine as an adjunct to opioids to manage chronic refractory cancer pain only appeared to affect worst pain rating and may cause adverse effects and increase psychotoxicity. Incidence of adverse events with ketamine infusion adjunctively with opioids in the management of refractory pain should be reevaluated when considering the patient population of advanced cancer.

To evaluate how nurse navigation affected care satisfaction and distress among women who were undergoing breast biopsy. Specifically, were there significant differences in women undergoing breast biopsy with and without nurse navigators?

• N = 137  
• AGE: Range = 18-89 years. Thirty-two percent were aged 50 years or younger; 68% older than age 50
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Non-pregnant women aged 18 years or older undergoing core needle breast biopsy procedure

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: Northern Appalachia

• PHASE OF CARE: Diagnostic

• Descriptive, cross-sectional survey

• Demographics were collected via a questionnaire.
• Distress was measured with the Hospital Anxiety and Depression Scale (HADS-A, HADS-D) and the State Trait Anxiety Inventory, State (STAI-S) scale.
• Satisfaction was recorded with the Patient Satisfaction Questionnaire (PSQ-18).

No significant between-group differences were noted in depression. Lower scores were shown for anxiety (significance p < 0.05) among patients who had navigation. There was no difference in overall satisfaction with care though there was an association between satisfaction and distress: that is, women with more satisfaction reported less distress. The population with nurse navigators shows stronger relationship-based characteristics. Significant differences were shown in five categories (accessibility, communication, finances, interpersonal manner, and time) for the navigated population and in two categories (accessibility, general satisfaction) for the non-navigated or usual care population.

Nurse navigation increased satisfaction with care. General satisfaction measured significantly higher in the non-navigated sample when compared to the navigated group. Distress screening followed by interventions of emotional support, education, and facilitating communication between and among providers are roles nurses can fulfill to improve satisfaction outcomes and lower distress levels.

Train nurse navigators in addressing key areas of patient-center interface: accessibility to care, communication among providers, financial support, interpersonal manner, time with care provider, and technical quality. Nurse navigators have knowledge and skill to manage care of women undergoing needle biopsy and, thereby, improve general satisfaction in specific areas.

To evaluate the role of auricular acupuncture (AA) in men receiving luteinizing-hormone releasing hormone (LHRH) analogues for prostate cancer on hot flash incidence and severity

The study enrolled 60 consecutive men with prostate cancer who were receiving on LHRH agonist treatment.  Their median age was74 years, and they received weekly AA for 10 weeks.

Patients recorded the frequency of hot flash episodes during the day and at night at 0, 4, and 10 weeks. Participants were asked to grade the intensity of their hot flashes on a 0–6 scale, with 6 representing maximum intensity, and they recorded these data at 0, 4, and 10 weeks.

95% of patients reported a decrease in the severity of symptoms, from a mean of 5.0 to 2.1 (Student’s test, p < 0.01).

Limitations of this study included using a convenience sample and absence of a control group.

To promote self-care by combining informal teaching with group support in a short-term, closed, multiprofessional group

A single group facilitator introduced multiprofessional input from a changing weekly speaker during six 90-minute weekly sessions.

Groups were capped at 12 caregivers and initially focused on patient issues. Transportation for caregivers and a patient-sitting service were provided when necessary.

Four groups were delivered with peer supervision to ensure consistency of the intervention.

The sample (N = 73) was adult, informal, unpaid caregivers of patients receiving palliative care (86% of patients had a cancer diagnosis).

• Home palliative care services
• London, England

A prospective, observational, comparative (no randomization) design was used between those who accepted the intervention (n = 36) and those who declined the intervention but agreed to data collection in the first wave (n = 37), with limitations in group assignment.

• Zarit Burden Inventory
• Palliative Outcome Scale
• Eastern Cooperative Oncology Group Performance Scale
• Coping Responses Inventory
• General Health Questionnaire–12
• State Anxiety Scale

The intervention was not found to affect outcomes for any measures at postintervention (eight weeks) or follow-up (five months).

• The study had no randomization.
• Participants had a choice of comparison group.
• Little information was given about the training or preparation of the group facilitator.
• The sample was mostly Caucasian.
• Attrition was a problem.

A short-term, closed, multiprofessional group aimed to promote self-care by combining informal teaching with group support.

A single group facilitator introduced multiprofessional input from a changing weekly speaker during six, 90-minute weekly sessions. Groups were capped at 12 caregivers.

The group initially focused on patient issues, and transportation for caregivers and a patient-sitting service were provided when necessary.

A total of four groups were delivered with peer supervision to ensure consistency of the intervention.

• N = 73 adult, informal, unpaid caregivers of patients receiving palliative care (86% of patients had a diagnosis of cancer)

• Home palliative care services in London, United Kingdom

The study design was a prospective, observational, comparative (no randomization) between those who accepted the intervention (n = 36) and those who declined the intervention but agreed to data collection in the first wave (n = 37); limitations existed in group assignment.

• Zarit burden inventory
• Palliative outcome scale
• Eastern Cooperative Oncology Group performance scale
• Coping responses inventory
• General health questionnaire-12
• State anxiety scale

The intervention was not found to affect outcomes for any measures at post-intervention (eight weeks) or follow-up (five months).

• The study had no randomization.
• Participants had a choice of comparison group.
• Little information was given about the training or preparation of the group facilitator.
• The sample was mostly Caucasian.
• Attrition was a problem.

To update and evaluate intervention studies and current state of the science regarding support for caregivers in a systematic review

• Databases used in the search were MEDLINE, CINAHL, and PsycINFO.
• Key words were carer; caregiver; cancer; palliative; end of life; and terminal.
• To be included in the review, studies had to involve adult caregivers/adult recipients, be English language, occur in the cancer palliative care setting, and be intervention-based (from 2001 to July 2010).
• Articles reporting case studies, interventions without evaluation data, and interventions during the bereavement phase, as well as articles included in Harding and Higginson's 2003 systematic review paper, were excluded.

• The search revealed a total of 10,817 references.
• Studies were evaluated using the Jadad Rating Scale and the Quality Rating Scale.
• Despite the exclusion of bereavement studies, multiple studies are included in table and summarized.
• An international sample of studies was represented.
• Despite intent to focus on cancer populations, nine studies were in palliative care (not clearly cancer); a few studies were based on program implementation (process), so no specific caregiver outcomes were reported.

• A total number of 33 studies were included in the review. 
• Sample range of subjects across studies was 2–2,000+ (less than 25 [n = 10]; 25–100 [n = 10]; more than 100 [n = 13]).
• Interventions were dyad (n = 16) or caregiver only (n = 17).

• End-of-life phase
• Palliative care

Group interventions were studied most often, although only two of the studies included reported a statistically significant benefit compared to controls. The next largest group of studies investigated one-on-one psychological interventions. Two of these showed a positive effect for patient/carer dyads. Overall findings were equivocal, with about the same number of studies showing significant improvement with the intervention as those showing no change or difference between groups. The nature and timing of interventions varied greatly across studies included.

The authors identified seven categories of interventions: (a) one-on-one psychological, (b) dyad psychological, (c) palliative care/hospice (delivery), (d) informational/training, (e) respite, (f) group intervention, and (g) physical.

Given the limitations, differences in the nature of interventions reviewed, and inconsistencies of findings across studies, this review does not provide strong support for any particular type of intervention.

This summary has limited guidance due to lack of synthesis to actually guide practice. There were also inconsistencies between the inclusion and exclusion criteria and the studies reported; not all have clear implications to cancer, affect active information caregivers, or measure caregiver outcomes.

MEDLINE, CancerLit, PsycInfo, and CINAHL databases using the search terms carer(s), caregiver(s), palliative, and cancer were used.

Twenty-two articles reported interventions for adults actively providing informal care to noninstitutionalized patients with cancer and patients receiving palliative care. Only six of the interventions had been evaluated: Two used a randomized, controlled trial design, three used single group design (two prospective, one retrospective), and one was evaluated by facilitator feedback.

The sample was comprised of caregivers from palliative or cancer care populations.

Problem-solving and education interventions led to overall improved caregiver burden, although the improvement was not significant; however, significant improvements were seen in a subsample of burdened caregivers (at baseline). Home nursing and respite care services improved caregiver satisfaction, quality of life, physical and emotional stress or distress, pain, health, and sleep in a few studies. Problem solving and education are likely to be effective in reducing caregiver burden.

• Too few studies evaluated interventions for caregivers.
• Most studies were of descriptive or cross-sectional design.
• Outcome measures within studies varied widely.
• Only two studies measured caregiver burden or strain as an outcome.