To identify the targets of intervention studies and obtain findings that will help in planning future intervention studies, support nursing, and promote the introduction of new family-centered nursing methods

• MEDLINE and CINAHL (2001–2006) databases were searched, in addition to hand searching of article references.
• Key words were nursing interventions, family, family health, family nursing, family members, caregivers, and spouse.
• Inclusion criteria included English-language studies with participants who were at least 18 years of age.
• Patients and family members, or family members only, described or tested a nursing intervention and its impact.

The initial search yielded 323 articles. The final analysis included 31 articles that met inclusion criteria. Evidence was assessed using the Finnish Federation of Nurses’ criteria, which is described in the article. Content analysis of interventions was used. The RE-AIM model was used to examine study findings. This model includes dimensions of reach, efficacy, adaptation, implementation, and maintenance. Only six of the studies were identified as a high level of evidence using the stated criteria.

• A final sample of 31 studies was used.
• Study sample sizes were not reported.
• Sample characteristics were not fully described, but the authors stated that the majority of interventions were aimed at patients with cancer.
• Other situations included patients with Alzheimer disease, dementia, stroke, and schizophrenia and their family members.

• Of the studies, 22 used quantitative methods, 4 used qualitative methods, and 5 used a combination of these.
• Support and counseling interventions on depressive symptoms of spouses of patients with Alzheimer disease were supported by the evidence.
• Education and support interventions were shown to help improve family members’ ability to control challenging behavior associated with Alzheimer disease and schizophrenia.
• Support and teaching interventions may enhance preparedness and social capability and alleviate depressive symptoms in family members of patients who experienced a stroke.
• Support and teaching interventions may help to improve quality of life in family members of patients with cancer.
• Interventions ranged in duration from 4 to 24 weeks and involved a variety of personal and group meetings and/or phone contact.
• The majority of studies were focused on a single family member and did not consider the wider family context.

• The studies included difficult categories of patients and families (e.g., cancer dementia) that have very different problems and needs, thereby decreasing the applicability of the results.
• Data from the studies was incomplete, such as dropout rates and missing data (particularly the differential dropout rate).
• Not all of the dimensions of RE-AIM were able to be assessed due to insufficient data.

• Interventions were not designed to achieve economic objectives, and consideration was not given to the costs of the intervention.
• Overall, interventions may be effective in alleviating burdens of care and depressive symptoms of family members, as well as assisting their coping. 
• These nursing interventions are in development and testing stages. Long-term effects and aspects of maintenance and implementation monitoring are not clear.
• Nursing interventions involving education, counseling, and incorporation of both individual and group activities can be effective in assisting caregivers. The most effective combinations of approaches, setting for provision, and long-term maintenance are not yet clear.

To determine the effectiveness of palonosetron in prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) for highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) in patients who had failed to respond to a different antiemetic 5-HT₃ antagonist during the first cycle; to determine differences in response between older adults and younger patients

On day 1, patients received 16 mg dexamethasone plus 250 mcg IV palonosetron before chemotherapy administration. For prophylaxis, patients received 8 mg dexamethasone every 12 hours on days 2–3 and 4 mg dexamethasone every 12 hours on days 4–5. Metoclopramide (20 mg) intramuscular was used at a maximum dose of 80 mg as rescue medication to treat CINV. Patients were asked to record daily episodes of vomiting, nausea, and use of rescue medication daily through day 5.

• The study sample consisted of 47 participants.
• Mean age was 60.7 years (SD = 3 years). Older adults (age 65 or older) had a mean age of 72.3 years (SD = 6 years), and those under age 65 had a mean age of 60.7 years (SD = 3 years).
• The majority of patients (59.6%) were male.
• Diagnoses included tumors at various sites (head and neck, lung-pleural mesothelioma, colorectal, ovary, breast, pancreas, prostate, malignant lymphoma, melanoma, sarcoma, biliary ducts, bladder, and stomach), stages II–IV.
• The chemotherapy regimen was the same as that of previous chemotherapy administered for the first cycle and for which the previous antiemetic treatment failed. Regimens were moderately or highly emetogenic.

The setting was not reported.

All patients were in active treatment.

This was a prospective design, phase II, open, nonrandomized trial.

The following were measured.

• Daily episodes of vomiting (number, duration, and time from chemotherapy administration), vomiting according to Common Terminology Criteria for Adverse Events (CTCAE 3.0) for days 1–5
• Nausea (grade 3–4, according to CTCAE 3.0) on days 1–5
• Use of rescue medication on days 1–5
• Complete response (CR), defined as no emetic episodes and no use of rescue medication during the first 24 hours (acute), and during 24–120 hours (delayed) following chemotherapy
• Complete control (CC), defined as no emetic episodes, no need for rescue medication, and no more than mild nausea in the acute, delayed, and overall periods

• CR and CC for the acute, delayed, and overall phases were not statistically different with the intervention between older adult and younger subjects, compared to the subsequent cycles of chemotherapy after intervention.
• Grade 1–2 toxicities were observed without group differences.
• The most frequently reported adverse events were constipation and anxiety.

Single-dose palonosetron (250 mcg) should be considered a safe second generation 5-HT₃ antagonist in the prevention of nausea and vomiting induced by HEC or MEC, irrespective of patient age.

• The study had fewer than 100 participants.
• The study combined HEC and MEC together but did not include aprepitant.
• The authors in this study concluded that palonsetron is older-adult friendly because the comparison between older adult and younger participants found no difference. However, younger age is a well-known predisposing factor for CINV.
• The sample consisted of patients who previously failed 5-HT₃.
• Anticipatory nausea would be likely but was not discussed.

Palonosetron provides control of CINV regardless of patient age.

The study's primary aim was to examine the relationship of changes in Hgb levels following erythropoietin treatment to changes in cognitive functioning, as studied in older adult patients with cancer undergoing chemotherapy treatment. Its secondary aim was to assess the relationship of changes in Hgb levels following erythropoietin treatment to changes in functions studied in the Comprehensive Geriatric Assessment.

The study's treatment cycle was 12 weeks. For the first 2 weeks, all patients were treated with 10,000 units of erythropoietin twice daily for 6 days a week. For the following 10 weeks, participants were administered 10,000 units of erythropoietin 3 times a week. Participants were also treated with 125 mg of intravenous sodium ferric gluconate complex weekly, or more than once a week if serum iron values were below the inferior limit of normal range. All assessments, including cognition (as based on the MMSE) were completed at baseline prior to treatment with erythropoietin, and at weeks 4, 8, and 12 of treatment.

• The number of participants was 10.
• The average participant age was 71.4, with a range of 68–75.
• 50% of participants were female and 50% were male.
• 40% of participants had non–small-cell lung cancer, 10% had oral cancer, 10% had ovarian cancer, 10% had breast cancer, 10% had endometrial cancer, 10% had colon cancer, and 10% had stomach cancer.
• All participants had an ECOG performance status of 0–2 and an initial MMSE score of 19 or greater. 

The study took place at a single-site location in Italy. 

The study was a prospective single-arm trial.

The Mini-Mental State Examination (MMSE) measured global cognitive function.

The Comprehensive Geriatric Assessment (CGA) is a multidimensional, interdisciplinary diagnostic process that determines the medical, psychological, and functional capabilities of a frail elderly person. It includes

• Activities of Daily Living Scale (ADL). Scores ranging between 0–8 were used to assess functional status for self-care activities.
• Instrumental Activities of Daily Living Scale (IADL). Scores ranging between 0–8 were used to assess functional status for higher-level activities.
• Geriatric Depression Scale (GDS), a 15-item questionnaire.
• The Mini Nutritional Assessment (MNA).

Nine participants (90%) showed significant improvement in cognitive function compared to baseline (p < 0.005), with eight of these patients also responders to erythropoietin in showing correction of anemia. All of these patients maintained improved MMSE scores after weeks 8 and 12 (p = 0.009 and 0.006). There was significant correlation between changes in Hgb levels and cognitive functioning (p = 0.049). There were no significant changes in ADL, IADL, GDS, or MNA scores as compared to baseline scores.

At baseline, the mean Hgb level was 10.3 g/dL, and 40% of patients displayed cognitive impairment (MMSE score < 24). After four weeks of treatment, Hgb levels increased significantly (p < 0.001). 

The study found that treating anemic patients undergoing chemotherapy significantly improved anemia, and that this improvement was correlated with an improvement in cognitive function. However, definitive conclusions cannot be drawn from this study because of multiple limitations.

• The study had a very small sample size for the participants' multiple types of cancer, regimens, and variability in stage of disease.
• The study lacked a control group as a comparison.
• All patients were anemic at baseline.
• The MMSE is not sensitive enough to detect subtle cognitive changes.
• There was a lack of alternate forms for repeated administration of MMSE, so practice effects may have influenced study outcomes.
• The study followed an atypical erythropoietin dosing schedule.

Patients with febrile neutropenia who developed lung infiltrates were included.

In these guidelines, prospective clinical trials involving patients with febrile neutropenia and lung infiltrates were reviewed. 

Categories of Evidence Used: 

Strength of Evidence:

• (A) Good evidence to support a recommendation for use
• (B) Moderate evidence to support a recommendation for use  
• (C) Poor evidence to support a recommendation
• (D) Moderate evidence to support a recommendation against use
• (E) Good evidence to support a recommendation against use. 

Quality of Evidence:

• (I) Evidence from ≥1 well-designed clinical trials
• (II) Evidence from  ≥1 well-designed clinical trials, without randomization; from cohort or case-controlled analytic studies (preferably from >1 center); from multiple time series; or from dramatic results from uncontrolled experiments 
• (III) Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.

Search Strategy

Databases searched were not specified.

Search keywords were lung infiltrate, treatment, aspergillosis, febrile neutropenia, and infection.

Patients receiving allogeneic hematopoietic stem cell transplantations were excluded.

Using systemic antifungals that are mold-active can improve outcomes for patients with neutropenia that has been present 10 or more days and who have developed fever and lung infiltrates (BII).  The recommended pre-emptive (i.e., administration of antimicrobial agents on the basis of clinical, imaging, or laboratory findings indicative of a particular infection in patients at risk for, but without proof of, this infection) antifungal therapy is voriconazole or liposomal amphotericin B.  Much of the content in this guideline is related to diagnosing and managing infections for neutropenic patients with lung infiltrates, not preventing infection, but reducing the risk of second and subsequent infections.

Specific pre-emptive therapy with voriconazole or liposomal amphotericin B in neutropenic patients can improve outcomes (BII).  Patients with cancer who are neutropenic and have respiratory failure–related lung infiltrates have better outcomes if transferred to intensive care units for care, including mechanical ventilation (AII).

Conflicts of Interest: Georg Maschmeyer has been a consultant for Gilead Sciences, MSD, Pfizer, Essex (Schering-Plough), Novartis, and Sanofi-Aventis and has been on the Speakers’ Bureau for Gilead Sciences, MSD, Pfizer, and Cephalon.  Dieter Buchheidt receives grants and research support from Gilead Sciences, MSD, Pfizer, and Essex (Schering-Plough) and has served on the Speakers’ Bureau for Gilead Sciences, MSD, Pfizer, and Essex (Schering-Plough).  Oliver Cornely has received grants and research support from Astellas, Basilea, Gilead Schinces, MSD, Pfizer, Essex (Schering-Plough), and Cephalon and has been a consultant for Astellas, Basilea, F2G, Gilead Sciences, MSD, Pfizer, Essex (Schering-Plough), and Cephalon and has served on the Speakers’ Bureau for Gilead Sciences, MSD, Pfizer, and Cephalon.  Hermann Einsele has been a consultant for MSD.  Werner Heinz has received grants and research support from Astellas, Gilead Sciences, MSD, Pfizer, and Essex (Schering-Plough); has been a consultant for Pfizer and Essex (Schering-Plough); and has served on the Speakers’ Bureau for Gilead Sciences, MSD, Pfizer, and Essex (Schering-Plough).  Claus Peter Heussel has received research support and grants from AstraZeneca, Bayer, Bracco, General Electric, Intermun, Merck, Novartis, Pfizer, PneumRx, PulmonRx, ROX, Essex (Schering-Plough), Siemens, Roche, Wyeth, and ZLB Behring and has been a consultant for AstraZeneca, Basilea, Baxter, Bracco, Essex (Schering-Plough), Systema, Gilead Sciences, Pfizer, Perceptive, Phillips, and Siemens.  Herbert Hof has been a consultant for Gilead Sciences and MSD and has served on the Speakers’ Bureau for Gilead Sciences, MSD, Pfizer, and Essex (Schering-Plough).  Michael Kiehl has been a consultant for Gilead Sciences and Essex (Schering-Plough) and has served on the Speakers’ Bureau for Gilead Sciences, MSD, and Essex (Schering-Plough).  Gloria Mattuizzi has received research support and grants from Astellas, MGI Pharma Inc., and Novartis.

Many of the interventions discussed were aimed at minimizing invasive fungal and other infections in patients, primarily neutropenic, who presented with lung infiltrates.  The pre-emptive B-II recommendation for antifungals lacked the strength of randomized, controlled trials.  The recommendation for intensive care to improve outcomes does not really address the prevention of infection.

To evaluate the effect of pregabalin as an add-on therapy on seizure control, quality of life, and anxiety in patients with brain tumor–related epilepsy.

Pregabalin was added as a first or second add-on drug at 75 mg/day to a maximum of 600 mg/day for specific drugs (i.e., clobazan, lamorigine, levetiracetam, oxcarbazepine, phenobarbital, valproate, and topiramate).

• N = 25 (final sample); 12 patients completed six-month follow-up
• AGE RANGE: 19–72 years
• MALES: 72%, FEMALES: 28%
• KEY DISEASE CHARACTERISTICS: Patients with brain tumor–related epilepsy
• OTHER KEY SAMPLE CHARACTERISTICS: Patients with brain tumor–related epilepsy who had received standard antiepileptic drugs (AED) and who had at least one seizure in the month preceding recruitment  despite AEDs being at the maximum tolerable dose

• SITE: Single site  
• SETTING TYPE: Not specified  
• LOCATION: Center for tumor-related epilepsy

• PHASE OF CARE: Active antitumor treatment

• Descriptive

• Quality of Life in Epilepsy Inventory
• Quality of Life in Cancer
• Hamilton Anxiety Rating Scale
• Zung Self-Rating Depression Scale
• Karnofsky Performance Status
• Seizure diary

The mean dose of pregabalin was 279 mg/day, and the mean follow-up period was 4.1 months. At the end of the follow-up, in the whole intention-to-treat population, nine patients were seizure free, 10 patients had a seizure reduction, and two patients were unchanged. There was a significant difference in the presence or absence of seizure between the baseline and the follow-up visit. There was a significant decrease in anxiety score (p = 0.002) between baseline and last available follow-up visit.

The study showed improvement in anxiety scores with pregabalins, but this is a pilot study with small sample size and a short follow-up period. Future studies with larger sample size and minimum dropout are indicated.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition) 
• Findings not generalizable
• Questionable protocol fidelity

Larger sample size is needed to evaluate the true impact of pregabalin on anxiety among patients with brain tumor–related epilepsy. There are not many implications for nursing because the intervention is drug related.

To investigate the effects of d-methylphenidate (d-MPH) on fatigue and cognitive function in women undergoing adjuvant chemotherapy for early breast cancer.

Patients were given 5 mg of placebo for the first chemotherapy cycle to assess for compliance and were then randomized to either d-MPH 5 mg twice daily (BID) or matched placebo. The dosage increased to 10 mg BID after one week and was taken in the morning and at noon.

• The sample was comprised of 57 women with breast cancer.
• Median age was 50 years. 
• Of the patients, 29 received d-MPH and 28 received placebo.
• Patients were eligible for the study if they were receiving four cycles of standard adjuvant chemotherapy.

• Multisite
• Three hospital outpatient clinics in Toronto, Canada

The study was a randomized, controlled trial with a placebo arm.

• High Sensitivity Cognitive Screen (HSCS)
• Hopkins Learning Test–Revised (HLT-R)
• Functional Assessment of Cancer Therapy–General (FACT-G)
• FACT–Fatigue (FACT-F) 
• Mini-Mental State Examination (MMSE)

All were measured at baseline, end of chemotherapy, and at six-month follow-up.

The difference between groups was not significant in cognitive function or fatigue.

The findings do not support the effectiveness of d-MPH at the doses given here in reducing fatigue during active treatment for breast cancer.

• The study had a small sample size, with less than 100 patients. 
• The study was underpowered; no trends suggest that d-MPH taken concurrently with adjuvant chemotherapy improves quality of life or fatigue.

D-MPH cannot be suggested as an intervention to relieve cancer-related fatigue or cognitive functioning.

To review the current published research from randomized controlled trials (RCTs) and crossover trials evaluating the efficacy of ginger for prevention of chemotherapy-induced nausea and vomiting (CINV)

Databases searched were PubMed, CINAHL, and Cochrane library.

Search keywords were ginger, cancer , chemotherapy, nausea, emesis, vomiting, and CINV.

Studies were included in the review if they

• Were RCTs or crossover trials.
• Involved ginger as the main intervention.
• Were in English language.

Study exclusions were not reported.

• A total of 27 references were initially retrieved.
• Studies were rated using the National Health and Medical Research Council hierarchy of evidence. 
• The overall body of evidence was rated according to the American Dietetic Association quality criteria checklist.

• Seven studies were included in the final review.
• Sample sizes ranged from 36-576 patients in each trial for a total of 1,013 patients across all studies.
• One study was of children. Samples included male and female participants.

• All patients were in active antitumor treatment.
• The report has applications for pediatrics.

• Four studies reported positive results with ginger, and three showed no benefit. 
• Varied ginger doses were used, and various comparisons were used.
• Only one study involved use of a 5-HT₃ or other recommended CINV treatment in the regimen. 
• All studies were rated as level II (with level I as the highest level); however, not all studies reported how CINV was measured, and one involved multiple emetogenicity levels.

At best, findings show mixed results for use of ginger.  Overall body of evidence was rated as “C’ in which “D” was the lowest possible level.

• The number of studies was limited.
• The quality rating method used was questionable, because all studies were highly rated for quality but some did not even define the method of CINV measurement. 
• The review did not take into account what treatments were used for control comparisons, and many did not include recommended treatments.

This review does not support the use of ginger for CINV prevention.

To compare the safety and efficacy of fosaprepitant with the safety and efficacy of aprepitant

Patients on cisplatin-based chemotherapy were randomly assigned to receive a single IV dose of fosaprepitant or a three-day dosing regimen of aprepitant. All also were given a dexamethasone regimen and ondansetron on day 1. Both groups could receive rescue therapy. Patients recorded nausea and vomiting episodes for the first 120 hours after chemotherapy.

• N = 272
• MEAN AGE =  50.5 years
• AGE RANGE = 19–79 years
• MALES: 73.5%, FEMALES: 24.5%
• KEY DISEASE CHARACTERISTICS: Patients had varied tumor types; lung and gastrointestinal cancers were most prevalent.

• SITE: Multi-site  
• LOCATION: India 

• PHASE OF CARE: Active antitumor treatment

• Subgroup analysis of a double-blind, randomized controlled trial

• Patient diary

No significant differences occurred between groups in complete response (CR) during the acute phase. In the delayed phase, 77.7% of patients on fosaprepitant had CR compared to 73.9% in the aprepitant group. This difference was not statistically significant. No differences existed in need for rescue medication. None of the patients experienced infusion site reactions with fosaprepitant.

The findings showed essentially equivalent efficacy of single dose fosaprepitant and a three-day aprepitant regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) with highly emetogenic chemotherapy.

• Risk of bias (no blinding)
• The study states a double-blind design and refers to a placebo, but the use of a placebo is not described in the report.

A single dose of fosaprepitant can provide the same essential prevention of CINV as a multiday aprepitant regimen as part of triple-drug therapy. Infusion site reactions have been described with fosaprepitant but were not shown in this particular analysis. Selection of the type of NK₁ use can be planned according to individual patient situations.

MEDLINE, PsycInfo, CancerLit, CINAHL, American College of Physicians Journal Club, Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effectiveness were searched using key words in groups (a) patient, ill, illness or health, (b) family, caregiver, caregiving, marriage, marital, spouse, spousal, couple, or partner, and (c) treatment, intervention, or support. ERIC, Social Work Abstracts, Expanded Academic ASAP, Academic Search Elite, PubMed, ISI Web of Knowledge and Web of Science, Economic and Social Research Council, Inter-University Consortium for Political and Social Research, and Physician Data Query/National Cancer Institute, as well as tables of contents of all Elsevier Publications medical journals, were searched using the key words family, caregiving or caregiver, and intervention or treatment.

• Seventy randomized trials comparing interventions with usual care were used.
• The sample was a mixture of family caregivers of individuals with chronic illness (Alzheimer disease, dementia, stroke, cardiac disease, chronic pain, rheumatoid arthritis, brain injury, and cancer).
• The sample included two large studies of 2,042 (Alzheimer) and 4,408 (post-myocardial infarction) participants.
• Excluding those two large studies, the average sample size was 87 caregivers.

Overall, evidence suggested that interventions reduced depressive symptoms in family members when the intervention focused on illnesses other than dementia. Family interventions targeted to patients and family members (as a dyad) or to family members alone were effective in reducing caregiver burden. Interventions offered to spouses alone or to a combination of family members were effective in reducing caregiver burden. Interventions had a stronger effect in reducing burden, depression, and anxiety when relationship issues between patients and caregivers were addressed.

No evidence was found that psychosocial interventions relieved anxiety in family members (uniform across studies).

A family intervention demonstrated the strongest evidence for improving family burden and was uniform across studies for spouses and for mixed groups of family members.

Only five studies included cancer populations.

To determine the effectiveness of manual lymph drainage (MLD) in reducing lymphedema in patients with breast cancer

Participants were randomly assigned to a control group and an experimental group. The control group received standard lymphedema treatment as well as a month of ambulatory treatment, daily bandaging from hand to shoulder for the first four weeks (removed at night), compression garments, and patient education regarding prevention guidelines and exercises to perform at home. The experimental group received the standard treatment plus MLD. MLD was performed before the bandaging occurred.

• The study sample (N = 58) was comprised of White female patients with breast cancer who had ipsilateral axillary lymphedema.
• Al patients
  • Had prior mastectomy, tumerectomy, or quadrantectomy and axillary lymphadenectomy
  • Finished radiotherapy or chemotherapy six months prior to study
  • Did not have rehab within three months prior to recruitment.

The study took place at a rehabilitation facility in Brazil.

Patients were undergoing active lymphedema treatment.

The study used a randomized controlled trial design.

• The measurement used to determine the effectiveness of MLD was the percentage of volume reduction after treatment using the water-displacement method.
• The investigators defined a good response to treatment as a 20% or more reduction in volume of the effected extremity.
• Measurements were taken at baseline and one, three, and six months.
• Patients also took a quality-of-life questionnaire for cancer in general and for breast cancer.

At 12 months the incidence of lymphedema in the intervention group was very similar to the control group: 24% and 19%, respectively. This difference is not considered statistically significant. There were no incidence differences at three and six months. There was also no difference in the time taken to develop lymphedema, secondary outcome measures of arm circumference, health-related quality of life, and patient reports.

Because of the lack of statistically significant changes in lymphedema incidence between control and intervention groups, it can be concluded that MLD is not effective in preventing lymphedema in the first year post-operatively in patients with breast cancer.

The study had a small sample size, with less than 100 participants.

The study indicates that MLD does not provide a statistically significant improvement in limb volume in patients with lymphedema. One of the greatest limitations of the study is the sample size. If the results of a repeated randomized controlled trial with a larger sample size yields similar results, MLD should not be taught to lymphedema patients because studies suggest it is unnecessary and ineffective.