The purpose of the study was to evaluate itraconazole solution or capsules compared with control (no treatment, placebo, oral polyenes, or fluconazole).

Searches were conducted through Cochrane Central Register of Controlled Trials and MEDLINE (January 1966 to July 2003); abstracts from the annual meetings of the American Society of Hematology, Interscience Conference on Antimicrobial Agents and Chemotherapy, European Hematology Association, European Group for Blood and Marrow Transplantation, German and Austrian Society of Hematology and Oncology, and the British Society for Hematology (1994–2003). Reference lists of relevant studies were reviewed. The pharmaceutical manufacturer of itraconazole was contacted.

13 randomized, controlled trials.

3,597 patients (1,812 on itraconazole and 1,785 controls) with hematologic malignancies who were neutropenic (absolute neutrophil count less than 500) following chemotherapy or bone marrow transplantation.

• A statistically significant decrease was found in the incidence of invasive fungal infections in the itraconazole solution group (49% reduction), but not in the itraconazole capsule group.
• A statistically significant decrease existed in the incidence of invasive yeast infections in the itraconazole solution group (60% reduction), but not in the itraconazole capsule group.
• A statistically significant decrease was found in the incidence of proven invasive aspergillus infections in the itraconazole solution group (48% reduction), but not in the itraconazole capsule group
• A statistically significant decrease was noted regarding mortality in the itraconazole solution group (42% reduction), but not in the itraconazole capsule group.
• No significant difference existed between the groups regarding mortality from any cause during the study period.

Antifungal prophylaxis with an itraconazole solution for neutropenic patients with hematologic malignancies reduces invasive fungal infections, invasive yeast infections, invasive aspergillus infections, and mortality. Bioavailability and dosing are significant factors because benefits are only derived from the oral or IV cyclodextrin solution and not the capsules.

The capsules are not recommended and the dosing should be at least 400 mg per day of the oral cyclodextrin solution or 200 mg per day of the IV solution.

To conduct a thorough systematic review of interventions aimed at families with chronically ill members and to describe and critically evaluate these interventions for caregivers of chronically ill persons

• PubMed MEDLINE, CINAHL, Cochrane Library, EMBASE, and PsycINFO (English only) databases were used. After the initial search, one additional search occurred in Web of Science, SocINDEX, Sociological Abstracts, and ERIC (no citations from the additional search were included).
• Key words were chosen based on predefined terms of each database, with main focus on the following words: intervention, caregivers, and diagnoses of diabetes, cardiovascular disease, cancer, or stroke.
• Studies included in the search addressed the selected diagnoses (stroke, cardiovascular disease, cancer, or diabetes) and were reviews and controlled studies published in English between 1997 and 2007.
• Studies that used patients younger than 18 years of age and dying adults were excluded.

• Forty-six studies were initially reviewed. Included in the report were 32 controlled studies (29 with randomization) described in 35 articles (stroke = 19, cancer = 10, cardiovascular disease = 3, and diabetes = 0). Study quality was addressed via author collaboration.
• Of the 32 studies, 12 were from the United States, and an additional 10 were completed in Western Europe. All patient with cancer/caregiver studies supported an international perspective.

• The final sample of 32 studies included 4,264 patients.
• Across studies, samples ranged from 30 to 1,040 caregiver/patient dyads.
• Very few studies addressed dropout rates and reasons for that occurrence.
• Participants were diagnosed mostly with stroke, then cancer, and least of all cardiovascular disease; no other information appears in the study information about samples.

Experimental interventions provided support to caregivers, patients, or both. Of the 32 studies, 4 interventions addressed caregivers alone and 32 interventions addressed both patients and caregivers. All experimental interventions included health professional–led discussion and guidance to increase knowledge, comfort, or resource allocation for persons addressed in the study. Educational delivery occurred at individual, couple, and group levels, and sessions occurred in a variety of inpatient and outpatient areas, including the patient’s/caregiver’s home. Half of the interventions involved home visits by a professional who taught, counseled, or helped a participant with practical home roles.

All studies involving patients with cancer or caregivers used hospital-based interventions and centered on alleviating physical and psychosocial concerns of patients with cancer. Although the focus of interventions was the same for patients experiencing stroke and cardiovascular disease, most interventions occurred in the home with a focus on caregiver well-being.

Educational interventions incorporated cognitive-behavioral therapy to support knowledge transfer that would improve participant well-being. Some studies compared different forms of an intervention (e.g., individual versus group), and some interventions included sites and telephone contacts. No studies considered or changed an intervention based on the participant’s social background. Professional actors of studies were mostly nurses and healthcare providers prepared at the bachelor's degree. The authors noted across disease groupings that interventions fit into the following areas: caregiver experience with burden, level of knowledge, skills mastery, and satisfaction.

Of 32 studies, 22 reported effects in one or more areas that the intervention targeted. Studies that showed a positive intervention effect mostly focused on caregiver burden and mastery of skills to provide care. However, the authors noted that it is not possible to support any consistency between interventions because many different instruments used in the 32 studies measured the same variable (e.g., 26 measures for depression).

The authors noted that the systematic review guides the following conclusions:

• There is a lack of knowledge supported by evidence about the effect of interventions on caregivers examined in this study; this inadequate level of evidence shows a need to challenge the quality of the studies.
• The effect of interventions targeting caregivers of chronically ill patients is inconclusive and recommendations on the type of intervention that would be most appropriate cannot be made. Few studies exist that document the effect of interventions on caregivers of chronically ill patients because most times the ill patient is the focus of the healthcare team. The few documented studies often lack sufficient rigor to support changed clinical practice for caregivers and the patients they serve.
• Interventions with a different, broader focus than short-term education or group dynamic process in a secondary healthcare setting should be considered.
• Further work should build on connections between randomized control studies with reliable and valid instruments and strong definition of an intervention that  may show significant intervention effects. This evidence will provide credible data for how to change and improve clinical practice.
• Additional qualitative work may inform understanding of ways health providers can create knowledge of caregivers through building on content and process of care already known to caregivers. This collaboration will allow tailoring of psychosocial and learning interventions for caregivers with unique histories and needs to support their health and ability to continue their caregiving role.

To evaluate the efficacy and safety of balugrastim compared to pegfilgrastim

Patients were randomized to receive either once per cycle 40–50 mg balugrastim or 6 mg pegfilgrastim by subcutaneous injection 24 hours after administration of chemotherapy. Blood samples were obtained twice weekly after post-nadir absolute neutrophil count (ANC) was greater than two, and temperature was measured twice daily.

• N = 238
• MEAN AGE = 49.9 years
• MALES: 0.04%, FEMALES: 99.6%
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer. Approximately one-third had metastatic disease.
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were excluded if they had received more than one prior chemotherapy cycle.

• SITE: Multi-site  
• SETTING TYPE: Not specified  
• LOCATION: Russia and Ukraine

• PHASE OF CARE: Active antitumor treatment

• Open-label randomized noninferiority trial

• Duration of severe neutropenia defined as ANC < 0.5 x 10⁹/L
• Incidence of febrile neutropenia (oral temp ≥ 38.2 C)
• Time to ANC nadir
• Duration and depth of ANC nadir
• Time to ANC recovery
• National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0

Difference in duration of severe neutropenia was less than one day between balugrastim and pegfilgrastim, and was similar in both dosages of balugrastim. Duration and incidence of severe neutropenia were reduced in subsequent cycles in all groups. There were no significant differences in incidence of febrile neutropenia. In cycle one, time to ANC recovery was shorted in the balugrastim group (2.0–2.1 days versus 2.6 days, p = 0.005). Adverse effects were similar in both groups. Presence of antibodies to the medication was similar in both groups.

A single fixed dose of balugrastim was not inferior to pegfilgrastim for management of neutropenia.

• Risk of bias (no blinding)

Balugrastim is an effective alternative to pegfilgrastim in patients with breast cancer receiving myelosuppressive chemotherapy. A single fixed dose per cycle was as effective as pegfilgrastim. Further research comparing various colony-stimulating factors (CSFs) and biosimilar agents are needed to continue to identify the most acceptable and cost-effective methods for hematopoetic support in patients receiving myelosuppressive chemotherapy with a high risk of febrile neutropenia.

To explore the effects of a prostate-specific program on physical activity, fatigue, mental distress, and quality of life (QOL).

Courses were conducted by a multidisciplinary team, including lectures, physical activity, and group sessions, lasting for six days. Activity was performed in groups of six to nine patients twice daily, including water gymnastics, walking, Nordic walking, resistance training, pelvic floor training, stretching, and relaxation for 60 to 90 minutes. Group sessions met for one hour daily and were led by a nurse with experience in group counseling. Lectures involved presentation of medical facts, treatment modalities, late effects, and social and other benefits of physical activity. Study measurements were obtained at baseline and at three-month follow-up.

• Sixty-eight patients (100% male) were included, and 51 completed the entire program. 
• Mean age was 67.4 years (range 48.5–81.2).
• All patients had prostate cancer.
• Of the patients, 14% had metastatic disease, 43% had undergone surgery and radiotherapy, 20% had received radiotherapy, and 16% had received hormonal therapy.
• Median time since diagnosis was 18.2 months.
• Most patients were retired, 50% had completed college education, and 86% were married or cohabitating.

• Single site
• Inpatient
• Norway

Patients were undergoing the active treatment phase of care.

This was a prospective, observational study.

• Godin Leisure-Time Exercise Questionnaire
• Fatigue Questionnaire (physical score range 0–21; mental score range 0–12)
• Memorial Anxiety Scale for Prostate Cancer (MAX-PC)
• Hospital Anxiety and Depression Scale (HADS)
• European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLC-C30 QOL) scale

Total fatigue scores declined from 16.1 to 14.0 (p = 0.001), and physical fatigue declined from 11.1 to 9.2 (p = 0.001). Those who did not complete the entire program had higher baseline fatigue scores. Anxiety results were mixed:  anxiety declined on the prostate specific measure (p = 0.001), but there was no change on the HADS scale. QOL measures did not change significantly.

Although there was a significant reduction in fatigue, the degree of change was small (2 of 33 points possible). The study did not provide strong support for the effectiveness of this program.

• The study had a small sample size, with less than 100 patients.
• No control or comparison group was used.
• The sample was highly variable in terms of the age range, and the rehabilitative needs of younger patients who may have undergone curative surgery can be expected to be different than those of older patients; this was not analyzed.
• Use of an inpatient setting for six days for this type of program can be expected to be expensive.
• Time from surgery to study entry varied, and final measures were three months after the program, with no interim assessment; it is not clear what the best timing of such interventions are in the disease trajectory.
• There was no information regarding continued activity prior to the final study measures being obtained.

The results suggested a small effect of this type of program on fatigue and no significant impact on overall anxiety or QOL.

To compare, in a population of initial-chemotherapy patients reporting pain and fatigue, a supportive nursing intervention plus conventional care versus conventional care 

The intervention consisted of an 18-week, 10-contact approach that included problem-solving strategies to manage symptoms and improve physical functioning and emotional health. Investigators conducted interviews at baseline and at 10 and 20 weeks. 

• The sample was composed of 113 patients, of which 60 patients were controls and 53 patients (the experimental group) underwent the intervention.
• Mean patient age was 58 years.
• Of all patients, 28% were male and 72% were female.  
• Breast and gynecologic cancers were most common cancer diagnoses in both groups, with lung and colon cancer representing the majority of the remainder of both groups.
• Eligible patients were within 56 days of initiating their first cycle of chemotherapy following cancer diagnosis. In the experimental group, 72% of patients were in late-stage cancer (stage III or IV); in the control group, 66% of patients were in late-stage cancer.
• At baseline, patients entered the study with an average of seven or more symptoms. Of all partients, 73% had at least some college education.

• Multisite
• Outpatient
• Four outpatient cancer treatment centers: two with comprehensive cancer centers, two community cancer treatment clinics

Phase of care: active treatment

Randomized clinical trial

• A scale to measure these symptoms: nausea, vomiting, pain, fatigue, insomnia, difficulty breathing, coordination problems, fever, cough, dry mouth, constipation, anorexia, diarrhea, and mouth sores 
• Two subscales of the Medical Outcomes Study 36 Short Form (SF-36), to measure the impact of the intervention on patients’ social and physical performance

At 22 weeks, patients in the experimental group reported 3.3 symptoms and patients in the control group reported 4.4 symptoms. Of those in both groups who reported neither pain nor fatigue at 20 weeks, the average number of other symptoms reported per patient was less than one symptom. At 20 weeks, authors noted no significant differences between groups in regard to pain or fatigue.

Patients who received the intervention reported a significant reduction in the number of symptoms experienced and improved physical and social functioning. Fewer patients in the experimental arm reported both pain and fatigue at 20 weeks.

• The disproportionately large number of patients with breast cancer in the sample may limit generalizability.
• Authors did not enter into the analysis all the covariates that could affect outcomes.
• Authors stated that the study was underpowered.

Findings suggest that behavioral interventions targeted to patients with pain and fatigue can reduce the symptom burden, improve the quality of the daily lives of patients, and demonstrate the value-added role of nursing care for patients undergoing chemotherapy. This study supports the work of Thomas et al. (2012), which evaluated a nursing-led cognitive behavioral intervention focused on improving symptom management and overall quality of life.

The symptom-tailored, evidence-based intervention was delivered at two-week intervals over a 20-week period. Six contacts were delivered in person and four via telephone. The intervention was targeted to systematically assess and intervene when patients experienced symptoms of nausea, vomiting, pain, fatigue, insomnia, difficulty breathing, coordination problems, fever, cough, dry mouth, constipation, anorexia, diarrhea, or mouth sores. Pain and fatigue were sentinel symptoms in this study, and the supportive nursing intervention was directed toward these symptoms, as well as 12 other common symptoms. When symptoms (as evaluated every two weeks) reached a threshold level of intensity or bother/interference with function and quality of life, interventions to manage the symptom were selected collaboratively by the nurse and patient and were initiated and continued until the symptom resolved or until the 20-week intervention period ended. Once a symptom had reached such a threshold, the interventions (including teaching, counseling, support, coordination, and communication) were initiated. Every two weeks, the efficacy of the intervention strategies and the status of problem resolution were reevaluated. Intervention strategies were then adjusted or stopped based on the result.

• The patients (intervention group, n = 53; control group, n = 60) had a mean age of 58 years, and 72% were female.
• The majority of patients had at least some college education, and most were not employed at the time of the study.
• Eligible patients were those who were within 56 days of initiating their first cycle of chemotherapy following a new cancer diagnosis.
• All patients had to have reported pain and fatigue at their screening interview.
• Breast and lung cancers were the most common diagnoses, and about 70% of the sample had advanced stage disease (stages III–IV).
• There were no differences between the intervention and control groups in baseline measures of fatigue; there was equivalency between the two groups relative to sociodemographic and medical/treatment variables. There were no differences between the two groups at baseline in symptom distress or self-reported physical and social functioning.

• Multicenter trial
• Two sites affiliated with comprehensive cancer centers and two community cancer treatment clinics

Patients were undergoing the active treatment phase of care.

This was a randomized, controlled trial with a usual care control group.

• Symptom Experience Scale (developed by the investigators)
• Physical and social functioning

Substantially more patients in the experimental group (n = 10) reported neither pain nor fatigue at the end of the 20-week intervention, compared with only three patients who reported neither pain nor fatigue, although it was not statistically significant. There were statistically significant benefits of the intervention relative to other outcomes, such as total symptom distress, role, and social functioning.

• The sample was inadequately powered.
• The study had a small sample size.
• Not all covariates that could affect the outcomes were entered in the analysis.
• Generalizability was limited by the large number of participants with breast cancer.
• The intervention was delivered by professionals; costs were offset by the fact that some of the intervention can be delivered by telephone.

Patients underwent a focused assessment that corresponded with specific symptom management interventions. The interventions recommended were based on a cognitive behavioral approach. The control arm received usual care. Patients were assessed for symptoms such as nausea, vomiting, insomnia, dyspnea, anorexia, fever, cough, dry mouth, constipation, mouth sores, pain, and fatigue. Symptoms identified with depression—fatigue, insomnia, anorexia, and poor concentration—were placed in a subindex.

Of 609 eligible patients, 237 patients and their family caregivers participated in the study. Patients had been diagnosed with a solid tumor and were within two months of the first cycle of chemotherapy. Patients who were receiving radiation or who had had previous chemotherapy were ineligible. The study include men and women who had been diagnosed with a variety of tumor types in various cancer stages.

Randomized control trial

• The Center for Epidemiological Studies Depression Scale
• Two-sample t tests, a chi-square test, and a general linear model

Among those with higher levels of baseline symptoms except depression, cognitive behavioral interventions lowered depression at 10 weeks. In patients with a higher level of depression at baseline, the cognitive behavioral interventions were less effective.

Cognitive behavioral interventions may lower depression indirectly by managing symptoms that do not have a component that is primarily affective. Symptoms with a physiologic and psychological component may be more difficult to modify and require long-term intervention.

• Medications used to treat depression were not standardized. A variety of medications were used at various doses.
• The study did not detail how the intervention sessions were completed, only that researchers conducted telephone interviews and in-person sessions of 30–60 minutes.
• The study did not identify the background and training of the nurses who provided interventions.
• The study did not provide specific symptom management interventions. Knowing symptom-management strategies and specific guidelines would have been helpful.

Dyads in the experimental group received four contacts over a 10-week intervention. (Two in-person contacts coinciding with regular visits to the oncology center; alternated with two telephone contacts approximately two weeks following each in-person contact.)

Cognitive behavioral intervention was directed toward the patient and caregiver dyad. Patients received information on self-care, cognitive reframing, coping strategies, and techniques for communicating needs for assistance with family members. Interventions for caregivers focused on etiology and strategies for managing symptoms, how to integrate into everyday activities, and how to better communicate with the patient and healthcare providers about symptom management. The intervention nurse assessed the caregivers’ perception of their involvement in and reaction to assisting the patient with symptom management; collaboratively selected strategies to implement; and evaulated the success of strategies to either continue or be revised.

• The sample included caregivers of patients with a solid tumor within their first two cycles of chemotherapy for treatment of new tumor (N = 125)—intervention (n = 59) versus standard of care (n = 66).

A properly designed randomized clinical trial was used.

• Center for Epidemiologic Studies Depression Scale (CES-D)
• Caregiver (burden) reaction to assisting with symptoms was measured by the following.
  • Total number of symptoms for which caregiver provided assistance
  • Total level of distress reported because of assisting with symptom management
  • Reaction (level of distress) score per symptom

Caregivers in the experimental intervention group reported significantly lower total negative reactions and fewer assistances at 10 weeks than caregivers in the standard of care arm (p < 0.01).

Patients of caregivers in the experimental group reported significantly lower levels of symptom severity for which caregivers provided assistance.

Female caregivers in the experimental group reported less negative reactions to providing assistance than female caregivers in the control group (p < 0.01). Males in the control group reported less negative reactions per assistance than males in the experimental group (p = 0.08).

Caregivers who were younger than their patients reported less negative reactions to assisting with symptom management than caregivers who were the same age or older than their patients (p = 0.06).

• Demographic information about race and ethnicity of the sample was not described.
• No description exists of the qualifications or training required for the intervention nurse nor do evidence-based guidelines exist for strategies used in symptom management.

PHASE OF CARE: Transition phase after treatment

Volume of articles retrieved is not reported. Provides a three-level strength of recommendation and three-level grading of evidence quality. Ten studies are summarized.

The studies defined risk factors for patients to be considered high risk in early, late, and very late phases post-transplantation. It is recommended that high-risk patients receive mold-active prophylaxis and all remaining patients receive Candida-active prophylaxis in the early and late phases. In the very late phase, it is recommended that those at high risk, based on severity and steroid refractory graft-versus-host disease, receive mold-active prophylaxis; those with a standard risk receive Candida-active prophylaxis; and those at low risk receive no prophylaxis. The studies provide an extensive definition of risk levels for use.

• There is limited evidence in children.
• All the evidence used was retrospective.

Studies provide information to determine level of risk in various transplantation phases and gives guidance regarding antifungal prophylaxis in each phase. Nurses need to be aware of changing risk in various transplantation phases of care.

To determine if, compared to individuals receiving usual care, participants in intervention groups would report lower levels of anxiety, depression, and unmet supportive care needs along with improved physical and emotional functioning

• Patients were randomly assigned to one of three supportive care models: UC (control), O/GP (oncologist/GP), or TCW (telephone caseworker). Participants completed three computer-assisted telephone interviews (CATIs) conducted by trained interviewers: one each at baseline and at three and six months.
• Data obtained from participants in the UC model were used only to assess the impact of supportive care models.
• The O/GP model included two copies of sheets listing concerns: One sheet was mailed to the oncologist, so he or she would know what concerns to discuss at the next appointment. The other sheet was for records.
• The TCW model consisted of telephone interviews conducted by oncology nurses with training in by-telephone interviewing. Interviewers discussed the content of TCW sheets, which listed issues of concern that patients had expressed. TCW interviewers followed up at six-week intervals to assess coping.

• The sample was composed of 356 participants.
• Mean patient age in the UC (control) group was 57.4 years. The age range in the UC group was 28–75 years. Mean patient age in the O/GP group was 58.3 years. The age range in the O/GP group was 37–75 years. Mean patient age in the TCW group was 57.8 years. The age range in the TCW group was 33–75 years.
• The number of females in the sample was 257. The percentage of females in the sample ranged from 71.8% through 72.5%. The number of males in the sample was 99. The percentage of males in the sample ranged from 27.5% through 28.2%.
• The percentage of participants with nonlocalized breast cancer ranged from 48.7% through 49.2%; with nonlocalized colon cancer, 50.8% through 51.3%

• Single site
• Home
• New South Wales, Australia

• Phase of care: active treatment and transition
• Clinical application: late effects

Parallel-group, prospective randomized controlled trial

• Hospital Anxiety and Depression Scale (HADS)
• European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire, version 3.0 (EORTC QLQ-C30 version 3.0)
• Supportive Care Needs Survey-Short Form (SCNS-SF34), to measure perceived need for care
• 10 items from the Needs Assessment for Advanced Cancer Patient (NA-ACP)
• Perceived improvement in patient communication with health care practitioners was measured at the third CATI by means of one question, on a 5-point Likert scale: “Participating in this study made it easier to discuss my health care needs and issues with my doctors and other health care practitioners.”

• Authors observed no overall intervention effect.
• Members of the TCW group were more likely (p < 0.0001) to have issues discussed and referrals recommended than were those in the O/GP group. This was particularly true in regard to unmet psychological need (p < 0.01), need relating to daily living (p < 0.01), health service/information need (p = 0.01), and physical need (p < 0.01).
• Compared to oncologists and GPs, case workers were more likely to discuss anxiety (p = 0.01) and unmet psychological needs (p < 0.01).
• Oncologists and GPs were more likely (p = 0.02) to discuss unmet patient care and support needs.
• Authors noted no significant intergroup differences in regard to proportion of participants with elevated anxiety and depression at any of the three time points.
• QOL scores improved within study groups across times, but authors detected no significant between-group differences.

Authors noted no significant intervention effect in this study, with the exception of improved physical functioning at six months for the TCW group.

• Individuals who were too distressed or unwell to participate were excluded from the study. These patients may have been the very ones who most needed the intervention. 
• Authors provided no information about or consideration of disease stage, treatment phase, or other symptoms that can affect the outcomes the study measured.

Nurses should continue to explore ways to reach patients, at the time of diagnosis and beyond treatment, that can assist patients in psychosocial functioning. The field needs tools to make this easier; nurses need ways to implement care efficiently. The study did not show telephonic intervention to be effective.