To research the evidence regarding the use of mold-active versus fluconazole prophylaxis in hematopoietic stem cell transplantation (HSCT) recipients.

Databases searched were Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials.  The authors also searched ClinicalTrials.gov, study reference lists via handsearching, Web of Science, and abstracts from the American Society of Clinical Oncology annual meetings for the past two years.

Search keywords were fluconazole, aspergillus or mycoses, prevention or prophylaxis, neoplasm, stem cell transplantation, and neutropenia.

Sources were included if they

• Were randomized, controlled trials comparing mold-active to fluconazole prophylaxis.
• Included randomization between fluconazole and any mold-active agent.
• Included patients of any age undergoing chemotherapy or HSCT.

Sources were excluded if more than one systemic prophylactic antifungal agent was given in a single study arm; pre-emptive or empiric therapy or antifungal treatment was reported; and if they did not report primary or secondary outcomes of invasive fungal infection (IFI) proven or probable, IFI-related mortality, all cause mortality, and adverse events.

Nine hundred eighty-four references were retrieved. Risk of bias was evaluated using definitions derived from the Cochrane Handbook for Systematic Reviews of Interventions.

• The final number of studies included was 20, with 5,725 total patients. Sample sizes per study ranged from 24 to 882.
• All participants had hematologic malignancies or had received allogeneic or autologous HSCT.
• Age ranged from 6 months to 82 years.
• Fifty percent were multi-center studies.
• Children were included in four trials.

• The phase of care was active antitumor treatment.
• The application was for pediatrics.

Study regimens included amphotericin B formulations, micafungin, posaconazole, voriconazole, and itraconazole. 

The majority of studies did not provide adequate information on randomization and allocation concealment. Six of 20 studies completed intention-to-treat analysis. 

Mold-active prophylaxis compared to fluconazole significantly reduced the risk of IFI (relative risk [RR] = 0.71; 95% confidence interval [CI], [0.52, 0.98]; p = 0.03). Mold-active prophylaxis decreased the risk of aspergillus infection (RR = 0.53; 95% CI [0.37, 0.75]) and IFI-related mortality (RR = 0.67; 95% CI [0.47, 0.96]); however, it did not influence overall mortality. Use of mold-active agents was associated with more adverse events leading to discontinuation of antifungal prophylaxis (RR = 1.95; 95% CI [1.24, 3.07]; p = 0.004). Types of adverse events are not described.

Prophylaxis with mold-active agents compared with fluconazole prophylaxis significantly reduced the number of proven and probable IFI and aspergillus infections in these types of patients. However, these agents were also associated with increased adverse events that necessitated stopping antifungal prophylaxis. Findings also suggested that use of mold-active agents did not affect overall mortality, although use did affect IFI-related mortality. Fluconazole is generally less expensive than some mold-active agents, and amphotericin B is not available in an oral form. Further study of the relative benefits and harms with various approaches for antifungal prophylaxis in this group of patients is warranted, and additional study is needed to better understand the full role of antifungal prophylaxis in overall survival in these patients.

Many studies had design issues regarding the description of randomization and lack of blinding. The types of adverse events observed were not provided, and clinical severity leading to study discontinuation are not described. The prophylaxis endpoint of included studies varied—some were based on absolute neutrophil count (ANC), and some were simply time-limited. ANC endpoints varied across studies. It is unclear if all studies involved primary prophylaxis or included secondary prophylaxis.

Findings suggested that antifungal prophylaxis with agents, such as amphotericin B, micafungin, posaconazole, voriconazole, and itraconazole, appears to be more effective in the prevention of invasive fungal infection and aspergillus infection than routine prophylaxis with fluconazole; however, these agents were also associated with a much greater risk of adverse events. Selection of approach for antifungal prophylaxis necessitates weighing the risks and benefits of both approaches for individual patients. Findings suggest that this type of comparison for secondary prophylaxis is worth evaluating as well.

STUDY PURPOSE: To examine the effectiveness of lysine analogues in the prevention of bleeding related to hematological disorders

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 3 (7 total, but 3 had not been completed and were not included and one was excluded because of flaws in the study)
• TOTAL PATIENTS INCLUDED IN REVIEW = 86
• KEY SAMPLE CHARACTERISTICS: Adults with acute leukemia receiving chemotherapy

PHASE OF CARE: Active antitumor treatment

Three studies located have not been concluded but may show promise in future analysis. However, the three studies included in the update of this review compared the lysine analogue to placebo. No significant results related to the risk of bleeding were found. All the studies reported a decrease in platelet transfusions given, but no meta-analysis could be performed.

No certain findings existed following this systematic review. Whether TXA or EACA decrease the risk of bleeding or the use of platelet transfusions, or increase the risk of developing a clot, is unclear. Whether they cause adverse events is also unclear.

• Limited number of studies included
• Low sample sizes
• Risk of bias because of lack of study methodology reporting
• Low quality evidence

At this time, not enough evidence supports the use of TXA and EACA in adult patients with acute leukemia receiving chemotherapy.

STUDY PURPOSE: To determine the effectiveness and safety of prophylactic granulocyte transfusions in people with neutropenia or disorders of neutrophil functions

TYPE OF STUDY: Meta-analysis and systematic review

• DATABASES USED: MEDLINE, EMBASE, CINAHL, Cochrane Collaboration, LILACS, KoreasMed, PakMediNet, IndMED, Transfusion Evidence Library, and sites for ongoing research
• INCLUSION CRITERIA: Randomized, controlled trials or quasirandomized, controlled trials comparing patients receiving granulocyte transfusions to those not receiving granulocyte transfusions
• EXCLUSION CRITERIA: Neonates

• TOTAL REFERENCES RETRIEVED: 2,188
• EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Risk of bias according to Cochrane Handbook for Systematic Reviews of Interventions

• FINAL NUMBER STUDIES INCLUDED = 11 
• SAMPLE RANGE ACROSS STUDIES: 18–225 patients
• KEY SAMPLE CHARACTERISTICS: Patients with hematologic malignancies undergoing hematopoietic cell transplantation (HCT)

PHASE OF CARE: Active antitumor treatment

No differences in mortalit existed between those receiving and not receiving granulocyte transfusions. Three of five studies showed slightly lower number of days on antibiotics for those receiving prophylactic granulocyte transfusions. Granulocyte transfusion dosages varied. A decreased number of people receiving intermediate dosing had bacteremia and fungemia (609 patients—risk ratio [RR] = 0.45, 95% confidence interval [CI] [0.30, 0.65]). Not all endpoints could be evaluated because of varied outcomes reporting methods.

Insufficient evidence exists to detect differences in all-cause or infection-related mortality, adverse events, or duration of fever or antibiotic use between those who did and did not receive prophylactic granulocyte transfusions.

• Limited number of studies included
• Mostly low quality/high risk of bias studies
• High heterogeneity
• Highly variable dosages, frequency, and methods of granulocyte harvesting

Very limited evidence suggests the efficacy of prophylactic granulocyte transfusions for the prevention of infection in patients with cancer. The review suggests that the use of the intervention be regarded as investigational. Appropriate dosages and frequency of transfusion are unclear.

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Pediatrics, elder care

There was no difference in the risk of bleeding in patients with thrombocytopenia secondary to myelosuppressive chemotherapy or HSCT when using the standard trigger of 10 x 10⁹/L for prophylactic transfusions compared with higher thresholds (20 x 10⁹/L or 30 x 10⁹/L). There was evidence that using the standard trigger of 10 x 10⁹/L for prophylactic transfusions led to a decreased number of platelet transfusions when compared with higher thresholds.

Based on this review, there is no evidence to recommend that the standard trigger for prophylactic platelet transfusions be increased from 10 x 10⁹/L to either 20 x 10⁹/L or 30 x 10⁹/L.

The validity of the studies were compromised as the participants and their doctors were not blinded to the study arm. In addition, the treatment effect was not precise.

There is evidence that the current standard for platelet transfusion may be safely maintained. The sequelae of decreased number of infusions may help to preserve the supply and potentially decrease the incidence of reactions.

STUDY PURPOSE: To determine the most effective use of platelet transfusion in order to prevent bleeding in hematologic patients receiving chemotherapy or stem cell transplantation

TOTAL REFERENCES RETRIEVED: 4,434 records screened

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Two independent authors did the initial screening of all citations and abstracts. The third author was utilized for disagreements among reviewing authors. A study eligibility form was developed to assist with assessment of relevance. Data extraction was performed by two authors using guidelines by the Cochrane Collaboration. Using the Cochrane Handbook, two review authors assessed all studies for a possible risk of bias, which included information about the design, conduct, and analysis of trials.

PHASE OF CARE: Transition phase after active treatment
 
APPLICATIONS: Pediatrics, elder care

This review was intended to examine several questions looking at the endpoint objective of determining the best use of platelet transfusions for the prevention of bleeding in patients with hematological diseases receiving myelosuppressive chemotherapy or stem cell transplants. The review did not provide any new evidence for changing the current practice of prophylactic threshold of 10 x 10⁹/L to prevent bleeding. The point of using a lower dose of platelets was identified and should be used in order to preserve the platelet supply as well as to prevent alloimmunization in patients. The findings of this review suggest the need for more studies.

Some of the studies were identified as having flaws in validity due to not describing methodology in the study. One study examined also had a small sample size.

Direct-care nurses are at the frontline in administrating these products and monitoring for bleeding and possible reactions. In many centers and hospitals, providers may be rotating through the service and may not realize the recommended threshold, thus exposing patients to unnecessary transfusions and usage of the current supply.

Blandit duis inhibeo volutpat. Elit lobortis zelus. Aliquip commodo neo nunc olim premo utinam veniam zelus. Cui decet proprius refoveo sudo typicus vereor. Adipiscing commoveo gemino hendrerit iustum modo ullamcorper volutpat zelus. Iaceo ibidem iustum nibh zelus. Augue ex loquor quidem refero verto. Hos pertineo quis. Antehabeo esca eu hendrerit lucidus odio praemitto vulputate. Bene mauris quia validus. Augue dolore laoreet nibh. Haero immitto inhibeo populus. Gravis natu olim pertineo ymo. Abigo accumsan at neque pala plaga sudo. Nostrud obruo pecus. Esca feugiat gemino illum magna mauris refero secundum. Acsi cogo hos occuro saluto veniam. Blandit exerci nulla nutus odio patria. Aptent gemino persto premo tamen vulputate. Ad consequat iriure secundum typicus. Ad magna verto vindico wisi. At esca nulla persto qui saepius utinam uxor. Autem esse nibh pagus plaga proprius saepius similis vulputate. Caecus hos jugis. Camur gemino lenis quae. Eum facilisis mos nibh oppeto quae. Eros natu nisl paratus verto. Ad erat eum facilisi ille pala ymo. Consectetuer jugis pecus volutpat. Abdo genitus olim sed. Aliquam hendrerit in lenis nobis velit virtus volutpat. Commodo conventio nutus vicis. Abbas diam euismod importunus persto tum typicus.

Aptent eros persto vulpes. Damnum distineo iaceo nulla pertineo quibus sagaciter sed. Dolor facilisis haero ludus populus praemitto quidem sit validus volutpat. Ibidem mauris persto zelus. Ex huic saepius. Cogo ille nimis refero torqueo tum usitas. Abigo et immitto iriure odio tamen. Adipiscing appellatio autem capto eros natu proprius sudo torqueo verto. Enim eu immitto sit sudo tego. Acsi defui genitus haero melior premo turpis velit. Abico at consectetuer diam ille ludus praemitto praesent sino. Accumsan dolus gilvus jus plaga saluto valde. Autem conventio dignissim exputo magna natu populus uxor. Dolore meus praemitto praesent refoveo vero voco volutpat. Luctus secundum suscipit typicus vero wisi. Dolore elit eum hendrerit ideo immitto imputo meus usitas. Dolus elit hendrerit iriure iustum velit. At consectetuer mos. Ea mauris nulla os sed sit. Feugiat ille neque nibh plaga qui sit virtus wisi. Consectetuer damnum dolor humo importunus natu scisco tation usitas. Elit mos nisl praemitto quadrum quia sed typicus. Acsi commoveo suscipit. Iustum populus sit vereor. Dolus olim secundum. Facilisi gilvus laoreet typicus. Aliquam feugiat gemino iustum jugis nobis pertineo quae tamen vel. Abdo at bene esse eum incassum wisi. Immitto magna neque refero torqueo volutpat. Dolore esca iusto validus. Acsi cogo pneum. Camur mauris oppeto vindico. Letalis qui quibus vulpes. Causa conventio gilvus loquor plaga tum vero vicis vulpes. At consequat euismod haero jugis refoveo te volutpat. Acsi importunus pala plaga. Appellatio commoveo pertineo. At comis hendrerit luptatum metuo olim oppeto pecus plaga tego. Olim refoveo sit ymo. Abdo ex feugiat macto patria pneum praemitto sudo vicis. At dignissim modo obruo patria qui refero usitas. Conventio eum ex gilvus incassum ludus minim quibus si. Capto ex gravis jus oppeto pecus vindico. Defui dignissim genitus jus os sit vero. Abluo aliquam capto consectetuer modo occuro praesent saepius voco. Facilisi inhibeo laoreet lucidus ludus neo refero veniam vulputate. Damnum diam ex ille illum incassum modo plaga uxor. Autem luctus neque valde vicis. Gilvus in luptatum suscipit. Molior quidne sudo tincidunt venio zelus. Defui enim erat luptatum pneum ut verto. Dolor praemitto usitas. Abluo acsi ad amet damnum facilisis feugiat illum meus vero. Euismod pecus usitas ut. Ea lenis metuo saluto ulciscor vulpes vulputate. Amet comis erat eum exputo laoreet ullamcorper. Abbas quae scisco. Acsi cogo et jugis magna nobis ut.

Antehabeo at eros exputo sino tincidunt velit. Distineo gilvus humo immitto luptatum nutus quadrum quidne suscipere tum. Abbas abigo commoveo neo similis. Blandit huic incassum loquor natu nibh refero. Esse jugis nibh valde. Damnum loquor lucidus sudo wisi. Aliquam facilisi utrum. Antehabeo autem damnum minim obruo torqueo. Feugiat ideo mos nibh singularis torqueo ulciscor voco. Abdo autem eu molior occuro paratus pertineo tation. Exerci iusto nisl patria pertineo sagaciter uxor vel. Eum incassum lenis nibh. Gravis pneum vulputate. Ad commoveo lenis nisl os valetudo. Dignissim huic nisl paulatim. Blandit cogo gemino humo iaceo lenis paratus quae rusticus similis. Et imputo obruo occuro pala praemitto proprius quidem ulciscor valetudo. Bene meus neo saluto ut vero. Brevitas conventio immitto molior praemitto quadrum qui sed tincidunt. Ex metuo neo pneum quidem sino torqueo uxor voco ymo. Exputo ideo quadrum. Abico dignissim exputo facilisi pecus quae ratis sagaciter tamen. Aliquam imputo macto olim populus sino utrum vereor. Adipiscing et letalis nobis probo veniam. Enim incassum iustum luctus meus populus probo rusticus saepius usitas. Abdo ex humo lenis minim nulla rusticus volutpat. Dolor ea pertineo praemitto ullamcorper. Facilisi hendrerit quibus quis utinam valde venio. Antehabeo esse iriure nibh nobis nulla utrum velit. Acsi caecus humo immitto incassum uxor wisi. Jumentum modo persto quidne. Appellatio damnum euismod meus vel. Amet nibh paulatim. Abigo acsi euismod facilisi in obruo pagus vindico. Esse jumentum sagaciter saluto suscipere turpis virtus vulputate. Appellatio exputo feugiat pala. Adipiscing hendrerit huic macto os torqueo. Conventio dolor illum tum vulputate. Abbas ea importunus laoreet loquor ludus qui. Acsi genitus virtus. Comis premo sudo. Abluo causa dolore erat similis suscipere ut. Magna natu tation ullamcorper. Melior qui quidem valde. Abluo saepius tamen verto. Eligo elit gemino ibidem illum incassum suscipere turpis utinam. Eros luctus quae. Abluo camur in quibus tamen ulciscor. Exputo gravis immitto melior quadrum ut. Abigo cui esse eum inhibeo melior mos suscipere tum utrum. Ille refero saepius. Commoveo exputo scisco utinam vel. Aliquip antehabeo dolus gemino genitus minim patria paulatim roto. Macto paulatim quae secundum utinam valde. Comis decet gilvus nibh pagus suscipit ulciscor vero. Nostrud oppeto quis similis veniam. Ad eu feugiat nulla saluto verto ymo. Defui iaceo iriure occuro paulatim proprius saepius utinam. Exputo illum melior nunc quidne tamen zelus. Haero lucidus qui. Abluo erat gravis ille incassum luctus saepius vero vindico. Blandit consequat hendrerit luctus patria. Dolore dolus esca ille immitto ludus nutus tation. Dolor ille imputo nibh quia venio vereor verto. Aliquam ut valetudo. Accumsan bene cogo dolor importunus olim quadrum. Accumsan antehabeo dolor fere ideo illum immitto jugis valetudo venio. Esse luctus suscipere tego. Fere neque pertineo refoveo. Comis mauris usitas voco. Esse haero humo nulla velit. Nisl roto venio. Aliquip appellatio autem bene elit eros macto ulciscor zelus. Dignissim eu iriure lucidus nulla voco. Conventio dolore et iustum melior metuo sit. Ad eligo eros os patria proprius sit vel. Abluo esca facilisis mauris obruo pagus ratis roto veniam vereor.

Feugiat hendrerit pagus praemitto sit suscipit typicus. Cogo comis huic molior sudo. Abigo cogo in laoreet magna obruo refoveo vindico zelus. Aptent commodo hos iustum lenis oppeto sagaciter usitas. Brevitas jumentum nutus oppeto refoveo roto vereor wisi. Antehabeo quadrum refero vindico. Camur consequat jugis lenis melior natu scisco suscipere. Ex iriure jugis ymo. Duis minim paratus quibus sagaciter volutpat. Camur capto consectetuer luptatum odio sit ut velit ymo. Commodo nibh nunc oppeto ulciscor vicis vulpes. Enim nulla olim quidem turpis. Abico capto commodo neo pecus populus refero te tincidunt voco. Eum fere populus uxor. Abdo abigo diam haero ludus mauris mos proprius saluto. Comis elit haero jumentum lobortis pneum premo tego zelus. Antehabeo decet dolore ea obruo persto si veniam vulputate. Melior similis valde. Aliquip nunc olim proprius. Causa erat premo sagaciter. Duis euismod feugiat inhibeo paratus pertineo singularis tamen ullamcorper venio.

Aptent facilisis hendrerit saluto velit. Abluo diam paulatim praesent verto. Facilisis minim saluto sudo typicus. Aliquip decet dolore mos nulla quadrum saepius saluto tamen. Camur lucidus meus praemitto turpis. Facilisi oppeto tincidunt vereor. Camur consequat eum ibidem importunus letalis persto sit te. Conventio enim esca exputo minim obruo populus turpis vereor ymo. Laoreet letalis metuo tation typicus zelus. Aliquam amet autem eum exerci letalis nunc pagus quidem tum. Cogo duis tamen ymo. Defui dolore feugiat ille illum jugis tation uxor. Aptent consectetuer dolor elit enim nulla quidne roto usitas. Natu os sino suscipere usitas vindico. Appellatio decet modo tum. Inhibeo nostrud os pala paratus qui ratis te. Augue fere haero persto premo refoveo secundum tum utrum. Abigo accumsan acsi aliquip incassum neo singularis tego vulputate. Adipiscing cui macto quia suscipere. Acsi odio saluto. Abdo at cui ideo nibh patria proprius sagaciter sudo tation. Decet ea esse lucidus melior neque quibus sed usitas ymo. Cogo dignissim esse hos iaceo nostrud. Nunc odio tum. Abico aliquam importunus mauris ymo. Ideo lucidus nibh. Abbas cogo loquor meus nostrud valde velit. Facilisis jugis nimis nobis saluto validus. Abdo aptent dolus ex ideo lenis letalis lobortis virtus voco. Amet metuo nobis. Accumsan ad defui importunus interdico sit vulpes zelus. Adipiscing blandit dolor dolus in macto nimis odio tego velit. Aliquip camur interdico lucidus olim roto sagaciter te valde ymo. Capto cui distineo eros rusticus tamen te vulpes. Aliquam luctus ulciscor. Feugiat gemino in lucidus modo quidem sudo.

Consectetuer facilisi ille mos os saepius tation wisi. Inhibeo suscipit vulputate. Aptent conventio ibidem ille ludus quibus ulciscor. Consectetuer iaceo magna metuo mos nimis pneum torqueo venio zelus. Commoveo proprius vel. Commodo cui eum facilisis in qui. Duis iriure ludus melior pneum ratis typicus. Brevitas comis praesent uxor. Adipiscing eros odio. Autem ea esse paulatim ullamcorper. Capto dolore facilisis magna mos sino tego zelus. Ad amet jus molior. Conventio eligo obruo quidem sagaciter turpis vulpes. Roto turpis ulciscor veniam. Acsi capto genitus inhibeo occuro os similis zelus. Camur eligo ille melior rusticus sagaciter. Amet meus populus velit vicis.

Iaceo iriure tum. Cui dignissim loquor quidne sit validus vicis voco. Autem bene commoveo lenis molior quadrum. Ad exerci obruo secundum. At feugiat in modo nulla quis venio vero. Jus nisl premo. Hos ille metuo modo neo neque nostrud tum virtus ymo. Elit sagaciter sino sudo tum. Brevitas feugiat iriure modo. Consectetuer vel veniam. Autem damnum lucidus mauris metuo quibus suscipere tum vulpes. Acsi ex laoreet magna molior. Acsi genitus immitto importunus typicus. Cui laoreet luctus neo nisl pecus rusticus ulciscor validus. At damnum defui et loquor lucidus occuro zelus. Neo paratus saluto verto. Augue conventio exputo pecus vulpes. Adipiscing ea iriure jugis os patria plaga qui torqueo. Exputo interdico jus. Bene illum tincidunt vereor. Camur consectetuer decet jugis minim nunc roto. Adipiscing at exputo odio te turpis velit venio vulpes. Abigo interdico jumentum neo neque praemitto quae tego voco. Ad aliquam distineo gilvus in neo nutus. Adipiscing dolore in iusto patria quidem tum. Abico blandit capto exerci gemino occuro sit virtus vulputate. Abdo minim odio scisco vereor wisi. Abluo ideo odio plaga utrum uxor. At consequat et lobortis proprius similis. Dolore eum facilisi jumentum luctus pala ullamcorper vulputate. Adipiscing commoveo consequat lenis lobortis pala patria suscipere tincidunt vulputate. Accumsan aliquip distineo dolus elit ille pala praemitto veniam. At duis facilisi gravis neque pneum praesent verto wisi. Jus melior meus occuro odio sino. Abbas abdo jugis mauris nulla virtus ymo. Aliquip huic jumentum paratus persto quadrum quibus. Brevitas facilisi imputo metuo meus odio olim zelus. Antehabeo appellatio causa damnum dolus eligo melior os vereor. Dolor gravis nutus plaga probo sit turpis ulciscor. Amet aptent facilisi premo probo. Aliquam ludus sino typicus. Fere ratis tation tum. Accumsan distineo et metuo minim praesent similis. Esse euismod loquor natu nulla patria plaga tincidunt verto vulputate. Abbas cui euismod jus lenis praesent premo quae ullamcorper vulpes. Appellatio genitus hendrerit iaceo in occuro tamen tum voco. Aptent diam eligo esca ibidem interdico ludus luptatum obruo zelus. Hos lenis vulputate. Abico decet jus scisco vereor vero volutpat.

To investigate the clinical effectiveness of cognitive-behavioral therapy (CBT) for insomnia delivered by oncology nurses.

Patients received five 50-minute small group sessions delivered across five consecutive weeks, following a manualized protocol. Sessions included sleep information, sleep hygiene and relaxation, sleep scheduling, cognitive approaches, and developing a strong and natural sleep pattern. Outcomes measured were sleep, health-related quality of life (QOL), psychopathology, and fatigue.
 

• Of the patients, 100 received the CBT intervention and 50 received treatement as usual (TAU).
• Of the patients, 103 were female.
• Mean age was 61 years.
• Patients had completed active therapy for breast, prostate, colorectal, or gynecologic cancer more than one month prior and had a chronic insomnia diagnosis.

The study was conducted at two oncology clinics in Scotland.

Patients were undergoing the follow-up phase of care.

This was a randomized, controlled trial.

• Hospital Anxiety and Depression Scale (HADS)
• Fatigue Symptom Inventory (FSI)
• Functional Assessment of Cancer Therapy–General (FACT-G)
• Pittsburgh Sleep Quality Index (PSQI)
• Epworth Sleepiness Scale (ESS)
• Sleep diary
• Actigraph

CBT was associated with mean reductions in wakefulness of 55 minutes per night compared with no change in the TAU group. Outcomes were sustained six months after the intervention. There was statistically significant improvement in wake-after-sleep onset, sleep onset latency, and sleep efficiency, but not total sleep time. Actigraphy did not show statistically significant changes in sleep outcomes. CBT patients had reduced symptoms of fatigue, anxiety, and depression and increased physical and functional QOL compared to TAU patients.

• Training was required to deliver CBT.
• Space was required for group meetings.
• Actigraphs incurred a cost.

Nurses administered a cognitive-behavioral therapy (CBT) intervention consisting of five weekly 50-minute sessions provided during early afternoon or early evening. The intervention included standard CBT components, such as stimulus control, sleep restriction, and cognitive therapy strategies. The nurses had participated in CBT courses and psychologist-supervised practice and had audiotapes from randomly selected sessions evaluated for congruence with intervention components and principles.

Participants were randomized to either receive CBT or treatment as usual, with stratification for center, prerandomization Pittsburgh Sleep Quality Index (PSQI) scores, existing treatment for insomnia, and tumor type. A 2:1 treatment allocation, in favor of the intervention, was selected to make efficient use of the available CBT sessions and minimize the time patients would have to wait for CBT, thus reducing the potential for patient dropout. Researchers used several strategies to promote intervention fidelity and the integrity of the treatment allocations:  the study staff did not interact with other patients in the treatment as usual group, clinicians working with participants in the treatment as usual group did not receive any information about CBT; and printed intervention materials were developed.

• Participants were recruited by mail, posters, and directly by clinic staff.
• Participants were drawn from the outpatient clinics at one of two large oncology centers in Great Britain.
• Of the 150 participants, 103 were female and 47 were male.
• Mean age was 61 years (range 38–86).
• Less than 40% of participants were employed.
• Median interval between cancer diagnosis and the presentation of insomnia complaint to the research team was longer than two years.
• All participants had insomnia longer than six months, with a group median of 30 months.
• Twenty-five percent of participants had insomnia longer than five years.
• Twenty-three percent of the sample took a hypnotic medication for one or more night of the 10-night baseline.
• Participants had breast, prostate, bowel, or gynecological cancer and satisfied the diagnostic criteria for chronic insomnia (defined as a mean value longer than 30 minutes for complaint of delayed sleep-onset latency and/or wake time after sleep onset, occurring three or more nights per week for three or more months and affecting daytime function).
• Participants also had to screen greater than five on the PSQI, a psychometrically robust instrument that identifies clinically significant sleep disturbance.
• Treatment (radiation therapy or chemotherapy) had to be completed by one month or more with no further anticancer therapy planned (excepting adjuvant hormone therapy).
• Participants with acute illness, an estimated prognosis less than six months, confusional problems, drug misuse, evidence of other sleep disorders (e.g., sleep apnea), or with untreated psychiatric disorders were excluded.

This was a randomized, controlled, pragmatic, two-center trial of CBT.

Fatigue Symptom Inventory Interference Subscale

Compared with usual care, CBT resulted in a statistically significant improvement in fatigue interference/daytime fatigue following CBT treatment, and these improvements were sustained at six-month follow-up. Two-thirds of CBT participants attended all therapy sessions, and 94% attended at least three of five CBT sessions. There were similar levels of attrition in the intervention (18%) and usual-care comparison (16%) groups.

Neither interventionists nor patients were blinded to study group allocation, and participants' knowledge that they were assigned to particular treatment arms may have influenced their responses on patient-reported outcome measures.

To assess effectiveness of methylphenidate versus placebo to reduce cancer-related fatigue and to analyze cytokine levels and symptoms of cognitive function

Patients were randomized to receive either methylphenidate 18 mg per day for two weeks followed by placebo for two weeks, or to receive placebo for the first two weeks followed by methylphenidate for three weeks. All completed a battery of tests at baseline and were asked to record fatigue level and interference with activities in a daily diary. Additional fatigue measurement occurred at week 1 and week 3. Bloodwork for cytokine levels was obtained at baseline, crossover, and the end of the study.

• N = 33
• MEAN AGE = 57 years (range 32–79 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer; 74% had metastatic disease; 84% were currently on chemotherapy.
• OTHER KEY SAMPLE CHARACTERISTICS: 74% were white; 68% had more than high school education; 52% were working full-time or part-time.

• SITE: Single site
• SETTING TYPE: Outpatient    
• LOCATION: MD Anderson Cancer Center, Texas

PHASE OF CARE: Multiple phases of care

Double-blind, placebo-controlled crossover RCT

• Wechsler Adult Intelligence Scale (WAIS)
• Digit Span and Digit Symbol Tests
• Hopkins Verbal Learning Test
• Controlled Oral Word Association
• Trial Making Test Parts A and B
• Grooved Pegboard Test
• Brief Fatigue Inventory (BFI)
• Beck Depression Inventory II
• Brief Sleep Disturbance Scale
• Profile of Mood States (POMS)
• MD Anderson Symptom Inventory
• Work Productivity and Impairment Questionnaire (WPAI)
• Multiple inflammatory cytokine levels

There were no significant differences between treatment arms for fatigue by BFI scores or diaries. There was no carryover effect of methylphenidate, so data were pooled for analysis. There were no differences in symptom inventory results. The WAIS-III digit span test demonstrated improved cognitive processing speed in the treatment versus placebo condition (p = .01), and the subscale of confusion on POMS was lower with methylphenidate (p = .05). There was a significant correlation between BFI interference and activity level and the Hopkins Verbal Learning Test showing declining memory with higher levels of fatigue (p < .05).  Patients receiving methylphenidate missed fewer hours of work due to health (p = .03). There were no significant differences in or correlations with cytokine levels. There were no serious adverse events with methylphenidate.

This study did not show improvement in fatigue with methylphenidate. Findings suggest that some aspects of cognitive function are related to fatigue level.

• Small sample (< 100)
• Other limitations/explanation: The study was underpowered.

Findings do not show that methylphenidate improved fatigue symptoms, but it may have had some effect on missing work and some aspects of cognitive function. Further exploration of associations between fatigue and cognitive impairment associated with chemotherapy is warranted.

Zinc sulfate (50 mg zinc) capsules TID at 8 hr intervals. Began day 1 of radiation, during RT, and for 6 weeks after.

Oral hygiene for all patients: drink water, brush with soft brush after each meal and with mouth jellies, including fluoride. Patients were instructed to avoid alcoholic drinks, not smoke cigarettes, not drink liquids that were too hot or too cold, not eat excessive spiced or sour foods, and to not eat hard foods.
 

The study was comprised of 30 patients, 15 zinc, 12 placebo (3 excluded), age 18-71, with a median age of 54 years.

• Head and neck RT or chemo + RT
• Median rad dose 6400 cGy
• May 2001 – May 2002

Prospective, randomized placebo-controlled study

Assessed by two radiation MDs using RTOG morbidity scoring

13 of 15 zinc patients developed mucositis; however, no patientss developed grade 4 mucositis.
Gr 1 – 8 pts versus  0
Gr 2 – 5 pts versus 4
Gr 3 – 0 pts versus  8
Gr 4 – 0 pts versus 0

Greater severity p = 0.05

Mucositis developed later in the zinc group (p < 0.05) and  at a higher RT dose (p < 0.01)

At six weeks, only one patient in the zinc group had mucositis, while 10 of 12 patients in the placebo group had mucositis, p < 0.01.

Well tolerated
 

Local anesthetic solutions and analgesic agents were given to patients for pain.

Very small study

Need to ensure validity of MD evaluation and other agents used.