Test the effects of a group cognitive rehabilitation program on memory and attention in cancer survivors

Patients randomly were assigned to the treatment or a wait-list control group. The intervention consisted of hourly trainings that incorporated didactic teaching methods, focusing primarily on memory aids and skills, as well as mindfulness meditation. A portion of each session was dedicated to reviewing and practicing skills.  The intervention was offered weekly over seven consecutive weeks, delivered in a group format. Homework was assigned to the participants with the expectation that they practice the intervention independently at home. Objective measures were evaluated twice at baseline (in an attempt to eliminate potential practice effects) and one month after completion of the intervention. Subjective measures were evaluated at baseline and one month after completion of the intervention. Control group participants underwent subsequent testing seven to eight weeks after their initial evaluation.

• N = 28    
• MEAN AGE: 58.9 years (SD = 2.4 years)
• MALES: 7%, FEMALES: 93%
• KEY DISEASE CHARACTERISTICS: All subjects had completed cancer therapy at least six months ago and had concerns about their cognitive functioning.

• SITE: Single site  
• SETTING TYPE: Outpatient    
• LOCATION: Fred Hutchison Cancer Research Center, Seattle, WA

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Late effects and survivorship

Randomized clinical trial

• Functional Assessment of Cancer Therapy-Cognition (FACT-Cog)
• Rey Auditory Verbal Learning Test
• Stroop Color and Word Test
• Wechsler Adult Intelligence Scale (WAIS)-Digit Symbol Subtest
• WAIS-Digit Span Subtest
• Patient Health Questionnaire-9 (PHQ-9)
• Beck Anxiety Inventory (BAI)
• Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)

Patients who received the cognitive rehabilitation intervention had improvements in perceived cognitive function (p < 0.01), perceived cognitive abilities (p < 0.01), and cognitive quality of life (p < 0.01) as measured by the FACT-Cog and in one measure of attention, digit span backward (p < 0.01). In contrast, differences were not found between the treatment and control groups in other objective measures of cognition. No significant differences between groups over time were found for anxiety, depression, or fatigue.

Findings from this study suggest that cognitive rehabilitation may improve attention and perceived cognitive functioning, but not memory, in patients with cancer. The fact that significant differences were not found in anxiety, depression, or fatigue suggests that they were not related to the any improved cognitive functioning.

• Small sample (< 30)
• Risk of bias (no appropriate attentional control condition)
• Intervention expensive, impractical, or training needs
• Subject withdrawals ≥ 10%
• Feasibility may be an issue. In addition, the results may be influenced by subject withdrawal prior to the completion of the intervention as well as variability in the number of sessions attended (may indicate that the “treatment” is too burdensome).

Although this study found improvements in perceived cognitive function and one objective measure of attention, it was underpowered and patient compliance was inconsistent. Further research with larger sample sizes is warranted to determine effectiveness. In addition, longer follow-up is required to determine the sustainability of any improvements in cognitive functioning.

To evaluate the efficacy of class IV laser therapy in pediatric patients affected by severe oral mucositis (OM)

Laser treatments were performed twice daily for four consecutive days, all over the oral cavity in ulcerated and erythematous areas. Treatment was started on average 7.5 days after the end of chemotherapy.

• N = 18     
• AGE: 10–17 years 
• MEDIAN AGE: 13 years
• MALES: 12 (67%); FEMALES: 6 (33%)
• KEY DISEASE CHARACTERISTICS: 10 patients (55.4%) were affected by acute lymphoblastic leukaemia, 4 patients (22.2%) by non-Hodgkin lymphoma, 1 patient (5.6%) by Ewing’s sarcoma, 1 patient (5.6%) by acute myeloid leukaemia, one patient (5.6%) by aplastic anaemia, and one patient (5.6%) by osteosarcoma. All patients underwent chemotherapy with various drugs depending on their neoplasia, whereas six patients also had been subdued to hematopoietic stem cell transplantation prior to total body irradiation.

• SITE: Single site 
• SETTING TYPE: Inpatient  
• LOCATION: Pediatric Hemato-Oncology Department at the Institute for Maternal and Child Health—IRCCS Burlo Garofolo, Italy

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

• Single-blind, quasi-experimental

• World Health Organization (WHO) Oral Mucositis Grading Objective Scale
• Visual analog scale to assess pain  
• A validated questionnaire 
• Photographs of lesions were taken during each session.
• Patients were re-evaluated 11 days after the first day of laser therapy.

The use of class IV laser therapy (high-power laser therapy [HPLT]) was effective and induced better healing, reduced inflammation, and limited thermal damage along with maintained tissue integrity as compared to traditional low-power laser therapy (LPLT). All patients experienced a statistically significant decrease in pain sensation the day after the first laser application, with lesions healing by day 11.

The innovative protocol used, HPLT, employs high power and high wavelength as compared to traditional protocols and was effective, safe, and non-invasive for the treatment of OM. It accelerates healing time and causes reduction of pain and inflammation of OM. The efficacy of LPLT in pediatric patients with cancer has been established. Thus, laser light therapy has proved to be successful in the prevention and treatment of chemotherapy-induced OM. In the present study, all patients perceived a great improvement in all lesions and functional capacity.

• Small sample (< 30)
• Risk of bias (no random assignment)
• Findings not generalizable
• Subject withdrawals ≥ 10%

A gap indicates a lack of knowledge regarding dosing levels of laser therapy (low versus high, adult versus pediatric), so additional research is needed. More double-blind, randomized, controlled studies are needed, as well as laser protocols.

• FINAL NUMBER STUDIES INCLUDED = 22 in qualitative synthesis (six studies of CINV) and five in meta-analysis
• TOTAL PATIENTS INCLUDED IN REVIEW = 2,459
• SAMPLE RANGE ACROSS STUDIES: 51–480 patients
• KEY SAMPLE CHARACTERISTICS: Various cancer types

PHASE OF CARE: Active antitumor treatment (for CINV trials)

All studies favored pharmacopuncture over the control group, but outcome measures varied. Five out of six studies reported response rates as an outcome measure. Two studies calculated response rate using emesis episodes. One study (26) used two outcome measures, the total number of emesis episodes in 21 days and the proportion of emesis-free days in the same period.

The level of evidence was not strong enough to draw any conclusions. There was a careful suggestion that pharmacopuncture may help alleviate cancer-related pain, CINV, and other symptoms such as ileus, hiccups, fever, quality of life, and gastrointestinal disturbances.

The findings of this meta-analysis should be interpreted with consideration of its limitations. Additional rigorously designed and conducted studies are required.

The primary aim of this study was to evaluate the effect of triclosan-coated sutures on cervical surgical wound infection rates. A secondary aim was to analyze the risk factors for wound infections in patients undergoing surgery for head and neck cancer.
 

The study sample was comprised of patients who were admitted to the Tri-Service General Hospital, National Defense Medical Center, in Taipei, Taiwan, from January 2007 to December 2009. The patients were admitted for tumor ablation after a diagnosis of head and neck cancer and they received reconstructive surgery after wide excision of the tumor. The patients also had an exploration of the cervical area for radical neck lymph node disection or vascular examination for microsurgical anastomoses.

Patients were randomized into the triclosan group or a control group by a flip of a coin.

All surgical procedures were the same. All patients received IV prophylactic antibiotics (1 g cephazolin every eight hours for three days and 80 mg of gentamycin every 12 hours for three days). Dressings were changed daily for wound care and evaluation. The closed suction neck drain was removed when there was less than 10 ml per day of drainage. Infections were inspected for and defined as local erythematous change in the sutured wound with purulent discharge, cervical wound dehiscence, or neck skin necrosis. Surgical wound and intra-oral flap sutures were removed two weeks post-surgery and evaluated for delayed healing defined as intra-oral wound dehiscence and surgical complications, such as flap necrosis, intra-oral flap dehiscence, oral-cervical fistula, and neck wound infection.

The total sample was 241 participants.

Mean age in the triclosan group was 53.6 years (SD = 9.8); the mean age in the control group was 51.1 years (SD = 11.3).

Males made up 93.4% of the sample; females made up 6.6%.

138 patients were stage T1 or T2 (58 in the triclosan group; 80 in the control group) and 103 were stage T3 or T4 (54 in the triclosan group; 49 in the control group)

67 patients had prior head and neck reconstruction (29 in the triclosan group; 38 in the control group), 91 had preoperative radiotherapy (46 in the triclosan group; 45 in the control group), 55 had diabetes (30 in the triclosan group; 25 in the control group), 219 underwent free flap transfer (102 in the triclosan group; 117 in the control group), flap sizes in the triclosan group were an average of 81 cm² (+ 57.9) and 72.7 cm² (+ 56.4) in the control group, and the length of stay for participants in the triclosan group was 35.3 days (+ 14.3) and 35.9 days (+ 21) in the control group.
 

A single-site inpatient setting in Taipei, Taiwan
 

Active treatment

Randomized, controlled trial

Thirty-six patients incurred infections, 17 in the triclosan group and 19 in the control group (p = 1.0). Risk factors for postoperative cervical wound infection included stages T3 and T4 (OR = 3.09, 95% CI [1.39, 6.87], p = 0.006); diabetes (OR = 2.01, 95% CI [0.88, 4.58], p = 0.098); delayed healing of intra-oral wound (OR = 5.82, 95% CI [2.66, 12.77], p < 0.001). Patients with infections had a statistically significantly longer length of stay (56.4 + 27.2 days) compared to no infection (32 + 13 days).

There was no statistically significant difference in infection rates between patients who received triclosan-coated sutures and controls. Advanced tumor stage, delayed intra-oral flap healing, and oral cavity contamination by normal flora were risk factors for infection.

Keeping the surgical site clean and clear from contamination is essential for infection prevention of surgical sites in patients with head and neck tumors. Study findings did not show a benefit with use of triclosan coated sutures in the surgical procedure.

To examine the effects of konjac glucomannan (KGM) supplementation on bowel habits and colonic environment in adults with constipation, and to examine the method by which KGM modulates bowel habits.

Patients who self-reported having constipation for more than six months were recruited from an outpatient clinic. The study comprised a three-week placebo (gelatin capsules containing corn starch) period, a one-week adaptation period in which KGM was gradually increased from 1.5 to 3 g per day, and a three-week KGM period (1.5 g KGM per meal or 4.5 g per day). Capsules were taken with 150 ml of water. Patients followed a typical low-fiber Chinese diet and were instructed to maintain their usual physical activity, lifestyle, and sleeping habits. Capsule consumption (compliance) was verified daily.

• The study reported on a sample of seven women.
• Mean patient age was 45.9 years (SD = 2.7).
• Patients self-reported having constipation (less than one bowel movement per day or straining with bowel movements).
• None of the patients used laxatives or enemas.

Taiwan

This was a single-blind, placebo-controlled, crossover study.

• Patients recorded the following on a daily basis: ease of bowel movements, symptoms (e.g., feeling of incomplete evacuation, abdominal cramping, borborygmi, bloating, flatulence), and stool consistency.
• Participants collected their stools on days 15 through 21 during the placebo- and KGM-periods to determine fecal weight, composition, microflora, pH, and short-chain fatty acid content.

• Frequency of defecation and feelings of relief after bowel movements significantly improved (p < 0.05) by the second and third weeks of KGM.
• Ease of passage of bowel movements and reduction in the severity of borborygmi significantly improved (p < 0.05) by the third week of KGM.
• Flatulence significantly increased (p < 0.05).
• KGM did not significantly decrease abdominal cramping or bloating or significantly soften feces.
• KGM significantly increased proportions (percentage of total bacteria) of bifidobacteria and lactobacilli, and decreased the relative proportion of clostridia, compared with placebo (p < 0.05).

Adding KGM (4.5 g per day) to a low-fiber diet may increase frequency of bowel movements and improve colonic ecology.

• The sample size was extremely small.
• Participants were all women and volunteers.
• Patients with cancer were not included. 
• The design was only single blinded.

KGM (4.5 g per day) may increase frequency of bowel movements in adults with mild constipation (participants did not use laxatives or enemas). The ecology of the colon may improve with KGM supplementation because the proportion of fecal clostridia and fecal pH decreased. Additional studies are warranted that include an oncology population and a larger sample size.

To evaluate the impact of melatonin on survivors of breast cancer with data analysis of secondary quality-of-life outcomes (sleep, mood, hot flashes)

Participants were randomized using 1:1 randomization format and received four months of 3 mg melatonin or placebo nightly at 9 pm.

• N = 85
• MEAN AGE: 59 years
• RANGE: 38-81 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Stage I-III primary nonmetastatic breast cancer, ductal carcinoma in situ, lobular carcinoma in situ, completed with active treatment (surgery, radiation, chemotherapy, and hormonal therapy) 60 days prior to enrollment.
• OTHER KEY SAMPLE CHARACTERISTICS: There was no history of other cancers except nonmelanoma skin cancer; no night-shift work; no active seizures with medication; and no beta-blocker, warfarin, hormonal therapy, black cohosh, flaxseed, soy, or sleep-aid use. There was also no melatonin use 30 days prior to enrollment.

• SITE: Single site
• SETTING TYPE: Outpatient
• LOCATION: Dana-Farber/Harvard Cancer Center, Boston, MA

PHASE OF CARE: Transition phase after active treatment

• Secondary analysis of the effect of melatonin on sleep, mood, and hot flashes
• Original study was a double-blind, placebo-controlled, randomized trial

• Subjective measures included Pittsburgh Sleep Quality Index (PSQI) (19-item scale)
• Center for Epidemiologic Studies Depression (CES-D) (20-item scale)
• North Center Cancer Treatment Group hot flash diary (frequency and intensity of hot flashes over seven days, and severity [1 = mild to 4 = very severe]).
• Diary data summed but number of and severity of hot flashes per day, calculation of hot flash score using frequency and severity

No baseline differences in characteristics were noted between groups (n = 48 melatonin; n = 46 placebo). Sleep outcomes included significant improvement in sleep quality, daytime dysfunction, and PSQI total scores in treatment versus placebo. Overall change of sleep over time using all time points, which was adjusted for multiple comparisons, showed overall high PSQI global scores in placebo group (1.67) (95% CI [0.67, 2.66]), indicating worse sleep quality. CES-D scores did not change over time. Hot flash frequency decreased over time for both treatment groups. Only grade 1-2 toxicities were reported.

The use of oral 3 mg of melatonin showed minimal side effects with possible impact on the improvement of subjective sleep quality. There was no exclusion for prior sleep disorders, limiting understanding of MOA of melatonin and preexisting sleep disorders. Sleep was a secondary outcome of this study and needs larger RCT trials to verify results.

• Small sample (less than 100)
• Details of randomization process are missing.
• Melatonin dose is often started low and increased as needed; yet the rationale for a stable 3 mg dose of melatonin in this study is unclear
• Underpowered for evaluation of effect on hot flashes

Oral 3 mg melatonin is potentially a safe and effective treatment for sleep disturbances in survivors of breast cancer with baseline poor sleep quality. However, additional larger scale-studies in which sleep is the primary variable outcome are needed using objective and subjective measures of sleep.

To compare the rate of febrile neutropenia and neutropenia grade 4 among patients receiving pegfilgrastim on the same day of chemotherapy and after 24 hours of the chemotherapy administration

A retrospective, single-center, non-randomized, cohort study was conducted that includes the evaluation of the eligible patient’s chart selected via an institutional electronic device. Patients should be 18 years and older. They have conducted this study from May 2007 to January 2013. In this study, researchers reviewed the administration of 6 mg of pegfilgrastim in patients on the same day of chemotherapy (day 1) or on day 2 or beyond (up to day 8) of CHOP chemotherapy with or without rituximab every three weeks for a total of eight cycles. The researchers highlighted the potential risk factors contributing to febrile neutropenia. The febrile neutropenia criteria includes temperature of at least 38 C and ANC < 500cells/mm3. 

• N = 141  
• AGE = 18 years and older
• KEY DISEASE CHARACTERISTICS: Non-Hodgkin lymphoma

• SITE: Single site    
• SETTING TYPE: Outpatient    
• LOCATION: United states of America

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care

Retrospective, non-randomized, cohort study was conducted that contains chart review through institution electronic records.

• Fisher exact test
• SPSS software

Patients who received pegfilgrastim on the same day of chemotherapy had the highest incidence of febrile neutropenia (9.4%) compared to those who received the drug on day 1 or beyond (5.1%), showing a significant difference among both groups. In addition, the highest rate of dose reduction scenario was found in the day 1 group as compared to the day 2 and beyond  group (51.7% versus 40%). On the contrary, hospital stay duration and ICU admissions were high in the day 2 or beyond group versus the day 1 group (four admissions versus one admission).

The incidences of febrile neutropenia was less among the day 2 or beyond group of R-CHOP or CHOP.

• Baseline sample/group differences of import
• Key sample group differences that could influence results
• Measurement validity/reliability questionable 
• Findings not generalizable
• Time and duration of grade 4 neutropenia was not cleared, chemotherapy regimens were not standardized, and doses and cycles also differed.
• The type of infection was not clarified.

Additional studies need to be conducted for more accurate and reliable results.

To compare two oral care protocols with children receiving chemotherapy using either benzydamine or chlorhexidine oral rinses

Patients used each mouthwash for three weeks and then crossed over. Patients also used a standard mouthcare protocol consisting of toothbrushing using the Bass method and mouth rinsing with either of the allocated rinses in the early morning and at bedtime, normal saline rinsing within 30 minutes of meals, and normal saline rinsing every 4 hours in the first and third week and every 2 hours in the second week after chemotherapy. Patients were instructed in using a ballooning and sucking motion of the cheeks for 30 seconds without swallowing. Researchers provided reinforcement practice sessions every week and a cartoon reminder.

• The study reported on 40 patients.
• Patients had a median age of 10.3 years with a range of 6–17 years.
• Patients had solid and hematologic tumors.

The study was conducted from April 2000 to April 2001.

This was a prospective randomized, non-blinded, two-period crossover study with continual sequential analysis.

• Patient diaries were used. Researchers checked the remainder of rinse weekly to assess compliance.
• Parents and children were interviewed at each assessment about oral performance. The nurse or investigator assessed patients two times per week.
• Eilers' Oral Assessment Guide (OAG) was used with minor modifications. Interrelater reliability was established.

• A total of 34 participants completed the two protocols.
• No significant differences were found in patients' mean area under the curve (AUC) or oral mucositis according to order of protocols (t = 1.31, p > 0.05). No carry-over effect was found from initial oral care protocol.
• Fewer patients receiving chlorhexidin developed ulcerative lesions (27% versus 59%).
• A statistically significant reduction in ulcerative lesions was found using AUC (p < 0.05) and severity of mucositis (p < 0.05) in children on the chlorhexidine protocol.

This study did not demonstrate the superiority of the oral rinses over oral care.

• The study used a crossover methodology for control.
• The sample size was small.
• The study was not blinded.
• The study involved a wide age range.
• Patients were receiving a variety of chemotherapy protocols.
• Patients continued systematic oral care along with the protocol.
• Results may not apply to adult populations.

The study was conducted over an eight-month period. The first four months were with the control group, which received routine care, no oral protocol, and the center's standard use of 0.9% sodium chloride (NaCl) and benzydamine hydrochloride rinse to control oral mucositis (OM) when it developed.

The last four months involved the experimental group, which received an oral care protocol consisting of patient education, maintenance of patient diaries, and rinsing with normal saline chlorhexidine every two hours on days 1–21. The oral protocol prescribed toothbrushing; NaCl solution rinse for gums, tongue, and soft tissue; and chlorhexidine rinse every morning and evening, as well as NaCl rinse after each meal and every two hours for the second week only.

• The study reported on 42 children (21 in the control group and 21 in the experimental group) with hemotological or solid malignancies.
• Mean age was 10.3 years and a range of 6–18 years.

This was a prospective, comparative study.

• Oral assessment was performed initially and two times per week in each group.
• The Eilers Oral Assessment Guide was used.
• The Faces Pain Scale was used.
• Patients were observed for fevers and neutropenia.

• The oral protocol group experienced a 38% reduction of OM.
• Severity of OM (p = 0.000002) and related pain (p = 0.0001) were significantly reduced in the intervention group.
• The mean neutrophil count varied significantly between the seven time point evaluations (p = 0.008). A moderate negative correlation was found between the presence of OM and neutrophil count of the control group (p = 0.46) and protocol group (p = 0.15). Intensity of OM pain was significantly correlated with score of OM in two groups (p = 0.007).

• Assessment was performed twice per week.
• The results may not be generalizable to adult patients.
• The sample size was smal.
• A variety of chemotherapy protocols were used.
• The experimental group may have experienced a study effect.
• Use of chlorhexidine recommendation is in conflict with Multinational Association of Supportive Care in Cancer (MASCC) recommendations.

Although the sample is small, the evidence supports the use of normal saline found in other studies.

STUDY PURPOSE: To evaluate the evidence related to the efficacy of pyridoxine (vitamin B6) in preventing hand-foot syndrome (HFS) caused by anti-cancer therapies

TYPE OF STUDY: Systematic review

PHASE OF CARE:  Active antitumor treatment
 
APPLICATIONS: Elder care

• Incidence of HFS: No statistically significant differences were found in the risk of HFS among patients receiving placebo compared to pyridoxine (RR 0.96; 95% CI, 0.86–1.06; n = 551).  
• Incidence of grade 2 or worse HFS: No statistically significant differences were found in the risk of grade 2–4 HFS among patients receiving a placebo compared to pyridoxine (RR 0.96; 95% CI, 0.73–1.24; n = 551). In regard to different doses of pyridoxine, significant differences were found for prevention of grade 2 or grade 3 HFS with pyridoxine 400 mg PO daily compared to 200 mg PO. (RR 0.55; 95% CI, 0.33–0.92; n = 56).  
• Time to development of grade 2 or worse HFS: The median time for development of grade 2 or worse HFS was reported in one trial. Although the pyridoxine 400 mg group (87 days) was slightly longer than the 200 mg group (61 days), no statistical significant difference was found (p = 0.44).  
• Quality of life (QOL): In 2 RCTs (n = 106 and n = 34), there were no significant differences in QOL between the pyridoxine group and the placebo groups.  

Based on the analysis of results of five randomized controlled trials, there is not sufficient evidence to make any recommendation for patients taking pyridoxine to prevent HFS caused by chemotherapy drugs. However, that data suggests that pyridoxine 400 mg was more effective in preventing grade 2 and grade 3 HFS than pyridoxine 200 mg. Future research studies that include large sample sizes are needed to continue to evaluate pyridoxine’s efficacy and safety, especially high doses of pyridoxine, in comparison with placebo.

• Information from primary studies was not sufficient to perform subgroup analysis by types of chemo regimen.  
• This review included only RCTs.  
• Adverse effects of pyridoxine were not assessed absolutely.

HFS is a relatively common skin toxic reaction to certain chemotherapy. Nurses may collaborate with physicians in identifying effective treatments. Although RCT results do not support using pyridoxine for preventing HFS caused by chemotherapy, pyridoxine 400 mg PO may have some efficacy in preventing grade 2 and 3 HFS.