Gasser, P., Holstein, D., Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., & Brenneisen, R. (2014). Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. Journal of Nervous and Mental Disease, 202, 513–520.
To evaluate previous findings regarding the effectiveness of lysergic acid diethylamide (LSD)-assisted psychotherapy
Participants were recruited through general information in media, flyers, cancer support groups, and hospitals. Patients were randomized to the LSD group receiving an oral dose of 200 mcg LSD or to an active placebo of 20 mcg LSD. Participants were required to taper off antidepressants and antianxiety medications and avoid alcohol and recreational drugs for 24 hours before sessions. Urine drug tests were done prior to each psychotherapy session. Two experimental sessions with LSD were completed. After each experimental session, three dug-free therapy sessions took place. A follow-up evaluation was completed two months after the second experimental session. At that time, participants in the placebo group could cross over to an identical open label treatment with LSD. The final evaluation was conducted 12 months after the last LSD-assisted session. About two-thirds of the LSD-assisted session was focused inward and one-third was brief conversation. The session ended after eight hours when acute effects subsided and was followed by a review of the day’s experience.
Placebo-controlled, randomized, controlled trial
The visit-by-group interaction testing for differences between groups showed a significant difference between groups (p = .033) and 65.5% power. Three of eight experimental group subjects dropped lower than the threshold of 40 on the anxiety inventory while all active placebo subjects experienced increases in anxiety. The two- and 12-month follow-up results of those who received LSD in either blinded or crossover conditions showed that benefits were sustained over time. Neither the experimental nor the placebo dose of LSD produced any severe drug-related adverse events. Adverse events reported were those commonly associated with LSD, and most resolved when the drug effects diminished. There were no events of prolonged anxiety or lasting psychotic or perceptional disorders.
This study demonstrated the safety of LSD-assisted psychotherapy sessions in a small group of patients with life-threatening diseases. There were positive trends of anxiety reduction after two LSD-assisted therapy sessions.
Findings from this small pilot study suggest that LSD-assisted psychotherapy may be beneficial to patients facing the end of life to reduce anxiety. Additional research studies to confirm its safety and efficacy are needed.
Garzon-Rodriguez, C., Casals Merchan, M., Calsina-Berna, A., Lopez-Romboli, E., & Porta-Sales, J. (2013). Lidocaine 5% patches as an effective short-term co-analgesic in cancer pain. Preliminary results. Supportive Care in Cancer, 21, 3153–3158.
To evaluate the short-term efficacy of lidocaine 5% patches for pain scars and pain caused by chest wall tumors
Patients seen in the palliative care outpatient clinic were included. They were instructed to apply up to a maximum of three patches at a time to cover the painful area for 12 hours each day. All patients had to have pain with a neuropathic component plus allodynia.
Mean duration of treatment was 29.2 days (range 3–90). Five patients discontinued in less than 10 days because of lack of efficacy. At the end of follow-up, pain scores declined by an average of two points (p < .05). Rating of breakthrough pain level declined significantly (p < .05).
Findings suggest that lidocaine patches might be helpful for some patients with pain from scarring and chest wall tumors, but the study had multiple limitations and findings lack strong support for the intervention.
Lidocaine patches might be of some help for patients with certain types of pain that are well localized and superficial. Although findings of this study were somewhat positive, the evidence is weak and this report has numerous limitations. Further well-designed, larger studies need to be done.
Gartner, R., Kroman, N., Callesen, T., & Kehlet, H. (2010). Multimodal prevention of pain, nausea and vomiting after breast cancer surgery. Minerva Anestesiologica, 76(10), 805–813.
To evaluate the effect of a multidrug, opiate-sparing regimen for prevention of postoperative pain, nausea, and vomiting in patients after surgery for breast cancer
For 1–2 hours preoperatively, patients received a drug combination consisting of 1g oral paracetamol, 8 mg dexamethasone, 30 mg dextromethorphan, 400 mg celecoxib, and 1200 mg gabapentin. In addition, patients who were anxious received 0.125 mg triazolam on request. All patients received the same anesthesia regimen. In the postanesthesia care unit (PACU), immediately after surgery, symptoms were recorded at 15-minute intervals for 12 hours. Patients who had moderate to severe pain with mobilization received 0.1 mg/kg IV morphine and 1 g oral paracetamol every six hours and 200 mg oral celecoxib on the evening of the operation and in the morning and evening of the following day. Patients who needed pain medication after the first day received 600 mg oral ibuprofen every six hours and 1 g paracetamol every six hours. Rescue medication consisted of 15 g oral morphine.
Prospective trial
Four-point symptom rating scale, 0= no complaints and 3 = severe complaints
The preoperative drug combination used here appeared to be effective in preventing postoperative nausea and vomiting and may have reduced postoperative pain at rest.
The specified combination of medications, administered preoperatively, appeared to reduce some postoperative symptoms in patients who had breast cancer surgery.
Garssen, B., Boomsma, M.F., Jager Meezenbroek, E., Porsild, T., Berkhof, J., Berbee, M., . . . Beelen, R.H. (2013). Stress management training for breast cancer surgery patients. Psycho‐Oncology, 22, 572–580.
To evaluate the psychological effects of presurgical stress management training
Subjects were randomized to the intervention or control group by week in the hospital. The intervention consisted of four sessions of meditative exercises, relaxation, guided imagery, and counseling to promote active coping and positive attitude. Sessions were completed on days 5 and 1 before surgery and days 2 and 30 postsurgery. Patients were given a CD with the same instructions to use at home. Assessments were done on days 6 and 1 before surgery and days 2, 5, 30, and 90 postsurgery. The control group received usual care.
Randomized, controlled trial
Anxiety decreased after surgery in both groups. Depression decreased in the intervention group after surgery and in the control group at three months postsurgery. Depression was significantly lower in the intervention group on day 5 after surgery (d = 0.47). Fatigue increased in the control group and was significantly higher than baseline at three months postoperatively. In the intervention group, fatigue decreased and was significantly below baseline at days 2 and 5 postoperatively. Sleep problems and pain did not change in either group. Across all study timepoints, differences between groups were inconsistent. Sometimes, symptoms were higher in the intervention group, and other times, they were lower in the intervention group. An analysis was done for changes from baseline for each group rather than between groups. There were only differences in the degree of change from baseline to postoperative days 2 and 5.
The effects of the intervention were inconsistent over time and appeared to be modest and short-lasting.
The findings here were somewhat confusing and inconsistent over time; however, there were some potential short-term benefits for fatigue and depression. The combination of relaxation therapies and counseling is a low-risk intervention that may be helpful for some patients.
Garnica, M., Nouer, S.A., Pellegrino, F.L., Moreira, B.M., Maiolino, A., & Nucci, M. (2013). Ciprofloxacin prophylaxis in high risk neutropenic patients: Effects on outcomes, antimicrobial therapy and resistance. BMC Infectious Diseases, 13, 356.
To evaluate the impact of quinolone prophylaxis during neutropenia on outcomes including resistance rates and hospital admissions
Researchers compared data from hospitalizations during two time periods, representing an intervention group and a control group. The intervention group included patients who received quinolone prophylaxis from 2006–2008. Prophylaxis consisted of 500 mg oral ciprofloxacin twice a day or 200 mg IV twice a day if oral medication was not tolerated. The control group included patients who received no antibiotic prophylaxis during 2005. In the event of a fever, patients in both groups began IV cefepime. If patients had a history of a cefepime-resistant gram-negative infection, they were treated with a carbapenem instead. Analysis of demographics and clinical outcomes, including occurrence of fever, duration of empirical antibiotic therapy, duration of hospitalization, and quinolone resistance, were conducted using SPSS software. Chi-square tests and Mann-Whitney tests were used for categorical and continuous variables, respectively. To evaluate patterns of resistance, data from patients outside the intervention cohort, but also hospitalized from 2006–2008, also were analyzed for resistance.
For their methods, the researchers defined neutropenia as an absolute neutrophil count (ANC) less than 500/mm3. They defined bone marrow recovery as at least two consecutive days with ANC greater than 500/mm3. All blood cultures were processed using a BacT/ALERT® system. Susceptibility tests were completed using the VITEK® automated system. Other laboratory tests on stored bacterial cultures were used to evaluate susceptibility. These included, but were not limited to, disk diffusion, minimal inhibitory concentration, and polymerase chain reaction. Statistical tests, including Chi-square and Mann-Whitney, were completed using SPSS software.
Groups were similar in age and gender. The intervention group was statistically different from the control group in that they experienced slightly shorter periods of neutropenia (9 versus 11 days, p = 0.02), hospitalization (22 versus 24 days, p = 0.002), and antibiotic therapy (8 versus 11 days, p < 0.001); fewer febrile episodes (73 versus 93%, p < 0.001), decreased incidence of any grade mucositis (52% versus 70%, p = 0.003), and bacteremia (22% versus 33%, p = 0.04); and increased use of carbapenem (36% versus 14%, p < 0.001). The intervention group had a higher rate of quinolone-resistant bacteremia (6.77 versus 3.02 per 1,000 patients-day, p = 0.03). Quinolone-resistant enterobacteria was noted in the intervention group and patients outside the intervention cohort but hospitalized during the same time. The rate of extended spectrum beta-lactamase (ESBL)-producing enterobacteria was not significantly increased in the intervention group (0.38 in the control group versus 1.27 in the ciprofloxacin group, p = 0.26).
This study identifies benefits of quinolone prophylaxis in high-risk patients (i.e., patients with hematologic malignancies undergoing chemotherapy with an expected duration of neutropenia longer than seven days, or patients undergoing HCT), including decreased incidence of fever, bacteremia, duration of neutropenia, and length of hospitalization. Risks include an increased incidence of quinolone resistance and bacteremia because of ESBL-producing enterobacteria for the patient and hospital unit.
Quinolone prophylaxis can reduce the incidence of fever, bacteremia, duration of neutropenia, hospitalization, and duration of antibiotic therapy for select high-risk patients. Nurses should understand these benefits and the risk of quinolone resistance for individual patients in the surrounding hospital unit.
Garland, S.N., Rouleau, C.R., Campbell, T., Samuels, C., & Carlson, L.E. (2015). The comparative impact of mindfulness-based cancer recovery (MBCR) and cognitive behavior therapy for insomnia (CBT-I) on sleep and mindfulness in cancer patients. Explore, 11, 445–454.
To compare the impact of a mindfulness-based cancer recovery (MBCR) intervention versus cognitive behavioral therapy for insomnia (CBT-I) on mindfulness and dysfunctional sleep beliefs, to examine associations of insomnia severity and changes in mindfulness and dysfunctional sleep beliefs, and to compare changes in insomnia severity between treatment groups
MBCR was used on-site at weekly 90-minute group classes with one six-hour silent retreat between weeks 6 and 7 as an opportunity for extended practice. The program consists of several types of mindfulness practices and didactic instruction on application of mindfulness attitudes. The facilitator was a nurse with more than 10 years of experience delivering MBCR. The CBT-I program consisted of eight weekly 90-minutes sessions, including stimulus control, sleep restriction, relaxation, cognitive strategies aimed at dysfunctional sleep beliefs, and sleep hygiene. The facilitator for the CBT-I program was a doctoral level trainee in a nationally accredited clinical psychology program and was supervised by a PhD-level Clinical Health Psychologist.
Mindfulness outcomes not reported. There were significant group, time, and group X time effects on overall and subscale scores for the DBAS with large effect sizes. The CBT-I group had more improvements than the MBCR group. Baseline to post-program improvements were noted that persisted at three-month follow-up. Associations between DBAS subscale and total scores and insomnia severity were not reported. Aspects of mindfulness were negatively correlated with a number of DBAS subscales and total score. Insomnia severity was negatively correlated with mindfulness non-judging. Insomnia severity (severe, moderate, mild, none) was not significantly different at baseline, post-program, and follow-up between MBCR and CBT-I groups.
CBT-I has a greater impact on DBAS measures than MBCR, but both have large effect sizes on DBAS. Aspects of mindfulness account for some variability in DBAS scores. Both MBCR and CBT-I have a positive impact on insomnia severity over time.
Both CBT-I and MBCR may improve insomnia in survivors. CBT-I has a greater impact in decreasing dysfunctional beliefs about sleep.
Garland, S.N., Carlson, L.E., Stephens, A.J., Antle, M.C., Samuels, C., & Campbell, T.S. (2014). Mindfulness-based stress reduction compared with cognitive behavioral therapy for the treatment of insomnia comorbid with cancer: A randomized, partially blinded, noninferiority trial. Journal of Clinical Oncology, 32, 449–457.
To examine whether mindfulness-based stress reduction (MBSR) is noninferior to cognitive behavioral therapy for insomnia (CBT-I) for the treatment of insomnia in patients with cancer
Of 327 patients screened, 111 were assigned randomly (CBT-I, n = 47; MBSR, n = 64). MBSR was inferior to CBT-I for improving insomnia severity immediately after the program (p = .35), but MBSR demonstrated noninferiority at follow-up (p = .02). Sleep diary-measured sleep latency (minutes to fall asleep) was reduced by 22 minutes in the CBT-I group and by 14 minutes in the MBSR group at follow-up. Similar reductions in wake after sleep onset (in minutes) were observed for both groups. Total sleep time increased by 0.60 hours for CBT-I and 0.75 hours for MBSR. CBT-I improved sleep quality (p = .001) and dysfunctional sleep beliefs (p = .001), whereas both groups experienced reduced stress (p = .001) and mood disturbance (p = .001).
Although MBSR produced a clinically significant change in sleep and psychological outcomes, CBT-I was associated with rapid and durable improvement and remains the best choice for the nonpharmacologic treatment of insomnia.
Noninferiority of MBSR only was demonstrated at the five-month follow-up, suggesting that although MBSR may produce clinically significant improvements with time, the treatment effects of CBT-I are rapid and durable. Thus, CBT-I remains the treatment of choice for patients with cancer who have insomnia.
Garland, S.N., Johnson, J.A., Savard, J., Gehrman, P., Perlis, M., Carlson, L., & Campbell, T. (2014). Sleeping well with cancer: A systematic review of cognitive behavioral therapy for insomnia in cancer patients. Neuropsychiatric Disease and Treatment, 10, 1113–1124.
STUDY PURPOSE: To review the efficacy of cognitive behavioral therapy (CBT) on sleep and psychological outcomes in patients with cancer and cancer survivors
Four of four uncontrolled trials showed a positive significant effect of CBT on sleep problems. Of eight RCTs, five showed a positive significant effect and three showed no difference between groups. One of these compared CBT to mindfulness-based stress reduction rather than usual care. One study showed no long-term effectiveness. Review of the evidence shows overall efficacy of CBT in patients without cancer. The intervention has been delivered effectively in person, individually or in groups, telephonically, and via the internet or videos.
The majority of evidence shows that CBT has a positive effect on sleep-wake disturbance in patients with cancer. The most effective duration, timing, and “dose” is unclear, but this approach appears to be effective when delivered with varied methods.
Evidence supports the effectiveness of CBT for sleep problems in patients with cancer, and this approach appears to be provided effectively in very practical ways, such as through videos and websites. At present, as reported in this review, CBT is seen as the treatment of choice for insomnia in patients with cancer. Future research for comparative effectiveness of various interventions for sleep disturbances is needed.
Garland, S. N., Tamagawa, R., Todd, S. C., Speca, M., & Carlson, L. E. (2013). Increased mindfulness is related to improved stress and mood following participation in a mindfulness-based stress reduction program in individuals with cancer. Integrative Cancer Therapies, 12, 31–40.
To examine the effects of a mindfulness-based stress-reduction therapy (MBSRT) on stress and mood disturbances and to examine the relationship of improved mindfulness and mood changes.
Hospital staff referred patients to the study or patients self-referred to the study. MBSRT consisted of eight weekly sessions and a six-hour silent retreat held after the sixth session. Classes taught participants about the mind-body connection, principles of mindfulness, and yoga practice. Patients were encouraged to share experiences to generate support from group members. All were given CDs with guided meditation exercises, and all received a program manual. Patients were encouraged to practice meditation and mindful movement at least 45 minutes per day. Patients who did not attend at least five sessions were excluded from the analysis.
Patients were undergoing the transition phase after active treatment.
The study used a pre-/posttest design.
The findings supported the use of MBSRT approaches for managing the symptoms of anxiety, depression, and fatigue.
The findings suggested that a stress-reduction intervention involving group support, yoga, and mindfulness may help patients manage the symptoms of anxiety, depression, and fatigue. The various study limitations prevented firm conclusions from being drawn.
Gardner, A., Mattiuzzi, G., Faderl, S., Borthakur, G., Garcia-Manero, G., Pierce, S., & Estey E. (2008). Randomized comparison of cooked and noncooked diets in patients undergoing remission induction therapy for acute myeloid leukemia. Journal of Clinical Oncology, 26, 5684–5688.
This study was an evaluation of whether a diet including fresh fruits and vegetables increased the risk of infection in adult patients with cancer who were receiving induction chemotherapy for either acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) in a protective environment.
Patients were randomized to either a “raw group” (n = 75) that was allowed a general diet including fresh fruits and vegetables or to a “cooked group” (n = 78) that was restricted to a low-microbial diet of all cooked food but no fresh fruit or vegetables. Patients remained in a protective environment from the initiation of induction chemotherapy until recovery of the absolute neutrophil count (ANC) over 500 mcl.
Patients received routine antimicrobial prophylaxis with levofloxacin, valacyclovir, and an antifungal agent (itraconazole, voriconazole, or lipid amphotericin B).
Granulocyte–colony-stimulating factor was not used routinely.
Endpoints for the study were pneumonia, bacteremia, major infection, fever of unknown origin, and death.
A single institution
The statistical design was the Bayesian multiple outcome design of Thall and Sung. The X2 or Kruskal-Wallis test was used to compare various pretreatment characteristics.
There was no statistically significant difference in the rate of infection, pneumonia, fever of unknown origin, or overall survival between the raw and cooked groups. A significantly higher rate of bacteremia was found in the raw group; however, the authors noted that most of the organisms responsible for the baceteremia were not of enteric origin.
The median number of days with an ANC less than 500 mcl was 20 days in the cooked group and 21 days in the raw group.
The median number of days with an ANC less than 100 mcl was 15 in the cooked group and 16 in the raw group.
A diet that includes raw fruits and vegetables did not increase the risk of infection or death in patients with MDS or AML treated with remission induction chemotherapy in a protective environment when compared to a diet that restricted raw fruits and vegetables.
One strength of the study is that the sample was a population of high-risk patients who had an ANC less than 500 mcl for a median of 20 days. In comparison, patients with solid tumors treated with chemotherapy are at low risk for infection, and the patients that experience neutropenia generally have an ANC less than 500 mcl less than seven days. Because this study demonstrated an absence of efficacy of the low-microbial diet in high-risk patients; it is unlikely to be of benefit in low-risk patients with a much shorter duration of neutropenia. However, further research is warranted to confirm the findings in other populations of neutropenic patients.