Should palonosetron be a preferred 5-HT3 receptor antagonist for chemotherapy-induced nausea and vomiting? An updated systematic review and meta-analysis.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) continues to be a common side effect of systemic anticancer therapy, decreasing quality of life and increasing resource utilization. The aim of this meta-analysis was to investigate the comparative efficacy and safety of palonosetron relative to other 5-HT3RAs. METHODS: A literature search was carried out in Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Full-text references were then screened and included in this meta-analysis if they were an RCT and had adequate data regarding one of the five primary endpoints-complete response (CR), complete control (CC), no emesis, no nausea, or no rescue medications. RESULTS: A total of 24 RCTs were included in this review. Palonosetron was statistically superior to other 5-HT3RAs for 10 of the 19 assessed endpoints. Only one endpoint-emesis in the overall phase-had noticeable more favorable data for palonosetron to the point that it approached the 10% risk difference (RD) threshold as specified by the MASCC/ESMO antiemetic panel; another two endpoints (CR in the overall phase and nausea in the delayed phase) approached the 10% threshold. CONCLUSIONS: Palonosetron seems to be more efficacious and safe than other 5-HT3RAs-statistically superior in 10 of 19 endpoints. It is, however, only clinically significant in one endpoint and approached clinically significant difference in another two endpoints. Within the limits of this meta-analysis, our results indicate that palonosetron may not be as superior in efficacy and safety as reported in a previous meta-analysis, and supports the recent MASCC/ESMO, ASCO, and NCCN guidelines in not generally indicating palonosetron as the 5-HT3RA of choice.

Efficacy of olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis.

PURPOSE: Olanzapine is a potent antipsychotic medication that inhibits a wide variety of receptors. It has been used in trials for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV). This study systematically investigates the efficacy of olanzapine in relation to other antiemetics in the prophylaxis and rescue of CINV. METHODS: A literature search of Ovid MEDLINE, EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs) comparing olanzapine to other standard antiemetics for either prevention or rescue. The primary endpoints were the percentage of patients achieving no emesis or no nausea, in the acute, delayed, and overall phases. RESULTS: Ten RCTs in the preventative setting and three RCTs in the breakthrough setting were identified. Subgroup analysis demonstrated a similar degree of benefit from a 5- and 10-mg dose of olanzapine for the no emesis endpoint in the overall phase. In the prophylaxis setting, olanzapine was statistically superior in five of six endpoints and clinically superior in four of six endpoints. In the breakthrough setting, olanzapine was statistically and clinically superior in the only endpoint analyzed: no emesis. CONCLUSION: Olanzapine is more efficacious than other standard antiemetics for the rescue of CINV and its inclusion improves control in the prevention setting. Given the possible reduction in side effects, the use of a 5-mg dose of olanzapine should be considered. Future RCTs should compare the 5-mg versus the 10-mg dosages further and report on the efficacy and percentage of patients developing side effects. Further analyses should be done without the influence of corticosteroids.

Phosphodiesterase-4 Inhibition in Psoriasis.

Psoriasis is a chronic immune-mediated inflammatory disorder. Phosphodiesterase-4 (PDE-4) is an enzyme that mediates inflammatory responses and plays a role in psoriasis pathogenesis. PDE-4 degrades its substrate cyclic adenosine monophosphate (cAMP) to adenosine monophosphate (AMP), which subsequently leads to the production of pro-inflammatory mediators. Inhibitors of PDE-4 work by blocking the degradation of cAMP, which leads to a reduction in inflammation. Apremilast is the only approved oral PDE-4 inhibitor for the treatment of psoriasis. While it is effective for some patients, it may be limited by adverse effects in others. A topical PDE-4 inhibitor, roflumilast, is being investigated in psoriasis and showing promising results. Crisaborole, a topical PDE-4 inhibitor approved for use in atopic dermatitis, has also been investigated in psoriasis. This is an updated comprehensive review to summarize the currently available evidence for the PDE-4 inhibitors apremilast, roflumilast and crisaborole in the treatment of psoriasis, with a focus on data from randomized clinical trials.

Effects of a single-entry intake system on access to outpatient visits to specialist physicians and allied health professionals: a systematic review.

BACKGROUND: Canada lags behind other countries with respect to wait times for specialist physician and allied health professional consultations. We conducted a systematic review to assess the effects of a single-entry model on waiting time, referral volume and the satisfaction of patients and health care providers. METHODS: We searched MEDLINE, Embase, Cochrane CENTRAL and CINAHL databases from inception to December 2019. We included studies from countries in the Organisation for Economic Co-operation and Development that reported on the effects of a single-entry model on the time between referral to first assessment by a specialist physician or allied health professional, termed wait time 1 (WT1). Patient volume and the satisfaction of providers and patients were secondary outcomes. We conducted a narrative synthesis using descriptive statistics. RESULTS: Of the 4637 citations identified, 17 met the eligibility criteria, and we included 10 of these in the final analysis. All of the included studies reported an absolute reduction in WT1 after implementation of the single-entry model. The average percent reduction in WT1 across specialties was greatest for surgical referrals (57%) and urgent internal medicine referrals (40%). Higher initial WT1 was associated with a greater absolute reduction in WT1 after implementation of the single-entry model (p = 0.002). Patient and provider satisfaction with the single-entry model was high in all studies. The effect estimates from all included studies were at high risk of bias. INTERPRETATION: Single-entry models were associated with an absolute reduction in time from referral from primary care to consultation. These models represent a promising option to improve access to a range of health services, but there is a need for rigorous prospective evaluations to inform policy. PROSPERO REGISTRATION: CRD42018100395.

Pyoderma gangrenosum: proposed pathogenesis and current use of biologics with an emphasis on complement C5a inhibitor IFX-1.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis with no FDA-approved treatment. The complement pathway has received renewed attention because it is elevated in inflammatory cutaneous conditions such as hidradenitis suppurativa (HS) and psoriasis. IFX-1 is a complement C5a inhibitor which inhibits neutrophil activation, chemotaxis, and reduces inflammatory signaling and complement driven tissue damage in various diseases. AREAS COVERED: The article discusses a proposed pathogenesis of PG, early clinical investigations of IFX-1 for the treatment of HS and PG, its potential as a treatment for PG, and those other biologics currently under investigation. EXPERT OPINION: Further studies should explore how patients with PG and other neutrophilic conditions may respond to complement inhibitors such as IFX-1. C5a blockade led to a reduction in inflammatory tunnels in HS, and alteration in neutrophil migration and activation supports the role of this pathway in the development of PG. The main challenges to the approval of IFX-1 are the identification of the optimal dose, duration, and stage-dependent factors in cutaneous inflammatory disorders. Further studies are required; however, complement inhibitors such as IFX-1 could find a place in clinical practice in years to come for severe, resistant PG that does not respond to conventional therapies.

Efficacy of the combination neurokinin-1 receptor antagonist, palonosetron, and dexamethasone compared to others for the prophylaxis of chemotherapy-induced nausea and vomiting: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV), a common side effect of chemotherapy, can substantially impair a patient's quality of life, interfere with a patient's compliance with anticancer therapy, and result in the manifestation of adverse events such as electrolyte imbalance, dehydration and malnutrition. The most recent guidelines published by the Multinational Association of Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO) recommend the combination of dexamethasone (DEX), a 5-hydroxytrypatmine-3 receptor antagonist (5-HT3RA), preferably palonosetron (PALO), and a neurokinin-1 receptor antagonist (NK1RA) for prophylactic treatment of CINV in patients receiving highly emetogenic chemotherapy (HEC). The aim of this review was to examine the efficacy of triple agent, as reported in randomized controlled trials (RCTs), compared to any other prophylactic treatments. METHODS: A literature search was conducted in Ovid MEDLINE(R), Embase Classic & Embase, and the Cochrane Central Register of Controlled Trials. The primary endpoint was the proportion of patients achieving complete response (CR) in the acute, delayed and overall phase. Secondary endpoints included the percentage of patients who achieved complete control (CC), no nausea and no vomiting in the acute, delayed and overall phases. RESULTS: A total of 17 RCTs were included in this review, of which 3,146 patients were randomized to receive NK1RA, PALO and DEX, and 2,987 patients to receive other antiemetic treatments. The combination was not superior to other treatments in five endpoints-CC and CR in the acute phase, nausea and emesis control in the delayed phase, and nausea in the overall phase-but was superior in the other 11 endpoints. When looking only at HEC and moderately emetogenic chemotherapy (MEC) studies, the combination was only superior to others in three endpoints (delayed and overall CC, and overall emesis control) in HEC setting, which is less than the nine identified endpoints (delayed and overall CR, delayed and overall CC, acute and overall nausea control, and acute, delayed and overall phases for emesis control) in the MEC setting. CONCLUSIONS: The combination of NK1RA, PALO and DEX is superior in the majority of assessed endpoints of this meta-analysis. Further studies should investigate the efficacy and safety of the triple regimen compared to regimens lacking NK1RA, to add to the discussions about whether future CINV prophylaxis guidelines should include NK1RA as a first-line treatment in the MEC setting.

Does gender affect self-perceived pain in cancer patients? -A meta-analysis.

BACKGROUND: Pain is reported in approximately 50-70% of cancer patients. Studies on gender differences in perceived pain generally report lower pain thresholds and increased pain prevalence in women, which may be attributed to gender-specific behaviors, stereotypes, and unknown etiological factors. There are sparse and inconclusive results on gender differences in self-perceived pain in the cancer setting. The aim of this article was to examine the effect of gender on baseline perceived pain intensity in cancer patients through a meta-analysis. METHODS: A literature search was conducted using Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials [1947-2016] to identify observational studies and controlled trials that reported on gender-specific pain intensity in cancer patients. Using random-effects modeling, weighted mean differences and 95% confidence intervals (CI) were used to estimate the effect of gender on pain severity in cancer patients. A P value of less than 0.05 was considered statistically significant. RESULTS: Of the 1,911 search results reviewed, 13 studies were included. The weighted mean difference (95% CI) in pain intensity was as follows: -0.26 (95% CI: -0.57 to 0.04, P=0.09) for the 0-10 Numerical Rating Scale (NRS) group (n=3,752, 9 studies). When restricted to only patients with advanced cancer, the weighted mean difference was -0.08 (95% CI: -0.36 to 0.20, P=0.58) (n=2,762, 4 studies). The weighted mean difference in the Brief Pain Inventory scores between males and females was 0.03 (95% CI: -1.23 to 1.29, P=0.96) (n=521, 4 studies). CONCLUSIONS: Baseline perceived pain intensity in cancer patients did not significantly differ based on gender.

The accuracy of clinicians' predictions of survival in advanced cancer: a review.

The process of formulating an accurate survival prediction is often difficult but important, as it influences the decisions of clinicians, patients, and their families. The current article aims to review the accuracy of clinicians' predictions of survival (CPS) in advanced cancer patients. A literature search of Cochrane CENTRAL, EMBASE, and MEDLINE was conducted to identify studies that reported clinicians' prediction of survival in advanced cancer patients. Studies were included if the subjects consisted of advanced cancer patients and the data reported on the ability of clinicians to predict survival, with both estimated and observed survival data present. Studies reporting on the ability of biological and molecular markers to predict survival were excluded. Fifteen studies that met the inclusion and exclusion criteria were identified. Clinicians in five studies underestimated patients' survival (estimated to observed survival ratio between 0.5 and 0.92). In contrast, 12 studies reported clinicians' overestimation of survival (ratio between 1.06 and 6). CPS in advanced cancer patients is often inaccurate and overestimated. Given these findings, clinicians should be aware of their tendency to be overoptimistic. Further investigation of predictive patient and clinician characteristics is warranted to improve clinicians' ability to predict survival.

Latest advances in the management of radiation-induced pain flare, nausea and vomiting.

Palliative radiotherapy (RT) is an effective treatment for symptomatic bone metastases. However, pain flare, nausea and vomiting are common adverse effects associated with this treatment. The management of pain flare and radiation-induced nausea and vomiting (RINV) are important endpoints in palliative care. Our report documents the incidence, clinical importance, and advances in the management of these two adverse-effects. We recommend that antiemetic prophylaxis be given based on emetic risk category as outlined in the American Society of Clinical Oncology (ASCO) guidelines. Newer antiemetics investigated in the chemotherapy setting should also be studied in the radiation setting. As there are no guidelines for the use of pain flare prophylaxis at present, further research in this area is needed.

The impact of psychosocial intervention on survival in cancer: a meta-analysis.

BACKGROUND: The impact of psychosocial interventions on survival remains controversial in patients with cancer. A meta-analysis of the recent literature was conducted to evaluate the potential survival benefit associated with psychosocial interventions for cancer patients. METHODS: MEDLINE, EMBASE, and Cochrane Central were searched from January 2004 to May 2015 for all randomized controlled trials (RCTs) that compared survival outcomes between cancer patients receiving a psychosocial intervention and those receiving other, or no interventions. Endpoints included one-, two-, and four-year overall survival. Subgroup analyses were performed to compare group-versus individually-delivered interventions, and to assess breast cancer-only trials. RESULTS: Of 5,080 identified articles, thirteen trials were included for analysis. There was a significant survival benefit for the intervention group at one year [risk ratio (RR) =0.82; 95% confidence interval (CI), 0.67-1.00; P=0.04] and two years (RR =0.86; 95% CI, 0.78-0.95; P=0.003). However, no significant difference was detected at four years (RR =0.94; 95% CI, 0.85-1.04; P=0.24). Among patients with breast cancer, there was a significant survival benefit of psychosocial interventions at one year (RR =0.59; 95% CI, 0.42-0.82; P=0.002), but no difference at two years (RR =0.82; 95% CI, 0.67-1.02; P=0.07) or four years (RR =0.95; 95% CI, 0.73-1.23; P=0.68). Group-delivered interventions had a significant survival benefit favouring the intervention group at one year (RR =0.57; 95% CI, 0.41-0.79; P=0.0008), but no difference at two years (RR =0.84; 95% CI, 0.68-1.02; P=0.08) or four years (RR =0.94; 95% CI, 0.75-1.20; P=0.64). Individually-delivered interventions had no significant survival benefit at one year (RR =0.92; 95% CI, 0.79-1.08; P=0.32), two years (RR =0.87; 95% CI, 0.75-1.00; P=0.05), or four years (RR =0.93; 95% CI, 0.84-1.04; P=0.21). CONCLUSIONS: For the main analysis and group-delivered treatments, psychosocial interventions demonstrated only short-term improvements in survival. Individually-delivered interventions failed to show any survival benefit. Future studies with longer follow-up are warranted to investigate long-term survival outcomes.

Radiotherapy for the prophylaxis of heterotopic ossification: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Heterotopic ossification (HO) involves the formation of lamellar bone in nonosseous tissue. For HO, radiotherapy has been shown to be an effective prophylactic modality. OBJECTIVE: To compare HO outcomes following radiotherapy and to investigate the comparative efficacy of preoperative versus postoperative radiotherapy. METHODS: A systematic search was conducted on Ovid MEDLINE, EMBASE and Cochrane CENTRAL. Studies were included if they were randomized controlled trials (RCTs) that included patients who were prescribed prophylactic radiation for whom relevant HO progression outcomes were reported. RESULTS: From a literature search of 528 articles, 12 RCTs were included. There was a statistically significant reduction in HO prevalence with multiple as opposed to single fraction radiotherapy (p=0.04), however there was no statistically significant difference when examining HO progression (p=0.34). There was no statistically significant difference in HO progression when comparing a biologically effective radiation dose (BED) of >2500cGy versus ⩽2500cGy (p=0.28). As well, no statistically significant difference existed in HO progression between postoperative versus preoperative radiation (p=0.43). CONCLUSION: There was no difference between postoperative or preoperative radiotherapy in preventing HO progression. There seems to be no relationship between BED greater or less than 2500cGy and the efficacy of HO prophylaxis. Multiple fractions seem to be more effective than single fraction radiotherapy in preventing HO progression.

A Selected Review of the Mortality Rates of Neonatal Intensive Care Units.

INTRODUCTION: Newborn babies in need of critical medical attention are normally admitted to the neonatal intensive care unit (NICU). These infants tend to be preterm, have low birth weight, and/or have serious medical conditions. Neonatal survival varies, but progress in perinatal and neonatal care has notably diminished mortality rates. In this selected review, we examine and compare the NICU mortality rates and etiologies of death in different countries. METHODS: A literature search was conducted in Ovid MEDLINE, OLDMEDLINE, EMBASE Classic, and EMBASE. The primary endpoint was the mortality rates in NICUs. Secondary endpoints included the reasons for death and the correlation between infant age and mortality outcome. For the main analysis, we examined all infants admitted to NICUs. Subgroup analyses included extremely low birth weight infants (based on the authors' own definition), very low birth weight infants, very preterm infants, preterm infants, preterm infants with a birth weight of ≤1,500 g, and by developed and developing countries. RESULTS: The literature search yielded 1,865 articles, of which 20 were included. The total mortality rates greatly varied among countries. Infants in developed and developing countries had similar ages at death, ranging from 4 to 20 days and 1 to 28.9 days, respectively. The mortality rates ranged from 4 to 46% in developed countries and 0.2 to 64.4% in developing countries. CONCLUSION: The mortality rates of NICUs vary between nations but remain high in both developing and developed countries.

The Use of Nipple Shields: A Review.

INTRODUCTION: A nipple shield is a breastfeeding aid with a nipple-shaped shield that is positioned over the nipple and areola prior to nursing. Nipple shields are usually recommended to mothers with flat nipples or in cases in which there is a failure of the baby to effectively latch onto the breast within the first 2 days postpartum. The use of nipple shields is a controversial topic in the field of lactation. Its use has been an issue in the clinical literature since some older studies discovered reduced breast milk transfer when using nipple shields, while more recent studies reported successful breastfeeding outcomes. The purpose of this review was to examine the evidence and outcomes associated with nipple shield use. METHODS: A literature search was conducted in Ovid MEDLINE, OLDMEDLINE, EMBASE Classic, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL. The primary endpoint was any breastfeeding outcome following nipple shield use. Secondary endpoints included the reasons for nipple shield use and the average/median length of use. For the analysis, we examined the effect of nipple shield use on physiological responses, premature infants, mothers' experiences, and health professionals' experiences. RESULTS: The literature search yielded 261 articles, 14 of which were included in this review. Of these 14 articles, three reported on physiological responses, two reported on premature infants, eight reported on mothers' experiences, and one reported on health professionals' experiences. CONCLUSION: Through examining the use of nipple shields, further insight is provided on the advantages and disadvantages of this practice, thus allowing clinicians and researchers to address improvements on areas that will benefit mothers and infants the most.

Incorporation of life expectancy estimates in the treatment of palliative care patients receiving radiotherapy: treatment approaches in light of incomplete prognostic models.

Physician estimates of patients' survival times have historically been inaccurate. In particular, physicians have often been overly optimistic in their predictions. Our review begins by documenting some of the literature addressing these concerns and proceeds to a discussion of prognostic models that have been created to aid physicians in providing more accurate estimates. We then discuss new findings showing survival to be influenced by particular treatment factors. Given such findings, currently existing prognostic models are now incomplete. However, with the abundance of evidence-based treatment options in a wide variety of patient populations, we propose that radiation oncologists need no longer rely so heavily on the precise prognostic capacity of survival models. Patients of different age demographics and survival prognoses benefit from palliative radiation treatment. More specifically, our report documents studies which show that for uncomplicated bone metastases, a single 8 Gy fraction of radiation is an equally effective tool for palliation regardless of whether a patient will have a short or long duration of survival. In addition we discuss evidence-based treatment options for patients with complicated bone metastases, lung and brain metastases. Further research is required to incorporate treatment factors in future survival prediction models.

Re-irradiation for painful bone metastases: evidence-based approach.

The prognosis of patients with bone metastases has improved with the advent of increasingly effective systemic treatment and better supportive care. A growing number of bone metastases patients now outlive the duration of benefits from their initial treatment of radiotherapy (RT) while some patients fail to initially respond to RT. As such, re-irradiation (re-RT) may be required. The current review updates the literature on findings in the area of re-RT. In particular, the recent publication of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Symptom Control (SC20) trial shows that an 8 Gy treatment in a single fraction for re-RT is non-inferior and less toxic than 20 Gy in multiple fractions. Furthermore, patients responding to re-RT have experienced superior quality of life (QoL) and complain of less functional interference from pain; this provides a strong case in support of bone metastases patients being offered re-treatment. However, despite such findings, some specific patients will never respond to initial radiation or re-RT. New evidence suggests significant differences in bone markers between responders and non-responders, thus opening the possibility for further research into the use of such biomarkers for predicting prognosis and for the guidance of consequent treatment decisions.

Radiotherapy for the prophylaxis of heterotopic ossification: a systematic review and meta-analysis of published data.

INTRODUCTION: Following surgery, the formation of heterotopic ossification (HTO) can limit mobility and impair quality of life. Radiotherapy has been proven to provide efficacious prophylaxis against HTO, especially in high-risk settings. PURPOSE: The current review aims to determine the factors influencing HTO formation in patients receiving prophylactic radiotherapy. METHODS: A systematic search of the literature was conducted on Ovid Medline, Embase and the Cochrane Central Register of Controlled Trials. Studies were included if they reported the percentage of sites developing heterotopic ossification after receiving a specified dose of prophylactic radiotherapy. Weighted linear regression analysis was conducted for continuous or categorical predictors. RESULTS: Extracted from 61 articles, a total of 5464 treatment sites were included, spanning 85 separate study arms. Most sites were from the hip (97.7%), from United States patients (55.2%), and had radiation prescribed postoperatively (61.6%) at a dose of 700cGy (61.0%). After adjusting for radiation site, there was no statistically significant relationship between the percentage of sites developing HTO and radiation dose (p=0.1) or whether radiation was administered preoperatively or postoperatively (p=0.1). Sites with previous HTO formation were more likely to develop recurrent HTO than those without previous HTO formation (p=0.04). There was a statistically significant negative relationship between the HTO development and the cohort mean year of treatment (p=0.007). CONCLUSION: Decreases in rates of HTO over time in this patient population may be a function of more efficacious surgical regimens and prophylactic radiotherapy.