A phase II study on the efficacy and safety of procedural analgesia with fentanyl buccal tablet in cancer patients for the placement of indwelling central venous access systems.

BACKGROUND: Pain in cancer patients is often related to oncologic therapies and diagnostic procedures. The placement of fully implantable venous access systems is a very common procedure in oncology patients. Local anaesthesia is the method most commonly used to overcome pain related to this surgical procedure, but the local anaesthetic may be unable to completely eradicate all pain. This study investigates the effectiveness and safety of fentanyl buccal tablet (FBT), administered by OraVescent® technology, in reducing procedural pain related to the placement of indwelling central venous access systems (Ports) in opioid-naïve cancer patients. METHODS: Inpatients who required an indwelling vascular access (Port) were preoperatively assessed with a self-assessment questionnaire on anxiety and pain. A 100 µg FBT was administered 10 min before preparation of the operating field. A self-assessment scale for pain experienced during the procedure was administered at the end of the procedure. Vital signs and the presence of any side effects or bothersome symptoms were monitored during the procedure, at the end, and 4 h later. RESULTS: From October 2012 to June 2014, 65 patients were enrolled in the study. A total of 61 (93.9 %) patients perceived no or a little pain during the procedure. Four patients (6.2 %) reported a lot of pain. No patient reported very severe pain. This data is significant in terms of the lower than expected presence of pain (Fisher test p = 0.0018) as assessed in our previous experience without procedural analgesia. The most common side effects of FBT was drowsiness, experienced by 28 patients at the end of the procedure (43.1 %), significantly reduced (p < 0.01) to 8 patients after 4 h (12.5 %). Nausea was present in 6 cases at the end of the procedure (9.2 %) and in 7 cases 4 h later (10.9 %). Vomiting was present in 3 cases at the end (4.7 %) and in 2 other patients after 4 h (7.8 %). No significant change of vital parameters was observed between the baseline and the subsequent measurements in all patients studied. CONCLUSIONS: The significant improvement in the number of patients experiencing little or no pain, accompanied by a lower number of non-severe side effects, suggests that FBT is a valid, practical and safe method of procedural analgesia. It will be necessary to perform further studies, taking into account the need for standard antiemetic pre-medication to minimise the incidence of nausea and vomiting.

Nonsteroidal antiinflammatory drugs for cancer pain: comparison between misoprostol and ranitidine in prevention of upper gastrointestinal damage.

PURPOSE: The prophylactic strategy of nonsteroidal antiinflammatory drug (NSAID)-induced upper gastrointestinal (UGI) damage has largely been studied in arthritic patients, but not in cancer patients. The efficacy of misoprostol and ranitidine in the prevention of gastroduodenal damage in patients taking diclofenac for their cancer pain has been compared in this study. PATIENTS AND METHODS: Patients who needed high-dose (200 to 300 mg/d) diclofenac for cancer pain and without mucosal lesions at baseline gastroduodenal endoscopy were randomized to receive misoprostol (200 micrograms twice daily; M group) or ranitidine (150 mg twice daily; R group). UGI endoscopy was repeated after 4 weeks. RESULTS: Twenty-three patients treated with misoprostol and 26 treated with ranitidine concluded the study. The M group showed a significantly (P < .02) lower incidence of gastroduodenal lesions (two patients; 8.7%) than the R group (10 patients; 38.5%). Gastric ulcers occurred in one (4%) misoprostol-treated patient and in six (23%) ranitidine-treated patients. Six of seven patients with ulcers were asymptomatic. Seventy-one percent and 86% of ulcers occurred in patients older than 60 years and in those who received greater than 3.1 mg/kg of diclofenac, respectively. CONCLUSION: Misoprostol was significantly more effective than ranitidine in the prevention of gastroduodenal lesions in cancer patients receiving diclofenac.

Interferon-gamma detection in cultures of newborn cells exposed to Listeria monocytogenes.

Clearance of Listeria monocytogenes in experimental models of infection has underscored the importance of interferon-gamma (IFN-gamma) in host resistance to intracellular pathogens. Because L. monocytogenes infections are more severe in newborns than adults, we compared IFN-gamma accumulation in the supernatants of mononuclear cells infected in vitro from newborns with those from adults. Supernatants were assayed for IFN-gamma using an enzyme-linked immunosorbent assay. Uninfected newborn and adult mononuclear cells had less than 50 pg/ml of IFN-gamma at all times tested. IFN-gamma levels in supernatants from infected adult mononuclear cells at 24 h of culture (1.15 x 10(3) +/- 0.92 pg/ml) were greater than supernatants from infected newborn mononuclear cells (0.19 x 10(3) +/- 0.33 pg/ml). IFN-gamma concentrations in newborn cell cultures plateaued on day 3 of culture (1.6 x 10(3) +/- 1.1 pg/ml) and were not significantly less than concentrations from adult cells. However, adult cell IFN-gamma was further increased by day 5 (18.7 x 10(3) +/- 21.8 pg/ml). Because IFN-gamma plays a critical role in the host defense against L. monocytogenes, this delay in the release of IFN-gamma may be a factor in the increased susceptibility and severity of infection in the neonate.

Deficient tumor necrosis factor secretion by cord blood mononuclear cells upon in vitro stimulation with Listeria monocytogenes.

We examined the production of tumor necrosis factor (TNF) by mononuclear cells (MNC) after incubating adult or cord blood MNC with Listeria monocytogenes in vitro. With adult MNC cultures, we found that TNF activity reached a peak at 6 h (606 +/- 120 x 10(3) units/liter) and declined to the baseline by day 3. In contrast, using cord blood MNC, we found that TNF activity increased gradually reaching a peak at 24 h. In addition, the peak TNF activity using newborn MNC (189 +/- 26 x 10(3) U/liter) at 24 h was still lower than the peak using adult MNC at 6 h (p < 0.0002). In seeking an explanation for the decreased TNF secretion from newborn MNC, we examined the possibility that newborn cells produce TNF but failed to secrete it. However, lysates of newborn cells contained functionally and antigenically less TNF than adult cells. Based on these observations, we conclude that the overall TNF production by newborn cells incubated with L monocytogenes is decreased compared with similarly stimulated adult cells.

Early-onset pneumococcal sepsis in newborn infants.

Five infants with pneumococcal sepsis presented with respiratory distress and clinical signs of infection in the first day of life. Although there was no apparent epidemiological relationship among the patients, four of the five were seen within a 12-month period. Pneumonia, prolonged rupture of fetal membranes, and prematurity were features in these patients. Three infants died, two within 12 hours of diagnosis. Streptococcus pneumoniae was isolated from the vagina of three of the mothers; in two, the serotype was identical to that recovered from their infants. Clinical features of neonatal pneumococcal sepsis are similar to those of early-onset group B streptococcal infection. Like the group B Streptococcus, S. pneumoniae acquired from the maternal vagina is a potential life-threatening pathogen in the newborn period.

Production of interleukin 8 (IL-8) by cord blood mononuclear cells induced by Listeria monocytogenes.

The defective ability of human newborns to mobilize phagocytes to the site of infection led us to examine the ability of cord blood mononuclear cells to secrete interleukin-8, a major neutrophil chemotactic factor, in response to stimulation with Listeria monocytogenes. Adult or cord blood mononuclear cells were incubated with L. monocytogenes for varying lengths of time, and IL-8 was measured in the culture supernatants by the enzyme-linked immunosorbent assay (ELISA). Spontaneous IL-8 secretion by unstimulated cells was undetectable or at the minimal detection limit of the assay. By 24 h of cell incubation with L. monocytogenes, newborn cells produced as much IL-8 as adult cells did (300 +/- 113 versus 269 +/- 189 ng/ml, respectively). Over the next 2-4 days, IL-8 output by adult cells was slightly higher than that by newborn cells, but the difference was not statistically significant. The in vitro results suggested that newborns are as able as adults to produce IL-8, although they are defective in mobilizing neutrophils, the IL-8 target cells, to the site of infection.

Clinical course of pertussis in immunized children.

To describe the clinical course of Bordetella pertussis infection in a highly immunized childhood population, we studied prospectively endemic and epidemic pertussis in a metropolitan population with an immunization rate > 90% during an 8-year period from 1987 through 1994. Patients with a possible diagnosis of pertussis were referred by family or emergency room physicians for nasopharyngeal culture. Patients with a culture positive for B. pertussis were contacted by a nurse who completed a detailed questionnaire for the index case and all family members. Repeat home visits were made each week for 4 weeks. Of the 189 patients with pertussis who were evaluated 103 subjects were < 5 years of age. Congestion predated the onset of cough by up to 1 week in 35 (34%) cases. Seventy (68%) subjects < 5 years of age developed a paroxysmal cough within the first week of their illness. Ninety-one (88%) cases < 5 years old had a persistent paroxysmal cough for > 21 days. Coughing in this group lasted from 16 to 91 days (median 48). Erythromycin therapy appeared to shorten the duration of cough; however, patients were not randomized to receive erythromycin at a specific time. Despite adequate immunization some children develop pertussis. The clinical course in these patients is milder than in unimmunized subjects. Nevertheless the symptomatology in these children should still be readily identified by most physicians using classical clinical criteria of pertussis.

Demand for isolation beds in a pediatric hospital.

OBJECTIVE: To determine isolation bed use for community-acquired and nosocomial infections in a pediatric hospital. DESIGN: A prospective repeated point prevalence survey was conducted during a 14-month period. A questionnaire was sent to other free-standing Canadian children's hospitals to determine isolation practice and perceived needs. SETTING: A university-affiliated, 218-bed pediatric hospital in Halifax, Nova Scotia, Canada. PATIENTS: All inpatients on surveyed wards during the study period (n = 1634). RESULTS: Overall, 13.5% of patients required isolation (range 5.6% to 31% per month). Demand was seasonal, with 71% of isolation occurring from November to April. Demand exceeded supply by 2 to 22 beds (11% to 122%). Respiratory and enteric infections requiring contact isolation accounted for 80% of use (53% and 27%, respectively). Children younger than 24 months comprised 28% of admissions and used 57% of isolation beds. Of patients isolated, 25% had nosocomial infections and 75% had community-acquired infections. The percentage of infant rooms in Canadian children's hospitals that were single bed (considered optimal for infant isolation) varied: 0% to 20% for hospitals built before 1965 and 25% to 47% for newer hospitals. All hospitals with less than 33% single-bed infant rooms perceived this allocation to be inadequate (p < 0.01 Fisher Exact Test). CONCLUSIONS: Pediatric isolation bed use varies with patient age, season of year, and category-specific isolation requirements. An increasing need for single-bed rooms is identified. Isolation requirements must be considered during the design of new hospitals or renovation of existing ones.

Mycoplasma pneumoniae infection associated with central nervous system complications.

We describe two children who had central nervous system complications, encephalitis and meningoencephalitis, temporally associated with Mycoplasma pneumoniae. M pneumoniae was identified as the cause of the illnesses on the basis of at least a fourfold increase in complement fixation antibody titers. Despite extensive viral and bacterial investigation, no evidence of any other pathogen was found. Two strategies were used to determine whether M pneumoniae was directly invasive: (1) by examining cerebrospinal fluid using a M pneumoniae-specific DNA probe and (2) by determining whether complement-fixating antibody to M pneumoniae was produced locally through comparison of the cerebrospinal fluid/serum ratio of M pneumoniae antibody to the cerebrospinal fluid/serum ratio of immunoglobulin M. Both assessments were negative. M pneumoniae did not appear to directly invade the central nervous system in these two patients. We conclude that the direct invasion of the cerebrospinal fluid is not necessary in the pathogenesis of M pneumoniae-induced neurologic disease.

Changing pattern of clinical illness in children with group A streptococcal bacteremia.

OBJECTIVE: To test the hypothesis that bacteremia caused by group A streptococci (gas) has become more common and the presentation of the infection more severe in the Izaak Walton Killam Hospital for Children during the past decade. DESIGN: Retrospective analysis by laboratory log and chart review. SETTING: A pediatric teaching hospital providing primary and tertiary care. RESULTS: There was no difference in the frequency of detection of gas bacteremia between the two periods studied (1980 to 1988 and 1988 to 1991). However, severe gas infection with deep tissue invasion was more common in the last three-year period (77% versus 11%, P=0.01). Severity, as measured by length of hospital stay, was also greater in the recent group (17.9 days versus 3.3 days, P=0.03). A recent group of four children was identified with a unique clinical syndrome of rash, severe myalgias, hyperesthesia, and refusal to bear weight. CONCLUSION: The number of cases of severe gas disease has increased in the past several years, and gas infection should be included in the differential diagnosis of seriously ill children, gas infection must be managed aggressively with vigilance for additional deep tissue involvement, even while on appropriate antimicrobial therapy.

The Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of neonatal group B streptococcal infections in Canada.

OBJECTIVES: To determine the presentation and medical outcomes of neonatal group B streptococcus (GBS) disease in Canada, and describe maternal and obstetrical risk factors. DESIGN: Retrospective review of health records and laboratory databases using standardized data collection forms. SETTING: All neonates diagnosed with GBS infections in 1992 at 13 Canadian paediatric centres. RESULTS: A total of 105 infants meeting the criteria for neonatal GBS disease were identified. The majority of cases (78 or 74.3%) had early-onset disease (EOD); 78.9% (60 of 76) of these cases presented within 24 h of delivery. Rates of EOD (less than seven days) varied from 0.44/1000 live births to 2.1/1000 live births, with an overall rate of 1.2/1000 live births. Pneumonia was the most common clinical illness (43.8%), followed by bacteremia without focus (23.8%) and meningitis (16.2%). At least one maternal risk factor for neonatal GBS disease was noted in 46 of 78 (59%) infants with EOD. A median of one dose (range one to 23 doses) of intrapartum antibiotics was given in 18 of 75 (24%) of the pregnancies. Overall, the mean gestational age at birth was 36.2+/-4.7 weeks, with 38 of 96 (39.6%) infants having a gestational age at birth younger than 37 weeks (31 of 73 [42.5%] EOD cases were born with a gestational age younger than 37 weeks). The median birth weight was 3099 g (range 610 g to 4830 g). Thirty of 94 (31.9%) infants had a birth weight less than 2500 g. Seventeen (16.2%) infants died. CONCLUSIONS: In 1992, neonatal GBS disease was a significant cause of morbidity and mortality in Canadian infants. More than half of the cases identified in this study could have been potentially preventable by the use of intrapartum antibiotics for women with known risk factors. There is a need for prospective studies to better define risk factors and preventative measures for neonatal GBS infections in Canada.

MicroResearch: finding sustainable local health solutions in East Africa through small local research studies.

BACKGROUND: Sub-Saharan African countries have urged grassroots input to improve research capacity. In East Africa, MicroResearch is fostering local ability to find sustainable solutions for community health problems. At 5years, the following reports its progress. METHODS: The MicroResearch program had three integrated components: (1) 2-week training workshops; (2) small proposal development with international peer review followed by project funding, implementation, knowledge translation; (3) coaching from experienced researchers. Evaluation included standardized questions after completion of the workshops, 2013 online survey of recent workshop participants and discussions at two East Africa MicroResearch Forums in 2013. RESULTS: Between 2008 and 2013, 15 workshops were conducted at 5 East Africa sites with 391 participants. Of the 29 projects funded by MicroResearch, 7 have been completed; of which 6 led to changes in local health policy/practice. MicroResearch training stimulated 13 other funded research projects; of which 8 were external to MicroResearch. Over 90% of participants rated the workshops as excellent with 20% spontaneously noting that MicroResearch changed how they worked. The survey highlighted three local research needs: mentors, skills and funding - each addressed by MicroResearch. On-line MicroResearch and alumni networks, two knowledge translation partnerships and an East Africa Leaders Consortium arose from the MicroResearch Forums. CONCLUSION: MicroResearch helped build local capacity for community-directed interdisciplinary health research.

A harmonized immunization schedule for Canada: A call to action.

In Canada, the National Advisory Committee on Immunization systematically reviews the evidence for the effectiveness and safety of new and old vaccines, and sets a 'minimum' recommended schedule. However, in contrast to other industrialized countries where single, harmonized countrywide immunization schedules are de rigeur, Canada has a confusing system, with each province and territory defining its own schedule - and none are the same. The time has come to rectify this decades-old patient equity and safety problem. The Canadian Paediatric Society calls for a harmonized schedule to improve the health and safety of Canadian children and youth.

Home intravenous therapy: Accessibility for Canadian children and youth.

The administration of intravenous (IV) therapy at home is an alternative to hospitalization for treatment of infection and a number of other conditions, and has been demonstrated to be effective and safe, to reduce cost and to improve quality of life. While home IV therapy has many advantages for children, it is not uniformly available and access may be limited by age, geographical location and ability to pay. Physicians caring for children need to be aware of the indications for home IV therapy, its requirements and limitations, as well as whether this option is available for children in their care. Where access is limited, physicians should advocate for home IV therapy for children when it is medically indicated.

Meningococcal vaccines in Canada: An update.

Meningococcal infection is serious, often resulting in fulminant sepsis or meningitis. There are two main types of meningococcal conjugate vaccine currently available in Canada: serotype C meningococcal conjugate, and quadrivalent conjugate for serotypes A, C, Y, and W-135. The immunological characteristics that inform ongoing immunization policies, as well as some of the limits of current knowledge, are presented. All Canadian children should receive a conjugate meningococcal C vaccine (MCV-C) at 12 months of age, and either a booster dose of MCV-C or of quadrivalent meningococcal vaccine (MCV-4) in adolescence. Children at high risk of invasive meningococcal disease should start MCV-C at two months of age, and be given MCV-4 at two years of age.

A new meningococcal conjugate vaccine: What should physicians know and do?

A quadrivalent meningococcal conjugate vaccine for serogroups A, C, Y and W135 (MCV4 [Menactra, sanofi pasteur, Canada]) was introduced in Canada in 2007 for persons two years of age or older. MCV4 adds three serogroups to the meningococcal serogroup C conjugate vaccine, which has been used for several years. The rates of invasive meningococcal serogroup C infection have decreased over the past decade, attributable to the meningococcal C conjugate vaccine. However, the incidence of infection caused by serogroups A, B, Y and W135 have not changed substantially. MCV4 induces the production of protective antibodies to serogroups A, C, Y and W135 in adults and children older than two years of age. Serious adverse events from MCV4 are low. In view of the effectiveness of the meningococcal C conjugate vaccine for young infants and the historic high number of meningococcal serogroup C infections in Canada, physicians should encourage and promote publicly funded immunization programs for infants starting at two months of age. MCV4 should also be given to children aged two years who are at increased risk for meningococcal infection. MCV4 may also be considered for HIV-positive children two years of age or older. All adolescents should be offered a booster dose with MCV4 or a meningococcal C conjugate vaccine at approximately 12 years of age. Both vaccines are generally safe and well tolerated.