A phase IIa, randomized, double-blind, safety, immunogenicity and efficacy trial of Plasmodium falciparum vaccine antigens merozoite surface protein 1 and RTS,S formulated with AS02 adjuvant in healthy, malaria-naïve adults.

BACKGROUND: To improve the efficacy of Plasmodium falciparum malaria vaccine RTS,S/AS02, we conducted a study in 2001 in healthy, malaria-naïve adults administered RTS,S/AS02 in combination with FMP1, a recombinant merozoite surface-protein-1, C-terminal 42kD fragment. METHODS: A double-blind Phase I/IIa study randomized N = 60 subjects 1:1:1:1 to one of four groups, N = 15/group, to evaluate safety, immunogenicity, and efficacy of intra-deltoid half-doses of RTS,S/AS02 and FMP1/AS02 administered in the contralateral (RTS,S + FMP1-separate) or same (RTS,S + FMP1-same) sites, or FMP1/AS02 alone (FMP1-alone), or RTS,S/AS02 alone (RTS,S-alone) on a 0-, 1-, 3-month schedule. Subjects receiving three doses of vaccine and non-immunized controls (N = 11) were infected with homologous P. falciparum 3D7 sporozoites by Controlled Human Malaria Infection (CHMI). RESULTS: Subjects in all vaccination groups experienced mostly mild or moderate local and general adverse events that resolved within eight days. Anti-circumsporozoite antibody levels were lower when FMP1 and RTS,S were co-administered at the same site (35.0 µg/mL: 95 % CI 20.3-63), versus separate arms (57.4 µg/mL: 95 % CI 32.3-102) or RTS,S alone (62.0 µg/mL: 95 % CI: 37.8-101.8). RTS,S-specific lymphoproliferative responses and ex vivo ELISpot CSP-specific interferon-gamma (IFN-γ) responses were indistinguishable among groups receiving RTS,S/AS02. There was no difference in antibody to FMP1 among groups receiving FMP1/AS02. After CHMI, groups immunized with a RTS,S-containing regimen had âˆ¼ 30 % sterile protection against parasitemia, and equivalent delays in time-to-parasitemia. The FMP1/AS02 alone group showed no sterile immunity or delay in parasitemia. CONCLUSION: Co-administration of RTS,S and FMP1/AS02 reduced anti-RTS,S antibody, but did not affect tolerability, cellular immunity, or efficacy in a stringent CHMI model. Absence of efficacy or delay of patency in the sporozoite challenge model in the FMP1/AS02 group did not rule out efficacy of FMP1/AS02 in an endemic population. However, a Phase IIb trial of FMP1/AS02 in children in malaria-endemic Kenya did not demonstrate efficacy against natural infection. CLINICALTRIALS: gov identifier: NCT01556945.

The impact of multidisciplinary team decision-making in locally advanced and recurrent rectal cancer.

INTRODUCTION: Appropriate patient selection within the context of a multidisciplinary team (MDT) is key to good clinical outcomes. The current evidence base for factors that guide the decision-making process in locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) is limited to anatomical factors. METHODS: A registry-based, prospective cohort study was undertaken of patients referred to our specialist MDT between 2015 and 2019. Data were collected on patients and disease characteristics including performance status, Charlson Comorbidity Index, the English Index of Multiple Deprivation quintiles and MDT treatment decision. Curative treatment was defined as neoadjuvant treatment and surgical resection that would achieve a R0 resection, and/or complete treatment of distant metastatic disease. Palliative treatment was defined as non-surgical treatment. RESULTS: In total, 325 patients were identified; 72.7% of patients with LARC and 63.6% of patients with LRRC were offered treatment with curative intent (p = 0.08). Patients with poor performance status (PS > 2; p < 0.001), severe comorbidity (p < 0.001), socio-economic deprivation (p = 0.004), a positive predictive circumferential resection margin (p = 0.005) and metastatic disease (p < 0.001) were associated with palliative treatment. Overall survival in the curative cohort was 49 months (95% confidence interval [CI] 32.4-65.5) compared with 12 months (95% CI 9.1-14.9) in the palliative cohort (p < 0.001). The presence of metastatic disease was identified as a prognostic factor for patients undergoing curative treatment (p = 0.05). The only prognostic factor identified in patients treated palliatively was performance status (p < 0.001). CONCLUSIONS: Our study identifies a number of preoperative, prognostic factors that affect MDT decision-making and overall survival.

An unusual presentation of epigastric pain due to thrombophlebitis of a recanalised umbilical vein - case report.

INTRODUCTION: The umbilical vein can become recanalised due to portal hypertension in patients with liver cirrhosis but the condition is rarely clinically significant. Although bleeding from this enlarged vein is a known complication, the finding of thrombophlebitis has not been previously described. CASE REPORT: We report the case of a 62-year-old male with a history of liver cirrhosis due to alcoholic liver disease presenting to hospital with epigastric pain. A CT scan of the patients abdomen revealed a thrombus with surrounding inflammatory changes in a recanalised umbilical vein. The patient was managed conservatively and was discharged home the following day. CONCLUSION: Thrombophlebitis of a recanalised umbilical vein is a rare cause of abdominal pain in patients with liver cirrhosis.

Social deprivation in patients requiring pelvic exenterative surgery.

AIM: Pelvic exenteration is an aggressive operation for locally advanced rectal cancer. Social deprivation has been shown to reduce life expectancy and has been linked to a poorer outcome in patients with colorectal cancer. The aim of this study was to analyse the effect of social deprivation scores on the outcome in these complex patients. METHOD: A retrospective review of all patients undergoing pelvic exenteration for primary rectal cancer between 2006 and 2014 was performed. Deprivation scores were calculated for all patients using the Welsh Index of Multiple Deprivation. Patients were then grouped into quartiles, from Q1 (most deprived) to Q4 (least deprived). The primary outcome measure was 5-year survival. RESULTS: In all, 120 patients were included (65 female) with a median age of 64 (31-90) years. No differences between quartiles were identified for neoadjuvant therapy (P = 0.687) or type of exenteration (P = 0.690). The median length of stay was significantly higher in the most deprived groups (Q1-Q2; P = 0.023). There was a significant difference in survival between the groups, with lowest 5-year survival rates (53%) in the most deprived quartile (Q1) (P = 0.015). CONCLUSION: Social deprivation is significantly associated with postoperative length of stay and survival in patients undergoing pelvic exenteration for primary rectal cancer.

Practical guidelines for developing new palliative care services: resource management.

The data are relatively clear cut that palliative care improves quality of life and symptom control, improves quality of care by reducing aggressive but unsuccessful end of life care, and reduces costs. That should be an easy message to deliver to the public, health care administrators, payers, and governments. In fact, the arguments to develop palliative care services must be clear and concise, and make the clinical and financial case for the services that the palliative care team wants to deliver. Here, we discuss some of the types of models including consult services, outpatient programs, and inpatient units; the important components; some easy to use screening tools; components of the consultation team; a model medical record that increases "prompts" to do best palliative care; and data to report to supervisors.

Isolated metastatic primary peritoneal carcinoma to the breast: a rare site of disease recurrence.

Primary breast carcinoma is a common pathology in the UK. It can present with metastatic deposits but it is rare that lesions in the breast are the sole primary or secondary presentation for metastatic cancer from other sources. We present a case of a primary peritoneal cancer recurring after optimal treatment with a new breast lesion and the diagnostic difficulties that this can cause.

Varices of the round ligament mimicking an inguinal hernia--an important differential diagnosis during pregnancy.

Pregnancy is a recognised risk factor for the development of inguinal hernias due to an increase in intra-abdominal pressure. Whilst often managed conservatively until after the pregnancy, if the hernia presents acutely as a painful or tender groin lump, urgent or emergency repair may be required. Many clinicians rely heavily on clinical examination alone in order to diagnose the presence of such a hernia. In pregnancy, however, in order to prevent unnecessary surgery, the use of ultrasound has a more important role to play in reaching this diagnosis. We report a cautionary case that highlights the need for ultrasound evaluation of all painful groin lumps in pregnant women prior to considering surgery.

An implantable drug delivery system (IDDS) for refractory cancer pain provides sustained pain control, less drug-related toxicity, and possibly better survival compared with comprehensive medical management (CMM).

BACKGROUND: The randomized clinical trial of implantable drug delivery systems (IDDS) plus comprehensive medical management (CMM) versus CMM alone showed better clinical success at 4 weeks for IDDS patients. This 'as treated' analysis assessed if improvements in pain control, drug toxicity and survival were maintained over time. PATIENTS AND METHODS: We compared those who received IDDS with those who did not receive IDDS (non-IDDS). All patients had Visual Analogue Scores (VAS) for pain > or =5/10 on at least 200 mg morphine or equivalent daily. RESULTS: At 4 weeks, 46 of 52 (88.5%) IDDS patients achieved clinical success compared with 65 of 91 (71.4%; P=0.02) non-IDDS patients, and more often achieved > or =20% reduction in both pain VAS and toxicity [35 of 52 (67.3%) versus 33 of 91 patients (36.3%); P=0.0003]. By 12 weeks, 47 of 57 (82.5%) IDDS patients had clinical success compared with 35 of 45 (77.8%; P=0.55) non-IDDS patients, and more often had a > or =20% reduction in both pain VAS and toxicity [33 of 57 (57.9%) versus 15 of 45 patients (33.3%); P=0.01]. At 12 weeks the IDDS VAS pain scores decreased from 7.81 to 3.89 (47% reduction) compared with 7.21 to 4.53 for non-IDDS patients (42% reduction; P=0.23). The 12 week drug toxicity scores for IDDS patients decreased from 6.68 to 2.30 (66% reduction), and for non-IDDS patients from 6.73 to 4.13 (37% reduction; P=0.01). All individual drug toxicities improved with IDDS at both 4 and 12 weeks. At 6 months, only 32% of the group randomized to CMM and who did not cross over to IDDS were alive, compared with 52%-59% for patients in those groups who received IDDS. CONCLUSIONS: IDDS improved clinical success, reduced pain scores, relieved most toxicity of pain control drugs, and was associated with increased survival for the duration of this 6 month trial.

Are nurses adequately prepared for end-of-life care?

PURPOSE: To determine end-of-life (EOL) care core competencies and educational needs from practicing oncology nurses and to describe the characteristics of the respondents that are associated with selection of the leading core competencies. DESIGN AND METHODS: A researcher-developed mailed descriptive survey to members of the Oncology Nursing Society in Georgia, Virginia, Washington, and Wisconsin in late 1999. FINDINGS: Nearly all respondents indicated that EOL care was a part of their practice and that continuing education was important, but one-third of the respondents had less than 2 hours of continuing education in 2 years. How to talk to patients and families about dying was the top-rated core competency, consistent across age, educational level, practice role, and practice setting. Pain control and comfort care were also frequently selected as important EOL care issues about which more education is needed. CONCLUSIONS: Results show guidelines for improving educational curricula and considering characteristics of nurses when planning EOL educational programs.

Beyond the Supreme Court decision: nursing perspectives on end-of-life care.

PURPOSE/OBJECTIVES: To describe nurses' views of care of the terminally ill. DESIGN: Descriptive cross-sectional survey. SAMPLE: 300 nurses who completed a survey published in Nursing98 and Nursing Management and 2,033 nurses randomly selected from the Oncology Nursing Society (N = 2,333). METHODS: Mailed end-of-life (EOL) care survey. MAIN RESEARCH VARIABLES: Dilemmas, barriers, and effectiveness of EOL care and education and attitudes regarding assisted suicide and euthanasia. FINDINGS: EOL care dilemmas are common in nursing practice, and many barriers exist to providing quality EOL care. Issues of euthanasia and assisted suicide are particularly significant to nurses who struggle to provide pain and symptom relief amid a system characterized by deficiencies in EOL care. CONCLUSIONS: Improved care is contingent on adequate education of nurses as the primary caregivers of patients and families who are facing the end of life. Study findings provide direction for improved care of the terminally ill. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses are centrally involved in care of the terminally ill. Major reform is needed to provide quality EOL care.

Dignity in dying.

Barriers to effective end-of-life care encompass patient, professional, and system issues. Learn the findings of a landmark study on how well nurses meet the needs of dying patients.

Safety and efficacy of intravenous sodium stibogluconate in the treatment of leishmaniasis: recent U.S. military experience.

The efficacy and toxicity of sodium stibogluconate (SSG) at a dosage of 20 mg/(kg.d) for either 20 days (for cutaneous disease) or 28 days (for visceral, mucosal, or viscerotropic disease) in the treatment of leishmaniasis is reported. Ninety-six U.S. Department of Defense health care beneficiaries with parasitologically confirmed leishmaniasis were prospectively followed for 1 year. One patient was infected with human immunodeficiency virus; otherwise, comorbidity was absent. Clinical cure occurred in 91% of 83 cases of cutaneous disease and 93% of 13 cases of visceral/viscerotropic disease. Adverse effects were common and necessitated interruption of treatment in 28% of cases, but they were generally reversible. These included arthralgias and myalgias (58%), pancreatitis (97%), transaminitis (67%), headache (22%), hematologic suppression (44%), and rash (9%). No subsequent mucosal leishmaniasis was identified, and there were no deaths attributable to SSG or leishmaniasis.

The use of spinal opioids in cancer pain.

Approximately two-thirds of cancer patients suffer from significant pain. Until recently, less expensive and less costly conservative treatments have been utilized to treat these patients' pain, but the outcomes have been poor, with many experiencing inadequate pain relief. Although intraspinal opioid therapy is relatively new and more invasive than traditional treatments, it can provide most cancer patients better pain relief with less side effects. Intraspinal opioids can be used successfully to treat intractable malignant pain states.