EV-301 long-term outcomes: 24-month findings from the phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma.

INTRODUCTION: This exploratory analysis evaluated efficacy and safety data for enfortumab vedotin versus chemotherapy over a median follow-up of ∼2 years from EV-301. MATERIALS AND METHODS: Patients with locally advanced/metastatic urothelial carcinoma with prior platinum-containing chemotherapy and disease progression during/after programmed cell death protein 1/ligand 1 inhibitor treatment were randomized to enfortumab vedotin or chemotherapy (docetaxel, paclitaxel, vinflunine). Endpoints were overall survival (primary), progression-free survival (PFS), objective response, and safety. RESULTS: In total, 608 patients were included (enfortumab vedotin, n = 301; chemotherapy, n = 307). With a median follow-up of 23.75 months, 444 deaths had occurred (enfortumab vedotin, n = 207; chemotherapy, n = 237). Risk of death was reduced by 30% with enfortumab vedotin versus chemotherapy [hazard ratio (HR) 0.70 (95% confidence interval [CI] 0.58-0.85); one-sided, log-rank P = 0.00015]; PFS improved with enfortumab vedotin [HR 0.63 (95% CI 0.53-0.76); one-sided, log-rank P < 0.00001]. Treatment-related adverse event rates were 93.9% for enfortumab vedotin and 91.8% for chemotherapy; grade ≥ 3 event rates were 52.4% and 50.5%, respectively. Grade ≥ 3 treatment-related decreased neutrophil count (14.1% versus 6.1%), decreased white blood cell count (7.2% versus 1.4%), and anemia (7.9% versus 2.7%) were more common with chemotherapy versus enfortumab vedotin; maculopapular rash (7.4% versus 0%), fatigue (6.8% versus 4.5%), and peripheral sensory neuropathy (5.1% versus 2.1%) were more common with enfortumab vedotin. Of special interest adverse events, treatment-related skin reactions occurred in 47.3% of patients receiving enfortumab vedotin and 15.8% of patients receiving chemotherapy; peripheral neuropathy occurred in 48.0% versus 31.6%, respectively, and hyperglycemia in 6.8% versus 0.3%. CONCLUSIONS: After a median follow-up of ∼2 years, enfortumab vedotin maintained clinically meaningful overall survival benefit versus chemotherapy, consistent with findings from the EV-301 primary analysis; PFS and overall response benefit remained consistent. Adverse events were manageable; no new safety signals were observed.

The COVID-19 pandemic: the public health reality.

The coronavirus disease (COVID-19), while mild in most cases, has nevertheless caused significant mortality. The measures adopted in most countries to contain it have led to colossal social and economic disruptions, which will impact the medium- and long-term health outcomes for many communities. In this paper, we deliberate on the reality and facts surrounding the disease. For comparison, we present data from past pandemics, some of which claimed more lives than COVID-19. Mortality data on road traffic crashes and other non-communicable diseases, which cause more deaths each year than COVID-19 has so far, is also provided. The indirect, serious health and social effects are briefly discussed. We also deliberate on how misinformation, confusion stemming from contrasting expert statements, and lack of international coordination may have influenced the public perception of the illness and increased fear and uncertainty. With pandemics and similar problems likely to re-occur, we call for evidence-based decisions, the restoration of responsible journalism and communication built on a solid scientific foundation.

Chronic therapy with selective serotonin reuptake inhibitors and survival in newly diagnosed cancer patients.

Depression might be associated with shorter disease specific survival. Selective serotonin reuptake inhibitors (SSRIs) were previously reported to increase the risk of certain malignancies. We aimed to evaluate the impact of SSRIs on cancer mortality. Five retrospective cohort studies were conducted in a UK population-representative database that included all individuals with an incident diagnosis of melanoma, breast, prostate lung and colorectal cancer. The primary exposure of interest was continuous use of SSRIs with past use as the comparison reference. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). The study included 5,591 newly diagnosed cancer patients. Continuous SSRI use was associated with lower survival compared to past users for melanoma, breast, prostate, lung and colorectal cancers with HRs for the risk of death of 2.02 (95% CI 1.24-3.28), 1.91 (95% CI 1.53-2.38), 1.79 (95% CI 1.38-2.33), 1.44 (95% CI 1.19-1.75) and 1.51 (95% CI 1.21-1.72) respectively. The incidence of death during the first 2 years following cancer diagnosis associated with continuous SSRI use were elevated for breast (1.72, 95% CI 1.30-2.27), prostate (1.64, 95% CI 1.20-2.24) and lung cancers (1.45, 95% CI 1.26-1.66). In conclusion, continuous use of SSRIs might be associated with lower survival in cancer patients.

Efficacy of the nanoparticle-drug conjugate CRLX101 in combination with bevacizumab in metastatic renal cell carcinoma: results of an investigator-initiated phase I-IIa clinical trial.

BACKGROUND: Anti-angiogenic therapies are effective in metastatic renal cell carcinoma (mRCC), but resistance is inevitable. A dual-inhibition strategy focused on hypoxia-inducible factor (HIF) is hypothesized to be active in this refractory setting. CRLX101 is an investigational camptothecin-containing nanoparticle-drug conjugate (NDC), which durably inhibits HIF1α and HIF2α in preclinical models and in gastric cancer patients. Synergy was observed in the preclinical setting when combining this NDC and anti-angiogenic agents, including bevacizumab. PATIENTS AND METHODS: Patients with refractory mRCC were treated every 2 weeks with bevacizumab (10 mg/kg) and escalating doses of CRLX101 (12, 15 mg/m(2)) in a 3 + 3 phase I design. An expansion cohort of 10 patients was treated at the recommended phase II dose (RP2D). Patients were treated until progressive disease or prohibitive toxicity. Adverse events (AEs) were assessed using CTCAE v4.0 and clinical outcome using RECIST v1.1. RESULTS: Twenty-two patients were response-evaluable in an investigator-initiated trial at two academic medical centers. RCC histologies included clear cell (n = 12), papillary (n = 5), chromophobe (n = 2), and unclassified (n = 3). Patients received a median of two prior therapies, with at least one prior vascular endothelial tyrosine kinase inhibitor therapy (VEGF-TKI). No dose-limiting toxicities were observed. Grade ≥3 AEs related to CRLX101 included non-infectious cystitis (5 events), fatigue (3 events), anemia (2 events), diarrhea (2 events), dizziness (2 events), and 7 other individual events. Five of 22 patients (23%) achieved partial responses, including 3 of 12 patients with clear cell histology and 2 of 10 patients (20%) with non-clear cell histology. Twelve of 22 patients (55%) achieved progression-free survival (PFS) of >4 months. CONCLUSIONS: CRLX101 combined with bevacizumab is safe in mRCC. This combination fulfilled the protocol's predefined threshold for further examination with responses and prolonged PFS in a heavily pretreated population. A randomized phase II clinical trial in mRCC of this combination is ongoing.

Herbal and nutritional supplement use among college students in Qatar.

There is increasing demand for herbal and nutritional supplements in the Middle East. This study aimed to examine the use of supplements by college students in Qatar and to elucidate users' views about them. A total of 419 college students completed a self-administered questionnaire. Almost half of the respondents (49.6%) had used supplements (ever users), with 32.7% reporting using them in the previous 6 months (current users). Of the latter, 27.7% had used herbal supplements, 56.2% vitamins and minerals and 56.9% non-vitamin, non-mineral, non-herbal supplements. Many participants considered supplements to be safer and more effective than conventional medicines. Supplements were preferred over conventional medicines for the treatment of digestive conditions and common respiratory ailments and for weight management. Educating health-care providers about the benefits and risks of supplements is imperative and will enable health-care practitioners to guide patients in making informed decisions about supplement use.

Use of complementary and alternative medicine among midlife Arab women living in Qatar.

The prevalence of use of complementary and alternative medicine (CAM) is widespread and is growing worldwide. This cross-sectional study in Qatar examined the use of CAM and its correlates among Arab women in their midlife years. Women aged 40-60 years (n = 814) were recruited at primary care centres in Qatar and completed a specially designed, pre-tested questionnaire. Overall, 38.2% of midlife women in Qatar had used CAM in the previous 12 months. Nutritional remedies and herbal remedies were the most commonly used CAM therapies, followed by physical methods. Qatari nationality and higher level of education were independently associated with CAM use. Menopause transition status was not independently associated with use of CAM. The prevalence of CAM use by women in Qatar was high, consistent with other reports worldwide. It is essential to educate and inform patients and health-care providers about the benefits and limitations associated with CAM.

Lymph node evaluation and survival after curative-intent resection of duodenal adenocarcinoma: A matched cohort study.

BACKGROUND: Lymph node (LN) metastasis in patients with duodenal adenocarcinoma is associated with poor prognosis; however, the optimal extent of LN assessment and the interaction between LN assessment and adjuvant systemic therapy is poorly understood. METHODS: Resected non-metastatic duodenal adenocarcinoma patients (n = 1743) were identified in the National Cancer Database (1998-2011). Logistic regression analysis identified covariates associated with LN metastasis. The influence of increasing LN cut-off points on overall survival (OS) was analysed using the log-rank test and Cox proportional hazards modelling. Adjuvant chemotherapy (AC) and surgery alone cohorts were matched (1:1) by propensity scores based on the likelihood of nodal metastasis or survival hazard on Cox modelling. OS in the matched cohort was compared by Kaplan-Meier estimates. RESULTS: LN metastases were present in 865 (49.6%) patients. Increasing LN assessment was associated with an increased likelihood of nodal involvement (P = 0.008). In node-negative patients, increasing LN assessment was associated with a decreased risk of death, with the largest actuarial survival differences observed for ≥15 LN (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.48-0.82, P = 0.001). In the propensity score-matched cohort of node-negative patients, AC was associated with non-significant improvements in 5-year actuarial (66.1% versus 58.7%, HR 0.79, 95% CI 0.53-1.18, P = 0.249), and did not vary by adequacy of LN counts (<15 LNs: HR 0.79, 95% CI 0.51-1.24, P = 0.305; ≥15 LNs: HR 0.90, 95% CI 0.35-2.30, P = 0.900). CONCLUSIONS: The extent of LN identification has prognostic significance in resected node-negative duodenal adenocarcinoma, but cannot be implicated in the selection of node-negative patients for AC.

A comparative study of urban and rural tetanus in adults.

An analysis of 240 patients, aged 15+, admitted to the tetanus ward of Irwin Hospital, New Delhi, with clinically diagnosed tetanus is reported. 134 patients (55.8%) came from rural areas and 106 (44.2%) from urban areas. The male--female ratio for both groups was approximately 2:1. Rural patients were younger, showed a longer incubation period and experienced a lower crude case fatality rate. Traditional practices like the application of cow dung to wounds, ear piercing and tatooing, and chronic ear infections were important factors in developing tetanus, demonstrating a need for health education in rural communities.

Comparison of total costs of administering calcium polycarbophil and psyllium mucilloid in an institutional setting.

The total cost of administering calcium polycarbophil per unit dose (two tablets) was compared with that of administering psyllium mucilloid (one packet dissolved in 8 oz of water) in 20 elderly nursing-home residents. Times for printing labels, checking and initialing labels, gathering materials needed, and preparing and administering the medications were recorded during at least 50 observations in each treatment group. Total cost included nurses' and pharmacists' time, materials, and medications. Calcium polycarbophil doses were prepared and administered more quickly (mean, 49.5 sec) than psyllium mucilloid (105.3 sec). The mean cost of preparing and administering a unit dose was 28.2 for calcium polycarbophil tablets and 59.9 for psyllium mucilloid. The results suggest that the use of calcium polycarbophil tablets would save time and money in institutions in which laxatives are frequently administered.

Hospitalized advanced cancer patients: a profile.

More than half of all individuals diagnosed with cancer will not be cured and will require supportive care for some period. Nonetheless, few large scale studies have documented the prevalence and complexity of the problems of advanced disease. This study examined the demographic treatment and outcome variables for 1,103 admissions to a specialty acute care hospital devoted to the care of patients with advanced cancer. The population is profiled, and significant relationships among these variables are identified. The prevalence of major symptoms is documented. This data base study provides a foundation for further research.

Use of alternative therapies by a low income population.

Patients in a family health center clinic were surveyed about their use of alternative/complementary medicine. These were mostly low-income individuals on Medicaid. The aim was to estimate prevalence and patterns of use of medically unconventional therapies such as chiropractic, homeopathy, and acupuncture in this population. Nearly two hundred patients (N = 199) filled out questionnaires inquiring about medical conditions and illnesses, personal health habits (physical activity, tobacco smoking, alcohol intake, etc.), and use of preventive measures or therapies that are neither taught widely in US medical schools nor generally available in US hospitals, and which we refer to as 'alternative' therapies (ATs). The term 'alternative' is not intended to imply that ATs are necessarily chosen to replace, rather than to be used in combination with standard treatments, although that may indeed be so in specific cases. Twenty-nine percent of respondents (58/199) reported using at least one type of AT, as defined for the purposes of the survey. Frequency of use varied somewhat, with greatest AT use reported by those over 29 years of age with more education and higher incomes (p < 0.10, defined as chi 2 tests at p < 0.10). While no significant differences were found between AT users and nonusers with respect to exercise participation, alcohol intake or smoking, there was a difference with respect to the reporting of at least one medical condition (p < 0.01). Among those who have used ATs, 90% reported more than one medical condition. Of those reporting no AT use, 70% indicated only a single medical condition for which they had sought treatment. In conclusion, use of alternative therapy (AT) appears to be common in all socio-economic groups, although AT use is apparently slightly less among low-income persons than in the general population. It is therefore important for physicians and other medical providers to be aware that their patients may be using ATs. Obviously, such practices should be taken into account in case management.

Alternative approaches to the medical management of angina pectoris: acupuncture, electrical nerve stimulation, and spinal cord stimulation.

Complementary or alternative modalities of medical treatment have been gaining attention as primary or supplementary therapies in cardiovascular disease pain management. However, definitive research in these areas has been limited by the inability to perform placebo-controlled trials when evaluating these treatments. Preliminary studies have suggested a possible benefit from acupuncture, electrical nerve stimulation, and spinal cord stimulation in the treatment of patients with angina pectoris and coronary artery disease.

Use of intravenous methylprednisolone in acute idiopathic thrombocytopenic purpura.

Twenty newly diagnosed children with acute idiopathic thrombocytopenic purpura (ITP) with a platelet count (PC) of less than 20,000 were treated with intravenous methyl prednisolone (IVMP) 5 mg/kg/day in four divided doses until the platelet count increased to 50,000/mm3. They were then placed on oral prednisone at conventional doses for a total of three weeks of steroid therapy. The platelet counts increased by an average of 55,000/mm3 within 48 h of treatment. Within 72 h (day 3) of treatment all patients achieved a PC of greater than 20,000/mm3. By day 5, all 20 patients achieved a PC of greater than 50,000. IVMP is highly effective in rapidly raising the PC in acute ITP above the critical level of 20,000, thereby reducing the duration of risk for intracranial hemorrhage (ICH).

Malignant lymphomas in a population at risk for acquired immune deficiency syndrome.

Certain neoplasia are closely associated with acquired immune deficiency syndrome (AIDS). To evaluate this relationship the authors reviewed the occurrence of lymphomas in populations at high risk for AIDS; the study population included prisoners from New York State and nonprisoner intravenous drug abusers (IVDA). Non-Hodgkin's lymphoma was diagnosed in 16 prisoners, all of whom were IVDA, and four nonprisoner IVDA. The observed number of prisoners with non-Hodgkin's lymphoma (11) diagnosed between January 1, 1981 and December 12, 1984, significantly greater than the expected number (2.28) based on age adjusted incidence rates for the US population (P less than 0.001). The calculated average incidence rate for non-Hodgkin's lymphoma among New York State prisoners aged 20 to 49 years was 21.5/10(5) to 67.2/10(5), which was nearly sixfold to 18-fold higher than the general population. For prisoner IVDA, specifically, this incidence may be as high as 164/10(5), which represents a 40-fold increase in the relative risk compared with the general population. It is concluded that, non-Hodgkin's lymphoma is frequently a manifestation of AIDS among IVDA, and is the most common malignancy seen in IVDA with AIDS.