Real-world study of the impact of recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) on quality of life and productivity in Europe.

BACKGROUND: Although current therapy for patients with early-stage squamous cell carcinoma of the head and neck (SCCHN) is potentially curative, the recurrence rate is high. Patients with recurrent or metastatic (R/M) SCCHN have a poor prognosis and substantial disease burden, including impaired health-related quality of life (HRQoL), productivity loss and indirect costs, such as need for caregiver support. The aim of this study was to characterize the impact of R/M SCCHN and its first-line treatment on patient and caregiver quality of life, daily activities and work productivity using real-world evidence from Europe. METHODS: This was a multicentre retrospective study of patients with R/M SCCHN in France, Germany, Italy, Spain and the United Kingdom incorporating patient and caregiver surveys, and a physician-reported medical chart review, conducted between January and May 2019. Patients aged 18 or over with a physician confirmed diagnosis R/M SCCHN completed four validated measures of disease activity and its impact on quality of life and work productivity, while caregivers also completed questionnaire to assess the burden of providing care. Physicians provided data for clinical characteristics, patient management, testing history and treatment patterns. RESULTS: A total of 195 medical/clinical oncologists provided data for 937, predominantly male (72%) patients, with almost half of patients aged over 65 years. The most frequently reported symptoms were fatigue (43%), weight loss (40%), pain (35%) and difficulty swallowing (32%). The EXTREME regimen was the most common first line therapy in over half of patients, who reported moderate or extreme pain/discomfort, and anxiety/depression, and problems with self-care resulting in a diminished health status compared with the general population. Only 14% were employed with high absenteeism or presenteeism, and over half of patients had a caregiver for whom the burden of care was substantial. CONCLUSION: Our results provide real-world insight into the multi-faceted burden associated with R/M SCCHN. The combination of poor HRQoL and the impairment in daily activities, social life and employment illustrates the wider impact of R/M SCCHN on patients and their caregivers, and highlights a need for novel 1 L treatment regimens to improve the humanistic and productivity burdens of this cancer.

Toward Point-of-Care Drug Quality Assurance in Developing Countries: Comparison of Liquid Chromatography and Infrared Spectroscopy Quantitation of a Small-Scale Random Sample of Amoxicillin.

Substandard antibiotics are thought to be a major threat to public health in developing countries and a cause of antimicrobial resistance. However, assessing quality outside of a laboratory setting, using simple equipment, is challenging. The aim of this study was to validate the use of a portable Fourier transform infrared (FT-IR) spectrometer for the identification of substandard antibiotics. Results are presented for amoxicillin packages from Haiti, Ghana, Sierra Leone, Democratic Republic of Congo, India, Papua New Guinea, and Ethiopia collected over the course of 6 months in 2017, including two field trips with the FT-IR to Ghana and Sierra Leone. Canadian samples were used as a control. Regarding drug quality, of 290 individual capsules of amoxicillin analyzed, 13 were found to be substandard with total active pharmaceutical ingredients (API) lying outside the acceptable range of 90-110%. Of these 13, four were below 80% API. The FT-IR reliably identified these outliers and was found to yield results in good agreement with the established pharmacopeia liquid chromatography protocol. We conclude that the portable FT-IR may be suitable to intercept substandard antibiotics in developing countries where more sophisticated techniques are not readily available.

Novice clinical nurse educator's experience of a self-directed learning, education and mentoring program: a qualitative study.

BACKGROUND: Transition from a registered nurse to a clinical nurse educator (CNE) poses several challenges. Providing professional development opportunities to ease the transition from a registered nurse to a CNE is considered critical to a successful career and to effectively teach. A self-directed educational program and mentoring (SEM) program was designed and implemented to support nurse's transition from a novice to a confident CNE. AIMS: The aim of this study was to explore novice CNE's experience of learning and being mentored. DESIGN: Qualitative methodology was undertaken to conduct focus groups. METHODS: All CNEs who completed the SEM program were invited to participate in the study. Willing participants provided informed consent to complete an in-depth semi-structured focus group and to record the focus group interview. Focus groups were facilitated by an independent researcher. A second researcher attended the focus groups to collect detailed notes. Data were transcribed verbatim and participants were de-identified. Simple thematic analyses were undertaken. RESULTS: A total of 11 (58%) CNEs participated in the focus groups. Overall participants described their experience of the SEM program as positive. Three themes were identified: (1) perceived transformation of CNE practice, (2) beneficial relationships and (3) feeling connected. Mentoring relationships for some participants have continued beyond the self-directed learning, education and mentoring program. Barriers to the mentoring program included a theme of lack of time, role ambiguity and insufficient face to face education. CONCLUSIONS: Study findings highlight the benefits of providing professional development opportunities and mentoring programs for novice CNEs. Programs, such as the SEM enable transformation of a novice educator's practice, and the consolidation of new knowledge, skills and confidence to effectively educate less experienced nurses.

Exploring the experiences of neophyte nurse mentors: A qualitative study.

Mentoring has become an increasingly popular supportive method for empowering nurses and assisting them to progress in their careers. Evidence from the literature demonstrates that not all experienced and highly qualified nurses are effective mentors. The aim of this study was to explore and describe the experiences of neophyte nurse mentors following their first formal mentoring relationship using a qualitative exploratory design. Data were collected using dual moderated focus group methods. The focus group was digitally recorded and transcribed verbatim. Interviews were analysed using thematic analysis. Six neophyte nurse mentors participated in the focus group. The themes identified included (1) Readiness for mentoring, (2) Venturing into the unknown, (3) Having the right fit (4) Frustrations of mentoring (5) Reciprocal professional relationship. The findings highlight how neophyte nurse mentors perceive mentoring and the importance of providing them with adequate preparation and support in order to efficiently transfer valuable knowledge and skills to their mentees.

An Analysis of Substandard Propofol Detected in Use in Zambian Anesthesia.

BACKGROUND: In early 2015, clinicians throughout Zambia noted a range of unpredictable adverse events after the administration of propofol, including urticaria, bronchospasm, profound hypotension, and most predictably an inadequate depth of anesthesia. Suspecting that the propofol itself may have been substandard, samples were procured and sent for testing. METHODS: Three vials from 2 different batches were analyzed using gas chromatography-mass spectrometry methods at the John L. Holmes Mass Spectrometry Facility. RESULTS: Laboratory gas chromatography-mass spectrometry analysis determined that, although all vials contained propofol, its concentration differed between samples and in all cases was well below the stated quantity. Two vials from 1 batch contained only 44% ± 11% and 54% ± 12% of the stated quantity, whereas the third vial from a second batch contained only 57% ± 9%. The analysis found that there were no hexane-soluble impurities in the samples. CONCLUSIONS: None of the analyzed vials contained the stated amount of propofol; however, our analysis did not detect additional contaminants that would explain the adverse events reported by clinicians. Our results confirm the presence of substandard propofol in Zambia; however, anecdotal accounts of substandard anesthetic medicines in other countries abound and warrant further investigation to provide estimates of the prevalence and scope of this global problem.

Fatal Bacterial Meningitis Possibly Associated with Substandard Ceftriaxone--Uganda, 2013.

The burden of disease from bacterial meningitis is highest in low-income countries (1). Early initiation of antibiotic therapy is important in reducing the risk for mortality. Current treatment guidelines recommend the use of an expanded-spectrum cephalosporin (cefotaxime or ceftriaxone) (2), but these therapies increasingly are limited by drug resistance, and are threatened by the proliferation of substandard and falsified medicines (3,4). In February 2013, a case of bacterial meningitis following a middle ear infection was diagnosed in an adolescent at the Mulago National Referral Hospital in Kampala, Uganda. Once-daily treatment with 2 g of intravenous ceftriaxone administered according to guidelines failed, and the patient died. To determine whether the patient's treatment failure and subsequent death might be related to the ceftriaxone product administered, a sealed vial similar to the one administered to the patient was analyzed at the University of Ottawa, Canada, and was found to contain only 0.455 g of the drug, not 1 g as stated by the manufacturer. This would have resulted in subtherapeutic dosing. Substandard medicines are a global problem that disproportionately affects low-income countries, leading to fatal consequences and promoting the emergence of drug resistance (4).

Epicuticular compounds of Drosophila subquinaria and D. recens: identification, quantification, and their role in female mate choice.

The epicuticle of various Drosophila species consists of long-chain cuticular hydrocarbons (CHCs) and their derivatives that play a role in waterproofing and a dynamic means of chemical communication. Here, via gas chromatography and mass spectrometry, we identified and quantified the epicuticular composition of D. recens and D. subquinaria, two closely related species that show a pattern of reproductive character displacement in nature. Twenty-four compounds were identified with the most abundant, 11-cis-Vaccenyl acetate, present only in males of each species. Also exclusive to males were five tri-acylglycerides. The 18 remaining compounds were CHCs, all shared between the sexes and species. These CHCs were composed of odd carbon numbers (C29, C31, C33, and C35), with an increase in structural isomers in the C33 and C35 groups. Saturated hydrocarbons comprise only methyl-branched alkanes and were found only in the C29 and C31 groups. Alkenes were the least prevalent, with alkadienes dominating the chromatographic landscape in the longer chain lengths. Sexual dimorphism was extensive with 6/8 of the logcontrast CHCs differing significantly in relative concentration between males and females in D. recens and D. subquinaria, respectively. Males of the two species also differed significantly in relative concentration of six CHCs, while females differed in none. Female-choice mating trials revealed directional sexual selection on male CHCs in a population of each species, consistent with female mate preferences for these traits. The sexual selection vectors differed significantly in multivariate trait space, suggesting that different pheromone blends determine male attractiveness in each species.

Reactions of atomic metal anions in the gas phase: competition between electron transfer, proton abstraction and bond activation.

Bare metal anions K(-), Rb(-), Cs(-), Fe(-), Co(-), Ni(-), Cu(-), and Ag(-), generated by electrospray ionization of the corresponding oxalate or tricarballylate solutions, were allowed to react with methyl and ethyl chloride, methyl bromide, nitromethane, and acetonitrile in the collision hexapole of a triple-quadrupole mass spectrometer. Observed reactions include (a) the formation of halide, nitride, and cyanide anions, which was shown to be likely due to the insertion of the metal into the C-X, C-N, and C-C bonds, (b) transfer of H(+) from the organic molecule, which is demonstrated to most likely be due to the simple transfer of a proton to form neutral metal hydride, and (c) in the case of nitromethane, direct electron transfer to form the nitromethane radical anion. Interestingly, Co(-) was the only metal anion to transfer an electron to acetonitrile. Differences in the reactions are related to the differences in electron affinity of the metals and the Δ(acid)H° of the metals and organic substrates. Density functional theory calculations at the B3-LYP/6-311++G(3df,2p)//B3-LYP/6-31+G(d) level of theory shed light on the relative energetics of these processes and the mechanisms by which they take place.

Old acid, new chemistry. Negative metal anions generated from alkali metal oxalates and others.

A brief search in Sci Finder for oxalic acid and oxalates will reward the researcher with a staggering 129,280 hits. However, the generation of alkali metal and silver anions via collision-induced dissociation of the metal oxalate anion has not been previously been reported, though Tian and coworkers recently investigated the dissociation of lithium oxalate. The exothermic decomposition of alkali metal oxalate anion to carbon dioxide in the collision cell of a triple quadrupole mass spectrometer leaves no place for the electron to reside, resulting in a double electron-transfer reaction to produce an alkali metal anion. This reaction is facilitated by the negative electron affinity of carbon dioxide and, as such, the authors believe that metal oxalates are potentially unique in this respect. The observed dissociation reactions for collision with argon gas (1.7-1.8 × 10(-3) mbar) for oxalic acid and various alkali metal oxalates are discussed and summarized. Silver oxalate is also included to demonstrate the propensity of this system to generate transition-metal anions, as well.

A systematic shift in the electronic spectra of substituted benzene molecules trapped in helium nanodroplets.

Electronic spectra (S1<--S0) have been recorded from five separate substituted benzene derivatives trapped in helium nanodroplets. Each member of the series is found to exhibit a blueshift with respect to the equivalent transition in the gas phase. Taken together with previous results for benzene, the observed shifts show a remarkably good correlation with changes in electron density that occur within each of the aromatic rings as a result of electronic excitation.

Solvent coordination in gas-phase [Mn.(H(2)O)(n)](2+) and [Mn.(ROH)(n)](2+) complexes: theory and experiment.

An experimental gas-phase study of the intensities and fragmentation patterns of [Mn.(H(2)O)(n)](2+) and [Mn.(ROH)(n)](2+) complexes shows the combinations [Mn.(H(2)O)(4)](2+) and [Mn.(ROH)(4)](2+) to be stable. Evidence in complexes involving the alcohols methanol, ethanol, 1-propanol, and 2-propanol favors preferential fragmentation to [Mn.(ROH)(4)](2+), whereas the fragmentation data for water is less clear. Supporting density functional calculations show that both [Mn.(H(2)O)(4)](2+) and [Mn.(MeOH)(4)](2+) adopt stable tetrahedral configurations, similar to those proposed for biochemical systems where solvent availability and coordination is restricted. Calculated incremental binding energies show a gradual decline on going from one to six solvent molecules, with a step occurring between four and five molecules. The addition of further solvent molecules to the stable [Mn.(MeOH)(4)](2+) unit shows a preference for [Mn.(MeOH)(4)(MeOH)(1,2)](2+) structures, where the extra molecules occupy hydrogen-bonded sites in the form of a secondary solvation shell. Very similar behavior is seen on the part of water. As part of an analysis of the experimental data, the calculations have explored the influence different spins states of Mn(2+) have on solvent geometry. It is concluded that the experimental observations are best reproduced when the central Mn(2+) ion is in the high-spin (6)S ground state. The results are also considered in terms of the biochemical activity of Mn(2+) where the ion is capable of isomorphous substitution with Zn(2+), which itself exhibits a preference for tetrahedral coordination.