Clinical presentation, treatment, and outcome of 24 dogs with bacterial meningitis or meningoencephalitis without empyema (2010-2020).

BACKGROUND: Bacterial meningitis (BM) and meningoencephalitis (BMEM) are associated with high case fatality rates and neurologic sequelae in people, but limited data exists on outcome in dogs. HYPOTHESIS/OBJECTIVES: To report the clinicopathologic features, treatment and outcome of BM/BMEM in dogs, with a focus on clinical presentation, relapse and long-term neurological deficits. ANIMALS: Twenty-four client-owned dogs diagnosed with BM/BMEM without empyema. METHODS: Retrospective case series of dogs diagnosed with BM/BMEM from 5 veterinary referral hospitals between January 2010 and August 2020. RESULTS: Twenty-four dogs were included. Median duration of clinical signs was 2 days (range ≤24 hours to 30 days) and signs recorded included pyrexia (3) and cervical hyperesthesia (10). Neurological deficits were present in 18 dogs including altered mentation (12), ataxia (8), nonambulatory status (8), head tilt (8), and cranial nerve deficits (13). Intracellular bacteria were visualized on cerebrospinal fluid (CSF) analysis in 15/24 dogs, with positive CSF bacteriological culture in 8/21. Otitis media/interna (OMI) was diagnosed in 15/24 dogs, of which 6/15 dogs underwent total ear canal ablation and lateral bulla osteotomy. Twenty dogs survived to hospital discharge. Median duration of antibiotic administrations was 8 weeks (range, 2-16 weeks). Glucocorticoids were administered to 15 dogs. Median follow-up time was 92 days (range, 10-2233 days). Residual neurological deficits were reported in 9 dogs, with a single case of suspected relapse. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical signs were variable in dogs with BM/BMEM, the nidus of bacterial infection was often OMI and the majority of dogs made a full recovery with treatment.

Surveillance of Lung Cancer and Mesothelioma Patients With Noncurative Treatment Intent: A Narrative Review.

BACKGROUND: Lung cancer patients with advanced disease and no active treatment options currently face frequent follow-up visits to outpatient clinics, associated with significant anxiety, time commitment, and costs. Visits also place considerable strain on the health system. Evidence from other cancers and chronic health conditions suggests virtual or remote follow-up can lead to higher patient satisfaction without negatively impacting health outcomes such as survival time. OBJECTIVE: The aim of this review was to identify patient preferences for, and any evidence of relative effectiveness of, different surveillance protocols for patients who have noncurative treatment intent for lung cancer or mesothelioma. INTERVENTIONS/METHODS: MEDLINE, PubMed, and CINAHL Plus databases were searched for articles published between 1998 and June 2018. The search was restricted to English-language publications and included all original research. RESULTS: Nine studies met the inclusion criteria, with most studies being retrospective. Findings identified the need for reassurance and hope as part of surveillance, the importance of trust and relationship, and the lack of consistency and evidence around frequency and method of surveillance models. CONCLUSIONS: Current surveillance is based on expert opinion with little consideration of patient preferences, quality of life, impact on anxiety, and impact on survival outcomes. IMPLICATIONS FOR PRACTICE: Nurses play a key role in managing surveillance programs for noncurative lung cancer patients. Programs should be built using codesign approaches to ensure best outcomes. Further research needs to be conducted, ensuring directed surveillance models that meet the holistic needs of patients.

Development, testing and validation of a SARS-CoV-2 multiplex panel for detection of the five major variants of concern on a portable PCR platform.

Many SARS-CoV-2 variants have emerged during the course of the COVID-19 pandemic. These variants have acquired mutations conferring phenotypes such as increased transmissibility or virulence, or causing diagnostic, therapeutic, or immune escape. Detection of Alpha and the majority of Omicron sublineages by PCR relied on the so-called S gene target failure due to the deletion of six nucleotides coding for amino acids 69-70 in the spike (S) protein. Detection of hallmark mutations in other variants present in samples relied on whole genome sequencing. However, whole genome sequencing as a diagnostic tool is still in its infancy due to geographic inequities in sequencing capabilities, higher cost compared to other molecular assays, longer turnaround time from sample to result, and technical challenges associated with producing complete genome sequences from samples that have low viral load and/or high background. Hence, there is a need for rapid genotyping assays. In order to rapidly generate information on the presence of a variant in a given sample, we have created a panel of four triplex RT-qPCR assays targeting 12 mutations to detect and differentiate all five variants of concern: Alpha, Beta, Gamma, Delta, and Omicron. We also developed an expanded pentaplex assay that can reliably distinguish among the major sublineages (BA.1-BA.5) of Omicron. In silico, analytical and clinical testing of the variant panel indicate that the assays exhibit high sensitivity and specificity. This panel can help fulfill the need for rapid identification of variants in samples, leading to quick decision making with respect to public health measures, as well as treatment options for individuals. Compared to sequencing, these genotyping PCR assays allow much faster turn-around time from sample to results-just a couple hours instead of days or weeks.

Cancer care in a time of COVID: lung cancer patient's experience of telehealth and connectedness.

OBJECTIVE: To explore lung cancer patient's experiences of telehealth during COVID-19 restrictions. METHODS: Thirty patients with lung cancer were recruited. Data was collected using a qualitative exploratory design with semi-structured interviews. Transcripts were thematically coded using NVivo software. RESULTS: Five key themes were identified: maintaining resilience, participants acknowledged that they were self-reliant prior to their diagnosis and that the sense of their own internal capabilities was a source of comfort for them; importance of pre-established relationships with healthcare professionals, the sense of connection established prior to the telehealth consultation supported participants to engage with healthcare professionals where the need for connectedness was amplified by a sense of isolation; seeking help, participants sought help from services that they perceived as being "expert"; convenience, factors such as costs and saving time were highlighted; and preferences for consultation type, majority of participants identified physical and emotional comfort being in their own space. For a small number of patients, continuing a face-to-face assessment was important due to expectation based on previous experience. CONCLUSION: The use of telehealth was supported during the management of COVID-19. Connectedness and convenience were key to the level of comfort and confidence for patients with lung cancer using telehealth during "lockdown."

L2HGDH Missense Variant in a Cat with L-2-Hydroxyglutaric Aciduria.

A 7-month-old, spayed female, domestic longhair cat with L-2-hydroxyglutaric aciduria (L-2-HGA) was investigated. The aim of this study was to investigate the clinical signs, metabolic changes and underlying genetic defect. The owner of the cat reported a 4-month history of multiple paroxysmal seizure-like episodes, characterized by running around the house, often in circles, with abnormal behavior, bumping into obstacles, salivating and often urinating. The episodes were followed by a period of disorientation and inappetence. Neurological examination revealed an absent bilateral menace response. Routine blood work revealed mild microcytic anemia but biochemistry, ammonia, lactate and pre- and post-prandial bile acids were unremarkable. MRI of the brain identified multifocal, bilaterally symmetrical and T2-weighted hyperintensities within the prosencephalon, mesencephalon and metencephalon, primarily affecting the grey matter. Urinary organic acids identified highly increased levels of L-2-hydroxyglutaric acid. The cat was treated with the anticonvulsants levetiracetam and phenobarbitone and has been seizure-free for 16 months. We sequenced the genome of the affected cat and compared the data to 48 control genomes. L2HGDH, coding for L-2-hydroxyglutarate dehydrogenase, was investigated as the top functional candidate gene. This search revealed a single private protein-changing variant in the affected cat. The identified homozygous variant, XM_023255678.1:c.1301A>G, is predicted to result in an amino acid change in the L2HGDH protein, XP_023111446.1:p.His434Arg. The available clinical and biochemical data together with current knowledge about L2HGDH variants and their functional impact in humans and dogs allow us to classify the p.His434Arg variant as a causative variant for the observed neurological signs in this cat.

Nursing and Allied Health Research Priorities in the Care of Patients With Thoracic Malignancies: An International Cross-Sectional Survey.

BACKGROUND: There is currently no evidence of research priorities from nurses and allied health professionals working in the field of thoracic malignancies, which could provide strategic directions for funders, policy makers, and researchers. OBJECTIVE: The aim of this study is to identify the priorities for lung cancer and other thoracic malignancies research and practice in nurses and allied health professionals. METHODS: Descriptive cross-sectional web-based international survey conducted through international societies' membership lists. RESULTS: Participants included 152 nurses and allied health professionals. Key priority categories were related to developing and evaluation interventions; symptom management interventions; health care system issues; treatment-related research (immunotherapy; targeted therapies); persistent/late effects management (fatigue; pulmonary toxicity); risk reduction, and screening research. The specific topic with the highest endorsement (80.9%) was the development of interventions to improve quality of life. Symptom management interventions, particularly for pain, dyspnea, and fatigue, were also highly endorsed. Health care system topics were related to delivery of care and included nurse-/allied health-led care (67.5%), working with the multidisciplinary team (67.5%), continuity of care (69.2%), and access to care (67.5%). Topics around screening/early detection research were highly endorsed too. CONCLUSION: A clear focus (and need) for research in interventions to improve quality of life and symptom management, particularly for pain, dyspnea, and fatigue was also established, alongside healthcare system issues and screening research. IMPLICATIONS FOR PRACTICE: International societies and funding bodies could consider these topics in their funding decisions and in shaping their strategic directions in the care of patients with thoracic malignancies.

Osimertinib in NSCLC: Real-World Data From New Zealand.

INTRODUCTION: EGFR tyrosine kinase inhibitors (TKIs) are more effective than chemotherapy in patients with EGFR-mutant NSCLC. Disease progression on EGFR TKI therapy occurs most often owing to acquired resistance from the gain of an EGFR T790M mutation. Osimertinib, a third-generation EGFR TKI, significantly improves outcomes in patients with EGFR T790M mutation-positive NSCLC compared with platinum-pemetrexed chemotherapy. We retrospectively reviewed clinical outcomes for patients receiving osimertinib through a compassionate access program in New Zealand. METHODS: Patients with a biopsy-proven or plasma-circulating tumor-DNA-proven EGFR T790M mutation received osimertinib. Data on patient and tumor characteristics, treatments, and outcomes were collected retrospectively. Survival outcomes were calculated from the time of osimertinib commencement. RESULTS: A total of 39 patients were enrolled, and data from 37 patients were analyzed. EGFR T790M status was found from plasma samples in six of 37 (16%) patients. A total of 27 of 37 patients (73%) used osimertinib as a second-line treatment. At the time of data analysis, median follow-up was 18.8 months (range 1.5-29). Overall response rate was 70% (95% confidence interval [CI]: 53-84) (26 of 37). Progression-free survival (PFS) at 12 months was 62% (95% CI: 44.8-77.5), and median PFS was 14.6 months (95% CI: 12.4-16.8). Median overall survival was not reached. Osimertinib was well tolerated, with grade 1 gastrointestinal and skin toxicity as the most common adverse effects. Three patients required dose adjustments or cessation owing to toxicity. CONCLUSION: Osimertinib is an effective treatment for New Zealanders with EGFR T790M mutated NSCLC who have progressed after first or subsequent lines of therapy.

Patient response to use of tyrosine kinase inhibitors in lung cancer: a retrospective audit during funding changes.

BACKGROUND: The New Zealand Pharmaceutical Management Agency (PHARMAC) approved funding of erlotinib in October 2010 as second line therapy in all non-squamous non-small cell lung cancer after platinum-based chemotherapy with no requirement for epidermal growth factor (EGFR) mutation testing. Funding widened in August 2012 to include gefitinib as first line treatment for patients with a proven EGFR mutation. Then in January 2014, both tyrosine kinase inhibitors (TKIs) were approved for first line treatment, but only for disease with EGFR mutation. AIM: To report the clinical experience with TKIs in a New Zealand tertiary referral centre over a period of funding change. METHOD: Retrospective audit of all patients commenced on erlotinib from 1st October 2010 until 1st November 2011, and gefitinib from 1st August 2012 until 31st August 2013. Follow-up was two years for both groups. RESULTS: Each group had 42 patients. Median Progression Free Survival was 76 days in the erlotinib group and 255 days in the gefitinib group. Twenty-eight percent of erlotinib patients had grade 3 adverse events with one treatment related death; fourteen percent of gefitinib patients had grade 3 adverse events. Dose reduction or treatment breaks were required in 12% in each group. CONCLUSION: Response rate in these audits appear to reflect the change in funding criteria, with improved response rates likely to be associated with more targeted treatment.

Oppositional defiant disorder.

BACKGROUND: Oppositional defiant disorder (ODD) is defined as a repetitive and persistent pattern of opposition, defiant, disobedient and disruptive behaviours toward authority figures persisting for at least 6 months. OBJECTIVE: This article reviews the nature of ODD, its relationship to attention deficit hyperactivity disorder and conduct disorder, and considers the management options available to general practitioners. DISCUSSION: Many of the behaviours required to meet this diagnosis are not uncommon in the preschool child or adolescent. However, in children with ODD the behaviours are persistent, cause significant distress to the family system, and impact on the child's social and educational functioning. Oppositional defiant disorder usually presents in the preschool years, although it may become evident during adolescence. There is strong evidence that early intervention to increase positive factors in family relationships and to increase both the parents' and child's skill levels can assist in the prevention of more serious disorders and mental health issues.

NHS Professionals: good idea but it does not work.

I would like to reply to Nigel Northcott's letter about NHS Professionals (letters November 27). The trust I work for has been using NHS Professionals for about a year, pioneering the service in the south west.