An adaptable, reusable, and light implant for chronic Neuropixels probes.

Electrophysiology has proven invaluable to record neural activity, and the development of Neuropixels probes dramatically increased the number of recorded neurons. These probes are often implanted acutely, but acute recordings cannot be performed in freely moving animals and the recorded neurons cannot be tracked across days. To study key behaviors such as navigation, learning, and memory formation, the probes must be implanted chronically. An ideal chronic implant should (1) allow stable recordings of neurons for weeks; (2) be light enough for use in mice; (3) allow reuse of the probes after explantation. Here, we present the "Apollo Implant", an open-source and editable device that meets these criteria and accommodates up to two Neuropixels 1.0 or 2.0 probes. The implant comprises a "payload" module that is attached to the probe and is recoverable, and a "docking" module that is cemented to the skull. The design is adjustable, making it easy to change the distance between probes, the angle of insertion, and the depth of insertion. We tested the implant across seven labs in head-fixed mice, freely moving mice, and freely moving rats. The number of neurons recorded across days was stable, even after repeated implantations of the same probe. The Apollo implant provides an inexpensive, lightweight, and flexible solution for reusable chronic Neuropixels recordings.

Prospective Assessment of Penicillin Allergy (PAPA): Evaluating the performance of penicillin allergy testing and post-delabelling outcomes among Hong Kong Chinese.

BACKGROUND: Incorrect penicillin 'allergy' labels predispose patients to adverse outcomes but are under-recognised in many Asian countries. Studies on performance and post-delabelling outcomes of penicillin allergy evaluation among Chinese remain scarce. OBJECTIVE: To evaluate the diagnostic performance of allergy testing and post-delabelling outcomes among Chinese patients in a prospective penicillin allergy cohort - Prospective Assessment of Penicillin Allergy (PAPA). METHODS: All adult patients (age ≥ 18 years) who underwent penicillin allergy evaluation between January 2020 to December 2021 were recruited and prospectively reviewed by both medical records and individual interviews at least 6 months after delabelling or allergy confirmation. RESULTS: Out of 372 patients who completed penicillin allergy evaluation, 335 (90%) patients were delabelled. The overall negative predictive value of penicillin skin testing was 95%, but lower for patients with non-immediate type reactions (88%). History of non-immediate symptom onset (OR = 4.501 [95%CI = 2.085-9.716], p < 0.001) and duration since index reaction (OR = 0.942 [95%CI = 0.899-0.987], p = 0.012) were associated with positive skin testing. After at least 6 months, 60 (18%) of de-labelled patients had received penicillins again without any adverse reactions. Fluoroquinolone-use was significantly lower among delabelled patients compared to those with penicillin allergy (38[11%] vs 11[30%], p = 0.004). CONCLUSIONS: After at least 6 months, one in six delabelled patients already received penicillins again safely, with significantly lower fluoroquinolone usage. None experienced adverse reactions. History of non-immediate onset and shorter duration since index reaction were associated with genuine allergy. In patients with severe non-immediate reactions, skin tests should be supplemented with thorough clinical history and adjunct diagnostic evaluations.

Comparative Effectiveness, Safety, and Real-World Outcomes of a Nurse-Led, Protocol-Driven Penicillin Allergy Evaluation From the Hong Kong Drug Allergy Delabelling Initiative (HK-DADI).

BACKGROUND: There is a high prevalence of unconfirmed penicillin allergy, which is associated with a multitude of adverse clinical outcomes. With the overwhelming burden of currently incorrect labels and the lack of allergy specialist services, new delabeling strategies are urgently needed. OBJECTIVE: To assess the effectiveness, safety, and real-world outcomes of a nurse-led, protocol-driven evaluation of penicillin allergy, the Hong Kong Drug Allergy Delabelling Initiative (HK-DADI). METHODS: Adult patients with suspected penicillin allergy were recruited into HK-DADI. Allergy and postdelabeling outcomes were retrospectively compared between patients evaluated via HK-DADI or traditional allergist evaluation. RESULTS: A total of 312 completed penicillin allergy evaluation: 84 (27%) and 228 (73%) via HK-DADI and traditional pathways, respectively. Overall, 280 penicillin allergies were delabeled (90%). The delabeling rate between HK-DADI and traditional pathways was similar (90% vs 89%; P = .796). Among patients of the HK-DADI pathway, the delabeling rate was significantly higher among low-risk (LR) compared with non-LR patients (97% vs 77%; P = .010). Skin tests did not add diagnostic value among LR patients. No patients developed severe or systemic reactions during the evaluation. Upon 6- to 12-month follow-up (median, 10 months), 123 patients experienced infective episodes (44%) and 63 used penicillins again after delabeling (23%). This proportion was significantly higher in patients who were delabeled via HK-DADI compared with the traditional pathway (32% vs 19%; P = .026). CONCLUSIONS: The Hong Kong Drug Allergy Delabelling Initiative, a nurse-led, protocol-driven evaluation, was safe and effective in penicillin allergy delabeling. It led to an even higher rate of future penicillin use after delabeling and mitigated the need for unnecessary skin testing among LR patients.

Sensitisation profile of Chinese allergic rhinitis patients and effectiveness of a joint allergy-ENT clinic.

Purpose: House dust mite (HDM) is the predominant cause of allergic rhinitis (AR) in Hong Kong but remains under-diagnosed and -treated. The association between patient-reported outcome measures (PROMs) and nasoendoscopy findings for AR have also not been investigated. This study investigated the demographics, sensitisation patterns, quality of life, use of sublingual immunotherapy and the association of PROMs and nasoendoscopy findings in AR patients through the first allergist-otorhinolaryngologists AR joint (ARJ) clinic in Hong Kong. Methods: This single-centred, retrospective observational study was conducted between January 2021 and December 2021. Clinical data from AR patients attending the ARJ clinic were analysed to identify the prevalence of HDM allergens, change in PROMs and the association of PROMs with nasoendoscopy scores. Results: The three most common sensitising HDM allergens were Dermatophagoides pterynosinus (94.4%), Dermatophagoides farinae (88.9%) and Euroglyphus maynei (88.9%). At the 13- to 32-week follow-up (median 28 weeks), patients who attended the ARJ clinic had significant improvement in Total Nasal Symptom Score (TNSS; p = 0.038). The visual analogue scale (VAS) was associated with nasoendoscopy score (p = 0.018). Patients using SLIT (sublingual immunotherapy) showed overall improvements in PROMs. Conclusion: The ARJ clinic significantly improved AR symptoms. SLIT was effective and safe for patients who failed conventional treatments. VAS positively correlated with nasoendoscopy findings. Testing for Dermatophagoides pterynosinus as a single agent during skin testing was sufficient for the diagnosis of HDM AR and should be prioritized when resources are restricted. Further studies should be done to investigate the treatment outcome of AR patients and the effectiveness of SLIT in the Chinese population. Supplementary Information: The online version of this article (10.1007/s40629-022-00218-5) contains supplementary material, which is available to authorized users.

Factors affecting turnaround time of SARS-CoV-2 sequencing for inpatient infection prevention and control decision making: analysis of data from the COG-UK HOCI study.

BACKGROUND: Barriers to rapid return of sequencing results can affect the utility of sequence data for infection prevention and control decisions. AIM: To undertake a mixed-methods analysis to identify challenges that sites faced in achieving a rapid turnaround time (TAT) in the COVID-19 Genomics UK Hospital-Onset COVID-19 Infection (COG-UK HOCI) study. METHODS: For the quantitative analysis, timepoints relating to different stages of the sequencing process were extracted from both the COG-UK HOCI study dataset and surveys of study sites. Qualitative data relating to the barriers and facilitators to achieving rapid TATs were included from thematic analysis. FINDINGS: The overall TAT, from sample collection to receipt of sequence report by infection control teams, varied between sites (median 5.1 days, range 3.0-29.0 days). Most variation was seen between reporting of a positive COVID-19 polymerase chain reaction (PCR) result to sequence report generation (median 4.0 days, range 2.3-27.0 days). On deeper analysis, most of this variability was accounted for by differences in the delay between the COVID-19 PCR result and arrival of the sample at the sequencing laboratory (median 20.8 h, range 16.0-88.7 h). Qualitative analyses suggest that closer proximity of sequencing laboratories to diagnostic laboratories, increased staff flexibility and regular transport times facilitated a shorter TAT. CONCLUSION: Integration of pathogen sequencing into diagnostic laboratories may help to improve sequencing TAT to allow sequence data to be of tangible value to infection control practice. Adding a quality control step upstream to increase capacity further down the workflow may also optimize TAT if lower quality samples are removed at an earlier stage.

Reaching for equitable care: High levels of disability-related knowledge and cultural competence only get us so far.

BACKGROUND: Achieving equitable medical care for people with disabilities is a complex challenge with emphasis often placed on the need for improved physician knowledge and cultural competence. Physical medicine and rehabilitation (PM&R) is a specialty dedicated to maximizing patient function, where a focus on working with and learning from patients with complex disabilities informs physician training and patient care. OBJECTIVE: The purpose of this study was to assess barriers to equitable care in PM&R clinics through a structural checklist and semi-structured interviews with clinic staff and physicians. METHODS: We used qualitative analysis with a grounded theory approach to develop a unified explanation of how existing clinic processes and provider attitudes affect equitable access to medical care. RESULTS: We found physicians comfortable with and respectful of patient differences who described leveraging unpaid time and creativity to navigate structural, resource, and awareness barriers. Staff and physicians described current barriers as negatively affecting quality of care, clinic efficiency, and, in some cases, patient and staff safety. CONCLUSION: Our results suggest that high levels of physician disability-related knowledge and cultural competence may be insufficient to the challenge of achieving equitable care.

Surgical management of intrathoracic wooden skewers migrating from the stomach and duodenum in dogs: 11 cases (2014-2020).

OBJECTIVES: To describe the clinical presentation, management and outcome of cases presenting with intrathoracic wooden skewers originating from the abdominal gastrointestinal tract. MATERIALS AND METHODS: Clinical records of dogs presented and treated for an intrathoracic wooden skewer were reviewed from June to August 2020. Data included signalment, clinical presentation, duration of clinical signs, haematological and biochemical abnormalities, diagnostic imaging findings, surgical procedure, postoperative complications and outcome. RESULTS: Eleven dogs were included in the study. In all cases, the foreign body was identified as a wooden skewer. The most common clinical signs were anorexia/hyporexia (n=7), vomiting/regurgitation (n=7), lethargy (n=6), pyrexia (n=4) and gait abnormalities/lameness (n=3). CT correctly identified a wooden skewer in all cases when performed (n=7). A coeliotomy combined with transdiaphragmatic thoracotomy was performed in six of 11 cases (55%), a coeliotomy combined with median sternotomy in four of 11 cases (36%) and a median sternotomy alone was performed in one case. Foreign bodies penetrated from the stomach (n=10) or the duodenum (n=1). Intrathoracic trauma was most commonly identified to the lungs (n=3) and pericardium (n=3). Complications occurred in three of 11 cases (27%), two minor and one resulting in death. Ten of the 11 cases (91%) survived to discharge. Long-term outcome was available for seven of 11 cases (66%), all of them excellent. CLINICAL SIGNIFICANCE: Despite the challenges of managing wooden skewers penetrating the thoracic cavity from the abdominal gastrointestinal tract, the majority of the patients are stable to undergo diagnostic procedures, surgical exploration and management with low morbidity and excellent short- and long-term prognosis.

Early imaging predictors of fetal cerebral ischemic injury in monochorionic twin pregnancy complicated by spontaneous single intrauterine death.

OBJECTIVE: Monochorionic twin pregnancies are at increased risk of single intrauterine death (sIUD) and subsequent brain injury in the surviving twin owing to shared placentation. We assessed the association between middle cerebral artery peak systolic velocity (MCA-PSV) and cerebral injury on magnetic resonance imaging (MRI) and examined the association between cerebral findings on diffusion-weighted imaging (DWI) and those on T2-weighted imaging following spontaneous sIUD. METHODS: This was a retrospective cohort study of monochorionic pregnancies complicated by spontaneous sIUD followed at a tertiary center between January 2008 and January 2020. Pregnancies with sIUD following laser treatment, those with selective feticide, double IUD occurring on the same day or sIUD before 14 weeks' gestation were excluded, as were cases in which MCA-PSV was not measured or DWI-MRI was not performed. The ability of MCA-PSV Doppler to predict subsequent cerebral injury on MRI was assessed, and DWI findings were analyzed and compared with those on susceptibility-weighted imaging (SWI) and T2-weighted MRI to determine its diagnostic accuracy. RESULTS: We assessed 64 monochorionic pregnancies complicated by spontaneous sIUD. Of these, 47 (73.4%) pregnancies underwent fetal brain MRI and met the inclusion criteria. Sixteen (34.0%) of these fetuses demonstrated cerebral injury on MRI. The median interval between the diagnosis of sIUD and MRI examination was 5 days. Fetuses with increased MCA-PSV > 1.5 multiples of the median (MoM) following sIUD were significantly more likely to demonstrate cerebral injury on MRI than were those with normal MCA-PSV (68.8% vs 38.7%; P = 0.05). The sensitivity and specificity of MCA-PSV > 1.5 MoM for predicting cerebral injury on MRI were 68.8% (95% CI, 41.3-88.9%) and 61.3% (95% CI, 42.2-78.2%), respectively. Patterns of early cerebral injury on T2-weighted and SWI-MRI included acute or subacute tissue swelling (n = 6), parenchymal atrophy (n = 7), loss of cortical ribbon (n = 1) and hemorrhage (n = 8). Early MRI within approximately 2 weeks after the diagnosis of sIUD demonstrated abnormal DWI along with coexisting SWI and T2-weighted sequelae in 56.3% (9/16) of cases. When DWI was normal and a second MRI examination was performed later (n = 7), there were no ischemic changes evident on T2-weighted imaging. CONCLUSIONS: Increased MCA-PSV is associated with, but predicts poorly, cerebral injury after sIUD. Early MRI with DWI within approximately 2 weeks after the diagnosis of sIUD is valuable in identifying any cerebral injury. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Activated Charcoal and Bicarbonate for Aspirin Toxicity: a Retrospective Series.

INTRODUCTION: Aspirin overdose causes acid-base disturbances and organ dysfunction. Management is guided by research reported over 50 years ago when chronic aspirin toxicity was common and accounted for significant morbidity. We investigate our experience of aspirin overdose and the effectiveness of charcoal and bicarbonate administration over 20 years. METHODS: This is a retrospective series of acute aspirin overdose from two toxicology units from January 2000 to September 2019. Acute aspirin ingestions > 3000 mg were identified in each unit's database. Excluded were cases of chronic exposure, hospital presentation > 24 hours after ingestion, and cases without a salicylate concentration. Included in our analysis was demographic data, clinical effects, investigations, complications, and treatment. RESULTS: There were 132 presentations in 108 patients (79 females (73%)). The median age was 28 years (range: 13-93 years). The median dose ingested was 7750 mg (IQR: 6000-14,400 mg). There were 44 aspirin-only ingestions. Mild toxicity (nausea, vomiting, tinnitus or hyperventilation) occurred in 22 with a median dose of 160 mg/kg. Moderate toxicity (acid-base disturbance, confusion) occurred in 16 with a median ingested dose of 297 mg/kg. There were no cases of severe toxicity (coma or seizures) due to aspirin alone. The median peak salicylate concentration was 276 mg/L (IQR: 175-400 mg/L, range: 14-814 mg/L). There was a moderate association between dose ingested and peak concentration (Pearson r = 0.58; 95% CI 0.45-0.68). Activated charcoal was administered in 36 (27%) cases, which decreased the median peak salicylate concentration (34.2 to 24.8 mg/L/g (difference: 9.4, 95% CI: 1.0-13.1)). Bicarbonate was administered in 34 (26%) presentations, decreasing the median apparent elimination half-life from 13.4 to 9.3 h (difference: 4.2 h, 95% CI: 1.0-6.5 h). CONCLUSIONS: Acute aspirin overdose caused only mild to moderate effects in this series. Early administration of activated charcoal decreased absorption and use of bicarbonate enhanced elimination.

Gastroesophageal intussusception secondary to induction of emesis with subsequent development of septic pericardial effusion after corrective surgery.

A juvenile boxer dog was diagnosed with gastroesophageal intussusception that occurred after the induction of emesis with apomorphine. A ventral midline coeliotomy and diaphragmotomy were performed and the intussusception was manually reduced. Despite initial satisfactory recovery, the dog was diagnosed with cardiac tamponade 1 week post-operatively. Escherichia coli was cultured from pericardial and pleural effusion samples. During subtotal pericardiectomy surgery the pericardium was found to be markedly thickened with adhesions to the epicardium, thoracic wall and diaphragm. Substantial haemorrhage and refractory hypotension necessitated the administration of a blood transfusion during surgery. The dog entered cardiac arrest in the immediate post-operative period and cardiopulmonary resuscitation was unfortunately unsuccessful. Gastroesophageal intussusception should be considered a possible severe adverse effect of administering apomorhine to induce emesis in dogs. Additionally, septic pericardial and pleural effusions may occur post-reduction of gastroesophageal intussusception.

Investigation on Temperature Dependent Inductance (TDI) of a planar Multi-Layer Inductor (MLI) down to 4.2 K.

This paper presents an investigation of the temperature dependence characteristics specific to cryogenic planar Multi-Layer Inductors (MLIs). This paper establishes that the inductance of a planar MLI at a specific frequency varies with temperature when the sensor is cooled down to 4.2 K while providing a detailed analysis of various possible factors that might contribute to the variation in the sensor performance, such as the thermal deformation and the variation in the properties of sensor materials, using a combination of experiments and simulations. By calculating the interlayer capacitance, we have attempted to adopt a novel approach in the investigation of the effects of thermal deformation on the sensor. In order to arrive at that, the relative permittivity of the base material (G10CR-FR4) at cryogenic temperatures was obtained through experiments. The ANSYS static structural package was used for modeling thermally induced deformations, after which the deformed capacitance and inductance were obtained using Ansoft MAXWELL. From the analysis, we have concluded that the variation in the inductance of the sensor has a direct correlation with the electrical resistivity (hence the residual resistivity ratio) of the coil material. The number of inductor layers and the area of the component layer will also determine the temperature dependence phenomenon. These conclusions are not obvious from the established inductance models.

Diaphragmotomy to aid exposure during hepatobiliary surgery: a multi-centre retrospective review of 31 dogs.

OBJECTIVES: To report surgical technique, intra- and post-operative complications, and short- and long-term outcome following canine hepatobiliary surgery in which exposure of intra-abdominal hepatobiliary lesions was aided by diaphragmotomy. MATERIALS AND METHODS: Clinical records from four multi-disciplinary UK-based small animal referral hospitals were retrospectively reviewed for dogs in which diaphragmotomy was performed between January 2014 and May 2019. Signalment, diagnosis, surgery performed, diaphragmotomy technique, management of diaphragmotomy and pneumothorax, intra- and post-operative complications, short-term outcome and long-term outcome were recorded. RESULTS: Thirty-one cases were identified. The most common hepatobiliary surgeries performed alongside diaphragmotomy were single hepatic lobectomy (14/31) and cholecystectomy (11/31). The most common diagnoses were hepatocellular carcinoma (10/31), gall bladder mucocoele (7/31) and hepatic nodular hyperplasia (4/31). Peri-operative mortality rate was 9.7% (3/31 cases) though none of these deaths were considered attributable to diaphragmotomy. Post-operative complications were encountered in 67.9% (19/28) cases that survived the peri-operative period, of which 25.0% (7/28) suffered complications that were considered attributable or likely attributable to diaphragmotomy. These seven complications resolved following non-surgical intervention. Follow-up was available for 26 of 28 patients that survived to discharge at a median of 4-months (range 10 days to 24 months) following surgery and revealed no evidence of complications related to diaphragmotomy. CLINICAL SIGNIFICANCE: Diaphragmotomy appears safe and increases abdominal exposure of hepatobiliary lesions. The benefit of improved exposure must be carefully weighed up against the risks inherent in inducing pneumothorax.

Association between referral source and duration of untreated psychosis in pathways to care among first episode psychosis patients in Northern Malawi.

AIMS: To examine the association between referral source and duration of untreated psychosis (DUP) and explore determinants of referral source; when adjusting for pathways to care, positive and negative symptoms, diagnosis and socio-demographic characteristics. METHODS: A total of 140 subjects with first episode psychosis (FEP) were enrolled from a pilot early intervention service for psychosis in Northern Malawi between June 2009 and September 2012. Logistic regression analyses were used to quantify the associations between variables of interest. RESULTS: Age ranged between 18 and 65 at assessment, with median, 33. Median DUP was 12.5 months. First contact did not independently determine DUP. Long DUP (>6 months) was associated with referral from community based volunteer (CBV) or traditional healer (TH), a unit increase in severity of negative symptoms and having schizophrenia, which was also associated with referral from CBV or TH. Additionally, being unemployed was associated with referral from CBV or TH. However, a unit increase in the number of times religious advice (RA) was sought, GP was contacted and severity of positive symptoms was associated with referral by GP. CONCLUSIONS: Mental health awareness is justified for this population and collaboration with THs in identifying and treating patients with psychosis may help reduce treatment delays. Access to mental health services ought to improve, particularly for the unemployed group. Future studies should consider adjusting for referral source when ascertaining first contact source as a predictor of DUP.

STEMI in a patient with mirror-image dextrocardia.

ST-segment elevation myocardial infarction (STEMI) is a potentially life-threatening diagnosis that cannot be missed on ECG interpretation. However, ECG interpretation may not be straightforward in patients with dextrocardia. This case report discusses the presentation of a patient with situs inversus with dextrocardia who was found to have an acute inferior MI, and how this anatomical change results in an atypical ECG and clinical presentation.

Cost Savings Analysis of Early Extubation Following Congenital Heart Surgery.

The clinical benefit of early extubation following congenital heart surgery has been demonstrated; however, its effect on resource utilization has not been rigorously evaluated. We sought to determine the cost savings of implementing an early extubation pathway for children undergoing surgery for congenital heart disease. We performed a cost savings analysis after implementation of an early extubation strategy among children undergoing congenital heart surgery at British Columbia Children's Hospital (BCCH) over a 2.5-year period. All patients undergoing one of the eight Society of Thoracic Surgeons (STS) benchmark operations, ASD repair, or bidirectional cavopulmonary anastomosis were included in the analysis (n = 370). We compared our data to aggregate STS multi-institutional data from a contemporary cohort. We estimated daily costs for ICU care, ward care, medications, imaging, additional procedures, and allied health care using an administrative database. Direct costs, indirect costs, and cost savings were estimated. Simulation methods, Monte Carlo, and bootstrapping were used to calculate the 95% credible intervals for all estimates. The mean cost savings per procedure was $12,976 and the total estimated cost savings over the study period at BCCH was $4.8 million with direct costs accounting for 91% of cost savings. Sensitivity analysis demonstrated a mean cost savings range of $11,934-$14,059 per procedure. Early extubation is associated with substantial cost savings due to reduced hospital resource utilization. Implementation of an early extubation strategy following congenital heart surgery may contribute to improved resource utilization.