Experimental investigation and micromagnetic simulations of hybrid CoCr2O4/Ni coaxial nanostructures.

Multiphase CoCr2O4/Ni core-shell nanowires (NWs) have been synthesized within anodic aluminum oxide membranes by the combination of the sol-gel method with electrodeposition techniques. X-ray diffraction and x-ray photoemission spectroscopy results confirmed the formation of a cubic spinel structure of CoCr2O4 shell with space group Fd-3m (227). The morphology and composition of the as-grown NWs were studied by field emission scanning electron microscopy, as well as transmission electron microscopy. The magnetic properties of the CoCr2O4 NT shell and hybrid CoCr2O4/Ni NWs were measured at low temperature using a physical property measurement system. The temperature dependence of the magnetization curves showed that CoCr2O4 NTs undergo a transition from a paramagnetic state to a ferrimagnetic state at about 90 K and a spiral ordering transition temperature near 22 K. An enhanced coercivity and saturation field were observed for the CoCr2O4/Ni core-shell NWs compared to the single-phase Ni NWs. Micromagnetic simulation results indicated that there is a strong coupling between the shell and core layers during the magnetization reversal process. The combination of hard CoCr2O4 and soft Ni in a single NW structure may have potential applications in future multifunctional devices.

Appendiceal Duplication: A Comprehensive Review of Published Cases and Clinical Recommendations.

BACKGROUND: Duplex appendix is very rare (incidence 0.004%) but has clinical relevance given the frequency of appendicectomies performed. Failure to recognise duplication can result in failure of treatment and medico-legal consequences. A review of published cases was undertaken to identify factors that may help in managing this rare condition. METHODS: All English and non-English publications were identified in PubMed, Embase and Cochrane databases. Patient demographics, intraoperative findings, anatomical details and histopathology were analysed. RESULTS: A total of 141 cases were identified [male/female ratio 1.4:1, median age 20 years (range foetus to 69 years)]. Duplication of the appendix ranges from branching of the appendix trunk to a fully matured appendix located elsewhere along the colon. Most can be categorised by the Cave-Wallbridge classification. There were 22 Type A, 8 Type B1, 46 Type B2 and 10 Type C cases (Cave-Wallbridge). There were six cases of horseshoe and two cases of triple appendix. Six reports gave anatomical descriptions that could not be classified by Cave-Wallbridge categories and in 11 cases there were no anatomical descriptions. CONCLUSIONS: An anteriorly placed appendix, away from the convergence of the taenia, or a normal appendix in the presence of convincing clinical or radiological signs of appendicitis should instigate a careful examination of the caecal pole and possible exploration of the retrocaecal space for appendiceal duplication. If the patient had previous surgery for congenital abnormalities, Type B1 or Type C duplication should be considered.

The zebra sign: an unknown known.

A 65-year-old woman became obtunded following routine laminectomy and was found to have bilateral cerebellar haemorrhage and convexity subarachnoid haemorrhage. We discuss the possible mechanisms of remote cerebellar haemorrhage­cerebellar haemorrhage that develops after spinal or intracranial surgery­giving rise to the 'zebra sign' and the possible mechanism of convexity subarachnoid haemorrhage in this context [corrected].

A prospective trial of temporary sacral nerve stimulation for constipation associated with neurological disease.

AIM: This study assessed the effectiveness of temporary sacral nerve stimulation (SNS) in patients with constipation associated with neurological disease using an off-on-off design, and evaluated the long-term response in patients undergoing permanent SNS. METHOD: Patients with chronic constipation associated with neurological disease receiving specialist clinic care at the University Hospital North Durham over a 2-year period were recruited to a trial of SNS. Recordings of bowel function were made for 6 weeks (baseline) and a temporary electrode was then inserted and recordings were made for the next 3 weeks (stimulation). The electrodes were then removed and assessment was continued for a further 3 weeks (posttreatment). Patient-completed questionnaires were used to determine the severity of constipation (Global Assessment of Symptoms, Constipation, GA Constipation), symptoms (Patient Assessment of Constipation Symptoms score, PAC-SYM) and quality-of-life (Patient Assessment of Constipation-Quality Of Life score, PAC-QOL; European Quality of Life-Five-Domain score; European Quality of Life-Visual Analogue Score). Information was obtained on bowel function and medication. Physiological data were also available for transit and laser Doppler flow cytometry to measure mucosal blood flow. RESULTS: Twenty-two patients were recruited, of whom 18 completed the trial. GA Constipation reduced significantly during temporary SNS: -1.09 (95% CI -1.59 to -0.59; P = 0.0003). PAC-SYM and PAC-QOL scores showed similar improvements. There was also a significant fall in the time spent in the toilet (P = 0.04) and a decrease in laxative use (P = 0.03). Twelve (67%) patients responded to temporary SNS and received a permanent implant with long-term success in 50%. CONCLUSION: Sacral nerve stimulation can be effective in treating some patients with refractory severe neuroconstipation. A response to temporary SNS may predict long-term benefit in only half the patients undergoing permanent SNS.

Alzheimer's disease as a women's health challenge: a call for action on integrative precision medicine approaches.

Alzheimer's Disease (AD) is marked by pronounced sex differences in pathophysiology and progression. However, the field has yet to fully recognize AD as a women's health issue, delaying the development of targeted preventative strategies and treatments. This perspective explores the elements impacting AD in women, identifying sex specificity in risk factors, highlighting new diagnostic approaches with electronic health records, and reviewing key molecular studies to underscore the need for integrative precision medicine approaches. Established AD risk factors such as advancing age, the apolipoprotein E4 allele, and poorer cardiovascular health affect women differently. We also shed light on sociocultural risk factors, focusing on the gender disparities that may play a role in AD development. From a biological perspective, sex differences in AD are apparent in biomarkers and transcriptomics, further emphasizing the need for targeted diagnostics and treatments. The convergence of novel multiomics data and cutting-edge computational tools provides a unique opportunity to study the molecular underpinnings behind sex dimorphism in AD. Thus, precision medicine emerges as a promising framework for understanding AD pathogenesis through the integration of genetics, sex, environment, and lifestyle. By characterizing AD as a women's health challenge, we can catalyze a transformative shift in AD research and care, marked by improved diagnostic accuracy, targeted interventions, and ultimately, enhanced clinical outcomes.

Concordance of three approaches for operationalizing outcome definitions for multidrug-resistant TB.

BACKGROUND: The WHO provides standardized outcome definitions for rifampicin-resistant (RR) and multidrug-resistant (MDR) TB. However, operationalizing these definitions can be challenging in some clinical settings, and incorrect classification may generate bias in reporting and research. Outcomes calculated by algorithms can increase standardization and be adapted to suit the research question. We evaluated concordance between clinician-assigned treatment outcomes and outcomes calculated based on one of two standardized algorithms, one which identified failure at its earliest possible recurrence (i.e., failure-dominant algorithm), and one which calculated the outcome based on culture results at the end of treatment, regardless of early occurrence of failure (i.e., success-dominant algorithm).METHODS: Among 2,525 patients enrolled in the multi-country endTB observational study, we calculated the frequencies of concordance using cross-tabulations of clinician-assigned and algorithm-assigned outcomes. We summarized the common discrepancies.RESULTS: Treatment success calculated by algorithms had high concordance with treatment success assigned by clinicians (95.8 and 97.7% for failure-dominant and success-dominant algorithms, respectively). The frequency and pattern of the most common discrepancies varied by country.CONCLUSION: High concordance was found between clinician-assigned and algorithm-assigned outcomes. Heterogeneity in discrepancies across settings suggests that using algorithms to calculate outcomes may minimize bias.

Outcomes of WHO-conforming, longer, all-oral multidrug-resistant TB regimens and analysis implications.

BACKGROUND: Evidence of the effectiveness of the WHO-recommended design of longer individualized regimens for multidrug- or rifampicin-resistant TB (MDR/RR-TB) is limited.OBJECTIVES: To report end-of-treatment outcomes for MDR/RR-TB patients from a 2015-2018 multi-country cohort that received a regimen consistent with current 2022 WHO updated recommendations and describe the complexities of comparing regimens.METHODS: We analyzed a subset of participants from the endTB Observational Study who initiated a longer MDR/RR-TB regimen that was consistent with subsequent 2022 WHO guidance on regimen design for longer treatments. We excluded individuals who received an injectable agent or who received fewer than four likely effective drugs.RESULTS: Of the 759 participants analyzed, 607 (80.0%, 95% CI 77.0-82.7) experienced successful end-of-treatment outcomes. The frequency of success was high across groups, whether stratified on number of Group A drugs or fluoroquinolone resistance, and ranged from 72.1% to 90.0%. Regimens were highly variable regarding composition and the duration of individual drugs.CONCLUSIONS: Longer, all-oral, individualized regimens that were consistent with 2022 WHO guidance on regimen design had high frequencies of treatment success. Heterogeneous regimen compositions and drug durations precluded meaningful comparisons. Future research should examine which combinations of drugs maximize safety/tolerability and effectiveness.

Standards for clinical trials for treating TB.

BACKGROUND: The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.METHODS: A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.RESULTS: Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.CONCLUSION: These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.

Evaluating newly approved drugs in combination regimens for multidrug-resistant tuberculosis with fluoroquinolone resistance (endTB-Q): study protocol for a multi-country randomized controlled trial.

BACKGROUND: Treatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients. METHODS: endTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics. Study participation lasts up to 104 weeks post randomization. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 324 participants across 2 arms affords at least 80% power to show the non-inferiority, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per-protocol populations. DISCUSSION: This internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen. TRIAL REGISTRATION: ClinicalTrials.Gov NCT03896685. Registered on 1 April 2018; the record was last updated for study protocol version 4.3 on 17 March 2023.

Comparison of two fascial defect closure methods for laparoscopic incisional hernia repair.

PURPOSE: Currently there is no consensus regarding the optimal surgical approach to an incisional hernia measuring less than 10 cm. Certain hernia features including defect size, intra-abdominal adhesions, and overlying scar/skin properties contribute to choosing an open versus a laparoscopic approach. This retrospective cohort study was designed to compare incisional hernia defects repaired with laparoscopic suture closure to a hybrid approach with open defect closure, both with laparoscopic intraperitoneal onlay mesh (IPOM) reinforcement. METHODS: We identified 164 consecutive patients who underwent incisional hernia repair from two centers, North York General Hospital (NYGH) and Humber River Hospital (HRH) between 2015 and 2020. Patients were grouped by totally laparoscopic or hybrid fascial closure. Both techniques included laparoscopically placed intra-peritoneal mesh with 5 cm of overlap in all directions. Patients were analyzed by age, sex, body mass index (BMI), ASA class and hernia size. Primary outcomes included surgical site infection (SSI), other wound complications including seroma/hematoma, length of hospital stay, pain reported at follow-up appointment, and hernia recurrence. RESULTS: Post-operative pain, surgical site infections and seromas did not differ between the totally laparoscopic and hybrid approach. The recurrence rates were 5.8% and 6.8% for the laparoscopic and hybrid group, respectively, which were not significantly different. The time to recurrence was 15 months (range 8-12) in the laparoscopic group and 7 months (range 6-36) in the hybrid group, also not significantly different. The hernia defect size and BMI were significantly higher in the hybrid group, without increased wound complications. CONCLUSION: These results suggest that a hybrid approach to incisional ventral hernia repair with open defect closure is comparable to a totally laparoscopic closure. The hybrid technique can help facilitate fascial closure and resection of the hernia sac in patients with higher BMI and hernia defects up to 6 cm.

A case of Strongyloides Stercoralis induced duodenitis and pancreatitis.

Strongyloidiasis is endemic in tropical and sub-tropical regions however cases of strongyloidiasis have been reported in temperate climates. Corticosteroid use, immunosuppression, infection with human T-lymphotropic virus type 1 (HTLV1), and chronic alcohol use are the most common and well-established risk factors for strongyloidiasis. Due to Strongyloides stercoralis characteristic features of hyperinfection and dissemination, it can potentially cause a lethal infection in an immunocompromised individual. Strongyloidiasis is predominantly asymptomatic, however some unusual manifestations of strongyloidiasis include duodenal obstruction, ileus, reactive arthritis, ascites, hepatic lesions, and pancreatitis. Here we present a case of a 47-year-old-St. Lucian female who was found to have duodenitis and pancreatitis secondary to Strongyloides stercoralis in the setting of underlying HTLV-1 infection and chronic alcohol use.

The effect of lockdown during SARS-CoV-2 pandemic on maxillofacial injuries in a level I trauma centre: a comparative study.

INTRODUCTION: The SARS-CoV-2 pandemic forced many governments to impose nation-wide lockdowns. Government legislation forced limited travel on the population with restrictions on the normal way of life to limit spread of the SARS-CoV-2 virus. The aim of this study is to explore the effects of lockdown on the presentation of maxillofacial trauma in a level I trauma centre. METHODS: Comparative analysis was carried out using prospective and retrospective review of all consecutive patients admitted with any maxillofacial fracture in the lockdown period between 15th March and 15th June 2020 with the same period in 2019 to a Regional Trauma Maxillofacial Surgery Unit. Data included basic demographics and mechanism of injury including alcohol/drug influence, polytrauma, site of injury and treatment modality including escalation of care. RESULTS: Across both periods, there were a total of one hundred and five (n = 105) recorded episodes of traumatic fractures with fifty-three (n = 53) in the pre-lockdown cohort and fifty-two (n = 52) in the lockdown. Included patients were significantly (p = 0.024) older during lockdown (mean age 41.44 years SD 20.70, range 5-96) with no differences in gender distribution between cohorts (p = 0.270). Patients in lockdown were more likely to be involved in polytrauma (p < 0.05) and have sustained their injury by cycling/running or any outdoor related activity (p = 0.013). Lockdown saw a significant reduction in alcohol and drug related violence (p < 0.05). Significantly more patients required operative management (p = 0.038). CONCLUSION: Local lockdowns form part of the governments public health strategy for managing future outbreaks of SARS-CoV-2. Our study showed no significant reduction in volume of trauma during lockdown. It is vital that hospitals maintain trauma capacity to ensure that patients are treated in a timely manner.

Association of site of treatment with clinical outcomes following intravenous antimicrobial treatment of a pulmonary exacerbation.

BACKGROUND: In the STOP2 (Standardized Treatment of Pulmonary Exacerbations-2) study, intravenous (IV) antimicrobial treatment duration for adults with cystic fibrosis (CF) experiencing pulmonary exacerbations (PEx) was determined based on initial treatment response. The impact of home vs hospital care remains an important clinical question in CF. Our hypothesis was that STOP2 participants treated at home would have less improvement in lung function compared to those treated in the hospital. METHODS: Treating clinicians determined PEx treatment location, which was a stratification factor for STOP2 randomization. Lung function, weight, and symptom recovery were evaluated by treatment location. Propensity scores and inverse probability treatment weighting were used to test for differences in clinical response by treatment location. RESULTS: In all, 33% of STOP2 participants received IV antimicrobials in the hospital only, 46% both in the hospital and at home, and 21% at home only. Mean (95% CI) ppFEV1 improvement was significantly (p < 0.05) lower for those treated at home only, 5.0 (3.5, 6.5), compared with at home and in the hospital, 7.0 (5.9, 8.1), and in the hospital only, 8.0 (6.7, 9.4). Mean weight (p < 0.001) and symptom (p < 0.05) changes were significantly smaller for those treated at home only compared to those treated in the hospital only. CONCLUSIONS: Compared to PEx treatment at home only, treatment in the hospital was associated with greater mean lung function, respiratory symptom, and weight improvements. The limitations of home IV therapy should be addressed in order to optimize outcomes for adults with CF treated at home.

Health disparities between Muslim and non-Muslim countries.

We examined differences in health indicators and associated factors across countries according to the proportion of the population who are Muslim. Of 190 UN countries, 48 were classified as Muslim-majority countries (MMC) and 142 as non-MMC. Data on 41 potential determinants of health were obtained from 10 different data sources, and 4 primary outcome measures (male and female life expectancy, maternal mortality ratio and infant mortality rate) were analysed. Annual per capita expenditure on health in MMC was one-fifth that of non-MMC. Maternal mortality and infant mortality rates were twice as high in MMC as non-MMC. Adult literacy rate was significantly higher for non-MMC. Four significant predictors explained 52%-72% of the differences in health outcomes between the 2 groups: gross national income, literacy rate, access to clean water and level of corruption.

Orthopaedic Practices and Surgeries during COVID-19 in Pakistan - A Survey Based Study.

INTRODUCTION: The study aimed to target the current practices of the orthopaedic community in outpatient (OPD), emergency (ER) and surgical services (OT) during COVID-19. MATERIAL AND METHOD: This study surveyed 303 orthopaedic surgeons from all over Pakistan. The survey had 30 questions targeting the setup of outpatient, emergency and operation services in orthopaedic departments of different hospitals in Pakistan. RESULT: A total of 302 surgeons were included from 53 cities all over Pakistan. Between 35-48% of the respondents reported lack of availability of standard operating procedures in OPD, ER and in OT. Majority of the respondents noted that their OPD and surgical practice had been affected to some degree and 69% of the surgeons were only doing trauma surgery. This trend was higher in younger consultants of less than 45 years of age (p<0.001). Almost two-third of the surgeons, mostly senior (p=0.03) were using surgical masks as the only protective measure during various practices of OPD, ER and OT, while most of the setups were not assessing patients even for signs and symptoms of COVID. Almost 89% of the orthopaedic community is facing definite to mild stress during this pandemic and this has significantly affected the senior surgeons (p=0.01). CONCLUSION: Our study highlighted that COVID-19 has resulted in marked changes to the practices of the majority of Pakistani orthopaedic surgeons. Despite a sharp upsurge in the number of cases and mortality due to COVID-19, guidelines were still lacking at most of the settings and a substantial percentage of the orthopaedic community were not following adequate safety measures while attending to patients.

Longitudinal characterisation of haematological and biochemical parameters in cancer patients prior to and during COVID-19 reveals features associated with outcome.

BACKGROUND: Cancer patients are at increased risk of death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer and its treatment affect many haematological and biochemical parameters, therefore we analysed these prior to and during coronavirus disease 2019 (COVID-19) and correlated them with outcome. PATIENTS AND METHODS: Consecutive patients with cancer testing positive for SARS-CoV-2 in centres throughout the United Kingdom were identified and entered into a database following local governance approval. Clinical and longitudinal laboratory data were extracted from patient records. Data were analysed using Mann-Whitney U test, Fisher's exact test, Wilcoxon signed rank test, logistic regression, or linear regression for outcomes. Hierarchical clustering of heatmaps was performed using Ward's method. RESULTS: In total, 302 patients were included in three cohorts: Manchester (n = 67), Liverpool (n = 62), and UK (n = 173). In the entire cohort (N = 302), median age was 69 (range 19-93 years), including 163 males and 139 females; of these, 216 were diagnosed with a solid tumour and 86 with a haematological cancer. Preinfection lymphopaenia, neutropaenia and lactate dehydrogenase (LDH) were not associated with oxygen requirement (O2) or death. Lymphocyte count (P < 0.001), platelet count (P = 0.03), LDH (P < 0.0001) and albumin (P < 0.0001) significantly changed from preinfection to during infection. High rather than low neutrophils at day 0 (P = 0.007), higher maximal neutrophils during COVID-19 (P = 0.026) and higher neutrophil-to-lymphocyte ratio (NLR; P = 0.01) were associated with death. In multivariable analysis, age (P = 0.002), haematological cancer (P = 0.034), C-reactive protein (P = 0.004), NLR (P = 0.036) and albumin (P = 0.02) at day 0 were significant predictors of death. In the Manchester/Liverpool cohort 30 patients have restarted therapy following COVID-19, with no additional complications requiring readmission. CONCLUSION: Preinfection biochemical/haematological parameters were not associated with worse outcome in cancer patients. Restarting treatment following COVID-19 was not associated with additional complications. Neutropaenia due to cancer/treatment is not associated with COVID-19 mortality. Cancer therapy, particularly in patients with solid tumours, need not be delayed or omitted due to concerns that treatment itself increases COVID-19 severity.