Prevalence and Risk Factors for Obstructive Sleep Apnea Syndrome Among Children and Adolescents with Cleft lip and Palate: A Survey Study in Hong Kong.

OBJECTIVE: To investigate the prevalence of obstructive sleep apnea syndrome (OSAS) risk and related risk factors among children and adolescents of Hong Kong with cleft lip and/or palate (CL/P). DESIGN: Retrospective survey study adopting three questionnaires, obstructive sleep apnea-18 (OSA-18), pediatric sleep questionnaire-22 (PSQ-22), and modified Epworth Sleepiness Scale (ESS). SETTINGS: Multicenter study in two public hospitals. PATIENTS: A total of 351 Chinese children and adolescents with non-syndromic CL/P (6-18-year-old, 57% males) visited between September 2017 and November 2019, with primary palatal repair surgery done before 3-year-old. MAIN OUTCOME MEASURE: Positive OSAS risk was determined based on cut-off ≥60 for OSA-18, ≥8 for PSQ-22, and >8 for ESS. Age, sex, overweight presence, cleft type, embryonic secondary palate involvement, palatal repair surgery, palatal revision surgery, and orthodontic treatment were analyzed as possible risk factors. RESULTS: A total of 9.5% of patients had positive OSAS risk based on OSA-18, 13.6% based on PSQ-22, and 13.2% according to ESS. A higher prevalence of patients with positive OSAS risk was of younger age (OSA-18, p = .034), had cleft involving embryonic secondary palate (PSQ-22, p = .009), and history of fixed orthodontic treatment (ESS, p = .002). The regression model identified only involvement of embryonic secondary palate as a risk factor (PSQ-22, odds ratio = 3.7, p = .015). CONCLUSIONS: OSAS risk among children and adolescents of Hong Kong with CL/P was 9.5% to 13.6%. Patients at higher risk were those with cleft involving embryonic secondary palate. OSAS risk assessment may be influenced by different aspects of the disease spectrum, and a multimodal approach should be considered for such assessment.

Surgical margin clearance and extended chemotherapy defines survival for synchronous oligometastatic liver lesions of the ductal adenocarcinoma of the pancreas.

BACKGROUND: The role of surgery for circumscribed synchronous hepatic lesions of the pancreatic ductal adenocarcinoma (PDAC) remains controversial. Thus, the aim of our study was to compare survival outcome (OS) after surgery of patients with hepatic metastases (M1surg) to patients with only localized disease. METHODS: Correlation analysis of clinicopathological data and OS after resection of M1surg patients and patients with localized PDACs (M0) was performed. Patients were included for survival analysis only if a complete staging including perineural, venous and lymphatic invasion was available. RESULTS: Out of the study collective, 35 patients received extended surgery (M1surg), whereas 131 patients received standardized surgery for localized disease (M0). Length of hospitalization and mortality was similar in both groups. FOLFIRNOX as an adjuvant treatment regime was administered in ~ 23 and ~ 8% of M1surg and M0 patients, respectively. In subgroup analysis of R0 resected patients and in multivariate analysis of the total cohort, there was no difference in overall survival between both groups. Only the resection status (R1 vs R0) and venous invasion (V1) were identified as independent prognostic factors. Site of recurrence in R0 resected M1surg patients and in M0 patients were homogenously distributed. CONCLUSION: This is the first study demonstrating a survival benefit after extended surgery for synchronously hepatic-metastasized PDACs. We found no difference in survival outcome of metastasized patients when compared to patients with localized disease. FOLFIRINOX as an adjuvant treatment regime for resected M1surg presumably is worthwhile. Larger multicenter studies are still needed to validate our results.

Orthodontic plate for management of obstructive sleep apnoea in infants with Pierre Robin sequence: experience and protocol in Hong Kong.

OBJECTIVE: To present the application of the pre-epiglottic baton plate (PEBP) in infants with Pierre Robin sequence (PRS) in the Southern Chinese population (Hong Kong) and to present the diagnosis and management protocol of these infants in our centre. DESIGN: Retrospective case series of three patients with PRS. SETTING: Neonatal Intensive Care Unit in Kwong Wah Hospital and Craniofacial Orthodontic Centre in United Christian Hospital, Hong Kong. PARTICIPANTS: Three new-born infants (two girls, one boy) with PRS and upper airway obstruction due to glossoptosis. METHODS: A protocol for the diagnosis and management of these infants in the Southern Chinese population (Hong Kong) was presented. The three patients received nasal high-flow oxygen and/or continuous positive airway pressure (CPAP) as first-line respiratory support, followed by PEBP for 3-5 months. A two-stage approach was undertaken to ensure accurate positioning of the PEBP. RESULTS: All three infants had improvement in clinical signs, symptoms and polysomnography upon discharge. PEBP and other respiratory aids were weaned off at 3-6 months. CONCLUSIONS: The PEBP, combined with other respiratory support, is a useful modality in the treatment of obstructive sleep apnoea in infants with PRS.

Measuring colposcopy quality in Canada: development of population-based indicators.

Background: Colposcopy is a key part of cervical cancer control. As cervical cancer screening and prevention strategies evolve, monitoring colposcopy performance will become even more critical. In the present paper, we describe population-based colposcopy quality indicators that are recommended for ongoing measurement by cervical cancer screening programs in Canada. Methods: The Pan-Canadian Cervical Cancer Screening Network established a multidisciplinary expert working group to identify population-based colposcopy quality indicators. A systematic literature review was conducted to ascertain existing population and program-level colposcopy quality indicators. A systems-level cervical cancer screening pathway describing each step from an abnormal screening test, to colposcopy, and back to screening was developed. Indicators from the literature were assigned a place on the pathway to ensure that all steps were measured. A prioritization matrix scoring system was used to score each indicator based on predetermined criteria. Proposed colposcopy quality indicators were shared with provincial and territorial screening programs and subsequently revised. Results: The 10 population-based colposcopy quality indicators identified as priorities were colposcopy uptake, histologic investigation (biopsy) rate, colposcopy referral rate, failure to attend colposcopy, treatment frequency in women 18-24 years of age, re-treatment proportion, colposcopy exit-test proportion, histologic investigation (biopsy) frequency after low-grade Pap test results, length of colposcopy episode of care, and operating room treatment rate. Two descriptive indicators were also identified: colposcopist volume and number of colposcopists per capita. Summary: High-quality colposcopy services are an essential component of provincial cervical cancer screening programs. The proposed quality and descriptive indicators will permit colposcopy outcomes to be compared between provinces and across Canada so as to identify opportunities for improving colposcopy services.

Cloning, overexpression, purification, and modeling of a lectin (Rhinocelectin) with antiproliferative activity from Tiger Milk Mushroom, Lignosus rhinocerus.

A lectin gene from the Tiger Milk Mushroom Lignosus rhinocerus TM02® was successfully cloned and expressed via vector pET28a in Escherichia coli BL21(DE3). The recombinant lectin, Rhinocelectin, with a predicted molecular mass of 22.8 kDa, was overexpressed in water-soluble form without signal peptide and purified via native affinity chromatography Ni-NTA agarose. Blast protein analysis indicated the lectin to be homologous to jacalin-related plant lectin. In its native form, Rhinocelectin exists as a homo-tetramer predicted with four chains of identical proteins consisting of 11 beta-sheet structures with only one alpha-helix structure. The antiproliferative activity of the Rhinocelectin against human cancer cell lines was concentration dependent and selective. The IC50 values against triple negative breast cancer cell lines MDA-MB-231 and breast cancer MCF-7 are 36.52 ± 13.55 µg mL-1 and 53.11 ± 22.30 µg mL-1 , respectively. Rhinocelectin is only mildly cytotoxic against the corresponding human nontumorigenic breast cell line 184B5 with IC50 value at 142.19 ± 36.34 µg mL-1 . The IC50 against human lung cancer cell line A549 cells is 46.14 ± 7.42 µg mL-1 while against nontumorigenic lung cell line NL20 is 41.33 ± 7.43 µg mL-1 . The standard anticancer drug, Doxorubicin exhibited IC50 values mostly below 1 µg mL-1 for the cell lines tested. Flow cytometry analysis showed the treated breast cancer cells were arrested at G0/G1 phase and apoptosis induced. Rhinocelectin agglutinated rat and rabbit erythrocytes at a minimal concentration of 3.125 µg mL-1 and 6.250 µg mL-1 , respectively.

"Ears of the Lynx" MRI Sign Is Associated with SPG11 and SPG15 Hereditary Spastic Paraplegia.

BACKGROUND AND PURPOSE: The "ears of the lynx" MR imaging sign has been described in case reports of hereditary spastic paraplegia with a thin corpus callosum, mostly associated with mutations in the spatacsin vesicle trafficking associated gene, causing Spastic Paraplegia type 11 (SPG11). This sign corresponds to long T1 and T2 values in the forceps minor of the corpus callosum, which appears hyperintense on FLAIR and hypointense on T1-weighted images. Our purpose was to determine the sensitivity and specificity of the ears of the lynx MR imaging sign for genetic cases compared with common potential mimics. MATERIALS AND METHODS: Four independent raters, blinded to the diagnosis, determined whether the ears of the lynx sign was present in each of a set of 204 single anonymized FLAIR and T1-weighted MR images from 34 patients with causal mutations associated with SPG11 or Spastic Paraplegia type 15 (SPG15). 34 healthy controls, and 34 patients with multiple sclerosis. RESULTS: The interrater reliability for FLAIR images was substantial (Cohen κ, 0.66-0.77). For these images, the sensitivity of the ears of the lynx sign across raters ranged from 78.8 to 97.0 and the specificity ranged from 90.9 to 100. The accuracy of the sign, measured by area under the receiver operating characteristic curve, ranged from very good (87.1) to excellent (93.9). CONCLUSIONS: The ears of the lynx sign on FLAIR MR imaging is highly specific for the most common genetic subtypes of hereditary spastic paraplegia with a thin corpus callosum. When this sign is present, there is a high likelihood of a genetic mutation, particularly associated with SPG11 or SPG15, even in the absence of a family history.

The north-south and east-west gradient in colorectal cancer risk: a look at the distribution of modifiable risk factors and incidence across Canada.

Colorectal cancer (crc) is the 2nd most common cancer in Canada and the 2nd leading cause of cancer death. That heavy burden can be mitigated given the preventability of crc through lifestyle changes and screening. Here, we describe the extent of the variation in crc incidence rates across Canada and the disparities, by jurisdiction, in the prevalence of modifiable risk factors known to contribute to the crc burden. Findings suggest that there is a north-south and east-west gradient in crc modifiable risk factors, including excess weight, physical inactivity, excessive alcohol consumption, and low fruit and vegetable consumption, with the highest prevalence of risk factors typically found in the territories and Atlantic provinces. In general, that pattern reflects the crc incidence rates seen across Canada. Given the substantial interjurisdictional variation, more work is needed to increase prevention efforts, including promoting a healthier diet and lifestyle, especially in jurisdictions facing disproportionately higher burdens of crc. Based on current knowledge, the most effective approaches to reduce the burden of crc include adopting public policies that create healthier environments in which people live, work, learn, and play; making healthy choices easier; and continuing to emphasize screening and early detection. Strategic approaches to modifiable risk factors and mechanisms for early cancer detection have the potential to translate into positive effects for population health and fewer Canadians developing and dying from cancer.

Measuring patient-reported outcomes to improve cancer care in Canada: an analysis of provincial survey data.

Patient-reported outcomes measures (proms) are an important component of the shift from disease-centred to person-centred care. In oncology, proms describe the effects of cancer and its treatment from the patient perspective and ideally enable patients to communicate to their providers the physical symptoms and psychosocial concerns that are most relevant to them. The Edmonton Symptom Assessment System-revised (esas-r) is a commonly used and validated tool in Canada to assess symptoms related to cancer. Here, we describe the extent to which patient-reported outcome programs have been implemented in Canada and the severity of symptoms causing distress for patients with cancer. As of April 2017, 8 of 10 provinces had implemented the esas-r to assess patient-reported outcomes. Data capture methods, the proportion of cancer treatment sites that have implemented the esas-r, and the time and frequency of screening vary from province to province. From October 2016 to March 2017 in the 8 reporting provinces, 88.0% of cancer patients were screened for symptoms. Of patients who reported having symptoms, 44.3% reported depression, with 15.5% reporting moderate-to-high levels; 50.0% reported pain, with 18.6% reporting moderate-to-high levels; 56.2% reported anxiety, with 20.4% reporting moderate-to-high levels; and 75.1% reported fatigue, with 34.4% reporting moderate-to-high levels. There are some notable areas in which the implementation of proms could be improved in Canada. Findings point to a need to increase the number of cancer treatment sites that screen all patients for symptoms; to standardize when and how frequently patients are screened across the country; to screen patients for symptoms during all phases of their cancer journey, not just during treatment; and to assess whether giving cancer care providers real-time patient-reported outcomes data has led to appropriate interventions that reduce the symptom burden and improve patient outcomes. Continued measurement and reporting at the system level will allow for a better understanding of progress in proms activity over time and of the areas in which targeted quality improvement efforts could ensure that patient symptoms and concerns are being addressed.

The experience of patients with cancer during diagnosis and treatment planning: a descriptive study of Canadian survey results.

BACKGROUND: Communication with health care providers during diagnosis and treatment planning is of special importance because it can influence a patient's emotional state, attitude, and decisions about their care. Qualitative evidence suggests that some patients experience poor communication with health care providers and have negative experiences when receiving their cancer diagnosis. Here, we use survey data from 8 provinces to present findings about the experiences of Canadian patients, specifically with respect to patient-provider communication, during the diagnosis and treatment planning phases of their cancer care. METHODS: Data from the Ambulatory Oncology Patient Satisfaction Survey, representing 17,809 survey respondents, were obtained for the study. RESULTS: Most respondents (92%) felt that their care provider told them of their cancer diagnosis in a sensitive manner. Most respondents (95%) also felt that they were provided with enough information about their planned cancer treatment. In contrast, more than half the respondents who had emotional concerns upon diagnosis (56%) were not referred to services that could help with their anxieties and fears. Also, 18% of respondents reported that they were not given the opportunity to discuss treatment options with a care provider, and 17% reported that their care providers did not consider their travel concerns while planning for treatment. CONCLUSIONS: Measuring the patient experience allows for an understanding of how well the cancer control system is addressing the physical, emotional, and practical needs of patients during diagnosis and treatment planning. Although results suggest high levels of patient satisfaction with some aspects of care, quality improvement efforts are still needed to provide person-centred care.

Brain antibodies in the cortex and blood of people with schizophrenia and controls.

The immune system is implicated in the pathogenesis of schizophrenia, with elevated proinflammatory cytokine mRNAs found in the brains of ~40% of individuals with the disorder. However, it is not clear if antibodies (specifically immunoglobulin-γ (IgG)) can be found in the brain of people with schizophrenia and if their abundance relates to brain inflammatory cytokine mRNA levels. Therefore, we investigated the localization and abundance of IgG in the frontal cortex of people with schizophrenia and controls, and the impact of proinflammatory cytokine status on IgG abundance in these groups. Brain IgGs were detected surrounding blood vessels in the human and non-human primate frontal cortex by immunohistochemistry. IgG levels did not differ significantly between schizophrenia cases and controls, or between schizophrenia cases in 'high' and 'low' proinflammatory cytokine subgroups. Consistent with the existence of IgG in the parenchyma of human brain, mRNA and protein of the IgG transporter (FcGRT) were present in the brain, and did not differ according to diagnosis or inflammatory status. Finally, brain-reactive antibody presence and abundance was investigated in the blood of living people. The plasma of living schizophrenia patients and healthy controls contained antibodies that displayed positive binding to Rhesus macaque cerebellar tissue, and the abundance of these antibodies was significantly lower in patients than controls. These findings suggest that antibodies in the brain and brain-reactive antibodies in the blood are present under normal circumstances.

Choosing wisely in cancer control across Canada-a set of baseline indicators.

Value-based care, which balances high-quality care with the most efficient use of resources, has been considered the next frontier in cancer care and a means to maintain health system sustainability. Created to promote value-based care, Choosing Wisely Canada-modelled after Choosing Wisely in the United States-is a national clinician-driven campaign to identify unnecessary or harmful services that are frequently used in Canada. As part of the campaign, national medical societies have developed recommendations for tests and treatments that clinicians and patients should question. Here, we present baseline indicator findings about current practice patterns associated with 7 cancer-related recommendations from Choosing Wisely Canada and about the effects of those practices on patients and the health care system. Indicator findings point to substantial variations in cancer system performance between Canadian jurisdictions, most notably for breast cancer screening practices, treatment practices for men with low-risk localized prostate cancer, and radiation therapy practices for early-stage breast cancer and bone metastases. Extrapolating indicator findings to the entire country, it was estimated that 740,000 breast and cervical cancer screening tests were performed outside of the recommended age ranges, and within 1 year of diagnosis, 17,000 patients received treatments that could be low-value. A 15% reduction in the use of the 7 screening and treatment practices examined could lead to multiple benefits for patients and the health care system: 9000 false-positive results and 3000 treatments and related side effects could be avoided, and 4500 hours of linear accelerator capacity could be freed up each year. Interjurisdictional performance variations suggest potential differences in clinical practice patterns in the planning and delivery of cancer control services, and in some cases, in disease management outcomes. Although the cancer screening and treatment practices described might be unnecessary for some patients, it is important to realize that they could, in fact, be necessary for other patients. Further research into appropriate rates of use could help to determine how much cancer care represents overuse of practices that are not supported by evidence or underuse of practices that are supported by evidence.

The prevalence of proximal hamstring pathology on MRI in the asymptomatic population.

PURPOSE: Injury to the proximal hamstring complex (PHC) is becoming more frequently diagnosed. Patients attending our tertiary referral centre demonstrated 'pathological changes' in the unaffected normal contralateral PHC on MRI. The prevalence of PHC pathology, however, has not been previously documented in the literature in asymptomatic subjects. It is the hypothesis of this study that the natural history of asymptomatic pathological change on MRI in the PHC is not clear. The aim is to quantify the natural history of PHC degeneration. METHOD: Two hundred and fifty-three consecutive patients with an asymptomatic PHC were reviewed retrospectively between 2009 and 2010. The PHC was assessed in multiple MRI planes by a specialist musculoskeletal consultant radiologist. RESULTS: Five hundred and six proximal hamstrings complexes were reviewed. Eighty-nine patients (35 %) were radiological normal both sides, median age 51 years (range 13-88). Thirty-four patients (13 %) had unilateral pathology, median age 55 years (range 25-89). Of these, 3 patients (1 %) had presence of a complete tear, median age 81 years (range 72-87). Sixteen patients (7 %) had tendinosis, median age 60 years (range 37-78). Fifteen patients (6 %) had a unilateral partial tear, median age 57 years (range 35-78). One hundred and thirty patients (52 %) had bilateral pathology, median age 65 years (range 25-89). Fifty-three patients (21 %) had the presence of bilateral tendinopathy alone, median age 56 years (range 25-89). Twenty-seven patients (11 %) had a partial tear on one side and tendinosis on the other, median age 68 years (range 38-89). Thirty-nine patients (15 %) had evidence of bilateral partial tears, median age 63 years (range 36-89), with 52 % demonstrating a torn conjoined and semi-membranosus tendon. The remaining 48 % had either an isolated tear of the conjoined or the semi-membranosus (the more commonly injured tendon 74 % of the time). Four patients (2 %) had bilateral complete ruptures with a median age of 68 years (range 59-78). Six patients (2 %) had a complete tear on one side and a partial tear on the other, median age 68 years (range 34-83). One patient had a complete tear on one side and tendinosis on the other, age 81 years. CONCLUSION: There is a higher prevalence of pathology in the asymptomatic population, 15 % have bilateral partial tears, and 2 % have bilateral complete tears. The semi-membranosus being the most affected, this may help clinically stratify the need for surgical intervention. LEVEL OF EVIDENCE: I.

Use of low-value radiotherapy practices in Canada: an analysis of provincial cancer registry data.

BACKGROUND: As part of Choosing Wisely Canada (a national campaign to encourage patient-provider conversations about unnecessary medical tests, treatments, and procedures), a list of ten oncology practices that could be low-value in some instances was developed. Of those practices, two were specific to radiation therapy (rt): conventional fractionation as part of breast-conserving therapy (bct) for women with early-stage breast cancer, and multifraction radiation for palliation of uncomplicated painful bone metastases. Here, we report baseline findings for the current utilization rates of those two rt practices in Canada. RESULTS: The use of conventional fractionation as part of bct varied substantially from province to province. Of women 50 years of age and older, between 8.8% (Alberta) and 36.5% (Saskatchewan) received radiation in 25 fractions (excluding boost irradiation) as part of bct. The use of hypofractionated rt (that is, 16 fractions excluding boost irradiation)-a preferred approach for many patients-was more common in all 6 reporting provinces, ranging from 43.2% in Saskatchewan to 94.7% in Prince Edward Island. The use of multifraction rt for palliation of bone metastases also varied from province to province, ranging from 40.3% in British Columbia to 69.0% in Saskatchewan. The most common number of fractions delivered to bone metastases was 1, at 50.2%; the second most common numbers were 2-5 fractions, at 41.7%. CONCLUSIONS: Understanding variation in the use of potentially low-value rt practices can help to inform future strategies to promote higher-value care, which balances high-quality care with the efficient use of limited system resources. Further work is needed to understand the factors contributing to the interprovincial variation observed and to develop benchmarks for the appropriate rate of use of these rt practices.

Predictors of response to tenofovir disoproxil fumarate plus peginterferon alfa-2a combination therapy for chronic hepatitis B.

BACKGROUND: In patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG-IFN) for 48-weeks results in higher rates of hepatitis B surface antigen (HBsAg) loss than either monotherapy. AIM: To identify baseline and on-treatment factors associated with HBsAg loss at Week 72 and provide a model for predicting HBsAg loss in patients receiving combination therapy for 48 weeks. METHODS: A secondary analysis of data from an open-label study where patients were randomised to TDF (300 mg/day, oral) plus PEG-IFN (PI, 180 µg/week, subcutaneous) for 48 weeks (TDF/PI-48w); TDF plus PEG-IFN for 16 weeks, TDF for 32 weeks (TDF/PI-16w+TDF-32w); TDF for 120 weeks (TDF-120w) or PEG-IFN for 48 weeks (PI-48w). Logistic regression methods were used to identify models that best predicted HBsAg loss at Week 72. RESULTS: Rates of HBsAg loss at Week 72 were significantly higher in the TDF/PI-48w group (6.5%) than in the TDF/PI-16w+TDF-32w (0.5%), TDF-120w (0%) and PI-48w (2.2%) groups (P = 0.09). The only baseline factor associated with response was genotype A. HBsAg decline at Week 12 or 24 of treatment was associated with HBsAg loss at Week 72 (P < 0.001). HBsAg decline >3.5 log10 IU/mL at Week 24 in the TDF/PI-48w group resulted in a positive predictive value of 85% and a negative predictive value of 99% for HBsAg loss at Week 72. CONCLUSIONS: HBsAg decline at Week 24 of TDF plus PEG-IFN combination therapy may identify patients who, after completing 48 weeks of treatment, have a better chance of achieving HBsAg loss at Week 72.