Health Canada advisory impacts on the prevalence of oral codeine use in the Pediatric Canadian population: comparative study across provinces.

Health Canada (HC) has, since 2013, issued safety alerts restricting the use of codeine-containing drugs among breastfeeding women and children/adolescents under 18 years of age. These products are linked to breathing problems among ultra-rapid CYP2D6 metabolizers and early use of opioid can lead to future opioid misuse. Using a multi-province population-based cohort study, we estimate the impact of federal safety alerts on annual rates of codeine use in the Canadian pediatric population. We analyzed data from 8,156,948 children/adolescents in five Canadian provinces between 1996 and 2021, using a common protocol. Children/adolescents were categorized as: ≤ 12 years (children) or > 12 years (adolescents). We defined codeine exposure by ≥ 1 prescription filled for codeine alone or combined with other medications. For both age categories, we obtained province-specific codeine prescription filling rates per calendar year by dividing the number of children/adolescents with ≥ 1 codeine prescription filled by the number of person-time. Annual rates of codeine use per 1000 persons vary by province from 3.0 (Quebec) to 10.1 (Manitoba) in children, and from 5.5 to 51.3 in adolescents. After the 2013 HC advisory, exposure decreased in all provinces (adjusted level change from - 0.6 to - 18.4%) in children and from - 2.1 to - 17.9% in adolescents after the 2016 advisory. Annual rates declined over time in all provinces, following HC safety alerts specific to each of the two age categories.

The hospital frailty risk score in patients with heart failure is strongly associated with outcomes but less so with pharmacotherapy.

BACKGROUND: Although frailty is known to be an important prognostic factor in heart failure (HF), HF risk-adjustment models do not incorporate frailty measures and the interplay between frailty, age and pharmacotherapy is unclear. OBJECTIVES: To explore the relationships between frailty, pharmacotherapy and outcomes in heart failure (HF). METHODS: Retrospective cohort study of all adults in Alberta, Canada hospitalized for the first time for HF between 2004 and 2016. Frailty was defined using the Hospital Frailty Risk Score (HFRS). RESULTS: In 26 626 patients (mean age 77.4 years), the 8887 (33.4%) defined as frail (HFRS ≥ 5) were older, had higher Charlson scores and more prior emergency department visits or hospitalizations. The HFRS and the Charlson Score were only weakly correlated (r = 0.35). Whilst more common in older patients (41.4% of patients 80 or older), frailty was present in 22.4% of patients younger than 65. Frail patients had longer lengths of stay and worse outcomes postdischarge, but adding the HFRS to age, sex and Charlson score did not improve prediction of events (c-statistics 0.69 for 30-day mortality after admission, and 0.54 for 30-day readmission/ED visit/or death after discharge). Frail patients younger than 65 were significantly more likely than nonfrail patients 80 or older to be prescribed high-dose evidence-based HF therapies (27.1% vs. 22.2%, P = 0.003). CONCLUSION: Although the HFRS reflects aspects of frailty that patient age and Charlson scores do not, the addition of the HFRS to standard risk prediction equations provides little additional information. Prescribing practices correlate more with patient age than frailty status.

Elevated fasting vs post-load glucose levels and pregnancy outcomes in gestational diabetes: a population-based study.

AIMS: To examine the relative association between fasting plasma glucose vs post-load (1-h and 2-h) glucose levels based on the oral glucose tolerance test in pregnancy and large-for-gestational-age and hypertensive disorders of pregnancy outcomes. METHODS: All live singleton births between October 2008 and December 2014 in Alberta, Canada were included. Gestational diabetes mellitus was diagnosed using Diabetes Canada criteria. Logistic regression models were used to examine the association between fasting plasma glucose vs post-load values and large-for-gestational-age infants and hypertensive disorders of pregnancy after adjusting for maternal characteristics and pharmaceutical intervention in gestational diabetes pregnancies. RESULTS: Among 257 547 pregnancies, 208 344 (80.9%) had negative 50-g glucose challenge tests, 36 261 (14.1%) had negative 75-g oral glucose tolerance tests, and 12 942 (5.0%) had gestational diabetes based on either elevated fasting plasma glucose (n=4130, 1.6%) or elevated 1-h and/or 2-h oral glucose tolerance test values (n=8812, 3.4%). Large-for-gestational-age and hypertensive disorders of pregnancy rates were 8.1% and 5.1% in negative glucose challenge test pregnancies, 11.0% and 7.0% in negative oral glucose tolerance test pregnancies, 22.4% and 11.9% in gestational diabetes pregnancies with elevated fasting plasma glucose, and 9.1% and 8% in gestational diabetes pregnancies with elevated post-load levels, respectively. Among gestational diabetes pregnancies, those with elevated fasting plasma glucose were at higher risk of large-for-gestational age (adjusted odds ratio 2.66, 95% CI 2.39-2.96) and hypertensive disorders of pregnancy (adjusted odds ratio 1.51, 95% CI 1.33-1.72) outcomes relative to pregnancies with post-load glucose elevations only. Fasting plasma glucose remained significantly associated with adverse outcomes in gestational diabetes pregnancies with and without pharmacological intervention. CONCLUSIONS: Elevated fasting plasma glucose in women with gestational diabetes is a stronger predictor of large-for-gestational-age and hypertensive disorders of pregnancy outcomes than elevated post-load glucose.

History of mood or anxiety disorders and risk of gestational diabetes mellitus in a population-based cohort.

AIM: To examine the association between mood and anxiety disorders and the development of gestational diabetes mellitus in a retrospective population-based cohort study. METHODS: Clinical data from a provincial perinatal health registry were linked to physician claims, hospitalization records and emergency visits to identify any diagnoses of mood or anxiety disorders in the 2 years prior to pregnancy and a subsequent diagnosis of gestational diabetes during pregnancy. The study population included all singleton pregnancies in the Canadian province of Alberta from 1 April 2000 to 31 March 2010. Generalized estimating equations were used to determine the adjusted odds ratio of gestational diabetes, comparing women with and without a history of mood or anxiety disorders. RESULTS: Among 373 674 pregnancies from 253 911 women, 25.7% had a history of mood or anxiety disorders, and 3.8% developed gestational diabetes. The multivariate-adjusted odds of developing gestational diabetes were higher among women with a history of mood or anxiety disorders (odds ratio 1.10, 95% CI 1.06-1.14). CONCLUSIONS: Women with a history of mood or anxiety disorders had a moderately increased risk of developing gestational diabetes.

Patterns of glucose-lowering therapies and neonatal outcomes in the treatment of gestational diabetes in Canada, 2009-2014.

AIM: To examine patterns of use of different glycaemic control agents for treating gestational diabetes mellitus. METHODS: This was a large, retrospective, population-based cohort study of pregnant women with gestational diabetes from Alberta, Canada. We linked data from the Alberta Vital Statistics - Birth database with administrative claims data. Alberta Vital Statistics - Birth data were used to identify births that occurred between 1 January 2009 and 31 December 2014. We used International Classification of Diseases version 9/10 codes to identify women with gestational diabetes, and we excluded women with pre-existing diabetes. RESULTS: Our cohort consisted of 16 857 women with gestational diabetes, with a total of 18 761 birth events between 2009 and 2014. Over the study period, the proportion of women with gestational diabetes who were treated with glycaemic control therapies increased from 25.0% to 31.4% (P<0.0001). The number of pregnancies treated with insulin only increased (from 23.6% to 28.3%; P<0.0001), as did the number treated with metformin, +/- insulin (from 1.4% to 3.2%; P<0.0001). Rates of large-for-gestational-age infants were significantly higher among pregnancies treated with insulin only (17%) or metformin (16.5%) than among pregnancies that did not receive any pharmacological treatment (12.8%). CONCLUSIONS: Our findings show increasing use of insulin and metformin in women with gestational diabetes. Rates of large-for-gestational-age infants were similar among pregnant women receiving either pharmacological treatment, and higher than among pregnant women who did not receive any pharmacological treatment. Future research should explore the long-term outcomes and safety of metformin as an alternative for treating gestational diabetes.

Population-Level Outcomes with a 2-Step Approach for Gestational Diabetes Screening and Diagnosis.

OBJECTIVES: To examine outcomes associated with alternative glucose thresholds in a 2-step approach for screening and diagnosing gestational diabetes mellitus (GDM). METHODS: We studied 178,527 pregnancies between 2008 and 2012 in Alberta, Canada. They were categorized retrospectively as normal 50 g screen (n=144,191); normal 75 g oral glucose tolerance test (OGTT) (n=21,248); abnormal at glucose thresholds suggested by the International Association of Diabetes and Pregnancy Group (IADPSG) (HAPO 1.75, n=4308); abnormal at glucose thresholds associated with an odds ratio of 2.0 for adverse events in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. This latter group, which would have been treated for GDM based on customary care, was further divided into those with 1 (HAPO 2-1 n=5528) or 2 or more abnormal glucose values (HAPO 2-2 n=3252). Main outcomes were large for gestational age (LGA), induced labour and Cesarean-section rates. RESULTS: LGA rates were 8.2%, 10.5%, 14.2%, 11.8% and 16.5% among normal 50 g, normal 75 g OGTT, HAPO 1.75, HAPO 2-1, and HAPO 2-2 groups, respectively. Labour induction and caesarean-section rates were 29.6% and 36.2% in the IADPSG, 38.2% and 36.8% in the HAPO 2-1 group, and 42.3% and 41.1% in the HAPO 2-2 groups, respectively. Excessive maternal weight (≥91 kg) was associated with a higher risk for all adverse outcomes. CONCLUSIONS: The 2-step approach effectively identifies pregnancies at low risk for adverse outcomes. Labelling influences induction practice. Any glucose intolerance increases risk for adverse outcomes, and pregnancies with highest (2 or higher) abnormal glucose values remain at greatest risk. Further research is needed to determine whether glycemic thresholds for GDM diagnosis should incorporate information about maternal weight.

Validation of administrative data case definitions for gestational diabetes mellitus.

AIM: To examine, using administrative data, the validity of two algorithms for identifying gestational diabetes mellitus: 1) the current National Diabetes Surveillance System algorithm for excluding gestational diabetes cases and 2) gestational diabetes-specific ICD codes in the delivery-related hospitalization. METHODS: This was a retrospective study of all women, aged 18-54 years, residing in Alberta, Canada, with singleton deliveries between 1 April 1999 and 31 March 2010. We linked Alberta Perinatal Health Program data on all deliveries to administrative claims data from Alberta Health using the mother's personal health number. For both gestational diabetes algorithms, we calculated the sensitivity, specificity, positive predictive value, negative predictive value and agreement, using gestational diabetes identified in the Alberta Perinatal Health Program as the 'gold standard'. RESULTS: Our study sample consisted of 411 390 deliveries for 273 152 women. The mean (sd) age was 29.1 (5.6) years and 82.3% of the women were white. Crude rates of gestational diabetes were 3.9% (16 215 cases), 1.3% (5189 cases) and 4.0% (16 440 cases) according to the Alberta Perinatal Health Program, National Diabetes Surveillance System and ICD code-based algorithms, respectively. Compared with the Alberta Perinatal Health Program database, the National Diabetes Surveillance System algorithm had a sensitivity of 25% and specificity of 100%, whereas the gestational diabetes-specific ICD code-based algorithm had a sensitivity of 86% and specificity of 99%. CONCLUSIONS: The National Diabetes Surveillance System algorithm underestimates the number of gestational diabetes cases. A more valid mechanism to identify gestational diabetes prevalence using health administrative data is the use of gestational diabetes-specific ICD-9/10 codes in the delivery hospitalization.

Validation of administrative and clinical case definitions for gestational diabetes mellitus against laboratory results.

AIM: To examine the validity of International Classification of Disease, version 10 (ICD-10) codes for gestational diabetes mellitus in administrative databases (outpatient and inpatient), and in a clinical perinatal database (Alberta Perinatal Health Program), using laboratory data as the 'gold standard'. METHODS: Women aged 12-54 years with in-hospital, singleton deliveries between 1 October 2008 and 31 March 2010 in Alberta, Canada were included in the study. A gestational diabetes diagnosis was defined in the laboratory data as ≥2 abnormal values on a 75-g oral glucose tolerance test or a 50-g glucose screen ≥10.3 mmol/l. RESULTS: Of 58 338 pregnancies, 2085 (3.6%) met gestational diabetes criteria based on laboratory data. The gestational diabetes rates in outpatient only, inpatient only, outpatient or inpatient combined, and Alberta Perinatal Health Program databases were 5.2% (3051), 4.8% (2791), 5.8% (3367) and 4.8% (2825), respectively. Although the outpatient or inpatient combined data achieved the highest sensitivity (92%) and specificity (97%), it was associated with a positive predictive value of only 57%. The majority of the false-positives (78%), however, had one abnormal value on oral glucose tolerance test, corresponding to a diagnosis of impaired glucose tolerance in pregnancy. CONCLUSIONS: The ICD-10 codes for gestational diabetes in administrative databases, especially when outpatient and inpatient databases are combined, can be used to reliably estimate the burden of the disease at the population level. Because impaired glucose tolerance in pregnancy and gestational diabetes may be managed similarly in clinical practice, impaired glucose tolerance in pregnancy is often coded as gestational diabetes.

Success, clinical performance and patient satisfaction of direct fibre-reinforced composite fixed partial dentures - a two-year clinical study.

To evaluate the success, clinical performance and patient satisfaction of directly placed fibre-reinforced composite (FRC) fixed partial dentures (FPDs) in 2 years. One hundred sixty-seven FRC FPDs (120 subjects) were directly fabricated to restore a single missing tooth by six Advanced Education in General Dentistry (AEGD) residents. The FRC FPDs recipients were randomised into two groups according to the fibre materials (pre-impregnated glass or polyethylene). Clinical performance was evaluated at baseline (2 weeks), 6, 12 and 24 months by two calibrated evaluators for prosthesis adaptation, colour match, marginal discoloration, surface roughness, caries and post-operative sensitivity using modified United State Public Health Service (USPHS) criteria. Prosthesis appearance, colour, chewing ability and overall satisfaction were evaluated by patients using a visual analogue scale (VAS). Kaplan-Meier estimation was used to estimate the prosthesis success. Ninety-four patients with 137 FRC FPDs returned (21·67% attrition rate for study subjects, 17·94% for FRC FPDs). Seventeen FRC FPDs failed, due to one-end (n = 4) or two-ends (n = 4) debonding or pontic fracture (n = 9). The cumulative 2-year success rate was 84·32% and survival rate was 92·7%; there were no statistically significant differences between the groups according to different missing tooth location, retention type or fibre materials (P > 0·05). Patient satisfaction regarding prosthesis appearance, col-our, chewing ability and overall satisfaction was rated high on the VAS (mean >80 mm) for all criteria at all time points. The FRC FPDs (restoring single tooth) fabricated by AEGD residents achieved acceptable success and survival rates in a 2-year follow-up.

Impact of gestational diabetes mellitus and high maternal weight on the development of diabetes, hypertension and cardiovascular disease: a population-level analysis.

AIMS: To examine the association between gestational diabetes mellitus (GDM) and high maternal weight and the risk of development of chronic disease. METHODS: Women with singleton deliveries between April 1999 and March 2010 in Alberta, Canada, were categorized according to pre-pregnancy weight (overweight ≥ 91 kg) and GDM status. Obstetric and neonatal outcomes, as well as the long-term incidence of maternal diabetes, hypertension and cardiovascular disease were examined. RESULTS: Of 240 083 women, 213 765 (89%) had no GDM and were not overweight (reference group), 17 587 (7.3%) were overweight only, 7332 (3%) had GDM only and 1399 (0.6%) had GDM and were overweight. Significant differences in Caesarean section rates, induction rates and birthweight were observed across the four groups. During a median follow-up of 5.3 years, diabetes incidence was 36% in the GDM and overweight, 18.8% in the GDM only, 4.8% in the overweight only and 1.1% in the reference group. With respect to hypertension and cardiovascular disease, the GDM and overweight group had the highest rates (26.8% and 3.1%, respectively) and the reference group had the lowest rates (5.8% and 1.0%, respectively). However, rates were similar in the GDM only (14.9% and 1.9%, respectively) and overweight only groups (14.9% and 1.5%, respectively). CONCLUSIONS: Not surprisingly, the presence of both high maternal weight and GDM compounds the risk of developing diabetes. However, the association between overweight alone and GDM alone and hypertension and cardiovascular disease appears similar suggesting a need for effective interventions to manage both these conditions to improve the health of these patients.

[Intestinal occlusion by persistence of the omphalo-enteric conduct in a 10-year old child]. / Ocluzie intestinala prin persistenta de canal omfalo-enteric la un copil de 10 ani.

The persistence of the omphalo-enteric conduct is a rare, but possible, cause of pathology in children. Haemorrhage and intestinal occlusion are the most frequent clinical presentations, usually in infants. We describe the case of a 10 year old boy, who was admitted in our department for what seemed first to be an acute appendicitis. During hospitalization, the clinical picture turned on to an intestinal occlusion, and the patient finally required surgery. We performed exploratory laparotomy and we discovered a mechanical occlusion by persistence of the omphalo-enteric conduct, which was treated according to standard protocols. The post-operative course was good, and the child was discharged 8 days after surgery. This case emphasizes that the persistence of the omphalo-enteric conduct should be sought as the source of symptoms in any child presenting with intestinal occlusion.

[The advantages of Reprimum therapy in pulmonary sarcoidosis and other granulomatous diseases]. / Avantajele terapiei cu Reprimum în sarcoidoza pulmonara si alte boli granulomatoase.

In sarcoidosis and other granulomatous non-caseous diseases, the election treatment is immunosuppressive, mainly with cortisones that ensure more than 70% lasting remissions. Continuous use of cortisones for a long time (8-30 months) in high doses leads to serious side effects: gastric and intestinal ulcers, obesity, osteoporosis, suprarenal dysfunction, sensitivity to infections. Good results and elimination of the important side effects were obtained by treatment with Reprimum--a semisynthetic antibiotic with a wide spectrum and immunosuppressive properties--administered alone or with prednisone in small doses (15-20 mg once) in 6 weeks' series: 2 weeks--Reprimum 10/mg/kg daily +/- prednisone and for other 4 weeks--Reprimum 15 mg/kg twice a week +/- prednisone followed by two weeks' break. In 75 patients with histopathologically confirmed sarcoidosis (of whom 7-9.3% with outside-the-lung situs, too), the treatment with Reprimum gave: 94.7% lasting remission, only 5.3% failures, reduction of the treatment period to 6-12 months and the absence of any important side reaction. In other 37 sarcoidosis cases, failures of cortisone therapy (of which 11-30% relapses after 2-6 years), the treatment with Reprimum together with prednisone allowed recovery of 29 patients (78.4%). The same treatment with Reprimum, used in 22 patients with immunosuppressive treatment indication (dermatomyositis, Kaposi's syndrome, thrombocytopenias, nodose periarteritis, silicosis), of whom 18 (81.8%) were failures of the cortisone therapy, healed 20 of these cases (90.9%). Reprimum immunosuppressive property acts at the level of T4+ lymphocyte, involved in sarcoidosis pathogenesis. The functional blockage of T4+ lymphocyte can be also achieved by cyclosporine A.(ABSTRACT TRUNCATED AT 250 WORDS)