Polymeric additives to induce competitive crystallization of pharmaceutical compounds were explored. A cocrystal of theophylline and oxalic acid was used as a model system, and poly(acrylic acid), ...poly(caprolactone), and poly(ethylene glycol) were the additives. The cocrystal formation was selectively hindered with addition of poly(acrylic acid). First the size of the cocrystals were reduced, and eventually the cocrystallization was inhibited to generate neat theophylline crystals. The theophylline crystals were of a distinctively different crystal structure from known polymorphs, based on powder X-ray diffraction. They were also obtained in nanoscale size, when millimeter-scale crystals formed without poly(acrylic acid). Polymeric additives that could form specific interactions with crystallizing compounds seem to be useful tools for the phase and size control of pharmaceutical crystals.
•Polymeric additives as modifiers of pharmaceutical crystallization.•Effects of polymers on the cocrystallization of theophylline and oxalic acid.•Competitive crystallization between the cocrystal and neat theophylline.•Poly(acrylic acid) to inhibit the cocrystallization and form a theophylline polymorph.
Although the incidence of inflammatory bowel disease IBD is increasing in Asia, data on long-term epidemiological trends are limited. We performed a 30-year longitudinal study to investigate temporal ...trends in the epidemiology of Crohn's disease CD and ulcerative colitis UC in Seoul, Korea.
This population-based study included 1431 IBD patients 418 CD, 1013 UC diagnosed between 1986 and 2015 in the Songpa-Kangdong district of Seoul, Korea. Temporal trends in incidence, prevalence, and disease phenotype at diagnosis were analysed.
The adjusted mean annual incidence rates of CD and UC per 100 000 inhabitants increased from 0.06 (95% confidence interval CI, 0.05-0.07) and 0.29 95% CI, 0.27-0.31, respectively, in 1986-1990 to 2.44 95% CI, 2.38-2.50 and 5.82 95% CI, 5.73-5.92, respectively, in 2011-2015. Average annual percentage change in IBD incidence was 12.3% in 1986-1995, 12.3% in 1996-2005, and 3.3% in 2006-2015. The male-to-female ratio of the adjusted incidence rate was 3.3:1 for CD and 1.2:1 for UC. Perianal fistula/abscess was present in 43.3% of patients before or at CD diagnosis. At diagnosis, 54.3% of UC patients presented only with proctitis. The adjusted prevalence rate in 2015 was 31.59/100 000 95% CI, 31.10-32.07 for CD and 76.66/100 000 95% CI, 75.91-77.42 for UC.
The incidence and prevalence of IBD in Korea have continued to increase over the past three decades. Korean patients have distinct demographic and phenotypic characteristics, including a male predominance and high frequency of perianal fistula/abscess in CD and high proportion of proctitis in UC.
No population-based study has evaluated the natural course of UC over three decades in non-Caucasians. We aimed to assess the long-term natural course of Korean patients with UC in a population-based ...cohort.
This Korean population-based, Songpa-Kangdong IBD cohort included all patients (n=1013) newly diagnosed with UC during 1986-2015. Disease outcomes and their predictors were evaluated.
During the median follow-up of 105 months, the overall use of systemic corticosteroids, thiopurines and antitumour necrosis factor (anti-TNF) agents was 40.8%, 13.9% and 6.5%, respectively. Over time, the cumulative risk of commencing corticosteroids decreased, whereas that of commencing thiopurines and anti-TNF agents increased. During follow-up, 28.7% of 778 patients with proctitis or left-sided colitis at diagnosis experienced proximal disease extension. A total of 28 patients (2.8%) underwent colectomy, demonstrating cumulative risks of colectomy at 1, 5, 10, 20 and 30 years after diagnosis of 1.0%, 1.9%, 2.2%, 5.1% and 6.4%, respectively. Multivariate Cox regression analysis revealed that extensive colitis at diagnosis (HR 8.249, 95% CI 2.394 to 28.430), ever use of corticosteroids (HR 6.437, 95% CI 1.440 to 28.773) and diagnosis in the anti-TNF era (HR 0.224, 95% CI 0.057 to 0.886) were independent predictors of colectomy. The standardised mortality ratio in patients with UC was 0.725 (95% CI 0.508 to 1.004).
Korean patients with UC may have a better clinical course than Western patients, as indicated by a lower colectomy rate. The overall colectomy rate has continued to decrease over the past three decades.
There is little consensus about the best management of pediatric deep neck space infections (DNSIs) and limited information about the national disease burden. The purpose of this study is to examine ...the health care burden, management, and complications of DNSIs from a national perspective.
Retrospective administrative data set review.
National pediatric admission database.
Pediatric patients diagnosed with a parapharyngeal space and/or retropharyngeal abscess were identified from the 2009 KIDS' Inpatient Database. Patient demographic, hospital, and clinical characteristics were compared between patients who received surgical and nonsurgical management. All results for the analyses were weighted, clustered, and stratified appropriately according to the sampling design of the KIDS' Inpatient Database.
The prevalence of DNSIs was 3444 in 2009, and the estimated incidence was 4.6 per 100,000 children. The total hospital charges were >$75 million. The patients who were drained surgically had a 22% longer length of stay (mean = 4.19 days) than that of those who were managed without surgery (mean = 3.44 days). Mean hospital charges for patients who were drained surgically were almost twice those of patients who were managed medically ($28,969 vs $17,022); 165 patients (4.8%) had a complication.
There are >3400 admissions for pediatric DNSIs annually, and they account for a significant number of inpatient days and hospital charges. A randomized controlled trial of management may be indicated from a public health perspective.
Pharmaceutical eutectics are solid mixtures, where the crystals of active pharmaceutical ingredients (APIs) are finely divided in the phase-separated microstructures. The size reduction makes the ...eutectic formation a viable option to improve the dissolution rate of the poorly soluble APIs. In the present study, ibuprofen, naproxen, and sorafenib were investigated in terms of their phase behaviors with fatty alcohols, such as tetradecanol, octadecanol, and docosanol. Among the studied APIs, only ibuprofen was able to form eutectics with the fatty alcohols, and this was in agreement with the feasibility prediction based on the van ’t Hoff equation and solubility parameters. In vitro release behavior was significantly improved for the ibuprofen/octadecanol eutectic mixture, although the practical insolubility of octadecanol in water was the opposite of the outstanding hydrophilicity of usual eutectic formers. The feasibility prediction and the choice of eutectic formers in the present study will be useful in advancing the utility of the pharmaceutical eutectics.
The long-term course of Crohn's disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the longterm prognosis of Korean CD ...patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort.
Outcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015.
During a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p<0.001). The cumulative probability of behavioral progression was 54.5% at 20 years, and it significantly decreased during the anti-TNF era. Intestinal resection was required for 113 patients (27.0%). The cumulative probabilities of intestinal resection at 1, 5, 10, 20, and 25 years after CD diagnosis were 12.7%, 16.5%, 23.8%, 45.1%, and 51.2%, respectively. Multivariable Cox regression analysis identified stricturing behavior at diagnosis (adjusted hazard ratio aHR, 2.70; 95% confidence interval CI, 1.55 to 4.71), penetrating behavior at diagnosis (aHR, 11.15; 95% CI, 6.91 to 17.97), and diagnosis of CD during the anti-TNF era (aHR, 0.51; 95% CI, 0.35 to 0.76) as independently associated with intestinal resection. The standardized mortality ratio among CD patients was 1.36 (95% CI, 0.59 to 2.68).
The long-term prognosis of Korean patients with CD is at least as good as that of Western CD patients, as indicated by the low intestinal resection rate. Moreover, behavioral progression and intestinal resection rates have decreased over the past 3 decades.
Objectives To describe the prevalence of apnea in otherwise healthy term newborns, identify attributable length of stay (LOS) and healthcare utilization (cost) of apnea, and measure hospital ...variation in attributable LOS and cost of apnea in this population. Study design We conducted a secondary analysis of a national administrative dataset, the 2012 Kids' Inpatient Database, which included 3.4 million newborn discharges in the US. The birth hospitalizations of approximately 2.6 million otherwise healthy, full-term newborns were included for analysis. Attributable LOS and cost of apnea were calculated using multivariate analyses. Results Apnea was diagnosed in 1 in 1000 healthy full-term newborns. Multivariate analyses showed that newborns with apnea had 0.6 days longer LOS ( P < .001) and $483 greater costs ( P < .001) compared with healthy term newborns, per birth hospitalization. Newborns diagnosed with apnea plus hypoxia and/or bradycardia had 1.4 days longer LOS ( P < .001) and $653 greater costs ( P < .001). The attributable LOS and cost attributable to apnea varied between individual hospitals and differed by hospital region. Conclusions Apnea is associated with higher LOS and cost in the newborn hospitalization, with variation in hospital practice. This suggests the need for better comprehension of the underlying physiology and standardization of practice in its management in the term newborn.
We aimed to evaluate the clinical characteristics and long-term prognosis of elderly-onset ulcerative colitis (EOUC) in Korean patients over a 30-year period using a wellestablished population-based ...cohort in the Songpa-Kangdong district of Seoul, Korea.
Clinical characteristics and prognosis were compared between two groups: EOUC, defined as UC diagnosed in individuals aged ≥60 years and non-EOUC (N-EOUC), defined as UC diagnosed in individuals aged 18 to 59 years.
We identified 99 patients with EOUC (10.3%) and 866 patients with N-EOUC (89.7%) between 1986 and 2015. During the median follow-up of 104.5 months, the overall exposure to medications was comparable between patients with EOUC and N-EOUC (p=0.091 for corticosteroids, p=0.794 for thiopurines, and p=0.095 for anti-tumor necrosis factor agents). The cumulative risks of disease outcomes were also comparable between patients with EOUC and N-EOUC (22.4% vs 30.4% for proximal disease extension p=0.351, 11.9% vs 18.1% for hospitalization p=0.240, and 2.3% vs 1.8% for colectomy p=0.977) at 10 years after diagnosis. Multivariate Cox regression analysis revealed that corticosteroid use at diagnosis was an independent predictor of proximal disease extension (hazard ratio HR, 6.216; 95% confidence interval CI, 1.314 to 28.826) and hospitalization (HR, 11.241; 95% CI, 3.027 to 41.742) in patients with EOUC.
In this population-based study from Korea, the pattern of medication use seemed comparable between the EOUC and N-EOUC groups. Moreover, patients with EOUC and those with N-EOUC have a similar disease course in terms of proximal disease extension, hospitalization, and colectomy.
Hospital quality-of-care measures are publicly reported to inform consumer choice and stimulate quality improvement. The number of hospitals and states with enough pediatric hospital discharges to ...detect worse-than-average inpatient care remains unknown.
This study was a retrospective analysis of hospital discharges for children aged 0 to 17 years from 3974 hospitals in 44 states in the 2009 Kids' Inpatient Database. For 11 measures of all-condition or condition-specific quality, we assessed the number of hospitals and states that met a "power standard" of 80% power for a 5% level significance test to detect when care is 20% worse than average over a 3-year period. For this assessment, we approximated volume as 3 times actual 2009 admission volumes.
For all-condition quality, 1380 hospitals (87% of all pediatric discharges) and all states met the power standard for the family experience-of-care measure; 1958 hospitals (95% of discharges) and all states met the standard for adverse drug events. For condition-specific quality measures of asthma, birth, and mental health, 203 to 482 hospitals (52%-90% of condition-specific discharges) met the power standard and 40 to 44 states met the standard. One hospital and 16 states met the standard for sickle cell disease. No hospital and ≤27 states met the standard for the remaining measures studied (appendectomy, cerebrospinal fluid shunt surgery, gastroenteritis, heart surgery, and seizure).
Most children are admitted to hospitals in which all-condition measures of quality have adequate power to show modest differences in performance from average, but most condition-specific measures do not. Policies regarding incentives for pediatric inpatient quality should take these findings into account.
Background/Aims: The long-term course of Crohn’s disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the longterm prognosis ...of Korean CD patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort.
Methods: Outcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015.
Results: During a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p<0.001). The cumulative probability of behavioral progression was 54.5% at 20 years, and it significantly decreased during the anti-TNF era. Intestinal resection was required for 113 patients (27.0%). The cumulative probabilities of intestinal resection at 1, 5, 10, 20, and 25 years after CD diagnosis were 12.7%, 16.5%, 23.8%, 45.1%, and 51.2%, respectively. Multivariable Cox regression analysis identified stricturing behavior at diagnosis (adjusted hazard ratio aHR, 2.70; 95% confidence interval CI, 1.55 to 4.71), penetrating behavior at diagnosis (aHR, 11.15; 95% CI, 6.91 to 17.97), and diagnosis of CD during the anti-TNF era (aHR, 0.51; 95% CI, 0.35 to 0.76) as independently associated with intestinal resection. The standardized mortality ratio among CD patients was 1.36 (95% CI, 0.59 to 2.68).
Conclusions: The long-term prognosis of Korean patients with CD is at least as good as that of Western CD patients, as indicated by the low intestinal resection rate. Moreover, behavioral progression and intestinal resection rates have decreased over the past 3 decades. (Gut Liver 2022;16:216-227)
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