Background The purpose of this study is to help define the indications for rotator cuff repair by identifying predictors of failure of nonoperative treatment. Methods A prospective, multicenter, ...cohort study design was used. All patients with full-thickness rotator cuff tears on magnetic resonance imaging were offered participation. Baseline data from this cohort were used to examine risk factors for failing a standard rehabilitation protocol. Patients who underwent surgery were defined as failing nonoperative treatment. A Cox proportional hazards model was fit to determinethe baseline factors that predicted failure. The dependent variable was time to surgery. The independent variables were tear severity and baseline patient factors: age, activity level, body mass index, sex, Single Assessment Numeric Evaluation score, visual analog scale score for pain, education, handedness, comorbidities, duration of symptoms, strength, employment, smoking status, and patient expectations. Results Of the 433 subjects in this study, 87 underwent surgery with 93% follow-up at 1 year and 88% follow-up at 2 years. The median age was 62 years, and 49% were female patients. Multivariate modeling, adjusted for the covariates listed previously, identified patient expectations regarding physical therapy ( P < .0001) as the strongest predictor of surgery. Higher activity level ( P = .011) and not smoking ( P = .023) were also significant predictors of surgery. Conclusion A patient's decision to undergo surgery is influenced more by low expectations regarding the effectiveness of physical therapy than by patient symptoms or anatomic features of the rotator cuff tear. As such, patient symptoms and anatomic features of the chronic rotator cuff tear may not be the best features to use when deciding on surgical intervention.
Purpose To assess the effectiveness of a specific nonoperative physical therapy program in treating atraumatic full-thickness rotator cuff tears using a multicenter prospective cohort study design. ...Materials and methods Patients with atraumatic full-thickness rotator cuff tears who consented to enroll provided data via questionnaire on demographics, symptom characteristics, comorbidities, willingness to undergo surgery, and patient-related outcome assessments (Short Form 12 score, American Shoulder and Elbow Surgeons score, Western Ontario Rotator Cuff score, Single Assessment Numeric Evaluation score, and Shoulder Activity Scale). Physicians recorded physical examination and imaging data. Patients began a physical therapy program developed from a systematic review of the literature and returned for evaluation at 6 and 12 weeks. At those visits, patients could choose 1 of 3 courses: (1) cured (no formal follow-up scheduled), (2) improved (continue therapy with scheduled reassessment in 6 weeks), or (3) no better (surgery offered). Patients were contacted by telephone at 1 and 2 years to determine whether they had undergone surgery since their last visit. A Wilcoxon signed rank test with continuity correction was used to compare initial, 6-week, and 12-week outcome scores. Results The cohort consists of 452 patients. Patient-reported outcomes improved significantly at 6 and 12 weeks. Patients elected to undergo surgery less than 25% of the time. Patients who decided to have surgery generally did so between 6 and 12 weeks, and few had surgery between 3 and 24 months. Conclusion Nonoperative treatment using this physical therapy protocol is effective for treating atraumatic full-thickness rotator cuff tears in approximately 75% of patients followed up for 2 years.
Physiologically based pharmacokinetic (PBPK) modeling and simulation is a tool that can help predict the pharmacokinetics of drugs in humans and evaluate the effects of intrinsic (e.g., organ ...dysfunction, age, genetics) and extrinsic (e.g., drug–drug interactions) factors, alone or in combinations, on drug exposure. The use of this tool is increasing at all stages of the drug development process. This report reviews recent instances of the use of PBPK in decision‐making during regulatory review. The examples are based on Center for Drug Evaluation and Research reviews of several submissions for investigational new drugs (INDs) and new drug applications (NDAs) received between July 2008 and June 2010. The use of PBPK modeling and simulation facilitated the following types of decisions: the need to conduct specific clinical pharmacology studies, specific study designs, and appropriate labeling language. The report also discusses the challenges encountered when PBPK modeling and simulation were used in these cases and recommends approaches to facilitating full utilization of this tool.
Clinical Pharmacology & Therapeutics (2011) 89 2, 259–267. doi:10.1038/clpt.2010.298
Summary Background Since South Korea reported its first Middle East respiratory syndrome coronavirus (MERS-CoV) cluster on May 20 2015, there had been 186 confirmed cases, 38 deaths, and 16,752 ...suspected cases. Previously published research on South Korea's MERS outbreak has been limited to the early stages when limited data were available. Now that the outbreak has ended, albeit unofficially, a more comprehensive review is appropriate. Methods Data were obtained through the MERS Portal, by the Ministry for Health and Welfare (MOHW), and Korea Centers for Disease Control and Prevention, press releases by MOHW, and reports by the MERS Policy Committee of the Korean Medical Association. Cases were analyzed for general characteristics, exposure source, timeline, and infection generation. Gender, age, and underlying diseases were analyzed for the 38 deaths. Findings Beginning with the index case that infected 28 others, an in-depth analysis was conducted. The average age was 55, a little higher than the global average of 50; as in most other countries, more men than women were affected. The case fatality rate was 19·9%, lower than the global rate of 38.7%, and that ins Saudi Arabia (36·5%). 184 patients were infected nosocomially, while none were intra-community infections. The main underlying diseases were respiratory diseases, cancer, and hypertension. Main contributors to the outbreak were late diagnosis, quarantine failure of “super-spreaders”, familial care-giving and visiting, nondisclosure by patients, poor communication by the Government, inadequate hospital infection management, and "doctor shopping”. The outbreak was entirely nosocomial, and was largely attributable to infection management and policy failures, rather than biomedical factors.
Antimicrobial stewardship programmes (ASPs) are suggested as a vital strategy to address antimicrobial resistance.
To examine the current status of ASPs in Korean hospitals, to identify problems and ...challenges for the implementation of proper ASPs, and to provide a reference for developing more effective ASP policies.
A questionnaire based on the ‘Seven Core Elements of Hospital Antibiotic Stewardship Programs’ from the US Centers for Disease Control and Prevention was developed, modified from the previous questionnaire on ASPs in Korea, 2015. ASP-participating physicians such as infectious disease specialists (IDSs), paediatric IDSs, and directors of infection control departments were targeted. Only one ASP-associated physician per hospital participated in the survey.
The survey response rate was 88.4% (84/95). The median number of medical personnel participating in ASPs was 3 (interquartile range (IQR): 1–5), most of whom were IDS (median: 2; IQR: 1–2). Only 6.0% (5/84) of hospitals had full-time workers for ASPs. Whereas restrictive measures for designated antimicrobials were widely implemented among Korean hospitals (88.1%, 74/84), the proportion of hospitals with interventions for inappropriate long-term antimicrobial use and a conversion strategy from parenteral to oral antimicrobial administration was only 9.5% (8/84) and 1.2% (1/84), respectively. Lack of time, personnel, and appropriate compensation was perceived as the major barrier to establishing an ASP in Korean hospitals.
ASPs in Korean hospitals were primarily carried out by one or two IDSs, and programmes mostly comprised restrictive measures for designated antimicrobials. National-level support to implement appropriate ASPs in Korean hospitals is necessary.
Propofol and fentanyl can be administered at the end of sevoflurane anaesthesia to decrease the incidence and severity of emergence agitation (EA), although it has not been determined which agent has ...superior efficacy. The purpose of this study was to compare the effects of propofol and fentanyl on EA.
In this prospective, randomized, double-blind study, 222 children, 18–72 months of age, undergoing sevoflurane anaesthesia were randomly assigned to one of the three groups receiving either propofol 1 mg kg−1 (Group P), fentanyl 1 µg kg−1 (Group F), or saline (Group S) at the end of anaesthesia. The incidence and severity of EA were evaluated with the paediatric anaesthesia emergence delirium (PAED) scale. Time to recovery and incidence of nausea/vomiting were assessed.
The mean PAED score was 4.3 in Group P and 4.9 in Group F (P=0.682), which were lower than 9.0 in Group S (P<0.001). Nausea and vomiting were significantly more frequent in Group F than Groups P and S (adjusted P=0.003 and adjusted P<0.001). Group F had also longer stay in the post-anaesthesia care unit (PACU) than Group S (P<0.001), while Group P did not. However, the differences in PACU stays between the P and F groups were considered clinically insignificant.
Small doses of propofol or fentanyl at the end of sevoflurane anaesthesia comparably reduced EA. Propofol was better than fentanyl due to a lower incidence of nausea and vomiting.
Context. The near-Earth asteroid 3200 Phaethon (1983 TB) is an attractive object not only from a scientific viewpoint but also because of JAXA’s DESTINY+ target. The rotational lightcurve and spin ...properties were investigated based on the data obtained in the ground-based observation campaign of Phaethon. Aims. We aim to refine the lightcurves and shape model of Phaethon using all available lightcurve datasets obtained via optical observation, as well as our time-series observation data from the 2017 apparition. Methods. Using eight 12-m telescopes and an optical imager, we acquired the optical lightcurves and derived the spin parameters of Phaethon. We applied the lightcurve inversion method and SAGE algorithm to deduce the convex and non-convex shape model and pole orientations. Results. We analysed the optical lightcurve of Phaethon and derived a synodic and a sidereal rotational periods of 3.6039 h, with an axis ratio of a∕b = 1.07. The ecliptic longitude (λp) and latitude (βp) of the pole orientation were determined as (308°, −52°) and (322°, −40°) via two independent methods. A non-convex model from the SAGE method, which exhibits a concavity feature, is also presented.
Context:
Maternal diet during pregnancy has been linked to offspring adiposity, but it is unclear whether maternal polyunsaturated fatty acid (PUFA) status during pregnancy affects offspring body ...composition.
Objective:
We investigated the associations between maternal plasma n-3 and n-6 PUFA status at 34 wk gestation and offspring body composition.
Design and Setting:
A prospective United Kingdom population-based mother-offspring cohort, the Southampton Women's Survey (SWS), was studied.
Participants:
A total of 12,583 nonpregnant women were recruited into the SWS, among whom 1987 delivered a baby before December 31, 2003; 293 mother-child pairs had complete measurements of maternal plasma PUFA concentrations in late pregnancy and offspring body composition at both ages 4 and 6 yr.
Main Outcomes Measured:
We measured offspring body composition by dual-energy x-ray absorptiometry, yielding fat mass, lean mass, percentage fat mass, and percentage lean mass. Results are presented as β-coefficients for standardized variables, therefore reflecting the sd change of the outcome for every 1 sd of the predictor.
Results:
After adjustment for maternal factors and child factors including height and duration of breast-feeding, maternal plasma n-6 PUFA concentration positively predicted offspring fat mass at 4 yr (β = 0.14 sd/sd; P = 0.01) and 6 yr (β = 0.11 sd/sd; P = 0.04), but there was no association with offspring lean mass at either age (β = 0.005 sd/sd, P = 0.89; and β = 0.008 sd/sd, P = 0.81, respectively). Maternal plasma n-3 PUFA concentration was not associated with offspring fat mass at 4 yr (β = 0.057 sd/sd; P = 0.34) or 6 yr (β = 0.069 sd/sd; P = 0.21). Maternal plasma n-3 PUFA status was positively associated with offspring lean mass on univariate analysis (4 yr, β = 0.11, P = 0.06; 6 yr, β = 0.14; P = 0.02); however, this was confounded by a positive association with offspring height.
Conclusions:
This observational study suggests that maternal n-6 PUFA status during pregnancy might influence offspring adiposity in childhood.
To assess the prognostic value of myocardial pre-contrast T1 and extracellular volume (ECV) in systemic amyloid light-chain (AL) amyloidosis using cardiovascular magnetic resonance (CMR) T1 mapping.
...One hundred patients underwent CMR and T1 mapping pre- and post-contrast. Myocardial ECV was calculated at contrast equilibrium (ECV(i)) and 15 min post-bolus (ECVb). Fifty-four healthy volunteers served as controls. Patients were followed up for a median duration of 23 months and survival analyses were performed. Mean ECV(i) was raised in amyloid (0.44 ± 0.12) as was ECV(b) (mean 0.44 ± 0.12) compared with healthy volunteers (0.25 ± 0.02), P < 0.001. Native pre-contrast T1 was raised in amyloid (mean 1080 ± 87 ms vs. 954 ± 34 ms, P < 0.001). All three correlated with pre-test probability of cardiac involvement, cardiac biomarkers, and systolic and diastolic dysfunction. During follow-up, 25 deaths occurred. An ECV(i) of >0.45 carried a hazard ratio (HR) for death of 3.84 95% confidence interval (CI): 1.53-9.61, P = 0.004 and pre-contrast T1 of >1044 ms = HR 5.39 (95% CI: 1.24-23.4), P = 0.02. Extracellular volume after primed infusion and ECVb performed similarly. Isolated post-contrast T1 was non-predictive. In Cox regression models, ECV(i) was independently predictive of mortality (HR = 4.41, 95% CI: 1.35-14.4) after adjusting for E:E', ejection fraction, diastolic dysfunction grade, and NT-proBNP.
Myocardial ECV (bolus or infusion technique) and pre-contrast T1 are biomarkers for cardiac AL amyloid and they predict mortality in systemic amyloidosis.
Quality of life (QOL) after stroke is poorly characterized. We sought to determine long-term natural history and predictors of QOL among first ischemic stroke survivors without stroke recurrence or ...myocardial infarction (MI).
In the population-based, multiethnic Northern Manhattan Study, QOL was prospectively assessed at 6 months and annually for 5 years using the Spitzer QOL index (QLI), a 10-point scale. Functional status was assessed using the Barthel Index (BI) at regular intervals, and cognition using the Mini-Mental State Examination at 1 year. Generalized estimating equations estimated the association between patient characteristics and repeated QOL measures over 5 years. Follow-up was censored at death, recurrent stroke, or MI.
There were 525 incident ischemic stroke patients >/=40 years (mean age 68.6 +/- 12.4 years). QLI declined after stroke (annual change -0.10, 95% confidence interval -0.17 to -0.04), after adjusting for age, sex, race-ethnicity, education, insurance, depressed mood, stroke severity, bladder continence, and stroke laterality. This decline remained when BI >/=95 was added to the model as a time-dependent covariate, and functional status also predicted QLI. Changes in QLI over time differed by insurance status (p for interaction = 0.0017), with a decline for those with Medicaid/no insurance (p < 0.0001) but not Medicare/private insurance (p = 0.98).
In this population-based study, QOL declined annually up to 5 years after stroke among survivors free of recurrence or MI and independently of other risk factors. QLI declined more among Medicaid patients and was associated with age, mood, stroke severity, urinary incontinence, functional status, cognition, and stroke laterality.
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