The convergence of wearable sensors and personalized medicine enhance the ability to sense and control the drug composition and dosage, as well as location and timing of administration. To date, ...numerous stimuli-triggered smart drug-delivery systems have been developed to detect changes in light, pH, temperature, biomolecules, electric field, magnetic field, ultrasound and mechanical forces. This review examines the major advances within the last 5 years for the three most common light-responsive drug delivery-on-demand strategies: photochemical, photoisomerization and photothermal. Examples are highlighted to illustrate progress of each strategy in drug delivery applications, and key limitations are identified to motivate future research to advance this important field.
Background:
Outcomes after transtibial pull-out repair for posterior meniscal root tears remain underreported, and factors that may affect outcomes are unknown.
Purpose/Hypothesis:
The purpose of ...this study was to compare patient-centered outcomes after transtibial pull-out repair for posterior root tears in patients <50 and ≥50 years of age. We hypothesized that improvement in function and activity level at minimum 2-year follow-up would be similar among patients <50 years of age compared with patients ≥50 years and among patients undergoing medial versus lateral root repairs.
Study Design:
Cohort study; Level of evidence, 3.
Methods:
Inclusion criteria were patients aged 18 years or older who underwent anatomic transtibial pull-out repair of the medial or lateral posterior meniscus root by a single surgeon. All patients were identified from a data registry consisting of prospectively collected data in a consecutive series. Cohorts were analyzed by age (<50 years n = 35 vs ≥50 years n = 15) and laterality (lateral n = 15 vs medial n = 35). Patients completed a subjective questionnaire preoperatively and at minimum of 2 years postoperatively (Lysholm, Tegner, Western Ontario and McMaster Universities Osteoarthritis Index WOMAC, 12-Item Short Form Health Survey SF-12, and patient satisfaction with outcome). Failure was defined as revision meniscal root repair or partial meniscectomy.
Results:
The analysis included 50 knees in 49 patients (16 females, 33 males; mean age, 38.3 years; mean body mass index, 26.6). Of the 50 knees, 45 were available for analysis. Three of 45 (6.7%) required revision surgery. All failures were in patients <50 years old, and all failures underwent medial root repair. No significant difference in failure was found based on age (P=.541) or laterality (P = .544). For age cohorts, Lysholm and WOMAC scores demonstrated significant postoperative improvement. For laterality cohorts, all functional scores significantly improved postoperatively. No significant difference was noted in postoperative Lysholm, WOMAC, SF-12, Tegner, or patient satisfaction scores for the age cohort or the laterality cohort.
Conclusion:
Outcomes after posterior meniscal root repair significantly improved postoperatively and patient satisfaction was high, regardless of age or meniscal laterality. Patients <50 years had outcomes similar to those of patients ≥50 years, as did patients who underwent medial versus lateral root repair. Transtibial double-tunnel pull-out meniscal root repair provided improvement in function, pain, and activity level, which may aid in delayed progression of knee osteoarthritis.
As humans are the primary geomorphic agents on the landscape, it is essential to assess the magnitude, chronological span, and future effects of artificial ground that is expanding under modern ...urbanization at an alarming rate. We argue humans have been primary geomorphic agents of landscapes since the rise of early urbanism that continue to structure our everyday lives. Past and present anthropogenic actions mold a dynamic "taskscape" (not just a landscape) onto the physical environment. For example, one of the largest Pre-Columbian metropolitan centers of the New World, the UNESCO world heritage site of Teotihuacan, demonstrates how past anthropogenic actions continue to inform the modern taskscape, including modern street and land alignments. This paper applies a multi-scalar, long durée approach to urban landscapes utilizing the first lidar map of the Teotihuacan Valley to create a geospatial database that links modern and topographic features visible on the lidar map with ground survey, historic survey, and excavation data. Already, we have recorded not only new features previously unrecognized by historic surveys, but also the complete erasure of archaeological features due to modern (post-2015) mining operations. The lidar map database will continue to evolve with the dynamic landscape, able to assess continuity and changes on the Teotihuacan Valley, which can benefit decision makers contemplating the stewardship, transformation, or destruction of this heritage landscape.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To estimate whether those enrolled in the Veterans Health Administration (VHA) were less likely to use VHA‐delivered colorectal cancer screening colonoscopies after the MISSION Act.
Data ...Sources and Study Setting
Secondary data were collected on VHA‐enrolled Veterans from FY2017–FY2021.
Study Design
This retrospective cross‐sectional study measured the volume and share of screening colonoscopies that were VHA‐delivered over time and by drive time eligibility—defined as living more than 60 min away from the nearest VHA specialty‐care clinic. We used a multivariable logistic regression to adjust for patient and facility factors.
Data Extraction
Data were extracted for VHA enrollees (n = 773,766) who underwent a screening colonoscopy either performed or purchased by the VHA from FY2017–FY2021.
Principal Findings
In the 9 months after the implementation of the MISSION Act, and before the onset of the Covid‐19 pandemic, the average monthly VHA‐share of screening colonoscopies decreased by 3 percentage points (pp; 95% confidence interval CI = −4 to −2 pp) for the non‐drive time eligible group and it decreased by 16 pp (95% CI = −22 to −9 pp) for the drive time eligible group. The total number of screening colonoscopies did not significantly change in either group during this time period. After adjusting for patient characteristics, a linear time trend, and parent facility fixed effects, implementation of the MISSION Act was associated with a reduction in the probability of a VHA‐delivered screening colonoscopy (average marginal effect AME: −2.5 pp; 95% CI = −5.1 to 0.0 pp) for the non‐drive time eligible group. The drive time eligible group (AME: −9.4 pp; 95% CI = −13.2 to −5.5 pp) experienced a larger change.
Conclusions
The VHA‐share of screening colonoscopies among VHA enrollees fell in the 9 months immediately after the passage of the MISSION Act. This decline was larger for VHA enrollees who were targeted for eligibility due to a longer drive time. These results suggest that the MISSION Act led to more VHA‐purchased care among targeted VHA enrollees, though it is unclear whether total utilization increased.
Purpose The purpose of this study was to systematically review the literature on rerevision anterior cruciate ligament (ACL) reconstruction, focusing on patient outcomes. The secondary aims of this ...study were to (1) identify risk factors that contribute to multiple ACL reconstruction failures (defined as a complete tear of a revision ACL graft with knee instability) and (2) assess concomitant knee injuries, such as articular cartilage and menisci lesions. Methods A systematic review of the literature was performed. Inclusion criteria were as follows: outcomes of rerevision ACL reconstruction, English language, minimum of 2 years of follow-up, and human studies. We excluded cadaveric studies, animal studies, basic science articles, editorial articles, surgical technique descriptions, surveys, and rerevision ACL articles in which rerevision reconstruction subgroups were not reported independently of first-time ACL revision groups. Results Six studies met the inclusion criteria and were considered for review. One was a case-control study (Level III evidence), and 5 studies were case series (Level IV evidence). Compared with preoperative scores, patient outcomes improved after rerevision ACL reconstruction. However, more meniscal and cartilage pathologies were present in rerevision cases compared with after primary and revision ACL reconstruction. Conclusions Although rerevision ACL reconstruction can restore stability and improve functional outcomes compared with the preoperative state, outcomes remained inferior when compared with primary ACL reconstructions, particularly regarding a patient's ability to return to his or her preinjury level of activity. Additional factors that place increased stress on the ACL graft, such as increased posterior tibial sagittal plane slope or undiagnosed concomitant ligament injuries, should be investigated, especially in atraumatic failures. If present, operative treatment of these factors should be considered. Level of Evidence Level IV, systematic review of Level III and IV studies.
Multi-item adverse drug event (ADE) associations are associations relating multiple drugs to possibly multiple adverse events. The current standard in pharmacovigilance is bivariate association ...analysis, where each single drug-adverse effect combination is studied separately. The importance and difficulty in the detection of multi-item ADE associations was noted in several prominent pharmacovigilance studies. In this paper we examine the application of a well established data mining method known as association rule mining, which we tailored to the above problem, and demonstrate its value. The method was applied to the FDAs spontaneous adverse event reporting system (AERS) with minimal restrictions and expectations on its output, an experiment that has not been previously done on the scale and generality proposed in this work.
Based on a set of 162,744 reports of suspected ADEs reported to AERS and published in the year 2008, our method identified 1167 multi-item ADE associations. A taxonomy that characterizes the associations was developed based on a representative sample. A significant number (67% of the total) of potential multi-item ADE associations identified were characterized and clinically validated by a domain expert as previously recognized ADE associations. Several potentially novel ADEs were also identified. A smaller proportion (4%) of associations were characterized and validated as known drug-drug interactions.
Our findings demonstrate that multi-item ADEs are present and can be extracted from the FDA's adverse effect reporting system using our methodology, suggesting that our method is a valid approach for the initial identification of multi-item ADEs. The study also revealed several limitations and challenges that can be attributed to both the method and quality of data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Electronic health records (EHRs) are an important source of data for detection of adverse drug reactions (ADRs). However, adverse events are frequently due not to medications but to the patients' ...underlying conditions. Mining to detect ADRs from EHR data must account for confounders. We developed an automated method using natural‐language processing (NLP) and a knowledge source to differentiate cases in which the patient's disease is responsible for the event rather than a drug. Our method was applied to 199,920 hospitalization records, concentrating on two serious ADRs: rhabdomyolysis (n = 687) and agranulocytosis (n = 772). Our method automatically identified 75% of the cases, those with disease etiology. The sensitivity and specificity were 93.8% (confidence interval: 88.9–96.7%) and 91.8% (confidence interval: 84.0–96.2%), respectively. The method resulted in considerable saving of time: for every 1 h spent in development, there was a saving of at least 20 h in manual review. The review of the remaining 25% of the cases therefore became more feasible, allowing us to identify the medications that had caused the ADRs.
Clinical Pharmacology & Therapeutics (2012); 92 2, 228–234. doi:10.1038/clpt.2012.54
Background:
Meniscal repair in the setting of anterior cruciate ligament (ACL) reconstruction has demonstrated superior outcomes compared with isolated meniscal repair. Limited evidence exists for ...the effects of biological augmentation in isolated meniscal repair, particularly as compared with meniscal repair with concomitant ACL reconstruction.
Purpose/Hypothesis:
The purpose of this study was to compare the outcomes and survivorship of meniscal repair in 2 cohorts of patients: meniscal repair with biological augmentation using a marrow venting procedure (MVP) of the intercondylar notch, and meniscal repair with concomitant ACL reconstruction. We hypothesized that the clinical outcomes and survivorship of meniscal repair with concomitant ACL reconstruction would be improved compared with meniscal repair with biological augmentation.
Study Design:
Cohort study; Level of evidence, 3.
Methods:
Inclusion criteria were skeletally mature patients aged ≥16 years who underwent inside-out meniscal repair and either a concomitant MVP of the intercondylar notch or ACL reconstruction. Patients were excluded from this study if they were skeletally immature, underwent meniscus root or radial tear repair, or underwent meniscal repair with concurrent ligamentous reconstruction not limited to the ACL. At the preoperative evaluation and a minimum 2 years after the index meniscal repair procedure, patients were administered a subjective questionnaire. Differences in outcome scores, survivorship, and failure rates between the cohorts were assessed. Failure was defined as reoperation with meniscectomy or revision meniscal repair.
Results:
There were 109 patients (52 female, 57 male) who met the inclusion criteria for this study. There were 37 knees in cohort 1 (isolated meniscal repair plus MVP) and 72 knees in cohort 2 (meniscal repair plus ACL reconstruction). The failure status was known in 95 patients, and patient-reported outcome scores were obtained in 89 (82%) patients. Both cohorts demonstrated a significant improvement in all outcome scores, and there was no significant difference in any of the preoperative or postoperative outcome measures. The overall failure rate was 9.5% (9/95). There were 4 (12.9%) failures in cohort 1 and 5 failures (7.8%) in cohort 2, with no significant difference in failures between the cohorts (P = .429). There was a significant association between failure and female sex (P = .001).
Conclusion:
The most important finding in this study was that there was no difference in outcomes in meniscal repair performed with biological augmentation using an MVP versus that performed concomitantly with ACL reconstruction. The similar outcomes reported for meniscal repair with an MVP and meniscal repair with ACL reconstruction may be partly attributed to biological augmentation.
Abstract Restoration of anteroposterior laxity after an anterior cruciate ligament reconstruction has been predictable with traditional open and endoscopic techniques. However, anterolateral ...rotational stability has been difficult to achieve in a subset of patients, even with appropriate anatomic techniques. Therefore, differing techniques have attempted to address this rotational laxity by augmenting or reconstructing lateral-sided structures about the knee. In recent years, there has been a renewed interest in the anterolateral ligament as a potential contributor to residual anterolateral rotatory instability in anterior cruciate ligament–deficient patients. Numerous anatomic and biomechanical studies have been performed to further define the functional importance of the anterolateral ligament, highlighting the need for surgical techniques to address these injuries in the unstable knee. This article details our technique for an anatomic anterolateral ligament reconstruction using a semitendinosus tendon allograft.
Introduction Researchers have identified links between anxious and avoidant attachments and difficulties with self-compassion, giving others compassion, and receiving compassion. However, while ...compassion requires both awareness of opportunities for compassion and compassionate action, little is known about attachment-related differences in reporting compassionate opportunities. Further, most research relies on retrospective-reports that may not accurately assess compassionate behaviors in everyday life. Method Consequently, we collected 2,757 experience sampling survey responses from 125 participants (95 women, 27 men, 3 non-binary, M age = 18.74, SD age = 1.66) to investigate whether attachment anxiety, avoidance, or their interaction were associated with differences in propensity for reporting compassionate opportunities, actions, and emotional responses to opportunities in everyday life across self-compassion, giving compassion, and receiving compassion. Results Anxiety was associated with greater likelihood of reporting all types of compassionate opportunities and less positive responses to opportunities to receive compassion. Avoidance was associated with less likelihood of reporting opportunities to give and receive compassion and less positive responses to opportunities to give compassion. Those high in anxiety but simultaneously low in avoidance reported fewer self-compassionate actions, but we identified no further differences in compassionate action. Discussion This study highlights the potential role of awareness of compassionate opportunities in attachment-related differences in compassion.
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