The determinants of nonprofit hospital CEO compensation.

Hospital CEO salaries have grown quickly over the past two decades. We investigate correlates of rising nonprofit hospital CEO pay between 2012 and 2019 by merging compensation data from Candid's IRS 990 forms with hospital data from the National Academy for State Health Policy Hospital Cost Tool. Almost half of the measured increase in CEO compensation (44.5%) accrued to a "base case" CEO, who was leading a non-teaching hospital system or independent hospital with fewer than 100 beds that earned 0 profits and provided no charity care. Another 28.5% of the measured salary increase resulted from changes in the generosity with which observable metrics were rewarded, particularly the reward for heading a system with 500 or more beds. The remaining 27% resulted mostly from hospital systems or single hospitals that increased their profits or bed size over time. The increase in CEO compensation associated with leading larger healthcare systems and earning greater profits may explain the increase in healthcare system consolidation which has occurred over the last several years.

Positive Culture of Atypical Mycobacterium Avium Following Revision Total Knee Arthroplasty.

CASE: We report a rare case of mycobacterial periprosthetic joint infection (PJI) after primary total knee arthroplasty 14 years earlier. Progressive knee pain over three years with a negative PJI infectious workup led to revision total knee arthroplasty. A surprising result was isolation of Mycobacterium avium from tissue cultures taken at time of revision surgery. After six months of antibiotic treatment, the patient is alive with well- functioning pain-free TKA at over one-year follow-up. CONCLUSION: Periprosthetic joint infection can present acutely or chronically years following total knee arthroplasty. Depending on the infecting organism, patients can present with sepsis, or a more indolent slower course that mimics aseptic loosening. In the absence of positive pre-operative labs and cultures, and based on the Musculoskeletal Infection Society (MSIS) criteria, aseptic loosening is a diagnosis of exclusion. An atypical infectious organism should be considered a possible cause and may require specialized cultures of operative specimens.

Tibial Component Revision Arthroplasty Using Porous Tantalum Cone for Symptomatic Progressive Periprosthetic Proximal Tibial Ganglion Cyst about All-Polyethylene Tibia Primary Total Knee Replacement: A Case Report and Review of Literature.

Introduction: Intraosseous ganglion cysts are an uncommon variant found in the subchondral bone. We report here the development of an intraosseous ganglion cyst of the proximal tibia in the setting of a prior left total knee arthroplasty (TKA) with an all-polyethylene tibial component. Case Report: The cyst was diagnosed on routine follow-up radiographs approximately 4 years status post-TKA. Although initially asymptomatic, 1 year later the patient presented with progressive knee pain and ambulation limitations, so revision TKA was indicated. Computed tomography confirmed an osteolytic lesion suggestive of a penetrating ganglion. Given the absence of malrotation or malalignment of the well-fixed femoral component, the decision was made to proceed with tibial revision to stemmed component cemented through a porous tantalum cone. Postoperatively, the patient had complete resolution of pain and instability with 0-120° of stable range of motion, which has persisted to the latest follow-up at over 6 months post-operative, with radiographic resolution of the cyst. Conclusion: This case demonstrates a ganglion cyst surrounding total knee implants as a possible source of persistent pain following TKA. To our knowledge, this is the first report of such a case. This case demonstrates that refractory painful knee implants secondary to tibial ganglion cysts can be treated successfully with revision arthroplasty.

Revision Total Knee Arthroplasty for Catastrophic Tibial Post Failure: Rare Complication of Total Knee Replacement.

Tibial post failure is a rare but serious complication of posterior-stabilized total knee arthroplasty that requires revision surgery. Although tibial post fracture has previously been reported, this case involves an implant with a design feature that may predispose patients to the complication. The fracture also occurred later than observed in most other reports. A 72-year-old male who had undergone a posterior stabilized total knee arthroplasty seven years prior presented with knee pain and instability after a fall from standing. Although plain radiographs were not diagnostic, history and physical exam suggested failure of the tibial polyethylene post. This was confirmed during surgery when the fractured component was identified in the suprapatellar pouch. Given absence of malrotation or malalignment of the well-fixed femoral and tibial components, a polyethylene liner exchange was performed. Postoperatively, the patient had complete resolution of pain and instability with 0-120 degrees of stable ROM, which has persisted to latest follow-up at 6 months.

The Effect of Surgical Duration on Complications and Patient Reported Outcomes in Total Hip Replacement as Evaluated Through Multi-Surgeon Pooled FORCE Registry Data from a Tertiary Care Referral Total Joint Center.

BACKGROUND: The relationship between operative times and patient outcomes in total hip arthroplasty (THA) has not been well defined. METHODS: From January 2016 to December 2019, data were prospectively collected for THA patients in the FORCE-TJR registry and hospital EMR of an academic total-joint center. RESULTS: 1,123 patients were included. Operative times ranged from 36 to 366 minutes, with a mean operative time of 111.26+/-31.37 minutes. Unadjusted GLM showed HOOS pain, ADL, and QoL scores differed across operative times, with patients who had operative times between 106 and 120 minutes having significantly lower pain, higher function, and better quality of life at 12 months, especially compared to patients with operative times < 90 minutes. Patients who had operative times between 106 and 120 minutes had significantly better VR-12 PCS and MCS at 12 months. Although statistically significant, differences were small and did not persist after controlling for within-surgeon effects, patient socio-demographics and baseline patient-reported outcomes, suggesting that patient characteristics or within-surgeon effects may play a more significant role in these patient-reported outcomes than operative time. CONCLUSION: This study showed that among THA patients, operative times were significantly associated with patient-reported outcomes at 12 months post-operatively, but is one of many surgeon and patient-related factors with effect on THA outcome.

Nonprofit Hospitals: Profits And Cash Reserves Grow, Charity Care Does Not.

Using the National Academy of State Health Policy Hospital Cost Tool, we compared changes in hospital profits with changes in hospitals' charity care and cash reserves between 2012 and 2019. We estimated substantial growth in nonprofit hospital operating profits and cash reserves in this period but no corresponding increase in charity care.

Improvise, Adapt & Overcome: Successful Surgery-Sparing Prosthetic Hip Infection Antibiotic Suppression During COVID-19 Crisis.

CASE: A 79-year-old active male presented during the first COVID-19 pandemic surgery moratorium with late Staphylococcus lugdunensis periprosthetic total hip arthroplasty infection. Due to the unprecedented circumstances, novel treatment of IV and oral antibiotic suppression was trialed without preceding surgical intervention. At latest follow-up, the patient has two-year revision-free survival with normalization of inflammatory markers and MRI findings, and resolution of clinical symptoms. CONCLUSION: We report a novel surgery-sparing treatment for periprosthetic hip infection. Judicious caution should be used in the application of similar therapies, as host and organism characteristics likely contributed substantially to the success of this case.

Blood Lead Testing in Flint Before and After Water Contamination.

OBJECTIVE: Lead is a neurotoxicant that negatively affects health. Reducing lead exposure and early detection among children are important public health goals. Our objective with this study was to determine if the September 2015 lead advisory in Flint, Michigan affected lead testing among children when possible exposure was widely publicized. METHOD: This study included 206 001 children born in Michigan from 2013 to 2015 and enrolled in Medicaid, using 2013 to 2017 claims data to determine if and at what age an individual received a lead test. Difference-in-differences regression models were used to compare the receipt of lead tests among children in Flint with other cities in Michigan before and after September 2015, when a lead advisory was issued for the city warning about potential exposure to lead in publicly supplied water. RESULTS: Before the lead advisory, approximately 50% of children in Flint received a lead test by 12 months of age and nearly 75% received a lead test by 24 months of age. After the September 2015 advisory, the receipt of lead tests among children in Flint increased 10 percentage points by 12 months compared with other cities. Effects by 10-month cohorts, as of 2016, revealed a 20-percentage-point increase for children in Flint compared with other cities. CONCLUSIONS: Despite a highly publicized lead advisory, children in Flint enrolled in Medicaid received lead tests earlier, but the proportion of Medicaid-eligible children who were tested did not change. This suggests that increasing lead testing is a difficult policy goal to achieve and, therefore, supports recent efforts focusing on primary prevention to reduce lead exposure.

Concordance Between Self-Reported Medical Diagnosis of Mild Cognitive Impairment/Dementia and Neurocognitive Function Among Middle-Aged and Older Hispanic/Latino Adults: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

BACKGROUND: Population-based studies typically rely on self-reported medical diagnosis (SRMD) of mild cognitive impairment (MCI)/dementia; however, links to objective neurocognitive function have not been established. OBJECTIVE: Examine the association between SRMD of MCI/dementia and objective neurocognitive function among Hispanic/Latino adults. METHODS: We conducted a case-control study using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) baseline data and its ancillary SOL-Investigation of Neurocognitive Aging (SOL-INCA) at visit 2. Hispanic/Latino adults aged 50 years and older (n = 593) were administered neurocognitive tests: the Six-Item Screener (SIS), Brief-Spanish English Verbal Learning Test (B-SVELT Sum), B-SVELT Recall, Word Fluency Test (WF), Digit Symbol Substitution Test (DSS), and Trail Making Test A and B. Individual and global neurocognitive function scores were used for analyses. Propensity matching techniques and survey generalized linear regression models were used to compare SRMD of MCI/dementia with demographic, psychological, and cardiovascular risk matched controls. Complex survey design methods were applied. RESULTS: There were 121 cases of SRMD of MCI/dementia and 472 propensity matched controls. At baseline, compared to matched controls, cases showed no differences in neurocognitive function (p > 0.05). At SOL-INCA visit 2, cases had poorer scores in global neurocognitive function (p < 0.05), B-SEVLT Sum, B-SEVLT Recall, WF, DSS, and Trail A (p < 0.01). CONCLUSION: Observed differences in neurocognitive test scores between SRMD of MCI/dementia cases and matched controls were present at visit 2, but not at baseline in middle-aged and older Hispanic/Latino adults. These findings present initial evidence of the potential utility of SRMD of MCI/dementia in epidemiologic studies, where obtaining confirmation of diagnosis may not be feasible.

Out-of-Pocket Health Expenditures and Health Care Services Use Among Older Americans With Cognitive Impairment: Results From the 2008-2016 Health and Retirement Study.

BACKGROUND AND OBJECTIVES: The evidence base on health services use and cost burdens associated with transition to severe cognitive impairment (SCI) and dementia is underdeveloped. We examine how the change in cognitive impairment status influences nursing home use, hospitalizations, and out-of-pocket (OOP) expenditures. RESEARCH DESIGN AND METHODS: We use prospective data from the Health and Retirement Study (2007/2008-2015/2016) on adults 70 years and older meeting research criteria for cognitive impairment not dementia (CIND) at baseline (unweighted n = 1,692) to fit 2-part models testing how reversion to normal cognition, stability (CIND maintenance), and transition into SCI/dementia influence change in yearly nursing home use, hospitalizations, and OOP expenditures. RESULTS: Over 8 years, 5.9% reverted, 15.9% remained CIND, 14.9% transitioned to SCI/dementia, and 63.3% died. We observed substantial increases in the propensity of any nursing home use which were particularly pronounced among those who transitioned or died during follow-up and similar but less pronounced differences in patterns of inpatient hospitalizations. Average baseline OOP spending was similar among reverters ($1156 [95% confidence interval = 832-1,479]), maintainers ($1,145 [993-1,296]), and transitioners ($1,385 [1,041-1,730]). Individuals who died during follow-up spent $2,529 (2,101-2,957). By the eighth year of follow-up, spending among reverters increased to $1,402 (869-1,934) and $2,188 (1,402-2,974) and $8,988 (5,820-12,157) for maintainers and transitioners, respectively. Average spending at the wave preceding death was $7,719 (4,345-11,094). Estimates were only partly attenuated through adjustment to covariables. DISCUSSION AND IMPLICATIONS: A better understanding of variations in health services use and cost burdens among individuals with mild cognitive impairment can help guide targeted care and financial planning.

Diagnostic Testing of Vaginitis: Improving the Value of Care.

Vaginitis is one of the most common reasons women access health care in the United States. Despite its prevalence and disruptive impact, it is frequently misdiagnosed and untreated, resulting in unnecessary patient discomfort, follow-up visits, and health care costs. This study presents a costs analysis of diagnostic testing technologies to demonstrate the potential of molecular tests to improve the value of care for women with vaginitis. This study tracks health care spending among women diagnosed with vaginitis and finds that nucleic acid amplification tests (NAATs) are cost-effective for the diagnosis of vaginal symptoms. Women who receive a NAAT on the day of their diagnosis have significantly lower 12-month follow-up costs compared to women who receive a direct probe test or those women who are clinically evaluated without the use of a molecular test. However, despite Food and Drug Administration approval, widely available molecular diagnostics have not been incorporated into clinical guidelines, and many payer policies fail to cover these tests. Greater utilization of NAAT for the diagnosis of vaginitis has the potential to improve the care of women seeking treatment for this prevalent condition and facilitate sexually transmitted infection testing without additional visits.

Rolling back the gains: Maternal stress undermines pregnancy health after Flint's water switch.

Environmental disasters impact disadvantaged communities disproportionately both through the epidemiological challenge of exposure, but also by undermining the progress of public health efforts. This paper studies changes to smoking cessation, breastfeeding, and weight gain during pregnancy in the period following the switch in water supply in Flint, Michigan, in April 2014. As the switch resulted in immediate and significant deterioration in water quality, eventually leading to its contamination with lead, we estimate a 10.5 percentage point increase in smoking and a 2.1 percentage point decrease in breastfeeding. We show evidence that these changes in maternal behavior are linked to increased stress due to changing water quality. We estimate that the increase in smoking alone is responsible for most of the increase in incidence of low birthweight among infants in Flint, resulting in $700 additional costs per birth. Increased smoking during pregnancy and lower breastfeeding rates in Flint roll back years of public health efforts, resulting in lifetime higher rates of cardiovascular disease, diabetes, and cancer for mothers in the community.

Applicant Ranking Criteria in Adult Reconstruction Fellowship: Your Interview Counts When Applying for Fellowship.

Background The criteria for successful ranking in the fellowship match remains unclear. Although some data are available regarding the qualities sought after in medical students for the residency match, little information is available regarding the fellowship match. In this study, for arthroplasty applications to our institution, the interview was hypothesized to be the most important factor for ranking, with little impact from other commonly assessed variables. Methodology All 40 applicants who applied for fellowship were selected to interview for the 2017 Brown University Comprehensive Adult Reconstruction Fellowship and were evaluated on the interview, United States Medical Licensing Examination (USMLE) scores, letters of recommendation, personal statement, extracurricular activities, research, and caliber of undergraduate institution, medical school, and residency program. The interview score was based on a combined score of individual components of personality, program fit, and research. Results Of the 40 applicants who were interviewed, eight did not match. The interview score was the only statistically significant variable and had the highest correlation with ranking (r = 0.92). Moreover, extracurricular activities correlated with a higher ranking whereas USMLE Step 1/Step 2 scores had a relatively low correlation (r = 0.32 and 0.29, respectively). Recommendation letters and caliber of medical school, undergraduate education, and residency demonstrated low correlations. The personal statement and research components had the lowest correlations. Conclusions The combined interview score, in particular the personality and program fit components, was the most important determinant of successful ranking at our institution. Because all 40 applicants who applied for an arthroplasty fellowship at our institution were selected for an interview, there was no pre-interview selection bias that would confound these results. However, the ranking does not correlate with an applicant's success in fellowship, and further research is required to determine the qualifications of a successful surgeon.

Fluorescent-conjugated antibodies as rapid ex vivo markers for bacterial presence on orthopedic surgical explants and synovium: A pilot study.

Surgical infection is one of the most pressing problems in the field of orthopedic surgery; however, current detection methods are plagued by high costs and long wait times. This study seeks to demonstrate the ability of a novel assay using fluorescently conjugated antibodies and confocal laser scanning microscopy (CLSM) to accurately detect bacterial presence on orthopedic surgical explants, tissue, and synovial fluid in 30 min. Explanted hardware, tissue, and synovial fluid samples suspected to be infected were collected from human subjects with institutional review board consent. Samples were prepared using a 30-min protocol, consisting of rinsing, nonspecific blocking and staining steps, and imaged using CLSM. Images were analyzed using ImageJ (National Institute of Health) to determine the percent area of Gram positive and Gram negative bacteria. Results of the assay were compared to the hospital's microbiological laboratory and Gram staining results. Ninety three samples were collected and tested using the 30-min testing protocol; 75 samples were synovial fluid and 18 were tissue and explants. Seventy four of 75 (98.6%) synovial fluid samples correlated with the hospital laboratory's microbiological findings. Of the 18 explant and tissue samples, our assay found bacterial presence in 14 of 18 samples, while the hospital microbiology laboratory found bacterial presence in 13 of 18 samples. This assay reliably stained and rapidly identified the presence of Gram negative and Gram positive bacteria on surgical explants, tissue and synovial fluid in 30 min. This methodology may serve as a point of service tool for the determination of bacterial presence during surgical procedures.

Role of corrosion in taper failure and head disassociation in total hip arthroplasty of a single design.

Modular junctions have been associated with corrosion in total hip arthroplasty. In a small number of cases, disassociation of the femoral head from the stem following gross wear of the taper has been reported. The purpose of this study was to investigate the role of corrosion in the development of mechanical changes leading to disassociation. Twenty-one retrieved stems and heads of one design previously reported with head disassociation were identified in an IRB-approved database. Components were scored for corrosion and measured for material loss. Stem alloy hardness was measured. Parametric and non-parametric statistics were performed (α < 0.05). Seven of twenty-one stems demonstrated gross material loss of the stem taper and head disassociation. The maximum linear depth (MLD) of material loss on stem tapers without dissociation and all head bores was 7.63 ± 6.04 and 63.76 ± 60.83 µm, respectively. Hardness of the stem material was statistically distinct, but similar to other stem materials. Results suggest material loss via corrosion at the head bore loosens the taper lock, allowing relative motion leading to abrasive wear of the stem taper. All cases of disassociation occurred at greater than 65 months with a minimum of 50 µm of loss at on the head bore. It may be warranted to survey patients with systems reporting head disassociation; for this system, including recalled heads, risk appears to begin after 6 years in vivo. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2996-3003, 2018.

Minimum Five-Year Outcomes with Porous Tantalum Acetabular Cup and Augment Construct in Complex Revision Total Hip Arthroplasty.

BACKGROUND: The use of a trabecular metal revision shell with metal augmentation to fill segmental or irregular defects during complex revision hip arthroplasty has been shown to provide good short-term results in prior published series. Longer-term results of the several cup-augment constructs used clinically are not known. The objective of this study was to report, with minimum 5-year radiographic and clinical follow-up, the outcome of these various constructs in revision total hip arthroplasty. METHODS: Eighty-four patients (85 hips) underwent revision total hip arthroplasty with use of porous tantalum augments between 2000 and 2007 at a single institution and were retrospectively reviewed. Fifty-seven of the patients (58 hips) had clinical and radiographic follow-up at a minimum of 5 years. At the time of revision, the majority of the hips had acetabular defects classified as Paprosky Type 3A (28 of 58, 48%) or Type 3B (22 of 58, 38%). Eleven (19%) of the hips also had preoperative pelvic discontinuity. All hips were assessed clinically at a minimum of 5 years with use of the Mayo hip score. Postoperative radiographs were reviewed for implant stability, the presence and location of radiolucent lines and healing of the discontinuity if present. RESULTS: In 2 (3%) of the 58 hips, the constructs failed because of aseptic loosening of the acetabular component and re-revision was indicated. Six (10%) of the 58 hips demonstrated a radiolucent line between the trabecular metal shell and bone in DeLee and Charnley zone 3. In 1 hip that underwent re-revision and in 5 of the 6 hips with a zone-3 radiolucency, a pelvic discontinuity was present at the time of the index revision. The mean preoperative Mayo hip score was 35.7, which improved to 61.9 at 3 months and was 61.7 at the minimum 5-year follow-up. CONCLUSIONS: With failure defined as aseptic loosening requiring repeat revision surgery, this cohort demonstrated 97% survivorship and maintained satisfactory hip function at the minimum 5 years after the index revision surgery. Six of the 11 hips with preoperative pelvic discontinuity either failed or developed a radiolucency in zone 3 and are considered at risk for future revision. Pelvic discontinuity should prompt consideration of the addition of adjunctive fixation or the use of alternative techniques. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Modifiable Risk Factors in Total Joint Arthroplasty: A Pilot Study.

UNLABELLED: Strong evidence exists to suggest that morbid obesity, smoking, and poorly controlled diabetes mellitus are associated with poorer outcomes after total joint arthroplasty. To our knowledge, no study has reported the effect of the implementation of a risk reduction strategy. Risk factors, based on published data, were defined as Body Mass Index (BMI)>40, Hemoglobin A1c (HbA1c) >8.0, and use of any tobacco product. A retrospective pilot review was done of a 3-month period using this protocol in the practice of a single fellowship-trained academic arthroplasty surgeon (DRJ). Outcomes were evaluated in the subsequent 3-month period. Overall 19/29 (65.5%) patients identified to be "at risk" and offered support for modification followed up under the care of their index surgeon. 11/19 (57.9%) improved their risk factors and 8/19 (42.1%) ultimately met the specific goals set for surgery with 4 (21%) ultimately undergoing their replacement procedure during the 6-month study period. These initial results suggest that a significant proportion of our patients were willing and able to modify their risk before surgery. LEVEL OF EVIDENCE: Level III retrospective study. [Full article available at http://rimed.org/rimedicaljournal-2016-05.asp, free with no login].

Total joint arthroplasty in patients with chronic infectious liver disease.

The opportunity for total joint arthroplasty (TJA) in patients with chronic infectious liver disease is rapidly expanding. This is the product of both superior survival of chronic hepatitis patients, evolving implant technologies, and improvement of techniques in TJA. Unfortunately, treating this group of patients is not without significant challenges that can stem from both intrahepatic and extrahepatic clinical manifestations. Moreover, many subclinical changes occur in this cohort that can alter hemostasis, wound healing, and infection risk even in the asymptomatic patient. In this review, we discuss the various clinical presentations of chronic infectious liver disease and summarize the relevant literature involving total joint arthroplasty for this population. Hopefully, through appropriate patient selection and perioperative optimization, treating surgeons should see continued improvement in outcomes for patients with chronic infectious liver disease.

A randomized, controlled, prospective study evaluating the effect of patellar eversion on functional outcomes in primary total knee arthroplasty.

BACKGROUND: Patellar mobilization technique during total knee arthroplasty has been debated, with some suggesting that lateral retraction, rather than eversion, of the patella may be beneficial. We hypothesized that patients with knees surgically exposed using patellar lateral retraction would have comparable outcomes with patients with knees surgically exposed using patellar eversion. METHODS: After an a priori power analysis, 120 patients with degenerative arthrosis were prospectively enrolled and were randomized to one of two patellar exposure techniques during the primary total knee arthroplasty: lateral retraction or eversion. The primary outcome measure was one-year, dynamometer-measured quadriceps strength. The secondary outcome measures evaluated during hospital stay included the ability to straight-leg raise, visual analog scale in pain, walking distance, and length of stay. The secondary outcome measures that were evaluated preoperatively and through a one-year follow-up included the Short Form-36 Physical Component Summary and Mental Component Summary scores, range of motion, quadriceps strength, and radiographic rate of patella baja and tilt. RESULTS: A mixed-model analysis of variance showed no significant differences between the two groups in the one-year outcome measures. At one year postoperatively, quadriceps strength was not different between groups (p = 0.77), and the range of motion significantly improved (p < 0.01) from preoperative values by a mean value (and standard deviation) of 6° ± 17°, with no significant difference (p = 0.60) between groups. The Short Form-36 Physical Component Summary score and Mental Component Summary score significantly improved (p < 0.01) for both study groups from preoperatively to one year postoperatively with no significantly different effects between groups (time × group, p = 0.85 for the Physical Component Summary score and p = 0.71 for the Mental Component Summary score), and the scores were not different at one year after surgery. There were no significant differences between groups in the change in frequency of the radiographic patella baja (p = 0.99) or the radiographic patellar tilt (p = 0.77) from before surgery to one year after surgery. CONCLUSIONS: Lateral retraction of the patella did not lead to superior postoperative results compared with eversion of the patella during total knee arthroplasty as evaluated using our primary outcome measure of one-year, dynamometer-measured quadriceps strength or our secondary outcome measures. LEVEL OF-EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Conception through build of an automated liquids processing system for compound management in a low-humidity environment.

Boehringer Ingelheim's Automated Liquids Processing System (ALPS) in Ridgefield, Connecticut, was built to accommodate all compound solution-based operations following dissolution in neat DMSO. Process analysis resulted in the design of two nearly identical conveyor-based subsystems, each capable of executing 1400 × 384-well plate or punch tube replicates per batch. Two parallel-positioned subsystems are capable of independent execution or alternatively executed as a unified system for more complex or higher throughput processes. Primary ALPS functions include creation of high-throughput screening plates, concentration-response plates, and reformatted master stock plates (e.g., 384-well plates from 96-well plates). Integrated operations included centrifugation, unsealing/piercing, broadcast diluent addition, barcode print/application, compound transfer/mix via disposable pipette tips, and plate sealing. ALPS key features included instrument pooling for increased capacity or fail-over situations, programming constructs to associate one source plate to an array of replicate plates, and stacked collation of completed plates. Due to the hygroscopic nature of DMSO, ALPS was designed to operate within a 10% relativity humidity environment. The activities described are the collaborative efforts that contributed to the specification, build, delivery, and acceptance testing between Boehringer Ingelheim Pharmaceuticals, Inc. and the automation integration vendor, Thermo Scientific Laboratory Automation (Burlington, ON, Canada).