ABSTRACT
HIV post-treatment controllers (PTCs) are rare individuals who maintain low levels of viremia after stopping antiretroviral therapy (ART). Understanding the mechanisms of HIV post-treatment control will inform development of strategies aiming at achieving HIV functional cure. In this study, we evaluated 22 PTCs from 8 AIDS Clinical Trials Group (ACTG) analytical treatment interruption (ATI) studies who maintained viral loads ≤400 copies/mL for ≥24 wk. There were no significant differences in demographics or frequency of protective and susceptible human leukocyte antigen (HLA) alleles between PTCs and post-treatment noncontrollers (NCs, n = 37). Unlike NCs, PTCs demonstrated a stable HIV reservoir measured by cell-associated RNA (CA-RNA) and intact proviral DNA assay (IPDA) during analytical treatment interruption (ATI). Immunologically, PTCs demonstrated significantly lower CD4+ and CD8+ T cell activation, lower CD4+ T cell exhaustion, and more robust Gag-specific CD4+ T cell responses and natural killer (NK) cell responses. Sparse partial least squares discriminant analysis (sPLS-DA) identified a set of features enriched in PTCs, including a higher CD4+ T cell% and CD4+/CD8+ ratio, more functional NK cells, and a lower CD4+ T cell exhaustion level. These results provide insights into the key viral reservoir features and immunological profiles for HIV PTCs and have implications for future studies evaluating interventions to achieve an HIV functional cure.
Subject(s)
CD8-Positive T-Lymphocytes , HIV Infections , Humans , Killer Cells, Natural , Lymphocyte Activation , RNA , HIV Infections/drug therapy , HIV Infections/immunology , ViremiaABSTRACT
OBJECTIVE: The 24-item Early-Onset Scoliosis Questionnaire (EOSQ-24) is validated in patients with early onset scoliosis (EOS) aged 0 to 18 years and the 22-item Scoliosis Research Society (SRS-22) questionnaire is validated in idiopathic scoliosis patients 10 years and older. EOSQ-24 is completed by the caregiver and SRS-22 is completed by the patient. A prior study comparing patient-reported outcome measures completed by older pediatric patients and their parents showed a low level of agreement. Our purpose was to compare EOSQ-24 and SRS-22 scores completed at the same time point and at subsequent time points, in patients aged 5 to 18 years with idiopathic or congenital EOS without developmental delay. METHODS: This was a multicenter retrospective study. We identified pairs of EOSQ-24 and SRS-22 completed on the same day or within 6 months. Some patients had multiple pairs of surveys over time. EOSQ-24 and SRS-22 questions were matched and domain scores for Pain, Function, Mental Health, and Satisfaction were compared. Patients with a change in treatment between surveys were excluded. Pearson correlation coefficients ( r ) were used to compare domain scores, with r ≥0.7 indicating a strong relationship. RESULTS: There were 228 patient-caregiver dyads who completed 411 pairs of EOSQ-24 and SRS-22 on the same day. A strong correlation was found only for the Pain domain ( r =0.77). Function, Mental Health, and Satisfaction domains had positive but not strong correlations ( r = 0.58, r = 0.50, r = 0.41, respectively). Subanalysis based on age also showed a strong correlation only for Pain. There were 76 patient-caregiver dyads who completed 134 pairs of surveys with SRS-22 completed within 6 months after an EOSQ-24. All domains demonstrated a positive but not strong correlation, with Pain showing the highest correlation ( r = 0.64). CONCLUSIONS: EOSQ-24 and SRS-22 had a strong correlation only for Pain when completed at the same time point. EOSQ-24 and SRS-22 completed within 6 months lacked a strong correlation for all domains. Our findings suggest that parents and children with EOS may not share the same perspective on their health. Self-reported questionnaires should be used when possible to assess health-related quality of life in older children and adolescents with EOS who are developmentally neurotypical. LEVEL OF EVIDENCE: Level III-diagnostic.
Subject(s)
Caregivers , Quality of Life , Scoliosis , Humans , Scoliosis/psychology , Retrospective Studies , Child , Adolescent , Female , Caregivers/psychology , Male , Surveys and Questionnaires , Child, Preschool , Age of Onset , Patient Reported Outcome MeasuresABSTRACT
BACKGROUND: Identifying patients at risk for prolonged opioid use following surgery for symptomatic neuroma would be beneficial for perioperative management. The aim of this study is to identify the factors associated with postoperative opioid use of >4 weeks in patients undergoing neuroma surgery. METHODS: After retrospective identification, 77 patients who underwent surgery for symptomatic neuroma of the upper or lower extremity were enrolled. Patients completed the Patient-Reported Outcomes Measurement Information System (PROMIS) depression, Numeric Rating Scale (NRS) pain score, and a custom medication questionnaire at a median of 9.7 years (range: 2.5-16.8 years) following surgery. Neuroma excision followed by nerve implantation (n = 39, 51%), nerve reconstruction/repair (n = 18, 23%), and excision alone (n = 16, 21%) were the most common surgical treatments. RESULTS: Overall, 27% (n = 21) of patients reported opioid use of more than 4 weeks postoperatively. Twenty-three patients (30%) reported preoperative opioid use of which 11 (48%) did not report opioid use for >4 weeks, postoperatively. In multivariable logistic regression, preoperative opioid use was independently associated with opioid use of >4 weeks, postoperatively (odds ratio [OR] = 4.4, 95% confidence interval [CI]: 1.36-14.3, p = 0.013). CONCLUSION: Neuroma surgery reduces opioid use in many patients but patients who are taking opioids preoperatively are at risk for longer opioid use. Almost one-third of patients reported opioid use longer than 4 weeks, postoperatively.
Subject(s)
Analgesics, Opioid , Neuroma , Humans , Neuroma/surgery , Neurosurgical Procedures , Pain, Postoperative/drug therapy , Retrospective StudiesABSTRACT
BACKGROUND: Laboratory training courses have traditionally offered an attractive method to learn microsurgery in a low-risk environment. However, courses are often limited by cost, accessibility, and their one-time, nonlongitudinal nature. Our aims were to (1) describe our institution's microsurgical training course for hand surgery fellows, which is longitudinal and integrated within our fellowship curriculum and (2) investigate how this course affects the microsurgical confidence and competence of trainees throughout their fellowship year. METHODS: All hand fellows who trained in our 1-year combined hand surgery fellowship from 2016 through 2018 participated in this study. Baseline data on the type and duration of residency training, previous microsurgery experience and self-reported confidence, knowledge, and interest in microsurgery were recorded. Self-reported scores were documented using a continuous scale ranging from 0 to 10. An initial 3-day laboratory course combining the use of didactic teaching, a nonliving synthetic model, and a live rat model was conducted. Repeat laboratory training occurred thereafter at 6 and 12 months. At the end of each session, fellows repeated the baseline questionnaire and faculty assessed their microsurgical competence using a standardized global rating scale (GRS). RESULTS: A total of six fellows (2 years) were enrolled. At the end of the initial course, there was a statistically significant increase in mean self-reported confidence in microsurgery from 4.3 to 6.2 and knowledge from 4.7 to 6.5. Mean scores in interest were unchanged, from 9.2 to 9.3. There was also an increase in mean GRS score from day 3 to months 6 and 12. CONCLUSION: A longitudinal microsurgical training course integrated within a hand surgery fellowship is associated with increased confidence and microsurgical skill. This study describes our approach and its feasibility.
Subject(s)
Clinical Competence , Hand/surgery , Microsurgery/education , Animals , Curriculum , Fellowships and Scholarships , Humans , Internship and Residency , Microsurgery/standards , Rats , Simulation TrainingABSTRACT
OBJECTIVE: Fragility fractures are common among adults with cerebral palsy (CP), but clinical rehabilitation use after fracture and its effect on long-term health outcomes have not been sufficiently studied. The objectives of this study were to identify patterns of the use of physical therapy, occupational therapy, or both in the 6-month postfracture period and the association with 3-year mortality in adults with CP. METHODS: This retrospective cohort study included adults who were ≥18 years old, had CP, and had sustained an incident fragility fracture between January 1, 2014, and December 31, 2016, as identified from a random 20% Medicare fee-for-service dataset. Six-month outpatient physical therapy or occupational therapy use patterns after fracture were identified using group-based trajectory modeling. Cox regression determined the association between physical therapy or occupational therapy use trajectory patterns and mortality from 6 months to 3 years after fracture, adjusting for confounders. Effect modification by key characteristics was tested, including age, sex, and the modified Whitney Comorbidity Index (mWCI), which is a CP-specific comorbidity index that better captures overall medical complexity. RESULTS: Of the 2429 participants included, the majority (73.2%) were characterized as having little to no probability of physical therapy or occupational therapy use, whereas 16.0 and 10.7% were characterized as having early initiation and later initiation, respectively. Compared to the mortality rate for the little to no physical therapy or occupational therapy group, the mortality rates were 26% lower for the early physical therapy or occupational therapy initiation group (hazard ratio [HR] = 0.74; 95% CI = 0.55-1.00) and were 20% lower for the later initiation group (HR = 0.80; 95% CI = 0.57-1.12). There was effect modification by the mWCI. The mortality rate was lower when the early initiation and later initiation groups were compared to the little to no initiation group across all mWCI values examined (median and interquartile range), but the effect was stronger (ie, lower mortality rate) for lower mWCI values for both early initiation and later initiation groups. CONCLUSION: Most adults with CP underutilize outpatient physical therapy or occupational therapy services within 6 months postfracture. Early or later initiation versus little to no physical therapy or occupational therapy use was associated with a lower HR of mortality, although the effect was stronger and statistically significant among those with less medical complexity. IMPACT: Throughout their lives, the use of rehabilitation services in individuals with CP, including physical therapy and occupational therapy, dramatically declines despite the need for continued rehabilitation across their lifespans. This study characterized longitudinal physical therapy or occupational therapy use patterns in the 6 months following a fragility fracture among adults with CP and found that nearly 3 in 4 adults with CP had little to no physical therapy or occupational therapy use during this critical window to optimize postfracture health and function. Further, those who more regularly used physical therapy or occupational therapy services, regardless of the timing of initiation (early vs later), had significantly improved survival up to 3 years after fracture, suggesting the need for greater access to and delivery of clinical rehabilitation services.
Subject(s)
Cerebral Palsy , Fractures, Bone , Occupational Therapy , Adult , Aged , Humans , Cerebral Palsy/rehabilitation , Medicare , Outpatients , Retrospective Studies , United States/epidemiology , Male , FemaleABSTRACT
Objective The Accreditation Council for Graduate Medical Education (ACGME) guidelines require scholarly activity but do not specify what research-related activity is necessary to meet this requirement. The current components and opinions regarding research and its implementation that qualify as scholarly activity are unknown among US orthopedic surgery programs. We aimed to survey program directors of orthopedic surgery programs to evaluate and better understand the current state of research during training. Design A survey was sent to the program directors of all ACGME-accredited orthopedic surgery between 2019 and 2020 with questions evaluating each program's research requirements and barriers to improvement. Results One-hundred eighteen (N=118) surveys were collected from 94 academic (79.6%) and 24 community (21.4%) programs. Although nearly all (97.5%) programs required research for graduation, only 45% of them allotted protected time: 52 academic programs (55.3%) allotted a median of nine weeks (interquartile range (IQR): 8-12 weeks) of dedicated time and 13 community programs (54.2%) allotted six weeks (IQR: 4-28 weeks) (p=0.595). We distinguished dedicated research as either consecutive weeks or a formal research track for a year. All programs indicated a desire for an increased focus on basic science compared to the current focus on outcomes-based research (p=0.04). The greatest identified obstacle to research improvement reported by community programs was faculty and resource commitment (p=0.003). The overall level of satisfaction with the current research experience among directors is 50.8%. Conclusion Despite differences between academic and community programs, directors agree on shifting the focus of research toward basic science. To improve preclinical research, additional time may be required, and individualized improvement plans should be undertaken at academic and community programs alike.
ABSTRACT
BACKGROUND: The seesaw test consists of flexion and extension of the thumb metacarpal on the trapezium, with continuous axial pressure to keep the metacarpal base reduced in the carpometacarpal (CMC) joint. We aim to evaluate this maneuver compared with the grind test. METHODS: We prospectively enrolled 80 participants from March 2017 to March 2018 at a single institution, excluding those who had previous thumb surgery or pathology. Each participant underwent both seesaw and grind tests by 2 independent examiners. We included 24 patients with a mean age of 73 years in the CMC osteoarthritis group (Eaton stages 2-4) and 44 patients with a mean age of 66 years in the control group (Eaton stages 0 and 1). We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and multirater κ measure. RESULTS: The seesaw test had a higher sensitivity than the grind test (42%-71% vs 13%-17%), but a lower specificity (82%-86% vs 91%-98%). The PPV was more consistent between examiners for the seesaw test (63%-68% vs 42%-80%), and the NPV was higher (73%-84% vs 66%-68%). There was a slight agreement between the attending surgeon and the fellow performing the grind test (κ = 0.08) and a moderate agreement between the attending surgeon and the fellow performing the seesaw test (κ = 0.59). CONCLUSIONS: The seesaw test is superior to the grind test, with a much higher sensitivity, slightly lower specificity, more consistent PPV, and slightly higher NPV. Therefore, the seesaw test could be a valuable addition or even replacement for the grind test, and we recommend considering it in daily practice.
Subject(s)
Carpometacarpal Joints , Osteoarthritis , Trapezium Bone , Aged , Carpometacarpal Joints/surgery , Diagnostic Tests, Routine , Humans , Osteoarthritis/diagnosis , ThumbABSTRACT
BACKGROUND: This study aimed to (1) describe long-term patient-reported outcomes of surgically treated symptomatic radial sensory nerve neuromas on function, pain interference, pain intensity, and satisfaction; (2) assess which factors were associated with worse function, higher pain intensity, and more pain interference; and (3) describe the secondary surgery rate and factors associated with secondary surgery. METHODS: The authors conducted a retrospective review of patients surgically treated for radial sensory nerve neuroma from 2002 to 2016 (n = 54). Twenty-five of these 54 patients completed a follow-up survey including the Patient-Reported Outcomes Measurement Information System (PROMIS) upper extremity, pain interference, and depression scales; numerical rating scale pain and satisfaction instruments; and the global rating scale of change, at a mean period of 10.7 ± 4.3 years after neuroma surgery. RESULTS: The mean PROMIS scores were 45.0 ± 12.1 for upper extremity, 55.5 ± 10.3 for pain interference, and 49.9 ± 10.2 for depression, and were within 1 SD of the general population. Eight patients (32 percent) reported symptoms as unchanged or worse following neuroma surgery. The median numerical rating scale pain was 3 (interquartile range, 1 to 6) and the global rating scale of change satisfaction was 10 (interquartile range, 7 to 10). Older patients (p = 0.002) and patients with higher PROMIS pain interference (p < 0.001), higher numerical rating scale for pain (p = 0.012), and lower global rating scale of change scores (p = 0.01) had worse PROMIS upper extremity scores. The secondary surgery rate was 20 percent and was associated with the presence of multiple neuromas (p = 0.001). CONCLUSIONS: Radial sensory nerve neuromas remain difficult to treat. They have a high secondary surgery rate (20 percent), with only 68 percent of patients reporting improvement after surgical intervention. Patient-reported outcomes after surgery are similar to conditions of the general population; however, the range of outcomes is wide.
Subject(s)
Neuralgia/surgery , Neuroma/surgery , Neurosurgical Procedures/statistics & numerical data , Patient Reported Outcome Measures , Peripheral Nervous System Neoplasms/surgery , Radial Neuropathy/surgery , Adult , Female , Humans , Male , Middle Aged , Neuralgia/diagnosis , Neuralgia/etiology , Neuroma/complications , Neuroma/pathology , Pain Measurement/statistics & numerical data , Patient Satisfaction , Peripheral Nervous System Neoplasms/complications , Peripheral Nervous System Neoplasms/pathology , Radial Nerve/pathology , Radial Nerve/surgery , Radial Neuropathy/complications , Radial Neuropathy/pathology , Reoperation/statistics & numerical data , Retrospective Studies , Treatment OutcomeABSTRACT
Objective To determine the rate of salvage procedures and any other unplanned reoperations in patients with symptomatic Kienböck's disease who were treated with radial shortening osteotomy. In addition, we studied patient-reported outcome in the long term using Patient-Reported Outcome Measure Information System (PROMIS) instruments. Patients and Methods We performed a retrospective review of all patients who underwent radial shortening osteotomy for stage 2 and 3A Kienböck's disease. Patients who had concomitant revascularization were grouped separately. We collected demographic data, data regarding type of surgery and reoperations, and radiographic data. Patient-reported outcome measures were the PROMIS Upper Extremity Computer Adaptive Testing (CAT) and Pain Interference instruments, the abbreviated Disabilities of Arm, Shoulder, and Hand (QuickDASH), and the 0 to 10 numeric rating scale for pain and satisfaction. Results We included 48 patients who had radial shortening osteotomy alone, and 17 patients who had a combined procedure of radial shortening and direct revascularization. The rate of unplanned reoperations was 33% (16 of 48) in those who had radial shortening osteotomy and 24% (4 of 17) in those who had a combined procedure. Six (13%) of 48 patients underwent proximal row carpectomy due to failed radial shortening osteotomy. No salvage procedures were performed after combined radial shortening/revascularization. Median PROMIS Physical Function CAT scores were 56 (interquartile range [IQR]: 44-56) and 56 (IQR: 41-56), respectively. Median PROMIS Pain Interference scores were 39 (IQR: 39-52) and 39 (IQR: 39-49), respectively. Median QuickDASH scores were 2.3 (IQR: 0-23) and 4.5 (IQR: 2.3-14), respectively. Conclusion Radial shortening osteotomy for symptomatic Kienböck's disease yields reasonable long-term function. We observed that approximately one in eight patients underwent salvage surgery after radial shortening, and this should be taken into account when making the initial decision to treat Kienböck's disease surgically. There appeared to be no benefit of direct revascularization in addition to radial shortening in terms of patient-reported outcome in the long term. Level of Evidence This is a Level IV, therapeutic study.
ABSTRACT
Background: This study aims to describe the long-term patient-reported outcomes after surgery for hypothenar hammer syndrome (HTHS) and to identify factors associated with inferior outcomes. Methods: We retrospectively identified 27 patients who underwent surgical intervention for HTHS from 2002 to 2016. Fifteen patients (56%) completed outcome questionnaires: Quick Disabilities of the Arm, Shoulder, and Hand, Cold Intolerance Symptom Severity (CISS) survey, Patient-Reported Outcomes Measurement Information System Upper Extremity Computer Adaptive Test, and Patient-Reported Outcomes Measurement Information System Pain Interference Computer Adaptive Test. The median questionnaire follow-up was 7.2 years (interquartile range, 3.1-9.9). Outcomes were compared across different surgical techniques, and the influence of patient-related factors on outcomes was also evaluated. Results: Six (40%) patients experienced complete symptom resolution, 6 (40%) had improvement without complete resolution, 1 (7%) had resolution followed by recurrence, and 2 (13%) reported no improvement. The most common symptom after surgical intervention was cold intolerance. Questionnaire scores were similar across ligation, direct repair, and vein graft vascular reconstruction. Patients had better CISS scores if they had surgery on their nondominant hand (13.2 vs 38.6) and did not have a manual labor job (18.1 vs 40.5). Conclusions: Surgery for HTHS leads to moderate long-term improvement in patient-reported outcomes. Different surgical techniques yield similar symptomatic relief. Manual labor and surgery of the dominant hand are associated with worse CISS scores.
Subject(s)
Arterial Occlusive Diseases , Ulnar Artery , Hand , Humans , Patient Reported Outcome Measures , Retrospective StudiesABSTRACT
BACKGROUND: Local health care facilities are often unequipped to treat complex upper extremity injuries, and patients are therefore transferred to designated trauma centers. This study describes the characteristics of patients transferred to a Level I trauma center for hand and upper extremity injuries and to investigate the accuracy of the provided diagnosis at the time of referral. METHODS: Adult patients transferred from outside facilities to the authors' Level I trauma center by means of direct contract with the on-call fellow for the care of hand and upper extremity injuries were identified. Patient- and injury-related information was prospectively collected at the time of referral before patient transfer, and again following diagnostic evaluation by a hand surgeon at the authors' institution. RESULTS: Sixty-three patients were transferred to the authors' hand surgery service from outside facilities after direct contact with the on-call fellow. Most patients were referred by emergency medicine physicians [n = 47 (76 percent)], followed by midlevel emergency department providers (physician assistant or nurse practitioner) [n = 12 (19 percent)] or hand surgeons [n = 3 (5 percent)]. Six patients were transferred directly from a Level I trauma center. Twenty-one transferred patients (33 percent) had an inaccurate diagnosis at the time of referral. Factors associated with an inaccurate diagnosis included trauma level of the referring hospital and diagnoses of infection or dysvascularity. CONCLUSIONS: The diagnostic accuracy for hand injuries transferred from outside facilities by means of provider-to-provider communication is imperfect, and some injuries are misdiagnosed. Hand surgeons should continue to improve the triage and transfer process for patients with acute hand surgery injuries. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.
Subject(s)
Arm Injuries/diagnosis , Hand Injuries/diagnosis , Medical Overuse/statistics & numerical data , Patient Transfer/statistics & numerical data , Triage/statistics & numerical data , Adult , Female , Humans , Male , Middle Aged , Prospective Studies , Referral and Consultation/statistics & numerical data , Trauma Centers/statistics & numerical data , Young AdultABSTRACT
Features of the fission yeast Schizosaccharomyces pombe cAMP/PKA pathway make S. pombe particularly amenable for heterologous expression of cAMP pathway proteins such as GαS subunits and their cognate adenylyl cyclases, PKA catalytic and regulatory subunits, and cyclic nucleotide phosphodiesterases. We have constructed two PKA-repressed reporters for use in high-throughput screens to detect compounds that elevate or reduce PKA activity, thus facilitating the discovery of both inhibitors and activators of these target proteins. Here, we describe steps to construct screening strains and to optimize and conduct these screens.