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Article ; Online: RATeS (Re-Admissions in Trauma and Orthopaedic Surgery): a prospective regional service evaluation of complications and readmissions.

Ward, Alex E

Archives of orthopaedic and trauma surgery

2019 Volume 139, Issue 10, Page(s) 1351–1360

Abstract: Introduction: All the surgeries carry risks, which may lead to readmission at a later date. At present, there is limited Trauma and Orthopaedic (T&O) specific data in the literature. As a result, a prospective regional service evaluation aimed to ... ...

Abstract	Introduction: All the surgeries carry risks, which may lead to readmission at a later date. At present, there is limited Trauma and Orthopaedic (T&O) specific data in the literature. As a result, a prospective regional service evaluation aimed to discover the current complication and readmission rates across all T&O procedures and identify any factors associated with these outcomes. Methods: Data were collected at six sites across Yorkshire and Humber for all T&O procedures during October 2016. Patient demographics and procedure-specific data were collected. Post-operative complications and length of stay were recorded. All the patients were then followed up for 30 days post-discharge to determine if they experienced complications which resulted in readmission and further surgical intervention. Results: 1411 patients having a total of 64 operations were recorded with 1391 completing follow-up (98.5%). Overall in-patient complication rate was 8.4% with the readmission rate being 4.4%. An ASA grade of three or more was found to be associated with readmission. Procedure-related factors such as the use of VTE prophylaxis and prophylactic antibiotics, as well as the elective nature of certain operations were negatively associated with readmission. The largest subgroup of patients was those undergoing total hip (THR) or knee replacements (TKR). For these 234 patients, the readmission rate for TKR and THR being 3.77% and 3.13%, respectively. Conclusions: This large, multi-centre project describes readmission rates following trauma and orthopaedic surgery. In the presented study, the elective nature of the procedure was associated with a reduced risk of readmission.
MeSH term(s)	Adult ; Aged ; Elective Surgical Procedures/adverse effects ; Elective Surgical Procedures/statistics & numerical data ; England ; Female ; Humans ; Male ; Middle Aged ; Orthopedic Procedures/adverse effects ; Orthopedic Procedures/statistics & numerical data ; Patient Readmission/statistics & numerical data ; Postoperative Complications/etiology ; Prospective Studies ; Risk Factors ; Wounds and Injuries/surgery
Language	English
Publishing date	2019-03-20
Publishing country	Germany
Document type	Journal Article ; Multicenter Study
ZDB-ID	80407-1
ISSN	1434-3916 ; 0003-9330 ; 0344-8444
ISSN (online)	1434-3916
ISSN	0003-9330 ; 0344-8444
DOI	10.1007/s00402-019-03144-4
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Article ; Online: A case report of acute hypothermia during initial inpatient clozapine titration with review of current literature on clozapine-induced temperature dysregulations.

Burk, Bradley G / Ward, Alex H / Clark, Brooke

BMC psychiatry

2020 Volume 20, Issue 1, Page(s) 290

Abstract: Background: Here we describe a unique case of clozapine-associated hypothermia during initial titration of this medication in an acute inpatient psychiatry setting. Only a handful of cases on this topic have been published. We discuss possible ... ...

Abstract	Background: Here we describe a unique case of clozapine-associated hypothermia during initial titration of this medication in an acute inpatient psychiatry setting. Only a handful of cases on this topic have been published. We discuss possible pharmacologic mechanisms supporting or refuting the propensity of clozapine to induce hypothermia, as well as risk factors for clozapine-induced hypothermia, and a comparison to clozapine-induced hyperthermia. Case presentation: A 70 year-old African American female with treatment-refractory schizoaffective disorder developed hypothermia with a nadir temperature of 89 °F (31.7 °C) after 7 days on clozapine, on a total dose of 50 mg twice daily. Accompanying symptoms included bradycardia, hypotension, QTc prolongation, tachypnea, hypoxemia, and an absence of shivering. The patient was transferred to the ICU, and rewarmed within 10 h with the discontinuation of her clozapine, ziprasidone, and carvedilol. Broad spectrum antibiotics were initiated, but discontinued shortly after, as the patient had no leukocytosis, and blood cultures were negative. Discussion: While hypoglycemia, hypothyroidism, sepsis, and stroke were effectively ruled out, alternative drug-disease (including chronic kidney disease), and drug-drug interactions were considered possible contributing features. Benzodiazepines, valproic acid, ziprasidone, and the numerous antihypertensive agents the patient was taking were considered as either primary or compounding factors for hypothermia. After exclusion or inclusion of these alternative causes, we calculated a score of 4 (possible) for clozapine-induced hypothermia on the Naranjo Scale. Conclusions: Clozapine-induced hypothermia may occur more commonly than clinicians believe. Practitioners should be cognizant of this potentially fatal phenomenon, and monitor for temperature dysregulations while on clozapine, especially during initial titration, in those with multiple comorbid factors, and on additional medications that may contribute to hypothermia.
MeSH term(s)	Aged ; Antipsychotic Agents/administration & dosage ; Antipsychotic Agents/adverse effects ; Antipsychotic Agents/therapeutic use ; Body Temperature/drug effects ; Body Temperature Regulation/drug effects ; Clozapine/administration & dosage ; Clozapine/adverse effects ; Clozapine/therapeutic use ; Female ; Humans ; Hypothermia/chemically induced ; Inpatients
Chemical Substances	Antipsychotic Agents ; Clozapine (J60AR2IKIC)
Language	English
Publishing date	2020-06-09
Publishing country	England
Document type	Case Reports ; Journal Article ; Review
ISSN	1471-244X
ISSN (online)	1471-244X
DOI	10.1186/s12888-020-02695-w
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Article ; Online: Validation of automated complex head and neck treatment planning with pencil beam scanning proton therapy.

Hedrick, Samantha Grace / Petro, Scott / Ward, Alex / Morris, Bart

Journal of applied clinical medical physics

2021 Volume 23, Issue 2, Page(s) e13510

Abstract: Background: Pencil beam scanning (PBS) proton therapy offers dosimetric advantages for several treatment sites, including head and neck (H&N). However, to achieve the optimal target coverage and robustness, these plans can be complex and time consuming ... ...

Abstract	Background: Pencil beam scanning (PBS) proton therapy offers dosimetric advantages for several treatment sites, including head and neck (H&N). However, to achieve the optimal target coverage and robustness, these plans can be complex and time consuming to develop and optimize. Automating the treatment planning process can ensure a high-quality and standardized plan, reduce burden to the planner, and decrease time-to-treatment. We utilized in-house scripting to automate a four-field multi-field optimization (MFO) H&N planning technique. Methods and materials: Ten bilateral H&N patients were planned in RayStation v6 with a four-field modified-X beam configuration using MFO planning. Automation included creation of avoidance structures to control spot placement and development of standardized beams, PBS spot settings, robust optimization objectives, and patient-specific predicted planning constraints. Each patient was planned both with and without automation to evaluate differences in planning time, perceived effort and plan quality, plan robustness, and OAR sparing. Results: On average, scripted plans required 3.2 h, compared to 4.3 h without the script. There was no difference in target coverage or plan robustness with or without automation. Automation significantly reduced mean dose to the oral cavity, parotids, esophagus, trachea, and larynx. Perceived effort was scaled from 1 (minimum effort) to 100 (maximum effort), and automation reduced perceived effort by 42% (p < 0.05). Two non-scripted plans required re-planning due to errors. Conclusions: Automation of this multi-beam, the MFO proton planning process reduced planning time and improved OAR sparing compared to the same planning process without scripting. Scripting generation of complex structures and planning objectives reduced burden on the planner. With most current treatment planning software, this automation is simple to implement and can standardize quality of care across all treatment planners.
Language	English
Publishing date	2021-12-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2010347-5
ISSN	1526-9914 ; 1526-9914
ISSN (online)	1526-9914
ISSN	1526-9914
DOI	10.1002/acm2.13510
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Article ; Online: Pharmacogenetics as a predictor chemotherapy induced peripheral neuropathy in gynecologic cancer patients treated with Taxane-based chemotherapy.

Mysona, David / Dorr, Katherine / Ward, Alex / Shaver, Ellen / Rungruang, Bunja / Ghamande, Sharad

Gynecologic oncology

2022 Volume 168, Page(s) 114–118

Abstract: Background: This study investigated whether there are pharmacogenomic markers predictive of chemotherapy induced peripheral neuropathy (CIPN) as a result of taxane-based chemotherapy.: Methods: Patients were enrolled from August 2020 to November 2020 ...

Abstract	Background: This study investigated whether there are pharmacogenomic markers predictive of chemotherapy induced peripheral neuropathy (CIPN) as a result of taxane-based chemotherapy. Methods: Patients were enrolled from August 2020 to November 2020 in a prospective, case-control trial evaluating pharmacogenetic predictors of CIPN. All women were treated with at least 3 cycles of taxane-based chemotherapy for histologically confirmed gynecologic malignancies. Buccal saliva samples were used to test for 32 drug metabolism variations. All testing was performed by ⍺LPHA-GENOMIX laboratories. Fisher's Exact test was used to assess for event differences of categorical variables. Results: Of 102 enrolled patients, 58%, 28%, and 14% had ovarian, endometrial, or cervical cancers, respectively. The median age was 67, 72% were Caucasian and 25% were African American. 16% of patients were treated with 3-4 cycles, 57% received 5-7 cycles, and 27% received 8 or more cycles of chemotherapy that included paclitaxel. Grade 2 CIPN was experienced by 51 patients. There was no difference in age, race, disease site, or number of chemotherapy cycles (p > 0.05) between those who did or did not develop CIPN. CYP2D6 genotype (p = 0.009) and CYP3A5 genotype (p = 0.023) had different frequencies among those with and without CIPN. Patients classified as having poor or intermediate function of CYP2D6 had increased risk of CIPN (OR 1.63, 95% CI 1.04-2.57, p = 0.026). There was no difference in CYP2D6 phenotype by race (p = 0.29). No patients with normal function of CYP3A5 developed CIPN. There were no Caucasians with normal function of CYP3A5, but 28% of African Americans had normal CYP3A5 function (p < 0.001). Conclusions: Pharmacogenomics appear associated with the development of CIPN and may be able to help personalize treatment decision making.
MeSH term(s)	Female ; Humans ; Antineoplastic Agents/adverse effects ; Breast Neoplasms ; Cytochrome P-450 CYP2D6/genetics ; Cytochrome P-450 CYP3A/genetics ; Genital Neoplasms, Female/drug therapy ; Genital Neoplasms, Female/genetics ; Peripheral Nervous System Diseases/chemically induced ; Peripheral Nervous System Diseases/genetics ; Pharmacogenetics ; Prospective Studies ; Taxoids/adverse effects ; Case-Control Studies ; Aged
Chemical Substances	Antineoplastic Agents ; Cytochrome P-450 CYP2D6 (EC 1.14.14.1) ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; taxane (1605-68-1) ; Taxoids
Language	English
Publishing date	2022-11-23
Publishing country	United States
Document type	Clinical Trial ; Journal Article
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2022.10.021
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Article ; Online: A cilia-independent function of BBSome mediated by DLK-MAPK signaling in C. elegans photosensation.

Zhang, Xinxing / Liu, Jinzhi / Pan, Tong / Ward, Alex / Liu, Jianfeng / Xu, X Z Shawn

Developmental cell

2022 Volume 57, Issue 12, Page(s) 1545–1557.e4

Abstract: Bardet-Biedl syndrome (BBS) is a genetic disorder that affects primary cilia. BBSome, a protein complex composed of eight BBS proteins, regulates the structure and function of cilia, and its malfunction causes BBS in humans. Here, we report a cilia- ... ...

Abstract	Bardet-Biedl syndrome (BBS) is a genetic disorder that affects primary cilia. BBSome, a protein complex composed of eight BBS proteins, regulates the structure and function of cilia, and its malfunction causes BBS in humans. Here, we report a cilia-independent function of BBSome. To identify genes that regulate the C. elegans photoreceptor protein LITE-1 in ciliated ASH photosensory neurons, we performed a genetic screen and isolated bbs mutants. Functional analysis revealed that BBSome regulates LITE-1 protein stability independently of cilia. Through another round of genetic screening, we found that this cilia-independent function of BBSome is mediated by DLK-MAPK signaling, which acts downstream of BBSome to control LITE-1 stability via Rab5-mediated endocytosis. BBSome exerts its function by regulating the expression of DLK. BBSome also regulates the expression of LZK, a mammalian DLK in human cells. These studies identify a cilia-independent function of BBSome and uncover DLK as an evolutionarily conserved BBSome effector.
MeSH term(s)	Animals ; Bardet-Biedl Syndrome/genetics ; Bardet-Biedl Syndrome/metabolism ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; Cilia/metabolism ; Humans ; Mammals/metabolism ; Protein Transport/genetics ; Proteins/metabolism
Chemical Substances	Proteins
Language	English
Publishing date	2022-05-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2022.05.005
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Zs.A 5742: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Surgical vs non-surgical management of Weber B fractures: A systematic review.

Julian, Thomas Henry / Broadbent, Rosie Helen / Ward, Alex Elizabeth

Foot and ankle surgery : official journal of the European Society of Foot and Ankle Surgeons

2019 Volume 26, Issue 5, Page(s) 494–502

Abstract: Background: The aim of this systematic review was to compare surgical and non-surgical management of Weber B ankle fractures.: Methods: A systematic computer-based search was conducted using the MEDLINE (via OvidSP), EMBASE (via OvidSP) and Central ... ...

Abstract	Background: The aim of this systematic review was to compare surgical and non-surgical management of Weber B ankle fractures. Methods: A systematic computer-based search was conducted using the MEDLINE (via OvidSP), EMBASE (via OvidSP) and Central databases. Data were extracted regarding functional outcome, radiological union, range of motion (RoM), infection rate and quality of life (QoL). Results: There were no significant differences identified between surgical and non-surgical management of Weber B fractures with respect to functional outcome. There is a higher rate of complication following surgical management, including infection, reoperation, thromboembolic events and death. With respect to QoL and ankle RoM, this review identified no differences between surgical and non-surgical management. Conclusions: There is a need for further published literature evaluating the most efficacious management as there is a poverty of high-level research available. Currently, the available literature does not overwhelmingly favour a particular approach to Weber B ankle fractures.
MeSH term(s)	Ankle Fractures/diagnosis ; Ankle Fractures/physiopathology ; Ankle Fractures/surgery ; Ankle Joint/diagnostic imaging ; Ankle Joint/surgery ; Fracture Fixation/methods ; Humans ; Quality of Life ; Radiography ; Range of Motion, Articular ; Treatment Outcome
Language	English
Publishing date	2019-06-21
Publishing country	France
Document type	Journal Article ; Systematic Review
ZDB-ID	1424533-4
ISSN	1460-9584 ; 1268-7731
ISSN (online)	1460-9584
ISSN	1268-7731
DOI	10.1016/j.fas.2019.06.006
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Article: A robust and flexible baculovirus-insect cell system for AAV vector production with improved yield, capsid ratios and potency.

Marwidi, Yoko / Nguyen, Hoang-Oanh B / Santos, David / Wangzor, Tenzin / Bhardwaj, Sumita / Ernie, Gabriel / Prawdzik, Gregg / Lew, Garrett / Shivak, David / Trias, Michael / Padilla, Jada / Tran, Hung / Meyer, Kathleen / Surosky, Richard / Ward, Alex Michael

Molecular therapy. Methods & clinical development

2024 Volume 32, Issue 2, Page(s) 101228

Abstract: Manufacturing of adeno-associated viruses (AAV) for gene and cell therapy applications has increased significantly and spurred development of improved mammalian and insect cell-based production systems. We developed a baculovirus-based insect cell ... ...

Abstract	Manufacturing of adeno-associated viruses (AAV) for gene and cell therapy applications has increased significantly and spurred development of improved mammalian and insect cell-based production systems. We developed a baculovirus-based insect cell production system-the SGMO Helper-with a novel gene architecture and greater flexibility to modulate the expression level and content of individual Rep and Cap proteins. In addition, we incorporated modifications to the AAV6 capsid sequence that improves yield, capsid integrity, and potency. Production of recombinant AAV 6 (rAAV6) using the SGMO Helper had improved yields compared to the Bac-RepCap helper from the Kotin lab. SGMO Helper-derived rAAV6 is resistant to a previously described proteolytic cleavage unique to baculovirus-insect cell production systems and has improved capsid ratios and potency,
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2872938-9
ISSN	2329-0501 ; 2329-0501
ISSN (online)	2329-0501
ISSN	2329-0501
DOI	10.1016/j.omtm.2024.101228
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Zs.A 7107: Show issues

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Article ; Online: The Current UK Consensus on the Management of Weber B and Posterior Ankle Fractures: A Questionnaire Study as Part of the Acute Management of Ankle Fractures (AUGMENT) Audit.

Gourbault, Lysander James / Fennelly, Joseph Thomas / Stedman, Tobias / Price, Michael James / Ward, Alex Elizabeth

The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons

2021 Volume 60, Issue 4, Page(s) 669–675

Abstract: Ankle fractures are common conditions which are associated with significant morbidity when managed incorrectly. With the incidence due to triple by 2030, standards of practice were created by the British Orthopaedic Association and the British ... ...

Abstract	Ankle fractures are common conditions which are associated with significant morbidity when managed incorrectly. With the incidence due to triple by 2030, standards of practice were created by the British Orthopaedic Association and the British Orthopaedic Foot and Ankle Society to ensure optimal treatment. In spite of this, anecdotally there is still a variation in practice and therefore a questionnaire study was designed to explore clinician decision-making around Weber B and Posterior Malleolus ankle fractures. Five scenarios explored management regarding minimally and grossly displaced injuries, as well as the use of further imaging. The questionnaires were distributed via AUGMENT collaborators at their sites and at the British Orthopaedic Foot and Ankle Society congress 2018. About 315 questionnaires were completed and included in analysis. For Weber B injuries, overall there was a consensus across all respondents with minimally displaced and grossly displaced fractures being treated conservatively and operatively respectively. For Posterior Malleolus injuries, there was variation in practice between Foot and Ankle specialists and their non-Foot and Ankle colleagues. Computed tomography (CT) was more likely to be used to assess these injuries by specialists (97.50 vs 69.79%) and these injuries were more likely to be treated operatively across the board. This study identified key variation in practice of the management of Posterior Malleolar ankle fractures, including the use of imaging to further define the anatomy and the decision to operate. Foot and Ankle surgeons were more likely to organize CT scans and to surgically manage these injures.
MeSH term(s)	Ankle Fractures ; Ankle Injuries ; Consensus ; Fracture Fixation, Internal ; Humans ; Surveys and Questionnaires ; United Kingdom
Language	English
Publishing date	2021-02-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	1146972-9
ISSN	1542-2224 ; 1067-2516
ISSN (online)	1542-2224
ISSN	1067-2516
DOI	10.1053/j.jfas.2020.04.023
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Article: The acute management of ankle fractures (Augment) study: A prospective trainee led national collaborative audit of the Boast 12 guidelines.

Fennelly, Joseph T / Gourbault, Lysander J / Stedman, Tobias / Price, Michael J / Ward, Alex E

The surgeon : journal of the Royal Colleges of Surgeons of Edinburgh and Ireland

2021 Volume 19, Issue 5, Page(s) e237–e244

Abstract: Background: Ankle fractures are one of the most common fractures in adults aged 20-65 years. The British Orthopaedic Association (BOA) and British Orthopaedic Foot and Ankle Society (BOFAS) jointly produced Standards for Trauma (BOAST) BOAST 12, with ... ...

Abstract	Background: Ankle fractures are one of the most common fractures in adults aged 20-65 years. The British Orthopaedic Association (BOA) and British Orthopaedic Foot and Ankle Society (BOFAS) jointly produced Standards for Trauma (BOAST) BOAST 12, with the aim of reducing morbidity by standardising care of these injuries. The primary aim of the AUGMENT study was to determine the extent and clinical effect of variation from BOAST 12. Methods: AUGMENT was a multi-centre prospective trainee led audit of consecutive patients presenting with an ankle fracture within a four-week period. Data were collected on patient demographics, comorbidities, management and 12-week outcome. The BOAST 12 standards were divided into four subgroups; documentation, imaging, management and follow-up. Percentage compliance with each subgroup was analysed. A multivariate logistic regression analysis was used to determine impact of overall compliance on likelihood of discharge in follow-up period. Findings: 971 patients were included across 52 sites. The overall rate of BOAST 12 compliance was 41.7%. Variations in practice were observed in clinical documentation, especially of neurovascular status, (40.7%) and VTE assessment (61.5%). Patient management compliance with all 16 of the BOAST 12 standards was associated with a higher rate of discharge during the 12-week follow-up period (p = 0.005). Conclusion: AUGMENT has demonstrated that the management of ankle fractures is variable across the UK. Over half of patients had aspects of their care that were not BOAST 12 compliant. When compliance was observed, it was associated with earlier discharge from orthopaedic care.
MeSH term(s)	Adult ; Ankle Fractures/therapy ; Fracture Fixation, Internal ; Humans ; Lower Extremity ; Orthopedics ; Prospective Studies
Language	English
Publishing date	2021-01-05
Publishing country	Scotland
Document type	Journal Article
ZDB-ID	2102927-1
ISSN	1479-666X
ISSN	1479-666X
DOI	10.1016/j.surge.2020.11.001
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Article ; Online: Functional Outcomes Following Operative and Nonoperative Management of Weber C Ankle Fractures: A Systematic Review.

Yap, Rye Y / Babel, Aditi / Phoon, Kar M / Ward, Alex E

The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons

2019 Volume 59, Issue 1, Page(s) 105–111

Abstract: Weber C ankle fractures are unstable ankle fractures occurring above the syndesmosis. These fractures are often managed operatively, although a small population of patients are still selected for nonoperative management. This study primarily aimed to ... ...

Abstract	Weber C ankle fractures are unstable ankle fractures occurring above the syndesmosis. These fractures are often managed operatively, although a small population of patients are still selected for nonoperative management. This study primarily aimed to summarize the current evidence on functional outcomes for Weber C patients managed operatively and nonoperatively. Evidence on secondary outcomes such as complications and radiographic outcomes were also reviewed. This systematic search was conducted according to PRISMA guidelines. A literature search was conducted using the EMBASE, Medline, and Central databases. A total of 26 studies were included in the final analysis. All papers studied the management of Weber C fractures using open reduction and internal fixation (ORIF). Three main functional outcome scores were identified: American Orthopedic Foot and Ankle Society score, Olerud-Molander Ankle Score, and Foot and Ankle Outcome Score. Only 1 study compared operative and conservative management, which showed similar outcomes for either option (median Olerud-Molander Ankle Score 95 [range 20 to 95] vs 100 [70 to 100], respectively). Complications associated with operative management included infection, wound dehiscence, implant failure, and malunion or nonunion. The mean rate of syndesmosis malreduction was 18.2%. This study showed that operative management, regardless of the method of ORIF used, as well as nonoperative management resulted in good functional outcomes, indicating that patient selection for either method is important. However, there is limited evidence on the complications and radiographic outcomes associated with nonoperative management. We recommend further studies to compare all ORIF methods with conservative management and examine the complications associated with nonoperative management.
MeSH term(s)	Ankle Fractures/therapy ; Casts, Surgical ; Fracture Fixation ; Humans ; Recovery of Function ; Treatment Outcome
Language	English
Publishing date	2019-12-27
Publishing country	United States
Document type	Journal Article ; Systematic Review
ZDB-ID	1146972-9
ISSN	1542-2224 ; 1067-2516
ISSN (online)	1542-2224
ISSN	1067-2516
DOI	10.1053/j.jfas.2019.06.005
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