Objective: To report perioperative findings of patients with multiple failed-dacryocystorhinostomy (DCR) and to determine the success rate of revision external (rEx-DCR) performed by a modified technique.Methods: Thirty-one eyes of 31 patients  with recurrent dacryocystitis or epiphora following at least one previous failed-DCR were assessed regarding the time from initial surgery to recurrence and revision surgery, type of primary surgery , recurrence number, stent usage and the success rate. Relief of epiphora and positive dye test were established as functional and anatomical successes, respectively.Results: The mean age was 43.0 years (8-78), with a mean follow-up period of 21.4 months (6-46). The mean reoperation number was 1.4 (1-5). The mean time from initial surgery to recurrence was 15.2 months (1-55) and to rEx-DCR, 19.8 months (4-65). Untouched medial canthal ligament was observed in 28 (90.3%), improper rhinostomy location in 26 (83.8%), inadequate osteotomy size in 25 (80.6%), single-anterior-flap-only in 5 (16.1%), membranous ostial scar formation in four (12.5%) and no flap in three (9.6%) patients. The success rate was 93.5%, which was lower than our primary modified Ex-DCR (99.1%). Conclusions: The most common reasons for recurrence were small and unsuitable osteotomy locations with intact medial canthal ligaments. “Double-mucosal flap” approach with an anterior sacco-mucosal complex suspension increases the functional success rate, and stent implantation is not obligatory if canalicular problems or small/ atrophic sacs do not exist. The knowledge of technical strategy and teaching pearls improves the success rates of primary and revision surgeries. Abbreviations: DCR = dacryocystorhinostomy, Ex-DCR = external DCR, EE-DCR = endoscopic endonasal DCR, TC-LA-DCR = transcanalicular laser-assisted DCR Epiphora associated with complete nasolacrimal duct (NLD) obstruction is a common annoying symptom that patients encounter at any age, functionally and socially. Although primary probing may be tried as an initial option for the management of fresh NLD blockages in older children and adults .Among various reasons for surgical failure in traditional Ex-DCR, EE-DCR and TC-LA-DCR, endoscopic evaluations revealed insufficient bone removal, improperly positioned osteotomy site, procedural inability to identify the sac’s localization, adhesions between the anterior and posterior sacco-mucosal flap complexes or the nasal septum, and granulation tissue formation [8]. On the other hand, there are only a few papers that report the success rate of rEx-DCR for recurrences. In the present study, perioperative observational findings of rEx-DCR for failed cases were evaluated, a modified suspension technique of the anterior sacco-mucosal flap was used for the first time in revision cases, and the technical strategy with teaching pearls for success is stated.Although the success rates of surgeries for failed-DCRs are similar between revision (r) rEE-DCR, rTC-LA-DCR and rEx-DCR, numerous published articles have reported endoscopic findings and suggested that revision of failed-DCR cases be performed by rEE-DCR or rTC-LA-DCR surgeries, the results of which have been said to be praised . Perioperatively, if the medial canthal ligament was found to be untouched, it was opened  to expose the sac and lacrimal fossa. If the primary osteotomy site was placed improperly, a new bony window was created just beneath the medial canthal tendon  opposite to the level of the common canaliculus . Therefore, new anterior and posterior sacco-mucosal flaps were then created in untouched cases  that corresponded to the belly of the lacrimal sac, which was intact in most of the cases. In cases with untouched medial canthal tendon, it was observed that the osteotomy size was smaller than 10 x 10-mm in all cases. Therefore, if the final osteotomy size was insufficient and smaller than the desired 15 x 15-mm in diameter, it was enlarged in all directions using a Kerrison punch, but especially up to the lacrimal fossa superiorly, that corresponded again just below the medial canthal ligament along with minimal anterior ethmoidectomy. Then, anterior sacco-mucosal flaps  were sutured together up to the orbicularis oculi muscle  using the described “figure-of-eight vertical mattress suture technique”  to prevent collapse back onto the posterior sacco-mucosal anastomosis . Patients were discharged on the day of surgery with appropriate medication and followed up on the first week and 3-month intervals thereafter.All the recurrent cases had a modified surgery by Ex-DCR with “figure-of-eight vertical mattress suture technique” that was described for primary DCR in eyes with complete NLD obstructions . The gold standard in DCR is still an external approach as it has the highest success rate in experienced hands. Indeed, previously published articles of our team, with a total of 504 eyes with epiphora from dacryocystitis, have reported that the success rates after primary surgeries are (1) 45.2% for initial probing with or without silicone tube intubation in older children and adults with fresh NLD obstruction [1], (2) between 87.0% and 88.2% in conventional EE-DCR , (3) up to 89.8% in traditional Ex-DCR , and finally (4) 99.1% in modified Ex-DCR [2]. However, primary probing with or without silicone tube implantation is not recommended in cases with atrophic sacs, mucocele formation, trauma, acute or long-lasting chronic dacryocystitis, dacryocutaneous fistula and anamnesis of recurrence [1].Nasolacrimal system blockages distal to the common canaliculus are commonly encountered at the level of mid or lower NLD and reconstructive surgery with DCR in cases of epiphora from their complete obstructions is the basic treatment modality . These patients with previous failed-EE-DCR demonstrated a smaller ostium size when compared with failed-Ex-DCR, all of which were still smaller than the expected 15 x 15-mm diameter. Although the frontal process of the maxillary bone was opened by endoscopic approaches, the anterior ethmoidal bones were not sufficiently removed in most cases (82.6%), which decreased the horizontal dimension of the ostium. In addition, the creation of a posterior flap to cover exposed bones might decrease the incidence of adhesions and bony ingrowth at the newly created NLD ostium following surgery. Indeed, a recent study has reported about a 10-fold recurrence rate in single-flap EE-DCR when compared with the double-flap technique [11]. Endonasal and CT findings revealed that the most common causes for DCR failures are related to smaller intranasal ostium size due to insufficient bone opening during the initial operation along with new bone ingrowth, both of which induce shrinkage of the rhinostomy that reaches 50% of the initial size within the first month following stent removal and up to 35% of the initial size at 1 year postoperatively, resulting in re-obstruction . In addition, any granulation tissue was excised easily at the rhinostomy site, if present. Inadequate lacrimal bone removal was the third most frequent finding in 25/ 31 of failed-DCR patients. It is generally difficult to enlarge the small osteotomy site sufficiently by TC-LA-rDCR or EE-rDCR when compared with rEx-DCR. That is why the success rate of rTC-LA-DCR is known to be lower than that of rEx-DCR. However, in the present article, it was possible to enlarge the inadequately sized and improperly positioned former osteotomy openings by rEx-DCR that was re-positioned and/ or enlarged properly just below the medial canthal ligament near the upper lacrimal sac. Indeed, the size and the proper position of osteotomy are known to be vital factors for surgical success in primary DCR [13]. All our modified revised or primary modified Ex-DCR cases had both anterior and posterior sacco-mucosal flaps that may have contributed to the high success rates. Although some alternative approaches have been suggested for the treatment of failed cases, such as nasolacrimal recanalization (84.4%) [14], traditional approaches regarding the success rates of rDCRs revealed that rEE-DCR with silicone tube intubation has been reported to have a success rate of about 82.0% [15]. In the present Ex-DCR revision, none of the cases, except for 6 patients with atrophic sacs, required stent implantation, and the success rate was higher with the aid of sufficient bony opening in a proper location and anterior sacco-mucosal suspension. Revision surgeries show 88.2% success in rEE-DCR, 90.5% in TC-LA-rDCR and 93.0% in rEx-DCR [16]. It is clear that rEx-DCR still has the highest success rate among the various alternative approaches and our modified rEx-DCR in multiple failed cases is consistent with literature.On the other hand, the importance of flap construction and its number have been stressed in a recent study, which is again vital for preventing recurrence of EE-DCR [2], we recommended that such an approach may be beneficial in cases with small lacrimal sacs or small bony windows and in revision cases, in which induced scarring is a large concern as a result of previous failed surgery. Indeed, we used this technique in all revision cases to keep the anterior nasolacrimal-mucosal flap complex away from the reconstructed posterior flaps that prevent its collapse back onto the posterior anastomosis, which decreases the possibility of mucosal adhesions with nearby tissues and, therefore, fibrosis or granulation tissue formation. For this reason, a larger bony window was first re-created to obtain a sufficient nasal mucosal flap to compensate for the absence of adequate lacrimal sac flap, in which fibrotic reaction or scarring is a large concern, triggered from the previous operation. Therefore, a high success rate of rEx-DCR in the present study, which includes more than 1 revision surgery in some cases, can be attributed to the modified surgical technique that suspends the upper sacco-mucosal complex to the overlying tissues after a properly re-positioned and/ or enlarged bony window was re-created just under the medial canthal ligament. In our modified suspension technique for the anterior sacco-mucosal flap complex in primary Ex-DCR [17]. Therefore, as most proximal nasolacrimal sacs were found to be intact in the present study as a result of the abnormal inferior location of the initial surgical ostium, the use of the “figure-of-eight vertical mattress suture technique” for the suspension of the anterior sacco-mucosal flap may have contributed to the increased success rate of rEx-DCR. Such an anastomosis-suspension technique seems to be impossible to achieve by primary and rEE-DCR or rTC-LA-DCR approaches.The distance between the anterior and posterior sacco-mucosal flaps is another important factor for failures that are especially seen in complicated cases such as small or atrophic sacs, since contraction and scarring of the wound during the healing process aggressively occurs with multiple revision surgeries . The success rate of the present paper is higher than both studies. The possible reason is that the small osteotomy was enlarged if they were smaller than 15 x 15-mm, which was 10 x 10-mm in Akçay’s study [8]. In addition, the newly created anterior flap-complex was suspended to the overlying tissues to widen the fistulizing pathway. Moreover, silicone tubes were not used in most cases since leaving them may contribute to more granulation tissue formation. Endoscopic or TC-LA-DCR approaches need more surgeon experience with the need of expensive and sophisticated tools, though rEE-DCR has the advantage of less skin scarring along with the chance to treat the nasal anomalies, if present. In turn, revision surgery by external approach needs simple tools and is easy to perform if the critical steps are followed by the surgeon.Two articles reported 85.0% success rates for reoperation using rEx-DCR after failed-DCRs. However, the authors used silicone tube intubation with or without mitomycin-C [1) the middle turbinate is packed preoperatively with cottonoid strips soaked in vasoconstrictive agents; 2) a laterally curved skin incision, of at least 1.5-cm-long and 6-8-mm away from the medial canthal angle, is made; 3) the incision is carried superiorly 4-5-mm above the medial canthal ligament; 4) the muscle layer is bluntly separated; 5) the anterior crus of the medial canthal tendon is transected and detached near its periosteal attachment and reflects it laterally so that the largest belly of the lacrimal sac and its nearby fossa can be widely exposed; 6) the periosteum is vertically  cut and elevated upward to expose the nasal bone; 7) the bony window site is selected just below the medial canthal ligament around the lacrimal sac that corresponds to the level of common canaliculus; 8) the bony window is opened superiorly above the medial canthal ligament and for about 5-6-mm anterior to the anterior lacrimal crest; 9) the rhinostomy is extended downward to the entrance of the NLD and the frontal process of the maxillary bone, including the whole anterior lacrimal crest, is removed; 10) the lacrimal bone, including the posterior lacrimal crest, is removed; 11) minimal anterior ethmoidectomy is performed; 12) the surgical bony opening is completed for a final diameter of at least a 15 x 15-mm circular window, centering at the lacrimal fossa that stretches out centrifugally; 13) the lacrimal sac wall is incised vertically from its mid-line, where a lacrimal probe pouches out the medial saccal wall (not anteriorly or posteriorly); 14) large anterior, but smaller posterior traditional H-flaps of the nasal mucosa are constructed; 15) both the posterior and the anterior sacco-mucosal flaps are approximated and sutured; 16) no stent is implanted unless there is a canalicular problem or atrophic sac; 17) the rhinostomy site should not be packed perioperatively as postoperative bleeding is unusual and collapsing is not expected; 18) the anterior flap complex is suspended to the overlying orbicularis oculi muscle to keep it from collapsing back into the rhinostomy site and to prevent bone regrowth into the anastomosis site; 19) the pre-cut medial canthal tendon is repaired with a non-absorbable mattress suture; and finally 20) the surgery is finished by suturing the skin as usual. The present article offers detailed external observations of eyes with failed-DCR. Iatrogenic injury from improper technique, especially in an abnormal surgical location, decreases the success rate of this delicate surgery. The results of rEx-DCR are satisfactory if the surgeon knows the physiopathological anatomy of that small area. Therefore, to avoid early or late failure in primary Ex-DCR or to increase the success rate of rEx-DCR, a meticulously designed 20-technical-strategy should be accurately applied for every patient as follows: If applied appropriately, all these aforementioned teaching pearls will improve the surgeon’s learning curve for primary Ex-DCR even in complicated cases with small/ atrophic sacs and revision surgeries. Although the success rates for rDCRs are known to be lower than those found in primary DCRs, modified rEx-DCR may be the gold standard procedure for recurrent cases by the achievement of apposition and suspension of the sacco-mucosal flap. The present article demonstrated that rEx-DCR is a safe and effective method in patients with failed-DCRs and should be considered as a treatment of choice even for eyes with multiple revision surgeries by endonasal or transcanalicular approaches.Conflict of Interest statementAuthors state no conflict of interest.Informed Consent and Human and Animal Rights statementInformed consent has been obtained from all individuals included in this study.Authorization for the use of human subjectsEthical approval: The research related to human use complies with all the relevant national regulations, institutional policies, is in accordance with the tenets of the Helsinki Declaration, and has been approved by the Ethics Committee of Erciyes University Medical Faculty, Kayseri, Turkey (No: 2022/ 78).AcknowledgementsNone.Sources of FundingNone.DisclosuresNone.


In particular for inexperienced operators, the speed of the microcatheter position with the assistance of computer software is much faster than manual microcatheter shaping . In vivo, the time of the microcatheter position in the MMS group was significantly longer than that in the CAMS group . However, the mRS score at discharge, the 6-month follow-up, and aneurysm regrowth at the 6-month follow-up were all similar between the groups. Conclusions: Computer-assisted microcatheter shaping is a novel and safe method for microcatheter shaping that introduces higher accuracy in microcatheter shaping during the treatment of intracranial aneurysms. Significant: Endovascular coiling of intracranial aneurysms can be truly revolutionized through computer assistance, which could improve the endovascular treatment of aneurysms.Background: This study investigates the accuracy, stability, and safety of computer-assisted microcatheter shaping for intracranial aneurysm coiling. Methods: Using the solid model, a microcatheter was shaped using computer-assisted techniques or manually to investigate the accuracy and delivery of microcatheter-shaping techniques in aneurysm embolization. Then, forty-eight patients were randomly assigned to the computer-assisted microcatheter-shaping (CAMS) group or the manual microcatheter-shaping (MMS) group, and the accuracy, stability, and safety of microcatheter in the patients were compared between the CAMS and MMS groups. Results: The speed of the successful microcatheter position was significantly faster in the CAMS group than in the MMS group (114.4 ± 23.99 s vs. 201.9 ± 24.54 s,  Endovascular neurosurgery is a rapidly evolving field, with the continuous development of techniques and technologies . EndovasSafe and efficient microcatheter navigation within the parent vessel and aneurysmal sac during aneurysm coiling is crucial to avoid complications, such as aneurysm perforation or thrombosis. Stable and precise microcatheter shaping is fundamental to successful embolization. The convenience and safety of microcatheterization depend on the aneurysmal anatomy and the experience of the neurosurgeons. Microcatheter tips are traditionally shaped manually by the operators to achieve smooth navigation and stable packing of the coil into the aneurysmal sac; the modifications are guided using digital subtraction angiography (DSA)-based three-dimensional (3D) anatomy of the aneurysm and parent vessel. However, this shaping procedure is remarkably challenging for junior neurosurgeons with limited experience. Therefore, novel shaping methods to improve aneurysm accessibility, especially those at uncommon locations, are needed to ensure efficiency and reduce the risk of complications during the procedure. In addition, a specific coil-shaping methodology can improve intra-aneurysmal microcatheter positioning during an aneurysm embolization.Recent advancements in computer-based calculation software have facilitated computational assistance in several scientific and medical fields, including the neuro-interventional field ,5. TheseConsidering the above-mentioned theories and techniques, we believe that endovascular coiling of intracranial aneurysms can be truly revolutionized through computer assistance. We hypothesized that using 3D image parameter-analyzing algorithms to guide microcatheter shaping could improve the accuracy and stability of endovascular coils used during the treatment of intracranial aneurysms.To investigate the efficacy of the computer-assisted microcatheter-shaping technique on the microcatheter positioning for different seniority physicians, microcatheter shaping was performed by either experienced or inexperienced operators. This study used two datasets. Dataset 1 included 10 selected patients with intracranial aneurysms from January 2015 to June 2015 to construct hollow elastic models for an in vitro prospective controlled study. Dataset 2 enrolled consecutive patients with intracranial aneurysms from September 2021 to December 2021 who received endovascular treatment for an in vivo prospective randomized study. All patients were blinded to these cases. Patients were included if they presented with an unruptured intracranial saccular aneurysm, were aged between 18 and 75 ,7, had aThe 3D image data, including the aneurysm and parent artery, were loaded into a 3D measurement software  Technology Co., Ltd., Beijing, China) in the DICOM format of 3D-DSA. The aneurysms of interest and their corresponding parent vessels were interactively 3D-segmented using the image thresholding method ,12. The n = 10/group), including two experienced operators (case volume > 40 per year) and two inexperienced operators (case volume < 10 per year). Within each group, computer-generated randomization was used to determine whether the microcatheter  was shaped using computer-assisted techniques or manually.The same 10 aneurysm models were allocated to four operators, respectively  could be used for navigation if there were common patient-related technical difficulties, including anatomic variations in the aortic arch, stenosis, or serious tortuosity of the internal carotid artery (ICA) and vertebral artery, which can prevent the advancement of the guiding catheter . A camern = 24/group).From September 2021 to December 2021, 59 subjects were screened at Huashan Hospital, Fudan University; 11 subjects were excluded based on the exclusion criteria, and 48 met the inclusion criteria. The included subjects were assigned to either the computer-assisted microcatheter-shaping (CAMS) group or the manual microcatheter-shaping (MMS) group , mRS of 3–4 (moderate outcomes), and mRS of 5–6 (poor outcomes).All analyses were performed on the intention-to-treat population using SPSS 22. Categorical variables were compared between groups using Fisher’s exact test. Continuous variables were compared using a n = 20 in each group) for microcatheter insertion in the aneurysm models. All the aneurysms were in the distal section of the intracranial artery (ICA) or the anterior communicating artery. The comparison of different microcatheter-shaping methods showed that the position speed in the CAMS group was significantly faster than that in the MMS group . However, no significant difference in microcatheter delivery was detected between the groups . However, these differences were not significant for experienced operators in the groups.The subgroup analysis of the accuracy of the microcatheter position and the microcatheter delivery by experienced and inexperienced operators is provided in p = 0.0001). However, the accuracy of the microcatheter position and stability was similar between the groups. Meanwhile, the mRS at discharge and aneurysm regrowth at the 6-month follow-up were similar between the groups (Case presentation, treatment, and outcome details were assessed to confirm further the accuracy, stability, and safety of computer-assisted microcatheter shaping for aneurysm coiling in comparison to manual shaping. The patient and aneurysm characteristics, treatment details, and anatomical and clinical outcomes are shown in e groups .®. The optimal route for the microcatheter was then simulated and shaped. Subsequently, the microcatheter was positioned to embolize the aneurysm with stent-assisted coiling in approximately 2 min (Patient 27: A 46-year-old male patient with an incidental 5 mm left ICA ophthalmic aneurysm was embolized with the computer-assisted technique. The information on the aneurysm and parent artery was targeted and extracted with UKnowly 2 min .®. The optimal route for the microcatheter was then simulated and shaped. The microcatheter is successfully guided into the aneurysm within approximately 2 min (Patient 39: A woman in her 40s with a left ICA ophthalmic aneurysm was embolized using the computer-assisted technique. The information on the aneurysm and parent artery was targeted and extracted with UKnowly 2 min .Precise microcatheter navigation is an essential factor for the success of endovascular treatment of cerebral aneurysms. Although the use of an intermediate catheter increased the success rate of microcatheter navigation in a case of difficult vascular access anatomy , optimizCurrently, microcatheters are usually shaped by surgeons based on 3D-DSA images on a computer screen. However, 3D-DSA images lack in-depth information on vascular architecture, which makes it difficult for surgeons to obtain 3D anatomy information on aneurysms and parent arteries. Moreover, the microcatheter route is implemented according to the surgeon’s experience; therefore, several adjustments are needed before the surgeons can determine the real path of the microcatheter entering the parent artery and aneurysm sac.Recently, 3D printing technology has been used in microcatheter shaping for endovascular treatment of intracranial aneurysms. Surgeons can shape the microcatheter according to the 3D aneurysm model before embolization, which ensures both the accuracy and stability of the microcatheter for embolization. However, 3D printing technology has some notable limitations. First, printing a solid 3D model before the procedure is costly and time-consuming, making it difficult to apply to ruptured aneurysms. Moreover, the appropriateness of the selected pathway remains uncertain since the shape of the microcatheter relies on the route imagined by endovascular surgeons according to the solid 3D aneurysm model ,10,18,19Compared with microcatheter shaping using 3D-printed models and conventional manual shaping processes, computer-assisted microcatheter shaping is much safer and more effective. Simulating the optimal route of the microcatheter with computer-assisted techniques during the operation just requires several minutes and makes it accessible for surgeons to shape the microcatheter in one attempt without repeats. Although the packing density of the coils and the rate of stent assist technique usage between the groups showed no significant difference, all cases achieved good clinical outcomes after embolization. This demonstrates that computer-assisted microcatheter-shaping technology can achieve the same clinical outcome as experienced operators when embolizing intracranial aneurysms. In addition, both the in vivo and the in vitro models confirmed that the speed of microcatheter positioning by computer-assisted technique is significantly faster than that by traditional methods.Many factors can affect microcatheter shaping, such as the aneurysm anatomic characteristics, arterial paths to the aneurysms, microcatheter material, and treatment strategy for aneurysm embolization. The computer-assisted shaping technique can extract the anatomical information of the parent artery and aneurysm directly from 3D-DSA images within several minutes and then determine the most appropriate pathway. As the microcatheter material and treatment strategy of operators can also affect the microcatheter shaping, surgeons can adjust the position of the tip or support point to achieve a flexible path design. Moreover, the arbitrary resilience coefficient and shaping length can also be adjusted to ensure that the designed route is appropriate for different surgeons. Therefore, computer-assisted microcatheter shaping on 3D-DSA images will contribute to the selection of the most appropriate microcatheter route for aneurysm embolization, and this methodology would improve the effectiveness of intracranial aneurysm embolism procedures performed by inexperienced neurosurgeons and supplement their training. It should be emphasized that the traditional manual catheter-shaping technique is also a critical skill for endovascular coiling procedures. Computer-assisted microcatheter shaping is just a supplementary skill for traditional manual operator catheter shaping, which could be used as an adaptive learning tool to assist novice operators in catheter shaping. The efficacy and safety of computer-assisted techniques should be assessed by a multicenter, randomized, prospective study in the future.Computer-assisted microcatheter shaping is a novel and safe method for microcatheter shaping that introduces higher accuracy in microcatheter shaping during the treatment of intracranial aneurysms. This method can be employed for improved preparation for surgery and training support.


An 86-year-old male with progressive palpitations and dyspnea was referred to our hospital for heart failure treatment. Catheter ablation was performed for atrial flutter as we suspected tachycardia-induced cardiomyopathy as the cause of the patient's heart failure. Due to difficulty securing a peripheral venous route, a 6-Fr sheath was inserted via the right common femoral vein prior to administering general anesthesia. While attempting to insert a mapping catheter, the 6-Fr sheath became lodged and subsequently fractured during removal. Percutaneous transvenous retrieval using an 8-Fr sheath was unsuccessful, and a switch to a right internal jugular vein approach with a 16-Fr sheath was necessary for successful retrieval. The following two-step retrieval (“lock and dock”) was then performed: 1) lock: a vascular snare was used to catch the remaining wire crossing into the fractured sheath lumen to prevent the risk of sheath migration to the right ventricle or the pulmonary artery, and 2) dock: the same snare was subsequently used to catch the fractured sheath. The planned catheter ablation was then successfully performed, without any complications.Our case presents, “lock and dock,” a novel approach for percutaneous transvenous retrieval that involves two steps: a vascular snare is used to catch the wire and subsequently the fractured sheath. This use of a vascular snare and a large-diameter sheath through the right internal jugular vein effectively reduces the possibility of fractured sheath migration. As the number of percutaneous procedures increases, there will also be an increase in the number of cases of fractured sheath retrieval. Percutaneous endovascular retrieval is preferred to invasive, open surgery. Several retrieval techniques using a vascular snare have been reported . When peAn 86-year-old male who experienced progressive palpitations was referred to our hospital for heart failure. Because tachycardia-induced cardiomyopathy due to atrial flutter (AFL) was suspected as the cause of heart failure, we decided to perform catheter ablation for AFL. With the patient's consent, catheter ablation was performed under general anesthesia. At the beginning of the procedure, venous access was planned in the right common femoral vein (CFV) using an 8.5-Fr deflectable sheath , an 8.5-Fr sheath , and a 10-cm 6-Fr sheath . The intravenous line leaked and there was insufficient anesthesia, so a 6-Fr sheath was inserted after single puncture. The remaining two punctures were then performed. Afterwards, while attempting to insert a duodecapolar catheter (Biosense Webster Inc.) into the 6-Fr sheath, it became lodged. The sheath was likely kinked, so we attempted to insert an inner tube and wire, but although the wire reached the IVC, the inner tube did not advance. While attempting to completely remove the 6-Fr sheath, the terminal 6-cm tip of the sheath detached within the right CFV during venous withdrawal A.Fig. 1 was carried to the front of the fractured sheath over the remaining wire crossing into the fractured sheath lumen. The 8-Fr sheath was advanced to the distal portion of the fractured sheath B. SubseqOur first step (lock) reduces the risk of fractured sheath migration into the RV and PA. Specifically, the wire crossing into the lumen of the fractured sheath was grasped using the ONE SNARE™  inserted into the 16-Fr sheath A. AfterwAs the second step (dock), the fractured sheath was grasped by the same snare, which was then pulled , Video 2Fractured catheters that cannot be removed can cause serious complications, such as embolization and vessel perforation. The first-choice method for removing fractured catheters is percutaneous retrieval ,3. Most It is suspected that puncture needles for other sheaths may have passed through the 6-Fr sheath, causing it to become weakened or compromised. We performed an additional experiment and found that our puncture needle can indeed pass through the 6-Fr sheath E. After For sheath retrieval from the right CFV, it is necessary to insert a sheath that is thicker than the broken 6-Fr sheath by placing the wire crossing into the fractured sheath lumen. However, there is a risk that the fractured sheath will slip off the wire if the position of the wire moves, making it difficult to insert a thicker sheath. Moreover, the remaining wire crossing into the lumen of the fractured sheath only protruded approximately 12 cm out of the body. The thickest available one was a 10 cm 8-Fr sheath. Our plan was to advance a balloon on the 0.014-in. wire through the fractured sheath into the IVC, inflate it, and then retract the fractured sheath along with the 8-Fr sheath and the balloon. We were, however, unable to cross the 0.014-in. guidewire into the lumen of the fractured sheath because of the structure of the broken sheath  greatly reduces the risk of sheath migration.Video 1Video 2The following are the supplementary data related to this article.None.


Over 95% of cervical cancers are caused by the human papilloma virus (HPV). Locally advanced HPV-related cancers release tiny bits of tumour containing HPV-DNA into the blood (cHPV-DNA). The presence of cHPV-DNA in the blood can serve as a potential marker of cancer and should be absent in pre-cancerous conditions . We have developed an ultra-sensitive and specific test to measure blood cHPV-DNA levels. We performed a feasibility study to confirm our expectation that cHPV-DNA is not found in the blood of patients with CIN but is found in the blood of patients with very early cancers. In this study, we have confirmed that cHPV-DNA is absent in the plasma of women with CIN. In early cervical tumours, there was a low detection rate of cHPV-DNA. Therefore, more sensitive tests are required before cHPV-DNA can be used for the detection of very early cervical cancers.n = 52) and FIGO stage 1A-1B CC (n = 12) prior to treatment and at follow-up. DNA extraction from plasma, followed by NGS, was used for the detection of cHPV-DNA. Results: None of the patients with pre-invasive lesions were positive for CHPV-DNA. In invasive tumours, plasma from one patient (10%) reached the threshold of positivity for cHPV-DNA in plasma. Conclusion: Low detection of cHPV-DNA in early CC may be explained by small tumour size, poorer access to lymphatics and circulation, and therefore little shedding of cHPV-DNA in plasma at detectable levels. The detection rate of cHPV-DNA in patients with early invasive cervix cancer using even the most sensitive of currently available technologies lacks adequate sensitivity for clinical utility.Background: High-risk HPV infection is responsible for >99% of cervix cancers (CC). In persistent infections that lead to cancer, the tumour breaches the basement membrane, releasing HPV-DNA into the bloodstream (cHPV-DNA). A next-generation sequencing assay (NGS) for detection of plasma HPV circulating DNA (cHPV-DNA) has demonstrated high sensitivity and specificity in patients with locally advanced cervix cancers. We hypothesised that cHPV-DNA is detectable in early invasive cervical cancers but not in pre-invasive lesions (CIN). Methods: Blood samples were collected from patients with CIN ( In the UK, cervical cancer is the 14th most common cancer in females [Risk factors for cervical cancer are multiple , includiMany cancers are known to shed fragments of DNA  into the bloodstream. Most cervical cancers are causally related to the human papilloma virus (HPV) . In the Various studies investigating cHPV-DNA as a tumour marker in cervical cancer patients have demonstrated between 11% and 45% positivity rates of cHPV-DNA in patients with invasive cervical cancer at diagnosis, suggesting a low sensitivity of the PCR assays ,9,10.cHPV-DNA has also been detected in HPV-positive head and neck cancers, with many of the studies employing PCR methods, which have a sensitivity of 19–79% in locally advanced diseases. The use of digital droplet PCR (ddPCR) using probes for HPV 16 and 33 has been shown to increase the detection of HPV ctDNA in oropharyngeal squamous cell carcinomas (OPSCC) to almost 96% . SimilarHPV16-detect’) to assess the response to chemoradiotherapy in locally advanced head and neck cancer [Traditionally, HPV genotyping involved the amplification of a region of the L1 gene with next-generation sequencing (NGS) using specific primers. Lee et al. developed an amplicon-based next-generation sequencing assay to detect circulating plasma viral DNA (‘k cancer . This nopanHPV-detect) [panHPV-detect in diagnosing the high-risk HPV subtypes prior to treatment of anal squamous cell carcinoma. Furthermore, panHPV-detect was able to identify those patients who either had residual disease post-treatment or relapsed a few months later [In their other study, which included a cohort of HPV-related anal squamous cell carcinoma patients post-chemoradiotherapy, Lee et al. expanded the novel NGS assay to include HPV subtypes 16, 18, 31, 33, 35, 45, 52, and 58 (-detect) . This inhs later .panHPV-detect—for the detection of cHPV-DNA in both pre-invasive cervical lesions and early invasive cervical cancer. As HPV does not enter the bloodstream in its infective phase, we hypothesized that cHPV-DNA would not be detected in pre-invasive cervical disease but would be detectable in early-stage cancers.There has been some work surrounding early detection and follow-up of treated cervical disease, with circulating DNA playing a promising role. However, these studies tend to include advanced cancers rather than early invasive cancers. In this prospective cohort study, we aimed to investigate the use of this highly sensitive assay—+ve, and able to give informed consent. The exclusion criteria were those with a previous diagnosis of cancer, previous CIN treatment, and other HPV-associated lesions (VIN/VaIN/AIN). Following written, informed consent, 20 mL of venous blood was collected in EDTA tubes prior to treatment and then at the next appointment following treatment to assess for cHPV-DNA. The histological findings were correlated with the panHPV-detect result. Women who could not tolerate treatment in the outpatient setting or were undergoing general anesthesia for treatment of a larger lesion were seen in the clinic at the time of consent for their surgery and recruited to this study. A venous blood sample was then taken on the morning of surgery.This study was approved by the institutional board (Ref. no. CCR 4157) and ethics committee (Ref. no. 14/NE/1055). Patients who were referred to the colposcopy clinic at UCLH with cervical smears showing high-grade dyskaryosis or persistent mild dyskaryosis and HPV-positives, and who were attending for cervical treatment in the form of Large Loop Excision of the Transformation Zone (LLETZ) or knife cone biopsy, were recruited. Inclusion criteria were those over the age of 18, referred with HSIL and HPVA second cohort of patients with biopsy-proven early-stage (FIGO 2018 1A/1B) invasive disease was recruited from the UCLH Gynaecological Oncology clinic., in London. These patients were recruited to this study in the outpatient clinic based on radiological staging and prior to definitive treatment, which was typically a simple or radical hysterectomy.HPV16-detect demonstrated 100% sensitivity and 93% specificity in detecting HPV16-positive cancers at diagnosis. To have 80% power to detect a true sensitivity of 99%, we calculated that at least 19 HPV-positive, invasive cancer patients needed to be recruited. As approximately 95% of cervical cancer patients are HPV-positive, we aimed to recruit 22 patients with early invasive carcinoma. To confirm 93% specificity for pre-invasive disease, we required 37 patients with high-grade squamous intraepithelial lesions (HSIL) to be recruited.In the head and neck cancer pilot study, Whole blood sampling and plasma extraction were conducted at the Translational Research Laboratory at UCL, London, UK. The frozen plasma samples were then transported to the Chester Beatty Lab at the Institute of Cancer Research (ICR), London, UK for further analysis.g for 10 min within 48 h of collection. The resulting plasma was then centrifuged again at 1600× g for 10 min to remove any cell sediment, aliquoted, and frozen at −80 °C. DNA was extracted from 5 mL of plasma using the QIAamp Circulating Nucleic Acid Kit (Qiagen) according to the manufacturer’s instructions. DNA was eluted in 50 μL of AVE buffer and stored at −20 °C. Plasma DNA was quantified using a Bio-Rad QX200 ddPCR system , using ribonuclease P (RNase P) as a reference gene, as previously described [Additionally, 20 mL of blood was centrifuged at 1600× We performed an initial validation of panHPV-detect by testing its ability to correctly identify the HPV subtype in cervical cancer tissue samples. We obtained tumour DNA extracted from cervical cancer tissue previously typed for the HPV subtype using polymerase chain reaction (RT-PCR) for E6 and E7 mRNA using validated assays. Five samples for each of the eight high-risk HPV subtypes were obtained from the Scottish HPV archive. Samples from five HPV-negative patients with head and neck cancer were recruited in the head and neck cancer cohort of this study, and 19 patients with breast cancer enrolled in the prospective sample collection study  were used as negative controls. HPV status was confirmed as negative with E7 RT-PCR performed on RNA extracted from the samples. None of the negative controls were known to have pre-cancerous lesions. Written informed consent was obtained from all participants. Following the initial validation, we investigated whether panHPV-detect was able to detect cHPV-DNA in the pre-treatment plasma of patients recruited in this study.+ and HPV− samples using panHPV-detect in tissue, we set a threshold whereby a sample was classified positive if there were 10 reads present from more than 30% of different HPV amplicons for each subtype. To assess the threshold for the number of amplicons needed for a positive panHPV-detect readout in plasma, a ROC analysis was used. In the first step, HPV status and subtype were assigned in tissue using E7 mRNA to separate the two groups. The number of amplicons with greater than 10 reads at baseline was inputted for each patient to find a suitable threshold for this parameter. Sorting the values in both HPV+ and negative groups and averaging adjacent values in the sorted list generated a list of thresholds. Based on the ROC analysis, a threshold that gave the greatest sensitivity and specificity for each HPV subtype was selected as the threshold for the classification of plasma as HPV DNA-positive. Based on the ROC analysis, a threshold of 7 amplicons with more than 10 reads were the thresholds that gave the greatest sensitivity and specificity and were selected as the thresholds for the classification of plasma as HPV DNA-positive.To classify HPVDNA library preparation was performed, and then Ion Torrent qPCR Quantitation with final sequencing was performed at the Tumour Profiling Unit of the ICR. Ion Torrent Libraries were prepared using Ion Ampliseq Library Preparation kit 2.0  according to the manufacturer’s instructions using 5 ng of tissue DNA or 3 ng of plasma DNA per primer pool, except the volumes of the Ion Ampliseq Library Preparation kit and the Custom Primer Pools have been reduced by half. Reads were aligned to an amalgamated reference containing scaffolds for each of the HPV genotypes as well as the reference human targeting genes using default settings in module map4 of the TMAP on the Ion Torrent machine. Bedtools v2.23.0   was used+ and HPV− samples using panHPV-detect in tissue, we set a threshold whereby a sample was classified positive if there were 10 reads present from more than 7 different HPV amplicons for each subtype.In order to classify HPVThe cost of sample analysis was £132 per sample . The bulWe recruited 52 patients between November 2018 and January 2020. The COVID-19 pandemic necessitated the suspension of study recruitment and sample collection, including follow-up of already recruited patients, in January 2020. All non-urgent clinical studies were placed on hold as laboratory services and resources were diverted to the pandemic. In addition, there was a cessation of the cervical screening programme for 2 months, a restriction on colposcopy appointments, and the introduction of social distancing rules, which meant that further recruitment from and follow-up at clinics were halted.None of the recruited patients had a history of prior HPV vaccination. Patient demographics can be found in Of the 52 patients recruited, 12 had early invasive cervical cancer and 40 had pre-invasive disease . The meaUsing the pre-set threshold of 10 reads present from >7 HPV amplicons, only 2 of the 50 baseline samples were HPV positive. HPV reads were detected in 15 other samples but in no more than 6 amplicons per HPV subtype and therefore did not reach the threshold for positivity .Final histology was available after all plasma samples were analysed and DNA sequencing performed (including follow-up samples). Out of the 12 cancer samples, 2 were found to be at a more advanced stage (FIGO 2B) than the inclusion criteria and therefore had to be excluded from this study (1 of these reached the threshold for positivity for HPV). Of the remaining 10 samples, only one was positive for HPV as per threshold criteria. This sample came from a patient who had stage 1A1 cervical cancer and was found to be HPV 18-positive, which correlated with the HPV type on referral cytology. This patient was an ex-smoker, under 30 years old, and had a small tumour. The other five patients whose histology indicated FIGO stage 1A1 tumours, did not reach the threshold for HPV positivity in plasma. None of the four 1B1 tumours had HPV in the plasma at levels that reached the threshold for positivity.None of the plasma samples from patients with final histology showing CIN 1–3 or cervical glandular intraepithelial neoplasia (CGIN) reached the threshold for positivity for HPV . In 10 oOnly eighteen patients out of the cohort of 50 were followed up prior to the COVID-19 pandemic. Two of the patients (9 and 11) had to have follow-up samples analysed despite baseline samples not being available . It was not known at the time of the blood draw that the baseline plasma had failed the PCR and library preparation stages. Of these 18 follow-up samples, 10 had HPV reads detected but none at >6 amplicons, and therefore none of the follow-up samples reached thresholds for positivity . Sample Of the 10 samples that had HPV reads at follow-up, only 2 correlated with the baseline HPV read—in one case, there was no baseline sample to compare. Seven samples detected HPV types that were either new or did not correlate with the baseline HPV types .panHPV-detect could detect cHPV-DNA in the plasma of patients with early-stage cervical cancers, as it has previously been shown to have high sensitivity and specificity for locally advanced HPV-associated cervical, head and neck, and anal cancers [The aim of this project was to determine whether  cancers ,15. UsinThe low sensitivity of this study correlates with other similar studies. Pornthanakasem et al. investigated the diagnostic and prognostic potential of circulating cHPV-DNA in patients with cervical cancer . They coSathish et al. also looked at cHPV-DNA in cervical cancer patients. They collected cervical biopsies and plasma samples from 58 women with invasive cervical cancer. In addition, they also collected samples from 10 women with the pre-invasive disease and 30 control women matched for age. All paired samples for the control group were negative for HPV DNA; however, only eight (11.8%) were positive for cHPV-DNA in the cervical cancer group. In the CIN group, all 10 patients were positive for HPV in cervical biopsies, but none were positive in plasma samples. Of the eight patients who were plasma DNA positive, seven were HPV 16-positive, and six were at stage 3–4 cancer. Cervical tissue and plasma pairs were correlated on sequencing [Both the aforementioned studies used more conventional PCR techniques rather than the novel NGS assay used in this study, which we had expected to achieve greater sensitivity for the detection of disease.A systematic review by Trigg et al. investigated the possible factors that influence the quality and yield of circulating free DNA . The facpanHPV-detect in locally advanced cervical cancers in patients undergoing chemoradiotherapy. This study has demonstrated high sensitivity (88%) and specificity (100%) for our NGS assay in detecting cHPV-DNA at baseline and following treatment completion. This suggests that the stage or volume of tumour plays a role in the amount of circulating tumour DNA that may be released into the plasma.We have carried out a similar study , which eGu et al. published a recent meta-analysis of cHPV-DNA as a biomarker for cervical cancer . They foOn further analysis of each study, the detection of cHPV-DNA in plasma in early-stage cervical cancer showed mixed results, with two studies showing no detection at stage 1B ,23, thre3, or 12.5 mm in diameter, will release enough ctDNA to represent 0.01% of all circulating DNA [Fiala et al. described the challenges of using ctDNA for early-stage cancer diagnosis . There iting DNA ,28. TheyThe strength of this study is that it focused on early-stage cervical cancers only. The low sensitivity for the detection of cHPV-DNA in early-stage cervical cancer may be explained by not only the small size of the tumour but also the inherent difficulties in the design of a sufficiently accurate HPV assay. The high specificity, however, does give some assurance that a positive test is more likely to be a true positive.The limitation of this study is that we were unable to recruit the desired number of patients, particularly in the early cervical cancer cohort, due to the coronavirus pandemic, which also made follow-up difficult. The number did not meet the requirements of the power calculation. However, as only one cervical cancer sample was positive for cHPV-DNA, this likely would not have made a statistical difference. Another inherent limitation of this prospective cohort study was the difficulty of follow-up post-treatment. Again, as all but one of the baseline samples were negative, follow-up of these patients is unlikely to have added a significant finding to this study. Of the patients that were followed up, there were no discrepancies between baseline and follow-up samples, i.e., none became positive after treatment having had a negative baseline result. Most importantly, the sole positive patient was followed up and found to be negative after treatment.HPVdetect as a biomarker for the diagnosis of early-stage cervical cancers, given the low sensitivity demonstrated. However, we have shown that circulating HPV is not detectable in pre-invasive disease, supporting the hypothesis that such lesions do not shed DNA into the circulation. Patients with pre-invasive disease have an effective screening tool based on high-risk HPV detection and cytology in cervical samples. Whilst work is ongoing on the use of HPVdetect as a potential biomarker for monitoring treatment effectiveness and predicting recurrence in locally advanced cervical cancers, further research is needed to establish whether any cDNA assay has sufficient sensitivity for reliable detection of early-stage cervical cancer.Based on this study, we cannot recommend the use of


Family oral fluids (FOF) sampling has been described as a sampling technique where a rope is exposed to sows and respective suckling litters and thereafter wrung to obtain fluids. PCR-based testing of FOF reveals presence of PRRS virus RNA only at the litter level, as opposed to conventional individual-animal-based sampling methods that demonstrate PRRSV RNA at the piglet level. The relationship between the PRRSV prevalence at the individual piglet level and at the litter level in a farrowing room has not been previously characterized. Using Monte Carlo simulations and data from a previous study, the relationship between the proportion of PRRSV-positive (viremic) pigs in the farrowing room, the proportion of litters in the farrowing room with at least one viremic pig, and the likely proportion of litters to be positive by a FOF RT-rtPCR test in a farrowing room was characterized, taking into account the spatial distribution (homogeneity) of viremic pigs within farrowing rooms.There was a linear relationship between piglet-level- and litter-level prevalence, where the latter was always larger than the former. When the piglet-level prevalence was 1%, 5%, 10%, 20%, and 50%, the true-litter level prevalence was 5.36%, 8.93%, 14.29%, 23.21%, and 53.57%, respectively. The corresponding apparent-litter prevalence by FOF was 2.06%, 6.48%, 11.25%, 21.60%, and 51.56%, respectively.This study provides matching prevalence estimates to help guide sample size calculations. It also provides a framework to estimate the likely proportion of viremic pigs, given the PRRSV RT-rtPCR positivity rate of FOF samples submitted from a farrowing room.The online version contains supplementary material available at 10.1186/s40813-023-00309-x. Porcine reproductive and respiratory syndrome virus (PRRSV) poses a significant challenge to the swine industry causing spikes in mortality rates, abortion rates, feed conversion ratios, time to market, and costs of medication; it was estimated to cost the US swine industry over 600 million USD annually , 2.Monitoring and surveillance systems remains an integral component of PRRSV control and elimination programs; and ascertaining the PRRSV status of weaning-age pig populations is crucial to guide decisions on health interventions and pig flow . EfficieDifferent sample types are routinely submitted to veterinary diagnostic laboratories in the United States for PRRSV reverse transcription real time polymerase chain reaction (RT-rtPCR) tests; these would include samples taken from individual pigs such as serum, swabs, semen, and post-mortem tissues; or aggregate samples taken from multiple pigs such as processing fluids and oral fluids . These sThe number of samples submitted for pathogen investigation is crucial to the success of a surveillance/monitoring exercise. Guided by epidemiological and statistical assumptions, the sample size should have enough power to detect at least one positive unit if the herd is truly positive for the pathogen of interest , 10.Estimated prevalence at the individual pig level is one of the key variables used in calculating sample size to demonstrate the presence of a pathogen in a herd , 11. TheAlmeida et al.  demonstrThe individual pig is the unit for which sample size is calculated when non-aggregate samples are collected, while the litter is the unit for which sample size is calculated when an aggregate sample such as FOF is to be collected , 15. To Therefore, the objective of this in-silico study was to characterize the relationship between the piglet-level prevalence (PP), true litter-level PRRSV prevalence (TLP) and apparent litter-level PRRSV prevalence (ALP) in a farrowing room.The probability of PRRSV RNA detection in FOF by RT-rtPCR increased with increasing proportion of PRRSV-positive piglets within a litter. There was a 95% probability of PRRSV detection in FOF when within-litter prevalence was 35% or higher Fig. : Fig. S1The clustering distribution across all sampled rooms had a minimum value of 0.00136, a median of 0.61000, a mean of 0.57000, and a maximum value of 1.0000. The distributions of the clustering parameter across all sampled rooms are presented in Fig. Table A sensitivity analysis was done to evaluate the effect of variations in clustering level and room size on the proposed relationship between piglet level prevalence and litter prevalence. The ALP was relatively more stable to changes in clustering and the number of crates compared to TLP. Generally, TLP and ALP increasingly converged to similar values with increasing clustering and increasing room size. Clustering changes appeared to have a more significant effect on ALP and TLP than changes in the number of crates in the room Fig. .Fig. 4GrThis study used mathematical models built upon earlier studies to characterize the relationship between piglet- and litter level PRRSV prevalence in a farrowing room. The use of mathematical models to describe disease dynamics in swine populations is not new. A few examples include the use of mathematical models to characterize and describe PRRSV transmission dynamics , 16–20 aEarlier studies described the non-homogenous distribution of PRRSV in pig barns , 23; the I, ohno, black-white, Geary’s c, and I pop [Some popular statistical methods used in veterinary epidemiology for detecting and evaluating spatial  clustering include Moran’snd I pop , howevernd I pop , 29.The restricted movement of pigs in conventional swine barns and the non-homogenous distribution of viremic animals have been historically recognized to make conventional sample size assumptions (to detect a disease pathogen) not an exact fit; some previously proposed solutions include replacing simple random sampling with fixed spatial sampling , risk-baClustering estimates the degree of homogeneity  of PRRSV between litters in a farrowing room. It may be overreaching to deterministically model a one-size-fits-all clustering for PRRSV because the spread of PRRSV between litters within a farrowing room depends on a variety of factors including: (1) management practices such as cross-fostering, and vaccination , 26, (2)The uncertainty in definitively ascertaining clustering level however does not undermine the importance of these results or pose a challenge to its utilization, on the contrary, considering/estimating clustering adds some precision to the estimated prevalence guiding sample size calculations for disease pathogen surveillance . This implies that ALP can be used directly to estimate FOF sample size and the only diagnostic performance that may need to be considered is that of the RT-rtPCR test kit. The AUC (0.9915) of the regression model that characterized the probability of PRRSV RNA detection in FOF by RT-qPCR based on the proportion of viremic pigs within a litter supports that the predictive model performs excellently.Another key application of the proposed tables is to help the swine practitioner estimate piglet-level prevalence given the results of FOF testing. Given that a representative number of litters were sampled , the proportion of positive FOF results on RT-qPCR tests  can be used to deduce the likely proportion of viremic pigs . In Additional file The referenced studies , 30 wereThis study explored the use of mathematical models to characterize the relationship between PP, TLP, and ALP in a farrowing room.When the piglet-level prevalence was 1%, 5%, 10%, 20%, and 50%, the true-litter level prevalence was 5.36%, 8.93%, 14.29%, 23.21%, and 53.57%, respectively. The corresponding apparent-litter prevalence by FOF was 2.06%, 6.48%, 11.25%, 21.60%, and 51.56%, respectively.Prevalence comparisons provided here are intended to help guide sample choice and sample size for PRRSV surveillance in weaning-age pigs. The likely proportion of viremic pigs can also be estimated from the PRRSV-RT-rtPCR positivity rate of tested FOF samples obtained from a farrowing room, using the tables provided.Further similar studies on other aggregate sample types, for other subpopulations and perhaps, for other pathogens will be helpful in guiding practitioners on how they can be up-to-speed with best practice surveillance as sampling methods evolve.A predictive model was first built using data from Almeida et al. , to charFarrowing rooms were thereafter simulated with a fixed number of litters; the number of pigs within each litter was obtained from the earlier mentioned discrete empirical distribution. A clustering factor was used to distribute viremic pigs between litters, with values ranging from 0 (randomly distributed PRRSV-positive pigs) to 1 (clustering of PRRSV-positive pigs within the fewest litters possible), the baseline clustering was obtained from the reference study. The True litter prevalence per iterated room was obtained as the proportion of litters with at least one viremic pig, and the apparent litter prevalence was obtained as the predicted proportion of the litters in an iterated room that will be PRRSV-positive by FOF testing. A total of 5000 rooms were iterated, and the median values of TLP and ALP were obtained.i = 1,…,199) was also sampled for FOF. The litters were sampled from 11 farrowing rooms across six different swine breeding farms .Based on a dataset from Almeida et al.  199 littglmer from library lme4 [pROC package [The effect of the proportion of PRRSV-viremic piglets  was modeled describing the most probable number of positive litters detected in a routine FOF sampling in a farrowing room. Assuming the probability of each litter being detected by FOF  and the room size (n) on the estimated relationship between pig-level-prevalence and litter-level prevalence, five values for c  and five values for n  were selected and combined in a factorial design for the sensitivity analysis, totaling 25 different scenarios. The minimum and maximum values for clustering and room sizes were conveniently chosen by the authors, the mid values are the baseline values; and the second and fourth values are calculated midpoints between the baseline and minimum value, and between the baseline and the maximum values respectively.To assess the effect of the clustering factor (Additional file 1. Table S1. A general description of the stochastic model used for this study, with pictorial illustrations. Table S2. The changes in the probability of PRRSV RNA RT-rtPCR detection in FOFs with increases in the proportion of PRRSV viremic piglets within a litter. Table S3. The relationship between PP, ALP, and TLP at different clustering levels and room sizes. Figure S1. The receiver operating characteristic curve assessing the predictive performance of the model built from Eq.


Using existing models of behavioral health promotion, specifically the Extended Parallel Process Model, previous research has identified factors that may impact engagement in preventive health behaviors during the COVID-19 pandemic such as perceived threat, perceived susceptibility to the threat, perceived severity, and perceived efficacy.This study aims to examine the role of perceived effectiveness of COVID-19 preventive behaviors, perceived susceptibility, perceived threat, and perceived severity of COVID-19 in participants’ intentions to engage in Centers for Disease Control (CDC)–recommended individual health behaviors in the first year of the pandemic.In October 2020, a representative sample of 506 US adults completed a web-based survey through the RAND American Life Panel.The study primarily found that participants who perceived that CDC-recommended health practices were effective had stronger intentions to engage in those practices. The second strongest correlate was participants’ perceived severity of COVID-19 across the United States. Perceived effectiveness of recommended practices accounted for the largest variance in behavioral intention. However, analysis of individual behaviors indicated a mismatch in the behaviors perceived to be the most effective (avoiding sick people and mask-wearing) and those participants indicated intention to engage in  in the next 30 days.The authors recommend tailoring public health messaging to address the perceived threat of COVID-19 and self-efficacy. Thus, health promotion efforts should emphasize the effectiveness of CDC-recommended practices while highlighting the pandemic’s severity. Additionally, rebuilding trust in public health messaging and messengers is necessary to increase perceived self-efficacy. As the COVID-19 pandemic continues, health messaging must continue to promote and build trust in CDC-recommended health practices and educate regarding the efficacy of vaccination and other preventive behaviors. Perceptions of both COVID-19 and the effectiveness of recommended health behaviors to prevent the spread of COVID-19 are important factors in reducing personal health risk. The United States’ response to the COVID-19 pandemic contrasts heavily with other countries that engaged in mandated lockdowns and other government-enforced measures . In the Assessing the perceived effectiveness of public health interventions can help experts design and modify health communication strategies to increase engagement in preventive behaviors. Theoretical models of behavioral health, such as the Health Belief Model, the Protective Motivation Theory, and the Extended Parallel Process Model (EPPM), posit perceived efficacy as an important predictor of behavioral engagement ,13. PrevTo determine what behavioral interventions could lead to wider engagement in preventive health practices, researchers are measuring the perceived efficacy of COVID-19 preventive behaviors -17. StudIn 2020, the Centers for Disease Control (CDC) recommended preventive health behaviors that formed the foundation for much of the public health messaging communicated within the United States. These recommendations shifted considerably as new information became available to the scientific community regarding COVID-19. For example, in March and April 2020, masking was not initially included in recommended behaviors. As more information became available regarding the transmission of COVID-19, the CDC added masking recommendations to the list of protective behaviors. Further research has examined the effectiveness of different types of masks and facial coverings  in mitigOne model of behavior change that assesses multiple factors impacting individual health decision-making is the EPPM. The EPPM postulates that perceived threat and efficacy shape individual behaviors to avoid or minimize the perceived threat . Health According to the EPPM, effective health communication must credibly communicate the existence of a health threat and the efficacy of engaging in the recommended behavior to reduce or eliminate that threat . EPPM haPerceived threat and severity of COVID-19 varies greatly by country of residence, gender, age, sexual orientation, and ethnicity -43. PrevThe success of ongoing public health efforts depends on understanding perceptions of the effectiveness of individual protective behaviors to mitigate the spread of COVID-19. Even as public trust in the government and scientific community has waned, we identify an ongoing need for credible and easy-to-understand public health messaging. Early research on public perceptions of the effectiveness of efforts to reduce the spread of COVID-19 showed general positive perceptions and trust in public health messaging ; howeverIn October 2020, at the time of this study, the CDC recommended ten behaviors to stop COVID-19’s spread: (1) wash your hands often with soap and water for at least 20 seconds especially after you have been in a public place, or after blowing your nose, coughing, or sneezing; (2) use a hand sanitizer that contains at least 60% alcohol if soap and water are not readily available for hand washing and cover all surfaces of your hands and rub them together until they feel dry; (3) avoid touching your eyes, nose, and mouth with unwashed hands; (4) limit contact with those outside of your household as much as possible; (5) avoid close contact with people who are sick; (6) keep about 6 feet between yourself and others in public settings; (7) cover your mouth and nose with a cloth face cover when around others in public settings; (8) always cover your mouth and nose with a tissue when you cough or sneeze or use the inside of your elbow; (9) throw used tissues in the trash; and (10) clean and disinfect frequently touched surfaces daily. This includes tables, doorknobs, light switches, countertops, handles, desks, phones, keyboards, toilets, faucets, and sinks.Studies examining the effectiveness of mask-wearing, social distancing, and hand washing globally and within the United States indicate the importance and efficacy of nonpharmaceutical interventions ,53,54. SStudies of hand hygiene’s efficacy have been sparse but also suggest increased morbidity and mortality among those with lower hand washing adherence in country-level data . Other CExisting messaging about COVID-19 uses visuals to communicate the importance of nonpharmaceutical interventions, visualizing the risk of being infected  and the Within the messages themselves, COVID-19 is often presented with health gain and loss framing , for exaFor this study, the researchers sought to determine if the perceived effectiveness of CDC practices predicted behavioral intention. The primary research questions posed by the researchers are as follows: (1) can perceived effectiveness be used to predict behavioral intention? (2) What CDC-recommended preventive behaviors do US adults view as most effective in mitigating the spread of COVID-19? The authors hypothesized that after controlling for demographic characteristics: (1) perceiving recommended COVID-19 prevention behaviors as effective would significantly account for intention to engage in those preventive health behaviors and (2) perceiving COVID-19 as a threat and would significantly account for intention to engage in CDC recommended behaviors.The COVID-19 Attitudes and Perceptions Survey was fielded via the internet between October 14 and 19, 2020, to participants from RAND’s American Life Panel, a probability-sampled internet-based panel study designed to represent US adults aged 18 and older . RAND’s All study materials and procedures were approved by the Kennesaw State University institutional review board  and the RAND Human Subjects Protection Committee. All participants in this IRB-approved study consented to participation in the survey following procedures for confidential survey participation.A single survey item was used to assess respondents’ perceived severity of COVID-19 on a scale of 1  to 4 (serious problem): “How problematic is COVID-19 in the United States?” . Perceived severity of COVID-19 has been measured using various statements referring to the consequences of contracting COVID-19, whether it is life-threatening, and how much of a problem COVID-19 is personally or for your community. As our study was a national study, wording focused on perceptions of COVID-19 as a problem in the United States -70. PartA single survey item was used to assess respondents’ perceived susceptibility to COVID-19 infection on a scale of 0-100%: “What do you think is the percent chance that you will get infected with coronavirus in the next month?” . Perceived susceptibility therefore measured perceptions of individual risk of contracting COVID-19.A single survey item was used to assess respondents’ perceived threat of a COVID-19 infection on a scale of 1  to 5 (extremely concerned): “If you were diagnosed with COVID-19 how concerned would you be about your ability to recover from it?” . Recovery from COVID-19 was used as a measure of perceived threat due to misinformation campaigns downplaying the threat of infection as similar to the flu or common cold. Though symptoms can be similar to both the flu and cold the risk of hospitalization, death, longer recovery, and long-term effects , especially among unvaccinated individuals is higher.In total, 8 items from the Balanced Inventory of Desirable Responding Short Form , ImpressRespondents were asked to rate the perceived effectiveness of 10 CDC-recommended COVID-19 personal protective practices on a scale of 0-100% (“What is the percent chance that this behavior will prevent you from catching COVID-19 over the next month?”). Responses to these items were averaged to create a mean perceived effectiveness score , which was included in the analysis as the primary variable of interest.Respondents were asked to report their likelihood of engaging in 10 CDC-recommended COVID-19 personal protective practices during the following month, on a scale of 0-100% (“What is the percent chance that you will carry out this behavior over the next month?”). Responses to these items were averaged to create a mean behavioral intention score.A path model was tested using Bayesian estimation in Mplus (version 8.5) software program  and follP value (PPp) and the deviance information criterion. PPp ranges from 0 to 1, with a value of .50 was considered a perfect model fit. PPp values of less than .10, or greater than .90, suggest a poor model fit with data [Model fit was assessed holistically using both the posterior predictive ith data .To test for perceived efficacy as a statistically significant indicator of behavior intention a regression model was estimated using Bayesian estimation in Mplus (version 8.5) software program  and follTo control for potential effects of respondents’ general perceptions about COVID-19, 3 additional covariates were included in the analysis: perceived COVID-19 severity, perceived COVID-19 susceptibility, and perceived COVID-19 threat. The following survey item was used to assess severity  on a scale of 1  to 4 (serious problem): “How problematic is COVID-19 in the United States?” The following survey item was used to assess susceptibility  on a scale of 0-100%: “What do you think is the percent chance that you will get infected with coronavirus in the next month?”The survey item used to assess threat perception  on a scale of 1  to 5 (extremely concerned) was: “If you were diagnosed with COVID-19 how concerned would you be about your ability to recover from it?”The path model demonstrated excellent model fit: PPp=.49, 95% Credibility Interval ; deviance information criterion=1267.92. As predicted by the EPPM, the perceived threat of COVID-19 significantly accounted for participants’ intentions to engage in preventive health practices. However, the perceived efficacy of CDC-recommended preventive health practices was a stronger indicator of intentions to engage in preventive health practices, accounting for 19% of the variance. Path coefficients for each model are displayed in Results indicate that participants’ perceptions of severity, susceptibility, and infection threat are appropriate indicators of their overall perception of the health threat posed by COVID-19. These results suggest that public health messaging combating COVID-19 misinformation will be effective for calibrating perceptions of the health threat posed by COVID-19. Findings also support previous research, which demonstrated perceived efficacy to be a significant predictor of practicing COVID-19 preventive behavior .The study sample perceived 3 practices as most effective for preventing COVID-19 infection: avoiding close contact with people who are sick (85%), limiting contact with those outside of your household as much as possible (75%), and covering your mouth and nose with a cloth face cover when around others in public settings 74%; See . These pAfter controlling for demographics and socially desirable responding, the Bayesian regression model indicated that US adults’ average perceived effectiveness of CDC-recommended COVID-19 personal protective behaviors was by far the strongest correlate  were lower than for other CDC-recommended behaviors such as throwing away tissues and covering one’s mouth when coughing or sneezing. The lowest behavioral intention related to social distancing and disinfecting frequently touched surfaces. For ongoing COVID-19 mitigation efforts, especially vaccination strategies, and future public health crises, the authors recommend designing targeted, evidence-based public health messaging to increase trust in public health promotion efforts and willingness to engage in preventive behaviors.These findings suggest that public health messaging should focus on highlighting the effectiveness of prevention efforts such as social distancing and mask-wearing to persuade people to engage in behaviors they believe to be effective. The behaviors that participants perceive to be most effective in mitigating COVID-19’s spread are also the behaviors most studied for efficacy in the current body of literature ,21,57. DTo persuade people to engage in the recommended personal protective practices, public health promotion efforts should emphasize the pandemic’s severity throughout the United States. Severity might be emphasized through facts and statistics related to the United States having the highest death toll of all nations, the severity of COVID-19 for certain age groups in the form of mortality or hospitalization rates, or emphasizing the average recovery time for people infected. Furthermore, as rates of COVID-19 infection vary across time and place, health promotion efforts should be tailored to reflect current risk for a given population.Shifting messaging from fear-based appeals or from overemphasizing personal responsibility to messages of efficacy may also be effective strategies for combating misinformation and encouraging behavioral uptake . Much haThe lack of conclusive, available data on the effectiveness of handwashing and sanitizing, and the limited data on mask-wearing and social distancing contributes to an ongoing lack of trust in public health messaging and officials. Data on the success of preventive behaviors should be shared in lay language. Hornik and colleagues  similarlAs vaccination has become the focus of current messaging campaigns, members of the public may be receiving fewer messages regarding COVID-19 as an ongoing threat or the effectiveness of individual behaviors in reducing transmission. Continued utilization of multiple forms of media for health promotion messaging including radio, television, and social media emphasizing both the efficacy of CDC-recommended behaviors and personal efficacy, while reiterating the ongoing threat from COVID-19 infection, is necessary to offset surges during vaccination efforts.Misinformation, especially when shared via social media, causes people to underestimate COVID-19’s severity, leading to risky behavior ,79. TranBased on study findings, the authors recommend that health messaging from trusted sources especially members of the medical community, continue to emphasize the effectiveness of mask-wearing, social distancing from infected persons, COVID-19 testing, getting tested after a known exposure, and hand hygiene as high impact individual behaviors that can be engaged in to reduce the spread of COVID-19. Maintaining consistent, evidence-based messaging as SARS-CoV-2 continues to mutate and cases occasionally spike in communities with lower vaccination rates can increase behavior engagement.This study’s strengths included the use of a nationally representative sample of US adults and the inclusion of survey items that mirrored language used by the CDC (at the time of data collection) to describe COVID-19 prevention practices. Limitations include the small (though representative) sample size, the use of an exclusively web-based survey format, and the availability of the survey solely in English. Though the study was representative, the researchers acknowledge that a larger sample of underrepresented groups who have been disproportionately impacted by COVID-19, especially African Americans and those identifying as Hispanic or Latinx, would have allowed for additional analysis of the impact of demographics on perceived efficacy and behavioral intention. This study also focused on future behavioral intentions rather than behavioral engagement. It should also be noted that, due to third-party survey restrictions, measurement of the latent variable “Perceived COVID Threat” was done using only 3 items. Though model fit statistics indicate this was not empirically tenuous in this study, the authors acknowledge that threat (and its perception) is a multifaceted construct that is typically assessed using a more comprehensive set of items. Additionally, previous research indicates that using percentage scales to assess threat risk—as was done in this study to assess perceived susceptibility—may result in bias as respondents may underestimate a threat rated at the scale’s midpoint . This stThe findings of this study and previous studies suggest the viability of using aspects of the EPPM model to design and implement health promotions. The application of the EPPM model to COVID-19, similar to other infectious diseases can assist health professionals, the government, schools, and businesses in encouraging preventive behaviors. Though current COVID-19 infections tend to be less severe in vaccinated individuals, the medical community is currently preparing for ongoing surges and future mutations that may increase the severity and infectiousness of COVID-19, as well as the possibility of other pandemics. The development of timely and effective models that address cognitive aspects of individual decision-making in the face of health threats is vital to ongoing public health efforts.


In a cohort of workers disabled by a work-related injury or illness, this study aimed to: (i) compare pre-injury prevalence estimates for common chronic conditions to chronic condition prevalence in a representative sample of working adults; (ii) calculate the incidence of chronic conditions post-injury; and (iii) estimate the association between persistent pain symptoms and the incidence of common chronic conditions.Eighteen months post-injury, 1832 workers disabled by a work-related injury or illness in Ontario, Canada, completed an interviewer-administered survey. Participants reported pre- and post-injury prevalence of seven physician-diagnosed chronic conditions, and demographic, employment, and health characteristics. Pre-injury prevalence estimates were compared to estimates from a representative sample of workers. Multivariable logistic regression was used to examine the association of persistent pain with post-injury chronic condition incidence.Age-standardized pre-injury prevalence rates for diabetes, hypertension, arthritis, and back problems were similar to prevalence rates observed among working adults in Ontario, while prevalence rates for mood disorder, asthma and migraine were moderately elevated. Post-injury prevalence rates of mood disorder, migraine, hypertension, arthritis, and back problems were elevated substantially in this cohort. High persistent pain symptoms were strongly associated with the 18-month incidence of these conditions.The incidence of five chronic conditions over an 18-month follow-up period post injury was substantial. Persistent pain at 18 months was associated with this elevated incidence, with population attributable fraction estimates suggesting that 37–39% of incident conditions may be attributed to exposure to high levels of persistent pain. One of every six injuries requiring medical attention among working-age adults in North America are caused by work exposures . InjurieWork-related injuries also result in consequences to workers’ long-term health, including deficits in physical health , mental Less attention has been given to a third perspective: the extent to which traumatic injury may predispose or accelerate the incidence of chronic conditions among working-aged adults. In one study of young US veterans, comparing 10 000 combat-injured personnel to a matched cohort with no combat injury, there was a moderately elevated incidence of hypertension and diabetes among the combat-injured over a median follow-up period of approximately eight years , 16. OthAmong the consequences of traumatic injury is a substantial incidence of persistent or chronic pain . In a reThis study pools two samples of workers experiencing a disabling work-related injury or illness to estimate the association between persistent pain 18 months post-injury and the incidence of physician-diagnosed chronic conditions. The study has three objectives: to (i) compare pre-injury prevalence of common chronic conditions to chronic condition prevalence in a representative sample of working adults, (ii) calculate the incidence of chronic conditions post-injury, and (iii) estimate the association between persistent pain symptoms and the incidence of common chronic conditions in the 18-month period post-injury. The study design oversampled disability benefit recipients with longer duration disability episodes and incorporated measures obtained at baseline from administrative records of workers’ compensation benefits with measures obtained from interviews with cohort members 18 months following the incidence of disabling injury or illness.We hypothesized that, once taking into account the length of claim duration, the prevalence of chronic conditions among cohort members before the disabling injury would be equivalent to prevalence rates observed in a representative sample of working adults in this setting. We also hypothesized that high persistent pain symptoms would be associated with a greater probability of incident chronic conditions . The incApproximately 70% of the seven million labor force participants in Ontario, Canada are employed by organizations that have a mandatory obligation to obtain work disability insurance coverage from the publicly administered, single-payer workers’ compensation insurance authority: the Workplace Safety & Insurance Board (WSIB). The WSIB administers benefits to entitled workers, covering medical care services and the provision of wage replacement benefits for workers whose recovery from a work-related injury or illness requires absence from work. In 2018, the WSIB administered benefits for approximately 200 000 compensation claims, of which 67 000 were claims resulting in one or more days absent from work.The Ontario Life After Work Injury Study (OLAWIS) pools information from two cohorts of workers in Ontario, Canada, who were disabled by a physical work injury or illness (herein referred to simply as injury) and received wage replacement benefits. Both cohorts were comprised of Ontario workers ≥18 years old, who were employed by an insured employer, able to conduct an interview in English or French, and had experienced a physical work-related injury or occupational disease that resulted in a WSIB accepted compensation claim for wage replacement benefits. To obtain sufficient representation of more serious and complex disability episodes, participants with longer wage replacement durations of three months or greater were oversampled. Workers with wage replacement benefit durations of one day to three months, representing 85% of all accepted claimants in this setting, comprised 41% of the combined sample.Participant recruitment for the first cohort, OLAWIS1, occurred between June 2019 and March 2020, among workers disabled by a work-related injury in the period from January to October 2018. From randomly sampled monthly quotas of lost-time claimants meeting eligibility criteria, 2816 claimants were contacted, of which 1132 completed an interviewer-administered telephone interview (40.2% of eligible claimants). Among participants, 358 (31.6%) were in the short-duration claim sample and 774 (68.3%) were in the long-duration claim sample. More details on the OLAWIS1 study cohort may be found elsewhere .Participant recruitment for the second cohort, OLAWIS2, occurred over the period September to November 2021. From a census of all claimants disabled by a work-related injury or illness in January or February 2020, 2309 randomly sampled claimants were contacted, of which 700 claimants (30.3% of eligible claimants) completed interviews. Among OLAWIS2 participants, 395 (56.4%) were in the short-duration claim sample and 305 (43.6%) were in the long-duration claim sample.Compared to potential participants who consented to the study but did not complete the survey, no differences were present in terms of age, gender, geographic location, industry, and employer size. However, duration of benefits was slightly longer among participants versus non- participants. Of those participants who completed the survey, a greater proportion of participants with medium (3–12 month) and long-term (12–18 months) claims agreed to link their survey response with their administrative claim data.The present study included all cohort members of the OLAWIS1 (N=1132) and OLAWIS2 cohorts (N=700), 1832 participants. The Health Sciences Research Ethics Board at the University of Toronto granted Research Ethics Board approval (Protocols 37525 and 41560).OLAWIS1 and OLAWIS2. Primary outcome measures and potential predictors of the primary outcomes were drawn from WSIB administrative records and an interviewer-administered telephone questionnaire 18 months after the original injury occurred. Information from an 18-month follow-up of administrative records of work disability insurance benefits, providing a measure of the nature of injury, was linked with the information obtained from the interviewer-administered questionnaire – 94% and 84% of OLAWIS1 and OLAWIS2 participants, respectively, consented to this linkage. To maximize statistical power, the two cohorts have been pooled.Canadian Community Health Survey. The Canadian Community Health Survey (CCHS) is an ongoing series of cross-sectional health interview surveys administered approximately every two years by Statistics Canada, the Canadian federal statistics agency , and incident conditions (those that occurred after the work-related injury).The validity of physician-diagnosed chronic conditions obtained from survey respondent self-report has been extensively evaluated in comparison to reference standards based on clinical diagnostic evaluation  and diagPersistent pain interference. OLAWIS participants were asked about current levels of pain interference with normal activities ?”), to which participants could respond: not at all, a little bit, moderately, quite a bit, or extremely , and the industry in which one was working in at the time of the injury. In the survey, participants were also asked about their healthcare experience, including if they were currently receiving healthcare for their injury. Nature of the work-related injury was obtained from administrative records, classified in five categories: superficial or open wound; sprain, strain or dislocation; fracture; internal injury (including concussion); or other. Those not agreeing to the use of their administrative records were coded as a “missing” category for analyses. We also included cohort (OLAWIS 1 or 2), as well as length of benefit duration (≤3 months) as covariates.Cohort-specific pre-injury and post-injury prevalence rates for seven chronic conditions were calculated, age-standardized to the age distribution of Ontario workers in the CCHS. Applying the Fay method, 95% confidence intervals (CI) were computed .The distribution of demographic, work, health, and injury measures were estimated for incident cases of asthma and for incident cases of three groups of disorders: arthritis and/or back problems, hypertension and/or diabetes, and mood and/or migraine disorders. Disorders were grouped together due to their common etiology and co-occurrence –39. As tFor the three incident chronic condition groups, logistic regression was used to calculate crude odds ratios of the association with persistent pain, as well as adjusted odds ratios from models including all covariates [crude odds ratios (OR) are available in the supplemental file]. Due to the small number of cases (N=18), incident asthma was excluded from these analyses. All analyses were weighted by the probability of selection to account for the oversampling of longer duration disability episodes. Sample weights were calculated as the inverse of the sampling fraction, which is estimated as the number of survey participants in a sample group divided by the number of eligible claimants in the sample frame. Sample weights were normalized. Analyses were completed in R software (version 4.2.0).Regression analyses were conducted using a complete case framework. As such, the regression for incident arthritis or back pain included 1695/1720 eligible participants . The logistic regression for incident hypertension or diabetes included 1728/1753 eligible participants , and the regression for incident migraine or mood disorder included 1739/1763 eligible individuals .Population attributable fractions, estimating the fraction of incident chronic conditions attributable to exposure to severe persistent pain, were calculated from adjusted OR obtained from multivariable regressions . The forFor diabetes and asthma, age-standardized prevalence rates 18 months post-injury were equivalent to the pre-injury prevalence rates in both OLAWIS cohorts. However, the post-injury prevalence rates were substantially elevated for five conditions in both OLAWIS cohorts, representing the incidence of new physician diagnosis over the 18-month period. The prevalence rate for mood disorders increased from 11.5–12.9/100 pre-injury to 19.4–20.7/100 post-injury. The prevalence rate for migraine disorder increased from 15.9–18.4/100 pre-injury to 28.5–28.7/100, hypertension from 10.8–11.4/100 to 14.7–16.0/100, arthritis from 11.5–14.0/100 to 19.1–24.8/100 and back problems from 15.1–16.2/100 to 31.7–32.3/100.Applying established approaches  for estiwww.sjweh.fi/article/4096) reports unadjusted OR for the association of independent variables and incident chronic conditions, which were generally similar in magnitude to fully adjusted estimates.Supplementary table S1  was roughly six times higher than the prevalence of high impact chronic pain (pain lasting ≥3 months) in adult populations in North America –25. PopuAmong workers disabled by a work-related injury, the utilization of healthcare services is frequently elevated beyond the period of acute management of the injury , 44. GivWhile pain interference prior to the work-related injury was not measured, it is unlikely that the high burden of persistent pain observed in this cohort of workers was prevalent prior to the injury. That all members of the cohort were actively employed at the time of the disabling injury or illness suggests a low prevalence of functional impairment prior to the injury. We note that respondents were specifically asked to describe pain intensity that they attributed to their disabling work-related injury, in addition to describing the degree of pain interference with normal activities.There are several potential limitations that are relevant to guide the interpretation of the study’s findings. While we are confident that the study participants are demographically and occupationally representative of the population of injured workers’ compensation claimants in Ontario once sampling design probabilities have been accounted for, we cannot exclude the possibility that study participants had comparatively poorer health and functional status prior to the injury or at the time of the survey. If this was the case, estimates of the burden of persistent pain and the incidence of chronic conditions may not be representative of the population of injured workers. However, this potential sample selection bias does not limit the validity of the observed association between persistent pain and chronic condition incidence. Of more consequence, perhaps, are potential limitations in the reliability and validity of the measurement of persistent pain and the self-reported incidence of physician-diagnosed chronic conditions. Readers should recognize that the measure of persistent pain applied in this study of disabled workers may be vulnerable to over-estimation, with the consequence that the substantial associations between pain and the incidence of chronic conditions demonstrated in this study may have been overestimated. The estimated association between persistent pain and the incidence of chronic conditions has been adjusted for the nature of the disabling injury, anticipating that specific injury morbidity may be a potential confounder, as a cause of both persistent pain and the incidence of chronic conditions. However, the coarse classification of the nature of injury applied in our analysis may have resulted in residual confounding.Related, it is possible that misclassification in chronic condition measures exist, in that each may be related to an underlying latent chronic condition. However, if this was the case, then separating this latent condition into separate disorders provides validity to our findings. There is some evidence that the probability of chronic condition incidence following traumatic injury is associated with injury severity . While tThe ascertainment of incident chronic conditions, based on participant self-report of a physician diagnosis, may not be concordant with clinical records. The potential threat to the validity of the association between persistent pain and the incidence of chronic conditions is unknown. Further, the OLAWIS survey interview and context were different than that of the CCHS, potentially threatening the validity of comparison between the two samples. Finally, a portion of the post-injury incidence of chronic conditions described in this study may be transient, as several chronic conditions included in this study have a remitting and relapsing natural history .Among the strengths of this study is the inclusion of a reference population based on a representative sample of Ontario workers. The OLAWIS cohort design, interviewing workers 18 months following a disabling work-related injury, demonstrates the importance of longer duration prospective cohort studies in understanding the consequences of traumatic injury. We also note that the findings reported in this study have been replicated in two independent samples of injured workers.Policies regarding the benefit administration of work disability insurance schemes in Canada include provisions for entitlement for permanent impairment benefits for conditions that arise secondary to a disabling injury. These provisions, which align with the findings of this study, acknowledge the potential incidence of post-traumatic osteoarthritis, post-traumatic headache and psycho-traumatic disability following a disabling injury . The admAs noted above, empirical research on the association between occupational injury and the subsequent incidence of chronic conditions is limited. It appears this limitation is also present in the broader field of all-cause traumatic injury among adults of working age. The associations documented in this study are plausibly generalizable to all traumatic injuries experienced by working-aged adults  and sugg