An Exploration of Wearable Device Features Used in UK Hospital Parkinson Disease Care: Scoping Review.

BACKGROUND: The prevalence of Parkinson disease (PD) is becoming an increasing concern owing to the aging population in the United Kingdom. Wearable devices have the potential to improve the clinical care of patients with PD while reducing health care costs. Consequently, exploring the features of these wearable devices is important to identify the limitations and further areas of investigation of how wearable devices are currently used in clinical care in the United Kingdom. OBJECTIVE: In this scoping review, we aimed to explore the features of wearable devices used for PD in hospitals in the United Kingdom. METHODS: A scoping review of the current research was undertaken and reported according to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. The literature search was undertaken on June 6, 2022, and publications were obtained from MEDLINE or PubMed, Embase, and the Cochrane Library. Eligible publications were initially screened by their titles and abstracts. Publications that passed the initial screening underwent a full review. The study characteristics were extracted from the final publications, and the evidence was synthesized using a narrative approach. Any queries were reviewed by the first and second authors. RESULTS: Of the 4543 publications identified, 39 (0.86%) publications underwent a full review, and 20 (0.44%) publications were included in the scoping review. Most studies (11/20, 55%) were conducted at the Newcastle upon Tyne Hospitals NHS Foundation Trust, with sample sizes ranging from 10 to 418. Most study participants were male individuals with a mean age ranging from 57.7 to 78.0 years. The AX3 was the most popular device brand used, and it was commercially manufactured by Axivity. Common wearable device types included body-worn sensors, inertial measurement units, and smartwatches that used accelerometers and gyroscopes to measure the clinical features of PD. Most wearable device primary measures involved the measured gait, bradykinesia, and dyskinesia. The most common wearable device placements were the lumbar region, head, and wrist. Furthermore, 65% (13/20) of the studies used artificial intelligence or machine learning to support PD data analysis. CONCLUSIONS: This study demonstrated that wearable devices could help provide a more detailed analysis of PD symptoms during the assessment phase and personalize treatment. Using machine learning, wearable devices could differentiate PD from other neurodegenerative diseases. The identified evidence gaps include the lack of analysis of wearable device cybersecurity and data management. The lack of cost-effectiveness analysis and large-scale participation in studies resulted in uncertainty regarding the feasibility of the widespread use of wearable devices. The uncertainty around the identified research gaps was further exacerbated by the lack of medical regulation of wearable devices for PD, particularly in the United Kingdom where regulations were changing due to the political landscape.

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes.

This review presents a comprehensive overview of transition-metal-catalyzed domino reactions of strained bicyclic alkenes, including both homo- and heterobicyclic alkenes. These compounds are important synthons in organic synthesis, providing an important platform for the construction of biologically/medicinally significant compounds which bear multiple stereocenters. The review has been divided according to the metal used in the reaction. An overview of the substrate scope, reaction conditions, and their potential applications in organic synthesis is discussed. A comprehensive outlook on the reactivity paradigms of homo- and heterobicyclic alkenes is discussed and should shed light on future directions for further development in this field.

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study.

An experimental and theoretical investigation on the iridium-catalyzed hydroacylation of C1-substituted oxabenzonorbornadienes with salicylaldehyde is reported. Utilizing commercially available [Ir(COD)Cl]2 in the presence of 5 M KOH in dioxane at 65 °C, provided a variety of hydroacylated bicyclic adducts in up to a 95% yield with complete stereo- and regioselectivity. The mechanism and origins of selectivity in the iridium-catalyzed hydroacylation reaction has been examined at the M06/Def2TZVP level of theory. The catalytic cycle consists of three key steps including oxidative addition into the aldehyde C-H bond, insertion of the olefin into the iridium hydride, and C-C bond-forming reductive elimination. Computational results indicate the origin of regioselectivity is involved in the reductive elimination step.

Iron-catalyzed domino coupling reactions of π-systems.

The development of environmentally benign, inexpensive, and earth-abundant metal catalysts is desirable from both an ecological and economic standpoint. Certainly, in the past couple decades, iron has become a key player in the development of sustainable coupling chemistry and has become an indispensable tool in organic synthesis. Over the last ten years, organic chemistry has witnessed substantial improvements in efficient synthesis because of domino reactions. These protocols are more atom-economic, produce less waste, and demand less time compared to a classical stepwise reaction. Although iron-catalyzed domino reactions require a mindset that differs from the more routine noble-metal, homogenous iron catalysis they bear the chance to enable coupling reactions that rival that of noble-metal-catalysis. This review provides an overview of iron-catalyzed domino coupling reactions of π-systems. The classifications and reactivity paradigms examined should assist readers and provide guidance for the design of novel domino reactions.

Palladium/Lewis Acid Cocatalyzed Ring-Opening Reactions of Unsymmetrical Oxabenzonobornadienes with Oximes.

The palladium/Lewis acid cocatalyzed ring-opening reaction of various C1-substituted unsymmetrical oxabenzonorbornadienes (OBD) with oxime nucleophiles was investigated. The effects of various C1 substituents were explored. Moderate to excellent yields and excellent regioselectivities were obtained for electron-withdrawing groups. The presence of electron-donating alkyl groups leads to isomerization of the corresponding OBD to afford the substituted naphthol derivatives. Additionally, a mechanism for the formation of C2 regioisomeric ring-opened products has been proposed.

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols.

The acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicylic alkene using alcohol nucleophiles were investigated. Although this acid-catalyzed ring-opening reaction did not cleave the cyclopropane unit as planned, this represent the first examples of ring-openings of cyclopropanated 3-aza-2-oxabicyclo[2.2.1]alkenes that lead to the cleavage of the C-O bond instead of the N-O bond. Different acid catalysts were tested and it was found that pyridinium toluenesulfonate in methanol gave the best yields in the ring-opening reactions. The scope of the reaction was successfully expanded to include primary, secondary, and tertiary alcohol nucleophiles. Through X-ray crystallography, the stereochemistry of the product was determined which confirmed an SN2-like mechanism to form the ring-opened product.

Palladium-catalyzed ring-opening reactions of cyclopropanated 7-oxabenzonorbornadiene with alcohols.

Palladium-catalyzed ring-opening reactions of cyclopropanated 7-oxabenzonorbornadiene derivatives using alcohol nucleophiles were investigated. The optimal conditions were found to be 10 mol % PdCl2(CH3CN)2 in methanol, offering yields up to 92%. The reaction was successful using primary, secondary and tertiary alcohol nucleophiles and was compatible with a variety of substituents on cyclopropanated oxabenzonorbornadiene. With unsymmetrical C1-substituted cyclopropanated 7-oxabenzonorbornadienes, the regioselectivity of the reaction was excellent, forming only one regioisomer in all cases.

Regioselective palladium-catalyzed ring-opening reactions of C1-substituted oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylates.

Palladium-catalyzed ring-opening reactions of C1 substituted 7-oxanorbornadiene derivatives with aryl iodides were investigated. The optimal conditions for this reaction were found to be PdCl2(PPh3)2, ZnCl2, Et3N and Zn in THF. Both steric and electronic factors played a role in the outcome of the reaction as increasing the steric bulk on the bridgehead carbon decreased the yield. These reactions were found to be highly regioselective, giving only one of the two possible regioisomers in all cases. A diverse collection of novel, highly substituted biphenyl derivatives were obtained.

Long-term adenoma recurrence following wide-field endoscopic mucosal resection (WF-EMR) for advanced colonic mucosal neoplasia is infrequent: results and risk factors in 1000 cases from the Australian Colonic EMR (ACE) study.

OBJECTIVE: Wide-field endoscopic mucosal resection (WF-EMR) is an alternative to surgery for treatment of advanced colonic mucosal neoplasia up to 120 mm in size, but has been criticised for its potentially high recurrence rates. We aimed to quantify recurrence at 4 months (early) and 16 months (late) following successful WF-EMR and identify its risk factors and clinical significance. DESIGN: Ongoing multicentre, prospective, intention-to-treat analysis of sessile or laterally spreading colonic lesions ≥20 mm in size referred for WF-EMR to seven academic endoscopy units. Surveillance colonoscopy (SC) was performed 4 months (SC1) and 16 months (SC2) after WF-EMR, with photographic documentation and biopsy of the scar. RESULTS: 1134 consecutive patients were enrolled when 1000 successful EMRs were achieved, of whom 799 have undergone SC1. 670 were normal. Early recurrent/residual adenoma was present in 128 (16.0%, 95% CI 13.6% to 18.7%). One case was unknown. The recurrent/residual adenoma was diminutive in 71.7% of cases. On multivariable analysis, risk factors were lesion size >40 mm, use of argon plasma coagulation and intraprocedural bleeding. Of 670 with normal SC1, 426 have undergone SC2, with late recurrence present in 17 cases (4.0%, 95% CI 2.4% to 6.2%). Overall, recurrent/residual adenoma was successfully treated endoscopically in 135 of 145 cases (93.1%, 95% CI 88.1% to 96.4%). If the initial EMR was deemed successful and did not contain submucosal invasion requiring surgery, 98.1% (95% CI 96.6% to 99.0%) were adenoma-free and had avoided surgery at 16 months following EMR. CONCLUSIONS: Following colonic WF-EMR, early recurrent/residual adenoma occurs in 16%, and is usually unifocal and diminutive. Risk factors were identified. Late recurrence occurs in 4%. Overall, recurrence was managed endoscopically in 93% of cases. Recurrence is not a significant clinical problem following WF-EMR, as with strict colonoscopic surveillance, it can be managed endoscopically with high success rates. TRIAL REGISTRATION NUMBER: NCT01368289.

Management of pancreatic collections with a novel endoscopically placed fully covered self-expandable metal stent: a national experience (with videos).

BACKGROUND: Recent medical literature on novel lumen-apposing stents for the treatment of pancreatic fluid collections (PFCs) is limited by small numbers, solo operators, and single-center experience. OBJECTIVE: To evaluate a recently developed lumen-apposing, fully covered self-expandable metal stent (FCSEMS) in the management of PFCs. DESIGN: Retrospective case series. SETTING: Thirteen tertiary and private health care centers across Australia. PATIENTS: Forty-seven patients (median age 51 years) who underwent endoscopic management of PFCs. INTERVENTION: Insertion of FCSEMS after PFC puncture under EUS guidance. A subgroup of 9 patients underwent direct endoscopic necrosectomy. MAIN OUTCOME MEASUREMENTS: Technical and clinical success rate, adverse event rate. RESULTS: The technical success rate was 53 of 54 patients (98.1%), and the initial clinical success rate was 36 of 47 (76.6%), which was sustained for more than 6 months in 34 of 36 (94.4%). Early adverse events included 4 cases (7.4%) of stent migration during direct endoscopic necrosectomy, 4 cases (7.4%) of sepsis, 1 case (1.9%) of bleeding, and 1 case (1.9%) of stent migration into the fistula tract. Late adverse events were 6 (11.1%) spontaneous stent migrations, 3 (5.6%) recurrent stent occlusions, 3 (5.6%) tissue ingrowth/overgrowth, and 2 (3.7%) bleeding into PFC. The majority of stents inserted (48 of 54, 88.9%) and removed (31 of 35, 88.6%) in our study were described by the operator as superior to pigtail stents with regard to ease of use. LIMITATIONS: Retrospective study. CONCLUSION: Although FCSEMSs are technically easier to insert and remove compared with traditional pigtail stents, there are significant limitations to the widespread use of FCSEMSs in the management of PFCs. These include cost, adverse events, and lower-than-expected resolution rates.

Risk factors for intraprocedural and clinically significant delayed bleeding after wide-field endoscopic mucosal resection of large colonic lesions.

BACKGROUND & AIMS: Wide-field endoscopic mucosal resection (WF-EMR) of large sessile colonic polyps is a safe and cost-effective outpatient treatment. Bleeding is the main complication. Few studies have examined risk factors for bleeding during the procedure (intraprocedural bleeding [IPB]) or after it (clinically significant post-endoscopic bleeding [CSPEB]). We investigated factors associated with IPB and CSPEB in a large prospective study. METHODS: We analyzed data from WF-EMRs of sessile colorectal polyps ≥ 20 mm in size (mean size, 35.5 mm), which were performed on 1172 patients (mean age, 67.8 years) from June 2008-March 2013 at 7 tertiary hospitals as part of the Australian Colonic Endoscopic Resection Study. Data were collected on characteristics of patients and lesions, along with outcomes of procedures and clinical and histologic analyses. Independent predictors of IPB and CSPEB were identified by multiple logistic regression analysis. RESULTS: Of the patients studied, 133 (11.3%) had IPB. Independent predictors included increasing lesion size (odds ratio, 1.24/10 mm; P < .001), Paris endoscopic classification of 0-IIa + Is (odds ratio, 2.12; P = .004), tubulovillous or villous histology (odds ratio, 1.84; P = .007), and study institutions that performed the procedure on fewer than 75 patients (odds ratio, 3.78; P < .001). All IPB was successfully controlled endoscopically. IPB prolonged procedures and was associated with early recurrence (relative risk, 1.68; P = .011). Seventy-three patients (6.2%) had CSPEB. On multivariable analysis, CSPEB was associated with proximal colon location (odds ratio, 3.72; P < .001), use of an electrosurgical current not controlled by a microprocessor (odds ratio, 2.03; P = .038), and IPB (odds ratio, 2.16; P = .016). Lesion size and comorbidities did not predict CSPEB. CONCLUSIONS: In a prospective study of patients undergoing WF-EMR of large sessile colonic polyps, IPB is associated with larger lesions, lesion histology, and Paris endoscopic classification of type 0-IIa + Is. IPB prolongs the duration of the procedure, is a marker for recurrence, and is associated with CSPEB. CSPEB occurs most frequently in the proximal colon and less when current is controlled by a microprocessor.

A management algorithm based on delayed bleeding after wide-field endoscopic mucosal resection of large colonic lesions.

BACKGROUND & AIMS: Bleeding is the main complication of wide-field endoscopic mucosal resection (WF-EMR) for large colonic lesions. Few studies have examined bleeding outcomes after WF-EMR, and there are no evidence-based guidelines for management of bleeding in this group. We analyzed outcomes of patients with clinically significant post-EMR bleeding (CSPEB) and present a management algorithm based on our findings. METHODS: In a prospective study, we collected data from WF-EMR of sessile colorectal polyps 20 mm or larger from 1039 patients who participated in the Australian Colonic Endoscopic resection multicenter study from July 2008 through May 2012. Data included patient and lesion characteristics and procedural, clinical, and histologic outcomes. Patients participated in a structured telephone interview 14 days after the procedure; independent predictors of a moderate or severe outcome by American Society of Gastrointestinal Endoscopists criteria, or any intervention for hemostasis, were identified. RESULTS: Sixty-two patients had CSPEB (6.0%); 34 were managed conservatively (55%) and 27 underwent colonoscopy (44%). One patient had primary embolization. Endoscopic therapy was applied in 21 cases; 14 had active bleeding. Two of the conservatively managed cases underwent colonoscopy for rebleeding after discharge. On multivariable analysis, moderate or severe bleeding events were associated with hemodynamic instability (odds ratio, 12.3; P = .046) and low level of hemoglobin at presentation (odds ratio, 0.50 per 1.0 g/dL; P = .005). Intervention for hemostasis was associated with hourly or more frequent hematochezia (odds ratio, 36.7; P = .001), American Society of Anesthesiologists grade 2 or higher (odds ratio, 20.1; P < .001), and transfusion (odds ratio, 18.7; P = .003). CONCLUSIONS: Based on a multicenter prospective study, CSPEB resolves spontaneously in 55% of patients. We developed a risk factor-based algorithm that might assist physicians in the management of bleeding. Patients responding to initial resuscitation can be observed, with a lower threshold for intervention in those with the identified risk factors.

Ruthenium-catalyzed asymmetric [2 + 2] cycloadditions between chiral acyl camphorsultam-substituted alkynes and bicyclic alkenes.

Ruthenium-catalyzed asymmetric [2 + 2] cycloadditions between chiral acyl camphorsultam-functionalized alkynes and bicyclic alkenes were examined, providing adducts with complete exo stereoselectivity in good overall yield and enantioselectivity (up to 99% and 166:1, respectively), as well as appreciable diastereoselectivity (up to 163:1). The diastereoselectivity showed dependence on the solvent and temperature, as well as on the substitution pattern of the reacting alkyne and bicyclic alkene components. In general, higher diastereoselectivities were observed for reactions conducted in ethereal solvents and at lower temperatures between N-propynoyl camphorsultams and bicyclic alkenes.

(3-Methyl-3a,4,7,7a-tetra-hydro-5H-4,7-methano-isoxazolo[4,5-d][1,2]oxazin-5-yl)(phen-yl)methanone.

The title compound, C14H14N2O3, is the exo isomer with a syn arrangement of two O atoms in the isoxazole and oxazine rings. The dihedral angle between the isoxazole and phenyl rings is 60.38 (4)°. In the crystal, weak C-H⋯O hydrogen bonds link the mol-ecules, forming a three-dimensional network. The isoxazole O atom is an acceptor for three of these hydrogen bonds.

5,8-Dimeth-oxy-3,9-dimethyl-3a,4,9,9a-tetra-hydro-4,9-ep-oxy-naphtho-[2,3-d]isoxazole.

The title compound, C15H17NO4, is the exo isomer with a syn arrangement of the O atom in the isoxazole ring to the methyl group of the bicyclic alkene. The dihedral angle between the isoxazole ring and the benzene ring is 7.42 (9)°. In the crystal, weak C-H⋯O hydrogen bonds link mol-ecules, forming a three-dimensional network. The isoxazole O atom is an acceptor for both weak hydrogen bonds.

1-(3-Hy-droxy-5,8-dimeth-oxy-4-methyl-1,2,3,4-tetra-hydro-1,4-ep-oxy-naphthalen-2-yl)ethan-1-one.

The stereochemistry and regioschemistry (exo) of the title compound, C15H18O5, were determined by the X-ray analysis. The meth-oxy groups essentially lie in the plane of the benzene ring to which they are attached, as described by the C-O-C C torsion angles of -176.80 (12) and 4.67 (19)°. In the crystal, O-H⋯O hydrogen bonds and weak C-H⋯O hydrogen bonds link the mol-ecules, forming chains of R 2 (1)(8) rings along [010].

cis-2-(4-Meth-oxy-phen-yl)-4-methyl-1,2-di-hydro-naphthalen-1-ol.

The stereochemistry and regiochemistry of the title compound, C18H18O2, were determined by the X-ray analysis. There are two independent mol-ecules in the asymmetric unit in which the dihedral angles between the benzene rings are 88.31 (4) and 86.27 (4)°. The cyclo-hexene rings are in half-chair conformations. In the crystal, O-H⋯O hydrogen bonds link alternating types of mol-ecules into chains along [010] with graph-set C 2 (2)(4).

N-O Cleavage reactions of heterobicycloalkene-fused 2-isoxazolines.

Transition metal-mediated N-O bond cleavage reactions of heterobicycloalkene-fused 3-methyl-2-isoxazolines were investigated. Optimal cleavage conditions were found with Raney nickel/AlCl3 mediation in aqueous methanol. The reaction provided a diverse collection of novel heterobicycle-fused ß-hydroxyketones with good to excellent yields (66-95%) and without the need for chromatographic purification.

Patient-controlled analgesia with inhaled methoxyflurane versus conventional endoscopist-provided sedation for colonoscopy: a randomized multicenter trial.

OBJECTIVE: Inhaled methoxyflurane (Penthrox, Medical Device International, Melbourne, Australia) has been used extensively in Australasia (Australia and New Zealand) to manage trauma-related pain. The aim is to evaluate the efficacy, safety, and outcome of Penthrox for colonoscopy. DESIGN: Prospective randomized study. SETTING: Three tertiary endoscopic centers. PATIENTS: Two hundred fifty-one patients were randomized to receive either Penthrox (n = 125, 70 men, 51.4 ± 1.1 years old) or intravenous midazolam and fentanyl (M&F; n = 126, 72 men, 54.9 ± 1.1 years old) during colonoscopy. MAIN OUTCOME MEASUREMENT: Discomfort (visual analogue scale [VAS] pain score), anxiety (State-Trait Anxiety Inventory Form Y [STAI-Y] anxiety score), colonoscopy performance, adverse events, and recovery time. RESULTS: Precolonoscopy VAS pain and STAI-Y scores were comparable between the 2 groups. There were no differences between groups in (1) pain VAS or STAI Y-1 anxiety scores during or immediately after colonoscopy, (2) procedural success rate (Penthrox: 121/125 vs M&F: 124/126), (3) hypotension during colonoscopy (7/125 vs 8/126), (4) tachycardia (5/125 vs 3/126), (5) cecal arrival time (8 ± 1 vs 8 ± 1 minutes), or (6) polyp detection rate (30/125 vs 43/126). Additional intravenous sedation was required in 10 patients (8%) who received Penthrox. Patients receiving Penthrox alone had no desaturation (oxygen saturation [SaO(2)] < 90%) events (0/115 vs 5/126; P = .03), awoke quicker (3 ± 0 vs 19 ± 1 minutes; P < .001) and were ready for discharge earlier (37 ± 1 vs 66 ± 2 minutes; P < .001) than those receiving intravenous M&F. LIMITATIONS: Inhaled Penthrox is not yet available in the United States and Europe. CONCLUSIONS: Patient-controlled analgesia with inhaled Penthrox is feasible and as effective as conventional sedation for colonoscopy with shorter recovery time, is not associated with respiratory depression, and does not influence the procedural success and polyp detection.

Argon plasma coagulation ablation versus endoscopic surveillance of Barrett's esophagus: late outcomes from two randomized trials.

BACKGROUND AND STUDY AIM: Argon plasma coagulation (APC) has been used to ablate dysplastic and nondysplastic Barrett's esophagus. We determined the longer-term efficacy of APC ablation within two randomized controlled trials of APC versus surveillance for Barrett's esophagus in patients in whom gastroesophageal reflux was controlled by either surgery or proton pump inhibitors. PATIENTS AND METHODS: 129 patients (surgical trial 70, medical trial 59) with Barrett's esophagus (nondysplastic or low grade dysplasia) were randomly allocated to either ablation using APC or to continuing endoscopy surveillance. Outcomes were determined at three time points: short-term (12 months), mid-term (42-75 months) and long-term (> 84 months). RESULTS: In the APC groups, initial ablation of > 95 % of the Barrett's esophagus was achieved in 61 of 63 patients; the > 95 % ablation persisted in 47 of 56 patients at short-term follow-up, in 33 of 49 at mid-term and in 21 of 32 at long-term follow-up. In the surveillance groups, the length of Barrett's esophagus reduced from a mean of 4.2 cm to 2.7 cm at long-term follow-up. High grade dysplasia (HGD) developed in 1 patient in the APC groups and in 3 in the surveillance groups. Low grade dysplasia developed in 1 APC patient and in 6 surveillance patients. CONCLUSIONS: APC ablation reduced the extent of Barrett's esophagus, and this reduction was maintained in some patients at longer-term follow-up. However, progression to HGD can still occur despite APC ablation, suggesting endoscopic surveillance is still required. CLINICAL TRIAL REGISTRATION: ACTRN012607000293460 and ACTRN12607000292471 (Australian Clinical Trials Registry).