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1.
Article in English | MEDLINE | ID: mdl-38871629

ABSTRACT

OBJECTIVES: Behavioral and psychological symptoms of dementia (BPSD) are common and impart a significant burden to patients, caregivers, and the health system. However, there are few pharmacological options for treating BPSD. We conducted a systematic review of clinical trials examining the efficacy of anticonvulsants in BPSD. METHODS: We searched five electronic databases through January 2023, for randomized controlled trials and systematic reviews evaluating the efficacy of non-benzodiazepine anticonvulsants for the treatment of BPSD. We used the Cochrane risk of bias tool to ascertain the risk of bias in included trials. Because statistical pooling of results using meta-analysis was not feasible, we synthesized findings using the Cochrane Synthesis Without Meta-analysis reporting guidelines. RESULTS: We identified 12 studies, including randomized controlled trials (RCTs) and 1 systematic review. Five RCTs evaluating valproic acid were synthesized by a recent Cochrane review which concluded that this drug is likely ineffective for BPSD. We extracted data from 6 trials involving 248 individuals comparing non-benzodiazepine anticonvulsants to either placebo or risperidone. Four trials (n = 97 participants) evaluated carbamazepine, only one of which demonstrated an improvement in the Brief Psychiatric Rating Scale measuring agitation, hostility, psychosis, and withdrawal/depression (effect size: 1.13; 95% confidence interval [CI]: 0.54-1.73) relative to placebo. Adverse effects were more common in patients receiving carbamazepine (20/27; 74%) relative to placebo (5/24; 21%). There is low quality evidence that oxcarbazepine is likely ineffective and that topiramate may be comparable to risperidone. CONCLUSION: Anticonvulsants are unlikely to be effective in BPSD, although the quality of existing evidence is low.

2.
BMJ Open ; 14(5): e079353, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38692712

ABSTRACT

OBJECTIVES: To evaluate whether a focused, expert medication management intervention is feasible and potentially effective in preventing anticoagulation-related adverse events for patients transitioning from hospital to home. DESIGN: Randomised, parallel design. SETTING: Medical wards at six hospital sites in southern Ontario, Canada. PARTICIPANTS: Adults 18 years of age or older being discharged to home on an oral anticoagulant (OAC) to be taken for at least 4 weeks. INTERVENTIONS: Clinical pharmacologist-led intervention, including a detailed discharge medication management plan, a circle of care handover and early postdischarge virtual check-up visits to 1 month with 3-month follow-up. The control group received the usual care. OUTCOMES MEASURES: Primary outcomes were study feasibility outcomes (recruitment, retention and cost per patient). Secondary outcomes included adverse anticoagulant safety events composite, quality of transitional care, quality of life, anticoagulant knowledge, satisfaction with care, problems with medications and health resource utilisation. RESULTS: Extensive periods of restriction of recruitment plus difficulties accessing patients at the time of discharge negatively impacted feasibility, especially cost per patient recruited. Of 845 patients screened, 167 were eligible and 56 were randomised. The mean age (±SD) was 71.2±12.5 years, 42.9% females, with two lost to follow-up. Intervention patients were more likely to rate their ability to manage their OAC as improved (17/27 (63.0%) vs 7/22 (31.8%), OR 3.6 (95% CI 1.1 to 12.0)) and their continuity of care as improved (21/27 (77.8%) vs 2/22 (9.1%), OR 35.0 (95% CI 6.3 to 194.2)). Fewer intervention patients were taking one or more inappropriate medications (7 (22.5%) vs 15 (60%), OR 0.19 (95% CI 0.06 to 0.62)). CONCLUSION: This pilot randomised controlled trial suggests that a transitional care intervention at hospital discharge for older adults taking OACs was well received and potentially effective for some surrogate outcomes, but overly costly to proceed to a definitive large trial. TRIAL REGISTRATION NUMBER: NCT02777047.


Subject(s)
Anticoagulants , Patient Discharge , Humans , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Anticoagulants/adverse effects , Anticoagulants/economics , Female , Male , Aged , Pilot Projects , Ontario , Middle Aged , Administration, Oral , Aged, 80 and over , Feasibility Studies , Quality of Life , Continuity of Patient Care
3.
Cornea ; 43(6): 720-725, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38236070

ABSTRACT

PURPOSE: The aim of this study was to report clinical observations suggesting the efficacy of topical 1% 5-fluorouracil (5-FU) in treating Demodex -associated blepharitis. METHODS: An observational retrospective review of 13 eyes from 13 individuals with conjunctival neoplastic lesions and concomitant Demodex lash infestation that received topical 1% 5-FU eye drops. Patients underwent slit-lamp examination at each follow-up visit. Clinical photographs of the lash line were obtained after treatment initiation. In a subset of patients, lashes were epilated bilaterally and microscopically analyzed for presence of Demodex mites before and after treatment initiation. RESULTS: The mean age of the population was 68 ± 14 years (range: 30-84 years) and 92% were male. In all 13 patients, a marked reduction in cylindrical dandruff was noted in the treated eye by slit-lamp examination after 2 cycles of 5-FU. There was complete resolution of cylindrical dandruff in 10 of 13 treated eyes compared with 0 resolution of cylindrical dandruff in untreated eyes ( P = 0.0001). In the 6 patients who received epilation, the lashes from the treated eye showed no Demodex , whereas lashes from the fellow untreated eye revealed persistent Demodex . CONCLUSIONS: Topical 1% 5-FU shows efficacy in treating Demodex -associated blepharitis. Further studies are indicated to reproduce our findings and evaluate the potential use of 5-FU as a treatment ingredient.


Subject(s)
Blepharitis , Eye Infections, Parasitic , Fluorouracil , Mite Infestations , Mites , Ophthalmic Solutions , Blepharitis/parasitology , Blepharitis/drug therapy , Blepharitis/diagnosis , Fluorouracil/therapeutic use , Fluorouracil/administration & dosage , Humans , Retrospective Studies , Mite Infestations/drug therapy , Mite Infestations/parasitology , Mite Infestations/diagnosis , Male , Aged , Middle Aged , Eye Infections, Parasitic/drug therapy , Eye Infections, Parasitic/parasitology , Eye Infections, Parasitic/diagnosis , Female , Aged, 80 and over , Adult , Animals , Eyelashes/parasitology , Antimetabolites/therapeutic use , Antimetabolites/administration & dosage , Administration, Topical
4.
Age Ageing ; 53(1)2024 01 02.
Article in English | MEDLINE | ID: mdl-38243403

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, telemedicine was widely implemented to minimise viral spread. However, its use in the older adult patient population was not well understood. OBJECTIVE: To understand the perspectives of geriatric care providers on using telemedicine with older adults through telephone, videoconferencing and eConsults. DESIGN: Qualitative online survey study. SETTING AND PARTICIPANTS: We recruited geriatric care physicians, defined as those certified in Geriatric Medicine, Care of the Elderly (family physicians with enhanced skills training) or who were the most responsible physician in a long-term care home, in Ontario, Canada between 22 December 2020 and 30 April 2021. METHODS: We collected participants' perspectives on using telemedicine with older adults in their practice using an online survey. Two researchers jointly analysed free-text responses using the 6-phase reflexive thematic analysis. RESULTS: We recruited 29 participants. Participants identified difficulty using technology, patient sensory impairment, lack of hospital support and pre-existing high patient volumes as barriers against using telemedicine, whereas the presence of a caregiver and administrative support were facilitators. Perceived benefits of telemedicine included improved time efficiency, reduced travel, and provision of visual information through videoconferencing. Ultimately, participants felt telemedicine served various purposes in geriatric care, including improving accessibility of care, providing follow-up and obtaining collateral history. Main limitations are the absence of, or incomplete physical exams and cognitive testing. CONCLUSIONS: Geriatric care physicians identify a role for virtual care in their practice but acknowledge its limitations. Further work is required to ensure equitable access to virtual care for older adults.


Subject(s)
Physicians , Telemedicine , Humans , Aged , Ontario , Pandemics , Physicians/psychology , Surveys and Questionnaires
5.
Drugs Real World Outcomes ; 11(1): 117-124, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38007818

ABSTRACT

BACKGROUND: Adverse drug events among older adults result in significant mortality, morbidity and cost. This harm may be mitigated with appropriate prescribing and deprescribing. We sought to understand the prescribing outcomes of an interdisciplinary geriatric virtual consultation service. METHODS: We conducted a retrospective, before-and-after feasibility study to measure prescribing outcomes for a medication optimization virtual interdisciplinary geriatric specialist (MOVING) programme comprised of expertise from geriatric clinical pharmacology, pharmacy and psychiatry for older adults (aged ≥ 65 years) between June and December 2018, Ontario, Canada. The primary outcome was the number of distinct prescriptions and the presence of polypharmacy (defined as ≥ 4 medications) before and after the service. Secondary outcomes included the number of as needed and regularly administered prescriptions, number of potentially inappropriate prescriptions as defined by the Beers and STOPP criteria, and number of prescriptions for psychotropics, long-acting opioids and diabetic medications. RESULTS: We studied 40 patients with a mean age of 80.6 [standard deviation (SD) 8.8] years who received a MOVING consult. We found no significant change in the mean total number of prescriptions per patient before (12.02, SD 5.83) and after the intervention (11.58, SD 5.28), with a mean difference of -0.45 [95% confidence interval (CI) -0.94 to 0.04; p = 0.07]. We found statistically significant decreases in as needed prescriptions (mean difference - 0.30, 95% CI - 0.45 to - 0.15; p<0.001), and potentially harmful medications as identified by the Beers (mean difference -1.25, 95% CI -2.00 to -0.50; p = 0.002) and STOPP (mean difference -1.65, 95% CI -2.33 to -0.97; p < 0.001) scores. Without including the cost savings from hospital diversion by a MOVING consult, the costs of a MOVING consult were $545.80-$629.80 per person, compared with the costs associated with traditional in-person consults involving similar specialist clinical services ($904.89-$1270.69 per person). CONCLUSION: A MOVING model of care is associated with decreases in prescriptions for potentially inappropriate medications in older adults. These findings support further evaluation to ascertain health system impacts.

7.
Can Geriatr J ; 26(2): 283-289, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37265985

ABSTRACT

During the COVID-19 pandemic, physicians provided virtual care to minimize viral transmission. This concurrent triangulation mixed-methods study assesses the use of synchronous telephone and video visits with patients and asynchronous eConsults by geriatric providers, and explores their perspectives on telemedicine use during the pandemic. Participants included physicians practicing in Ontario, Canada who were certified in Geriatric Medicine, or Care of the Elderly, or who were the most responsible physician in a long-term care for at least 10 patients. Participants' perspectives were solicited using an online survey and themes were generated through a reflexive thematic analysis of survey responses. We assessed the current use of each telemedicine tool and compared the proportion of participants using telemedicine before the pandemic with self-predicted use after the pandemic. We received 29 surveys from eligible respondents (87.9% completion rate), with 75.9% being geriatricians. The telephone was most used (96.6%), followed by video (86.2%) and eConsults (64%). Most participants using telephone and video visits had newly implemented them during the pandemic and intend to continue using these tools post-pandemic. Our thematic analysis revealed that telemedicine plays an important role in the continuity of care during the pandemic, with increased self-reported positive perspectives and openness towards use of virtual care tools, although limited by inadequate physical exams or cognitive testing. Its ongoing use depends on the availability of continued remuneration.

8.
Am J Physiol Regul Integr Comp Physiol ; 325(2): R107-R119, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37184226

ABSTRACT

Prolonged bedrest provokes orthostatic hypotension and intolerance of upright posture. Limited data are available on the cardiovascular responses of older adults to head-up tilt following bedrest, with no studies examining the potential benefits of exercise to mitigate intolerance in this age group. This randomized controlled trial of head-down bedrest (HDBR) in 55- to 65-yr-old men and women investigated if exercise could avert post-HDBR orthostatic intolerance. Twenty-two healthy older adults (11 female) underwent a strict 14-day HDBR and were assigned to either an exercise (EX) or control (CON) group. The exercise intervention included high-intensity, aerobic, and resistance exercises. Head-up tilt-testing to a maximum of 15 minutes was performed at baseline (Pre-Bedrest) and immediately after HDBR (R1), as well as 6 days (R6) and 4 weeks (R4wk) later. At Pre-Bedrest, three participants did not complete the full 15 minutes of tilt. At R1, 18 did not finish, with no difference in tilt end time between CON (422 ± 287 s) and EX (409 ± 346 s). No differences between CON and EX were observed at R6 or R4wk. At R1, just 1 participant self-terminated the test with symptoms, while 12 others reported symptoms only after physiological test termination criteria were reached. Finishers on R1 protected arterial pressure with higher total peripheral resistance relative to Pre-Bedrest. Cerebral blood velocity decreased linearly with reductions in arterial pressure, end-tidal CO2, and cardiac output. High-intensity interval exercise did not benefit post-HDBR orthostatic tolerance in older adults. Multiple factors were associated with the reduction in cerebral blood velocity leading to intolerance.


Subject(s)
Hypotension, Orthostatic , Orthostatic Intolerance , Male , Humans , Female , Aged , Orthostatic Intolerance/diagnosis , Orthostatic Intolerance/prevention & control , Bed Rest/adverse effects , Head-Down Tilt/adverse effects , Head-Down Tilt/physiology , Tilt-Table Test , Exercise , Blood Pressure , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/prevention & control , Heart Rate
9.
Can Geriatr J ; 26(1): 9-22, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36865408

ABSTRACT

Background: There is growing evidence of harm associated with trazodone and nonbenzodiazepine sedative hypnotics (e.g., zopiclone); however, their comparative risk of harm is unknown. Methods: We conducted a retrospective cohort study with linked health administrative data, which enrolled older (≥66 years old) nursing home residents living in Alberta, Canada, between December 1, 2009, and December 31, 2018; the last follow-up date was June 30, 2019. We compared the rate of injurious falls and major osteoporotic fractures (primary outcome) and all-cause mortality (secondary outcome) within 180 days of first prescription of zopiclone or trazodone with cause-specific hazard models and inverse probability of treatment weights to control for confounding; primary analysis was intention-to-treat and secondary analysis was per-protocol (i.e., residents censored if dispensed the other exposure drug). Results: Our cohort included 1,403 residents newly dispensed trazodone and 1,599 residents newly dispensed zopiclone. At cohort entry, the mean resident age was 85.7 (standard deviation [SD] 7.4), 61.6% were female, and 81.2% had dementia. New zopiclone use was associated with similar rates of injurious falls and major osteoporotic fractures (intention-to-treat-weighted hazard ratio 1.15, 95% confidence interval [CI] 0.90-1.48; per-protocol-weighted hazard ratio 0.85, 95% CI 0.60-1.21) and all-cause mortality (intention-to-treat-weighted hazard ratio 0.96, 95% CI 0.79-1.16; per-protocol-weighted hazard ratio 0.90, 95% CI 0.66-1.23) compared to trazodone. Conclusions: Zopiclone was associated with a similar rate of injurious falls, major osteoporotic fractures, and all-cause mortality compared to trazodone-suggesting one medication should not be used in lieu of the other. Appropriate prescribing initiatives should also target zopiclone and trazodone.

12.
Pilot Feasibility Stud ; 8(1): 166, 2022 Aug 02.
Article in English | MEDLINE | ID: mdl-35918731

ABSTRACT

BACKGROUND: Oral anticoagulants (OACs) are commonly prescribed, have well-documented benefits for important clinical outcomes but have serious harms as well. Rates of OAC-related adverse events including thromboembolic and hemorrhagic events are especially high shortly after hospital discharge. Expert OAC management involving virtual care is a research priority given its potential to reach remote communities in a more feasible, timely, and less costly way than in-person care. Our objective is to test whether a focused, expert medication management intervention using a mix of in-person consultation and virtual care follow-up, is feasible and effective in preventing anticoagulation-related adverse events, for patients transitioning from hospital to home. METHODS AND ANALYSIS: A randomized, parallel, multicenter design enrolling consenting adult patients or the caregivers of cognitively impaired patients about to be discharged from medical wards with a discharge prescription for an OAC. The interdisciplinary multimodal intervention is led by a clinical pharmacologist and includes a detailed discharge medication reconciliation and management plan focused on oral anticoagulants at hospital discharge; a circle of care handover and coordination with patient, hospital team and community providers; and early post-discharge follow-up virtual medication check-up visits at 24 h, 1 week, and 1 month. The control group will receive usual care plus encouragement to use the Thrombosis Canada website. The primary feasibility outcomes include recruitment rate, participant retention rates, trial resources management, and the secondary clinical outcomes include adverse anticoagulant safety events composite (AASE), coordination and continuity of care, medication-related problems, quality of life, and healthcare resource utilization. Follow-up is 3 months. DISCUSSION: This pilot RCT tests whether there is sufficient feasibility and merit in coordinating oral anticoagulant care early post-hospital discharge to warrant a full sized RCT. TRIAL REGISTRATION: NCT02777047.

13.
Drugs Aging ; 39(10): 811-827, 2022 10.
Article in English | MEDLINE | ID: mdl-35976489

ABSTRACT

BACKGROUND: Chronic non-cancer pain is common among older residents of long-term care (LTC) homes and often poorly recognized and treated. With heightened concerns regarding opioid prescribing in recent years, it is important to examine the current prevalence of opioid use and its association with resident characteristics to help identify those potentially at risk of medication harms as well as suboptimal pain management. OBJECTIVES: The aims were to estimate the prevalence and correlates of opioid use among non-palliative LTC residents and explore variation in opioid prevalence and correlates across strata defined by pain frequency and intensity. METHODS: We conducted a population-based cross-sectional study of all older (aged > 65 years) LTC residents (excluding those with cancer or receiving palliative care) in Ontario, Canada during 2018-2019. Health administrative databases were linked with standardized clinical assessment data to ascertain residents' health and pain characteristics and their opioid and other medication use. Modified Poisson regression models estimated unadjusted and adjusted associations between residents' characteristics and opioid use, overall and across strata capturing pain frequency and intensity. RESULTS: Among 75,020 eligible residents (mean age 85.1 years; 70% female), the prevalence of opioid use was 18.5% and pain was 29.4%. Opioid use ranged from 12.2% for residents with no current pain to 55.7% for those with severe pain. In adjusted models, residents newly admitted to LTC (adjusted risk ratio [aRR] = 0.60, 95% confidence interval [CI] 0.57-0.62) and with moderate to severe cognitive impairment (aRR = 0.69, 95% CI 0.66-0.72) or dementia (aRR = 0.76, 95% CI 0.74-0.79) were significantly less likely to receive an opioid, whereas residents with select conditions (e.g., arthritis, aRR = 1.37, 95% CI 1.32-1.41) and concurrently using gabapentinoids (aRR = 1.80, 95% CI 1.74-1.86), benzodiazepines (aRR = 1.33, 95% CI 1.28-1.38), or antidepressants (aRR = 1.31, 95% CI 1.27-1.35) were significantly more likely to receive an opioid. The associations observed for residents newly admitted, with dementia, and concurrently using gabapentinoids, benzodiazepines, or antidepressants were largely consistent across all pain strata. CONCLUSIONS: Our findings describe resident sub-groups at potentially higher risk of adverse health outcomes in relation to both opioid use and non-use. LTC clinical and policy changes informed by research are required to ensure the appropriate recognition and management of non-cancer pain in this setting.


Subject(s)
Chronic Pain , Dementia , Aged, 80 and over , Analgesics, Opioid/adverse effects , Benzodiazepines , Chronic Pain/drug therapy , Chronic Pain/epidemiology , Cross-Sectional Studies , Dementia/drug therapy , Dementia/epidemiology , Female , Humans , Long-Term Care , Male , Nursing Homes , Ontario/epidemiology , Practice Patterns, Physicians'
14.
Biosensors (Basel) ; 12(2)2022 Jan 25.
Article in English | MEDLINE | ID: mdl-35200325

ABSTRACT

In recent years, small-molecule biosensors have become increasingly important in synthetic biology and biochemistry, with numerous new applications continuing to be developed throughout the field. For many biosensors, however, their utility is hindered by poor functionality. Here, we review the known types of mechanisms of biosensors within bacterial cells, and the types of approaches for optimizing different biosensor functional parameters. Discussed approaches for improving biosensor functionality include methods of directly engineering biosensor genes, considerations for choosing genetic reporters, approaches for tuning gene expression, and strategies for incorporating additional genetic modules.


Subject(s)
Biosensing Techniques , Bacteria , Synthetic Biology
15.
J Eval Clin Pract ; 28(6): 1027-1036, 2022 12.
Article in English | MEDLINE | ID: mdl-35142014

ABSTRACT

RATIONALE AND OBJECTIVES: Education of patients is thought to be key to high-quality oral anticoagulant (OAC) medication management. Theoretically, improving patients' knowledge should improve their self-management skills and adherence. The study's objective was to explore the opinions of healthcare providers and patients on the desired content and format of patient education on OACs, in addition to perceived barriers to high-quality patient education. METHODS: We applied qualitative descriptive methods in a focus group study on OAC management. Five focus group discussions were conducted in two health regions in Southwestern Ontario from 2017 to 2018 with 19 patients, 7 caregivers and 16 healthcare providers (physicians, nurses and pharmacists). During the focus groups, participants discussed their experiences with OAC education and made suggestions about the content and format for patient education on OACs. Transcripts were analysed using conventional content analysis. RESULTS: We identified the five themes of patient education on OAC management: content of OAC education (rationale, risk and appropriate drug administration methods), the best times for providing OAC education (time of OACs initiation along with continuing education), preferred education delivery strategies (case management targeted patient information summaries from authoritative sources such as Thrombosis Canada and video education), patient and community pharmacist engagement in OAC education, and perceived barriers to optimal patient education (patients depending too much on their healthcare providers for advice, the limited time patients spend with healthcare providers, gaps in clear communication between providers and the lack of a nationally or provincially coordinated OAC management programme). CONCLUSION: Our findings suggest that patients, caregivers and healthcare providers support the need for education on OACs, including for patients taking DOACs. Specific important content and proper education format are needed. The optimal combination of content, format, duration, timing and sources for OAC education requires further research.


Subject(s)
Anticoagulants , Patient Education as Topic , Humans , Administration, Oral , Health Personnel , Ontario
16.
PLoS One ; 16(9): e0257798, 2021.
Article in English | MEDLINE | ID: mdl-34587197

ABSTRACT

BACKGROUND: Oral anticoagulants (OACs) are very commonly prescribed for prevention of serious vascular events, but are also associated with serious medication-related bleeding. Mitigation of harm is believed to require high-quality OAC management. This study aimed to identify barriers and facilitators for optimal OAC management from the perspective of patients, caregivers and healthcare providers. METHODS: Using a qualitative descriptive study design, we conducted five focus groups, three with patients and caregivers and two with health care providers, in two health regions in Southwestern Ontario. An expert facilitator led the discussions using a semi-structured interview guide. Each session was digitally recorded, transcribed verbatim and anonymized. Transcripts were analyzed in duplicate using conventional content analysis. RESULTS: Forty-two (19 patients, 7 caregivers, and 16 providers including physicians, nurses and pharmacists) participated. More than half of the patients received OAC for the treatment of venous thromboembolism (57.9%) and the majority (94.7%) were on chronic therapy (defined as >3 years). Data analysis organized codes describing barriers and facilitators into 4 main themes-medication-related, patient-related, provider-related, and system-related. Barriers highlighted were problems with medication access due to cost, patient difficulties with adherence, knowledge and adjusting their lifestyles to OAC therapy, provider expertise, time for adequate communication amongst providers and their patients, and health care system inadequacies in supporting communications and monitoring. Facilitators identified generally addressed these barriers. CONCLUSIONS: Many barriers to optimal OAC management exist even in the era of DOACs, many of which are amenable to facilitators of improved care coordination, patient education, and adherence monitoring.


Subject(s)
Anticoagulants/administration & dosage , Caregivers/psychology , Health Personnel/psychology , Venous Thromboembolism/drug therapy , Administration, Oral , Adult , Aged , Anticoagulants/therapeutic use , Female , Focus Groups , Humans , Interviews as Topic , Male , Middle Aged , Ontario , Patient Compliance , Practice Patterns, Physicians' , Qualitative Research , Quality of Health Care
17.
Am J Ophthalmol Case Rep ; 23: 101168, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34368494

ABSTRACT

PURPOSE: To report a case of recurrent corneal ulcer caused by an oropharyngeal cavity pathogen. OBSERVATIONS: A patient presented with recurrent corneal ulcers with hypopyon. Leptotrichia species was eventually isolated from the corneal ulcer on bacterial polymerase chain reaction (PCR) after many negative bacterial culture attempts. Due to correct identification of the pathogen, it was discovered that the patient was exposing her eye to saliva. Modification of patient behavior and initiation of the appropriate antibacterial treatment resulted in resolution of recurrent episodes of active infection. CONCLUSIONS: Although Leptotrichia species are not typically ocular pathogens, they can become pathogenic in the cornea with direct transmission from the oral cavity to the eye.

19.
Nat Commun ; 12(1): 3914, 2021 06 24.
Article in English | MEDLINE | ID: mdl-34168131

ABSTRACT

Pyrrolysine (Pyl, O) exists in nature as the 22nd proteinogenic amino acid. Despite being a fundamental building block of proteins, studies of Pyl have been hindered by the difficulty and inefficiency of both its chemical and biological syntheses. Here, we improve Pyl biosynthesis via rational engineering and directed evolution of the entire biosynthetic pathway. To accommodate toxicity of Pyl biosynthetic genes in Escherichia coli, we also develop Alternating Phage Assisted Non-Continuous Evolution (Alt-PANCE) that alternates mutagenic and selective phage growths. The evolved pathway provides 32-fold improved yield of Pyl-containing reporter protein compared to the rationally engineered ancestor. Evolved PylB mutants are present at up to 4.5-fold elevated levels inside cells, and show up to 2.2-fold increased protease resistance. This study demonstrates that Alt-PANCE provides a general approach for evolving proteins exhibiting toxic side effects, and further provides an improved pathway capable of producing substantially greater quantities of Pyl-proteins in E. coli.


Subject(s)
Biosynthetic Pathways/genetics , Directed Molecular Evolution/methods , Escherichia coli/genetics , Lysine/analogs & derivatives , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Coliphages/genetics , Escherichia coli/metabolism , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Lysine/biosynthesis , Microorganisms, Genetically-Modified , Mutation , Operon , RNA, Transfer/genetics , RNA, Transfer/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Solubility
20.
Phys Ther ; 101(7)2021 07 01.
Article in English | MEDLINE | ID: mdl-33710269

ABSTRACT

OBJECTIVE: Frontal plane knee alignment plays an integral role in tibiofemoral knee osteoarthritis development and progression. Accessible methods for obtaining direct or indirect measures of knee alignment may help inform clinical decision making when specialized equipment is unavailable. The present study evaluated the concurrent validity, as well as intersession (within-rater) and interrater (within-session) reliability of smartphone inclinometry for measuring static frontal plane tibial alignment-a known proxy of frontal plane knee alignment. METHODS: Twenty healthy individuals and 38 patients with knee osteoarthritis were measured for frontal plane tibial alignment by a pair of raters using smartphone inclinometry, manual inclinometry, and 3-dimensional motion capture simultaneously. Healthy participants were measured on 2 separate days. Bland-Altman analysis, supplemented with intraclass correlation coefficient (ICC)(2,k), was used to assess concurrent validity. ICC(2,k), SEM, and minimum detectable change with 95% confidence limits (MDC95) were used to assess measurement reliability. RESULTS: Compared against motion capture, smartphone inclinometry measured frontal plane tibial alignment with a mean difference of 0.7 and 1.1 degrees (biased toward varus) for healthy participants and participants with knee osteoarthritis, respectively (ICC[2,k] ≥ 0.87). Smartphone inclinometry measurements demonstrated adequate intersession (within-rater) relative (ICC[2,k] = 0.91) and absolute (SEM = 0.7 degrees; MDC95 = 1.8 degrees) reliability, which outperformed manual inclinometry (ICC[2,k] = 0.85; SEM = 1.0 degrees; MDC95 = 2.6 degrees). Interrater (within-session) reliability of smartphone inclinometry was acceptable in both cohorts (ICC[2,k] = 0.93; SEM = 0.4 degrees to 1.2 degrees; MDC95 = 1.2 degrees to 3.2 degrees). CONCLUSION: Smartphone inclinometry is sufficiently valid and reliable for measuring frontal plane tibial alignment in healthy individuals and patients with medial tibiofemoral knee osteoarthritis. IMPACT: Smartphones are readily accessible by clinicians and researchers. Our assessment of measurement validity and reliability supports the use of smartphone inclinometry as a clinically available tool to measure frontal plane tibial alignment without medical imaging or specialized equipment.


Subject(s)
Bone Malalignment/physiopathology , Mobile Applications/statistics & numerical data , Osteoarthritis, Knee/physiopathology , Range of Motion, Articular/physiology , Smartphone/standards , Tibia/physiology , Adult , Female , Humans , Male , Reproducibility of Results , Young Adult
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