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1.
Gerontol Geriatr Med ; 10: 23337214241246843, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628166

RESUMO

Background: Perturbation-based balance training (PBT) is a promising fall risk reduction method that involves inducing unexpected perturbations to balance to train participants reactive balance control. Due to the unpredictable nature of PBT, its acceptability to older adults could present a barrier to the implementation of PBT in the community. Aim/Purpose: The purpose of this study was to assess the perceived acceptability of a community-based PBT program to both older adults and healthcare professionals (HCPs). Methods: Nineteen older adults (aged 69.6 ± 6.6 years, 17 women, 2 men) and three HCPs participated in the qualitative study. Participants completed four PBT sessions facilitated in conjunction with HCPs. Interviews, based on the theoretical framework of acceptability, were conducted before and after PBT and analyzed using template analysis. Results: PBT was perceived as effective by older adults and HCPs. However, HCPs perceived the equipment cost as a substantial barrier to feasibility in the community.

2.
Sci Total Environ ; 928: 172348, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38614353

RESUMO

Many studies have characterised resistomes in river microbial communities. However, few have compared resistomes in parallel rural catchments that have few point-source inputs of antimicrobial genes (ARGs) and organisms (i.e., AMR) - catchments where one can contrast more nebulous drivers of AMR in rural rivers. Here, we used quantitative microbial profiling (QMP) to compare resistomes and microbiomes in two rural river catchments in Northern England, the Coquet and Eden in Northumberland and Cumbria, respectively, with different hydrological and geographical conditions. The Eden has higher flow rates, higher annual surface runoff, and longer periods of soil saturation, whereas the Coquet is drier and has lower flowrates. QMP analysis showed the Eden contained significantly more abundant microbes associated with soil sources, animal faeces, and wastewater than the Coquet, which had microbiomes like less polluted rivers (Wilcoxon test, p < 0.01). The Eden also had greater ARG abundances and resistome diversity (Kruskal Wallis, p < 0.05), and higher levels of potentially clinically relevant ARGs. The Eden catchment had greater and flashier runoff and more extensive agricultural land use in its middle reach, which explains higher levels of AMR in the river. Hydrological and geographic factors drive AMR in rural rivers, which must be considered in environmental monitoring programmes.

3.
Prev Vet Med ; 227: 106195, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38615535

RESUMO

Milk recording is a critical tool in dairy farming, providing individual cow information. When used effectively, this data contributes to on-farm productivity, herd health management decisions and supports prudent veterinary prescribing of antimicrobials. Although an industry and government priority, uptake has been relatively slow in Ireland. This multi-methods, three-part study aimed to gain a comprehensive understanding of the benefits to farm performance, and factors driving uptake of milk recording on Irish dairy farms. It involved an economic analysis of N=516 farms from 2008-2019, a workshop with N=26 stakeholders and an online survey of N=197 non-milk-recording farmers. Quantitative and qualitative data were analysed using econometric models and thematic analysis respectively. Results were synthesised using the COM-B model to gain a deeper understanding of what drives the target behaviour. The study revealed that agricultural education, farm location, farm specialisation in dairy and membership of a farmer discussion group were the main factors influencing uptake of milk recording. Milk recording was associated with a €39.04/cow increase in gross margin, a 177.58 litres/cow increase in milk yield and a reduction of 13,450 cells/ml in bulk milk tank somatic cell count readings. Infrastructural constraints, cost, lack of benefits and workload were the most reported perceived barriers to milk recording by farmers. The Behaviour Change Wheel illustrates how to utilise findings and systematically develop future interventions to increase milk recording uptake. This study highlights the importance of a multi-methods approach to agricultural technology adoption and the need for evidence-based methodology when developing behaviour change interventions.

4.
Beilstein J Org Chem ; 20: 830-840, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655556

RESUMO

Linear nitramines (R-N(R')NO2; R' = H or alkyl) are toxic compounds, some with environmental relevance, while others are rare natural product nitramines. One of these natural product nitramines is N-nitroglycine (NNG), which is produced by some Streptomyces strains and exhibits antibiotic activity towards Gram-negative bacteria. An NNG degrading heme enzyme, called NnlA, has recently been discovered in the genome of Variovorax sp. strain JS1663 (Vs NnlA). Evidence is presented that NnlA and therefore, NNG degradation activity is widespread. To achieve this objective, we characterized and tested the NNG degradation activity of five Vs NnlA homologs originating from bacteria spanning several classes and isolated from geographically distinct locations. E. coli transformants containing all five homologs converted NNG to nitrite. Four of these five homologs were isolated and characterized. Each isolated homolog exhibited similar oligomerization and heme occupancy as Vs NnlA. Reduction of this heme was shown to be required for NnlA activity in each homolog, and each homolog degraded NNG to glyoxylate, NO2- and NH4+ in accordance with observations of Vs NnlA. It was also shown that NnlA cannot degrade the NNG analog 2-nitroaminoethanol. The combined data strongly suggest that NnlA enzymes specifically degrade NNG and are found in diverse bacteria and environments. These results imply that NNG is also produced in diverse environments and NnlA may act as a detoxification enzyme to protect bacteria from exposure to NNG.

5.
Dis Esophagus ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580314

RESUMO

Esophagectomy and lymphadenectomy have been the standard of care for patients at high risk (HR) of lymph node metastasis following a diagnosis of early esophageal adenocarcinoma (OAC) after endoscopic resection (ER). However, recent cohorts suggest lymph node metastasis risk is lower than initially estimated, suggesting organ preservation with close endoscopic follow-up is a viable option. We report on the 3- and 5-year risk of lymph node/distant metastasis among patients diagnosed with early HR-T1 OAC undergoing endoscopic follow-up. Patients diagnosed with HR-T1a or T1b OAC following ER at a tertiary referral center were identified and retrospectively analyzed from clinical records between 2010 and 2021. Patients were included if they underwent endoscopic follow-up after resection and were divided into HR-T1a, low risk (LR)-T1b and HR-T1b cohorts. After ER, 47 patients underwent endoscopic follow-up for early HR OAC. In total, 39 patients had an R0 resection with a combined 3- and 5-year risk of LN/distant metastasis of 6.9% [95% confidence interval (CI): 1.8-25] and 10.9% (95% CI, 3.6-30.2%), respectively. There was no significant difference when stratifying by histopathological subtype (P = 0.64). Among those without persistent luminal disease on follow-up, the 5-year risk was 4.1% (95% CI, 0.6-26.1). Two patients died secondary to OAC with an all-cause 5-year survival of 57.5% (95% CI, 39.5-71.9). The overall risk of LN/distant metastasis for early HR T1 OAC was lower than historically reported. Endoscopic surveillance can be a reasonable approach in highly selected patients with an R0 resection and complete luminal eradication, but clear, evidence-based surveillance guidelines are needed.

6.
Case Rep Ophthalmol ; 15(1): 273-278, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549912

RESUMO

Introduction: This case report describes a rare case of fungal keratitis following femtoLASIK. Despite targetted antifungal therapy, this case necessitated an innovative surgical approach to manage an unexpected corneal perforation. Case Presentation: A 35-year-old male presented 3 weeks post-femtoLASIK for myopic astigmatism with discomfort and reduced vision in his right eye. He was diagnosed with fungal keratitis surgery caused by Purpureocillium lilacinum and was treated with a myriad of therapy. Unfortunately, the patient developed corneal perforation during flap lift and flap bed irrigation. An innovative approach involving a tectonic autograft using a viable LASIK flap, followed by prompt penetrating keratoplasty, was utilised. Conclusion: This technique was effective and able to mitigate the progression to an open globe.

7.
Hand (N Y) ; : 15589447241235339, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491777

RESUMO

BACKGROUND: Intramedullary screw fixation of phalangeal and metacarpal fractures has gained popularity as a method of providing rigid internal fixation with minimum tendon disturbance, allowing early mobilization and rehabilitation. Despite this, the literature on outcomes using this technique is limited. Thus, the aim of this study was to assess the short-term to medium-term outcomes of intramedullary screw fixation for proximal phalangeal fracture fixation in an Australian setting. METHODS: A retrospective analysis of consecutive patients with a fracture(s) of the proximal phalanx fixated using intramedullary screws between January 2020 and March 2023 was conducted via telehealth. RESULTS: Forty-six phalangeal fractures from 37 patients were included in this study. Mean Quick Disabilities of the Arm, Shoulder, and Hand score of 6.2 (range: 0-61.4, median: 0), mean pain visual analogue scale score of 1.8 (range: 1-7, median: 1), and mean total active motion of 231° (range: 132-282) were noted. A total of 4.4% of fractures sustained a major complication, and 94.6% of patients reported willingness to undergo intramedullary screw fixation again. CONCLUSION: This study concurs with the prior literature that intramedullary screw fixation is a safe and effective method of stabilizing extra-articular proximal phalangeal fractures in the short to medium term. Superior clinical outcomes, as well as cost-effectiveness and time-effectiveness, render it a viable alternative to plate fixation in this setting.

8.
J Biomech ; 166: 112062, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38555779

RESUMO

The purpose of this study was to determine the material stresses experienced in the femoral neck during the stepping phase of recovery from a forward loss of balance achieved both using release from a static forward lean and rapid treadmill accelerations in 8 older adults. A scalable musculoskeletal model with 23 degrees of freedom and 92 force actuators was used to calculate joint reaction forces. A finite element model of the femur used joint reaction forces calculated by the musculoskeletal model to calculate the material stresses during stepping. Balance recovery from a static forward lean angle had a greater joint contact force and greater maximum tensile stress than a recovery from treadmill induced perturbations both before and after a training session. Hip joint contact loads were found to be large in magnitude, however, all stresses experienced by the bone are less than critical yield stresses for trabecular bone. We suggest that stepping balance recovery is safe for older adults with no obvious loss of bone density or strength and that analyses such as finite element analysis are necessary to understand stresses in the material at the joint level.


Assuntos
Fêmur , Extremidade Inferior , Análise de Elementos Finitos , Articulação do Quadril , Colo do Fêmur , Estresse Mecânico
9.
Mol Psychiatry ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491344

RESUMO

Persons diagnosed with schizophrenia (SCZ) or bipolar I disorder (BPI) are at high risk for self-injurious behavior, suicidal ideation, and suicidal behaviors (SB). Characterizing associations between diagnosed health problems, prior pharmacological treatments, and polygenic scores (PGS) has potential to inform risk stratification. We examined self-reported SB and ideation using the Columbia Suicide Severity Rating Scale (C-SSRS) among 3,942 SCZ and 5,414 BPI patients receiving care within the Veterans Health Administration (VHA). These cross-sectional data were integrated with electronic health records (EHRs), and compared across lifetime diagnoses, treatment histories, follow-up screenings, and mortality data. PGS were constructed using available genomic data for related traits. Genome-wide association studies were performed to identify and prioritize specific loci. Only 20% of the veterans who reported SB had a corroborating ICD-9/10 EHR code. Among those without prior SB, more than 20% reported new-onset SB at follow-up. SB were associated with a range of additional clinical diagnoses, and with treatment with specific classes of psychotropic medications (e.g., antidepressants, antipsychotics, etc.). PGS for externalizing behaviors, smoking initiation, suicide attempt, and major depressive disorder were associated with SB. The GWAS for SB yielded no significant loci. Among individuals with a diagnosed mental illness, self-reported SB were strongly associated with clinical variables across several EHR domains. Analyses point to sequelae of substance-related and psychiatric comorbidities as strong correlates of prior and subsequent SB. Nonetheless, past SB was frequently not documented in health records, underscoring the value of regular screening with direct, in-person assessments, especially among high-risk individuals.

10.
Pharmacoepidemiol Drug Saf ; 33(3): e5772, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38449020

RESUMO

PURPOSE: In the United States, the National Death Index (NDI) is the most complete source of death information, while epidemiologic studies with mortality outcomes often rely on U.S. Medicare data for outcome ascertainment. The purpose of this study was to assess the agreement of death information between the Centers for Medicare & Medicaid Services (CMS) Medicare enrolment data and NDI. METHODS: Using Medicare and NDI data from 1999 through 2016, we identified Medicare beneficiaries who were reported dead in the CMS Medicare enrolment database (EDB) and Common Medicare Environment (CME), linked these beneficiaries to the NDI using CMS Health Insurance Claim number, and compared death dates between the two data sources. To assess agreement between our data sources, we calculated kappa scores; where a kappa of 1 indicates perfect agreement and a kappa of 0 indicates agreement equivalent to chance. We also examined CMS to NDI linkage and death date matching for stability over time. RESULTS: Of the 36 785 640, Medicare beneficiaries reported dead in CMS enrollment data from 1999 to 2016, 97.5% were linked to the NDI. A kappa score of 0.98 showed a near perfect agreement between NDI and CMS reported deaths. The percentage of linked cases exactly matching on death dates increased from 94.8% in 1999 to 99.4% in 2016. CONCLUSIONS: Our findings suggest strong concordance between death dates as recorded by CMS enrollment data and the NDI in the entire Medicare population.


Assuntos
Medicare , Idoso , Humanos , Estados Unidos/epidemiologia , Centers for Medicare and Medicaid Services, U.S. , Bases de Dados Factuais
11.
Gastroenterology ; 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38373637
12.
Pharmacoepidemiol Drug Saf ; 33(2): e5749, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38362655

RESUMO

PURPOSE: Pharmacy chains can differ with respect to the characteristics of their patient populations as well as their nonprescription products, services, and practices, and thus may serve as a surrogate for potential unmeasured confounding in observational studies of prescription drugs. This study evaluates whether a single-source drug can have different patient outcomes based on the dispensing pharmacy chain. METHODS: Separate analyses for two anticoagulant drugs, rivaroxaban and apixaban, were conducted using Medicare Fee-for-Service claims evaluating the association between dispensing pharmacy chain and outcomes of acute myocardial infarction, ischemic stroke, intracranial hemorrhage, gastrointestinal (GI) bleeding, all-cause mortality, and major GI bleeding. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates across pharmacy chain cohorts, and outcome association was assessed with a Cox Proportional Hazards model. RESULTS: We observed no differences in outcomes across pharmacy chains for apixaban recipients. Rivaroxaban recipients from pharmacy chain C, however, had lower rates of GI bleeding (adjusted HR 0.83; 95% CI 0.69-1.00) and ischemic stroke (adjusted HR 0.57; 95% CI 0.38-0.87) as compared to chain A in primary analyses with a 3-day grace period. The results moved closer to the null when 14- and 30-day grace periods were implemented. CONCLUSIONS: These results suggest that dispensing pharmacy chains may have the potential to act as a confounder of associations between drug exposure and outcome in some observational studies. Additional studies of potential confounding by pharmacy chain are needed. Further evaluation of potential pharmacy chain effects on safe use would be of value.


Assuntos
Fibrilação Atrial , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Humanos , Estados Unidos , Anticoagulantes/efeitos adversos , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/complicações , Dabigatrana/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Medicare , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , AVC Isquêmico/tratamento farmacológico , Piridonas/uso terapêutico , Estudos Retrospectivos
13.
Gut ; 73(3): 407-441, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38383142

RESUMO

At the end of the last century, a far-sighted 'working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle.The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.


Assuntos
Gastrite , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/patologia , Gastrite/diagnóstico , Gastrite/epidemiologia , Gastrite/patologia , Endoscopia , Neoplasias Gástricas/patologia , Mucosa Gástrica/patologia
14.
Diagnostics (Basel) ; 14(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38337817

RESUMO

Endoscopy is the gold standard for the diagnosis of cancers and cancer precursors in the oesophagus and stomach. Early detection of upper GI cancers requires high-quality endoscopy and awareness of the subtle features these lesions carry. Endoscopists performing surveillance of high-risk patients including those with Barrett's oesophagus, previous squamous neoplasia or chronic atrophic gastritis should be familiar with endoscopic features, classification systems and sampling techniques to maximise the detection of early cancer. In this article, we review the current approach to diagnosis of these conditions and the latest advanced imaging and diagnostic techniques.

15.
Helicobacter ; 29(1): e13061, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38411303

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) is strongly associated with peptic ulcer disease and gastric cancer. We evaluated two triple therapy regimens comprising esomeprazole, high dose bismuth, and different doses of amoxicillin for first-line H. pylori eradication. MATERIALS AND METHODS: Two hundred patients with dyspepsia and naive H. pylori infection were randomly assigned into two groups (n = 100). Both groups were treated for 14 days similarly with esomeprazole (40 mg, twice daily) and bismuth subcitrate (240 mg, three times daily), but the dose of amoxicillin was varied between Groups A (750 mg) and B (1000 mg) three times daily. Treatment compliance and side effect were evaluated following the therapies and after 8 weeks, a negative test of stool H. pylori antigen confirmed eradication. RESULTS: The two groups were comparable with respect to sex and age. According to intention to treat analysis, eradication rates were 80% (95% CI: 77.2%-82.8%) and 90% (95% CI: 84.1%-95.9%) in A and B groups, respectively (p = 0.22). Per-protocol eradication rates were 87% (95% CI: 80.4%-93.6%) and 92.8% (95% CI: 87.7%-97.9%), respectively (p = 0.23). Severe adverse effects were 3% and 2%, respectively (p = 0.34). CONCLUSION: High dose esomeprazole, amoxicillin and bismuth achieved 92.8% cure rates per protocol in a country with a high background rate of resistance. Additional studies are needed to ascertain whether this therapy can be further improved. Until then, it can be recommended as a first-line H. pylori eradication in north of Iran.


Assuntos
Amoxicilina , Esomeprazol , Infecções por Helicobacter , Helicobacter pylori , Compostos Organometálicos , Humanos , Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Quimioterapia Combinada/efeitos adversos , Esomeprazol/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Irã (Geográfico) , Compostos Organometálicos/administração & dosagem , Projetos Piloto , Masculino , Feminino
16.
J Hand Surg Am ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38310510

RESUMO

PURPOSE: This study aimed to evaluate short- and medium-term clinical and patient-reported outcomes of intramedullary compression screw fixation for extra-articular middle phalangeal fractures. METHODS: A retrospective study was performed on a series of 20 patients (with a total of 23 fractured digits) who underwent fixation of middle phalangeal fractures between January 2020 and March 2023. The results from this cohort were compared against those for plate and K-wire fixation in the literature. RESULTS: Total active motion was 246°; Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score was 4.9; verbal numerical pain score was 1.1 of 10; mean time for return to work was 62.5 days; and a single complication was noted in the entire cohort. CONCLUSION: Intramedullary screw fixation is a viable option in the treatment of extra-articular middle phalangeal fractures. It offers a favorable postoperative range of motion, good duration for return to function, excellent rates of complication, and low pain scores. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

17.
J Hand Surg Am ; 49(3): 247-252, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38206273

RESUMO

PURPOSE: To provide a biomechanical comparison of dorsal plating, lateral plating and intramedullary screw [IMS] fixation for extra-articular proximal phalangeal fractures. METHODS: Midshaft osteotomies were performed on 36 cadaveric proximal phalanges. The phalanges were fixed by dorsal plating, lateral plating or IMS fixation, and subjected to a four-point bending force. Force was applied to achieve displacement of 1 mm/s, until construct failure or to a maximum of 10 mm of displacement. Clinical failure was defined as 2 mm of displacement, and force required to result in 1 mm and 2 mm of displacement was recorded, as was mode of failure. RESULTS: Dorsal plating [127.5 N ± 52.6; 46.51-229.17] and lateral plating [77.1 N ± 25.1; 48.3-113.8] required significantly greater force to achieve 1 mm of displacement when compared to IMS [41.2 N ± 12.4; 20.6-62.3]. Dorsal plating [339.2 N ± 91.8; 158.5-538.6] required significantly greater force than lateral plating [154.5 N ± 33.8; 99.0 -204.4] and intramedullary screw fixation [110.0 ± 38.6; 51.1-189.3] to result in 2 mm of displacement. Lateral and dorsal plating constructs failed through plate bending, screw cut-out or plate failure, whilst IMS failed via implant deformity. All three constructs required greater force to result in even 1 mm of displacement than what is likely subjected through rehabilitation via active motion. CONCLUSIONS: Lateral plating and IMS fixation offer sufficient stiffness to withstand the likely forces subjected via early active motion without displacement. CLINICAL RELEVANCE: Dorsal plating required significantly greater force than lateral plating and intramedullary screw fixation to achieve 1 mm of displacement when used in extra-articular proximal phalangeal fractures in an in vitro setting. However, all three modalities confer enough stability to likely withstand the forces associated with active range of motion.


Assuntos
Fraturas Ósseas , Humanos , Fenômenos Biomecânicos , Cadáver , Fraturas Ósseas/cirurgia , Fixação Interna de Fraturas , Parafusos Ósseos , Placas Ósseas
18.
JAMA ; 331(6): 491-499, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38241060

RESUMO

Importance: Dialysis-dependent patients experience high rates of morbidity from fractures, yet little evidence is available on optimal treatment strategies. Chronic kidney disease-mineral and bone disorder is nearly universal in dialysis-dependent patients, complicating diagnosis and treatment of skeletal fragility. Objective: To examine the incidence and comparative risk of severe hypocalcemia with denosumab compared with oral bisphosphonates among dialysis-dependent patients treated for osteoporosis. Design, Setting, and Participants: Retrospective cohort study of female dialysis-dependent Medicare patients aged 65 years or older who initiated treatment with denosumab or oral bisphosphonates from 2013 to 2020. Clinical performance measures including monthly serum calcium were obtained through linkage to the Consolidated Renal Operations in a Web-Enabled Network database. Exposures: Denosumab, 60 mg, or oral bisphosphonates. Main Outcomes and Measures: Severe hypocalcemia was defined as total albumin-corrected serum calcium below 7.5 mg/dL (1.88 mmol/L) or a primary hospital or emergency department hypocalcemia diagnosis (emergent care). Very severe hypocalcemia (serum calcium below 6.5 mg/dL [1.63 mmol/L] or emergent care) was also assessed. Inverse probability of treatment-weighted cumulative incidence, weighted risk differences, and weighted risk ratios were calculated during the first 12 treatment weeks. Results: In the unweighted cohorts, 607 of 1523 denosumab-treated patients and 23 of 1281 oral bisphosphonate-treated patients developed severe hypocalcemia. The 12-week weighted cumulative incidence of severe hypocalcemia was 41.1% with denosumab vs 2.0% with oral bisphosphonates (weighted risk difference, 39.1% [95% CI, 36.3%-41.9%]; weighted risk ratio, 20.7 [95% CI, 13.2-41.2]). The 12-week weighted cumulative incidence of very severe hypocalcemia was also increased with denosumab (10.9%) vs oral bisphosphonates (0.4%) (weighted risk difference, 10.5% [95% CI, 8.8%-12.0%]; weighted risk ratio, 26.4 [95% CI, 9.7-449.5]). Conclusions and Relevance: Denosumab was associated with a markedly higher incidence of severe and very severe hypocalcemia in female dialysis-dependent patients aged 65 years or older compared with oral bisphosphonates. Given the complexity of diagnosing the underlying bone pathophysiology in dialysis-dependent patients, the high risk posed by denosumab in this population, and the complex strategies required to monitor and treat severe hypocalcemia, denosumab should be administered after careful patient selection and with plans for frequent monitoring.


Assuntos
Conservadores da Densidade Óssea , Hipocalcemia , Osteoporose , Estados Unidos , Humanos , Idoso , Feminino , Hipocalcemia/induzido quimicamente , Hipocalcemia/sangue , Denosumab/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Cálcio/uso terapêutico , Estudos Retrospectivos , Diálise Renal , Medicare , Osteoporose/tratamento farmacológico , Difosfonatos/efeitos adversos
19.
J Water Health ; 22(1): 64-76, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38295073

RESUMO

Prisons are high-risk settings for infectious disease transmission, due to their enclosed and semi-enclosed environments. The proximity between prisoners and staff, and the diversity of prisons reduces the effectiveness of non-pharmaceutical interventions, such as social distancing. Therefore, alternative health monitoring methods, such as wastewater-based epidemiology (WBE), are needed to track pathogens, including SARS-CoV-2. This pilot study assessed WBE to quantify SARS-CoV-2 prevalence in prison wastewater to determine its utility within a health protection system for residents. The study analysed 266 samples from six prisons in England over a 12-week period for nucleoprotein 1 (N1 gene) and envelope protein (E gene) using quantitative reverse transcriptase-polymerase chain reaction. Both gene assays successfully detected SARS-CoV-2 fragments in wastewater samples, with both genes significantly correlating with COVID-19 case numbers across the prisons (p < 0.01). However, in 25% of the SARS-positive samples, only one gene target was detected, suggesting that both genes be used to reduce false-negative results. No significant differences were observed between 14- and 2-h composite samples, although 2-h samples showed greater signal variance. Population normalisation did not improve correlations between the N1 and E genes and COVID-19 case data. Overall, WBE shows considerable promise for health protection in prison settings.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Prisões , Águas Residuárias , COVID-19/epidemiologia , Projetos Piloto , Reino Unido/epidemiologia
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