To assess the efficacy, safety, and predictors for poor responsiveness of botulinum toxin type A (BoNT-A) for chronic migraine in the adolescent and young adult population.
A retrospective analysis ...of 56 patients who received BoNT-A for chronic migraine with an age range from 13 to 21 years was performed. Of 56 patients, 34 were enrolled in the study based on the inclusion criterion. Patients who received three dosages of BoNT-A were assessed at nine months from the first injection. Variables including age, body mass index, headache intensity, frequency, character, and side effects were assessed. The patients were divided into two groups based on response to BoNT-A therapy, responders and nonresponders.
Overall among the 34 patients enrolled in the study, the average headache frequency decreased from 18.6 of 28 to 9.9 of 28 days, P value, <0.001 from baseline. There was significant decrease in the average headache intensity, 8.1 to 4.3. Of 34 patients, 25 (73%) patients responded to treatment with decrease in headache frequency by ≥ 50% from the baseline. Among the nonresponder patients, a significant number of patients (six of nine, 67%) had generalized anxiety disorder with Generalized Anxiety Disorder-7 score greater than 15 versus the responder group (six of 25, 24%, P value 0.040).
BoNT-A remains a safe and effective therapy for adolescent and young adult patients with chronic migraines at nine months of follow-up. Generalized anxiety disorder with Generalized Anxiety Disorder-7 score greater than 15 can be a major predictor of poor response to this therapy.
Previous studies have reported increased aquatic toxicity of UV-degraded nitroguanidine (NQ), but many details underlying the dynamics of NQ degradation and toxicity remain unknown. These data gaps ...represent critical barriers to assessing the environmental relevance of laboratory-generated UV-degradation results and extrapolation to environmental risk. In the present study, the toxicity of NQ increased with increasing proportional degradation of the parent compound. Specifically, while the LC50 of undegraded NQ was 1485 mg/L, the toxicity at the lowest degradation level examined (7% parent compound degraded) increased by nearly two-orders of magnitude (LC50 = 17.3 mg/L) and increased by nearly three-orders of magnitude (LC50 = 6.23 mg/L) in the highest percent NQ degradation (90%) treatment. Similar LC50 values between immediately tested and aged (8–13 days) NQ degradation products suggested the degradation product(s) causing the toxicity were stable, although concentrations of nitrite and nitrate increased after aging. Finally, experiments where NQ was degraded in natural sunlight confirmed increased toxicity in environmentally relevant D. pulex exposures; however, the two-order of magnitude increase in toxicity (LC50 = 21.3 mg/L) at 53% degradation was less than NQ degraded by a laboratory photoreactor by a similar percentage (46% degraded). Identification of principal toxic agents in the UV-degraded NQ product mixture remains a critical data gap. Mass balance calculations were generated for our experimental results and literature values revealing difficulty in accounting for all NQ degradation products. Products with suspected high potency in D. pulex were identified which require further testing including: nitrosoguanidine, nitrosourea, and hydroxylamine.
The toxicity of NQ increased with increasing UV-degradation where toxicity-inducing degradation products were stable over 1–2 weeks; increased toxicity was validated from natural-sunlight degradation of NQ, however toxicity was lower than UV-photoreactor degraded NQ; and the identity of specific toxic UV-degradation products remains elusive where carefully-designed mass-balance experiments and toxicity testing are needed to provide definitive identification.
Display omitted
•Toxicity to Daphnia pulex increased with increasing percent UV-degradation of NQ.•Sunlight-degraded NQ was less toxic: altered degradation products vs UV-photoreactor.•Carbon and nitrogen mass balance revealed missing UV-degradation products of NQ.•Aging UV-degraded NQ changed product mixture but was not cause of toxicity to D. pulex.
This study aimed to investigate the association between lifetime occupational history and risk of buccal mucosa cancer (BMC).
We utilized a multi-centric, hospital-based case-control study across ...five centres of Tata Memorial Centre, Mumbai, India. Cases included men aged 20–75-years with histological confirmed primary cancer of the buccal mucosa. Visitor controls were frequency matched to cases for age (10 years interval) and current residential zone. Study participants were interviewed face-to-face. Logistic regression was performed to estimate odds ratio (OR) and 95 % confidence intervals (CI).
Among ever employed males, we identified 1969 BMC cases and 2145 controls. We observed an increased risk of BMC in ‘Craft and Related Trades Workers’ (OR 1.37; 95 % CI 1.13–1.65), ‘Plant and Machine Operators and Assemblers’ (OR: 1.26; 95 % CI 1.01–1.56), and ‘Elementary Occupations’ (OR:1.33; 95 % CI 1.12–1.58). More specifically, the increased risk was observed for ‘Metal, Machinery and Related Trades Workers’, ‘Handicraft and Printing Workers’, ‘Drivers and Mobile Plant Operators’, and ‘Laborers in Mining, Construction, Manufacturing and Transport’.
Our findings suggest that certain occupations may be at a higher risk of BMC. Some fraction of BMC can be prevented by reducing exposure to hazardous agents used in these occupations. Further research is needed to identify which exposures are responsible for the increased risk. Moreover, tobacco control and early detection activities can be focused towards these occupations as tobacco consumption is also high in them, which may also be the reason for increased risk observed in these groups.
•We observed an increased risk of BMC in ‘Craft and Related Trades Workers’, ‘Plant and Machine Operators and Assemblers’, and ‘Elementary Occupations’.•More specifically, the increased risk was observed for ‘Metal, Machinery and Related Trades Workers’, ‘Handicraft and Printing Workers’, ‘Drivers and Mobile Plant Operators’, and ‘Labourers in Mining, Construction, Manufacturing and Transport’.•Even though we adjusted for tobacco use, the rates of chewing were high in these occupations, which may explain some of the associations that we observed.
Aim
The aim of the present study was to compare the treatment of gingival recession defects using a coronally‐advanced flap procedure with or without placental membrane.
Methods
Sixty teeth in 15 ...patients with single and multiple Miller's class I and II gingival recession defects bilaterally in the anterior and premolar region of the maxilla and mandible were divided into two groups. In group I (control), 30 recession defects were treated with coronally‐advanced flap alone using Zucchelli's technique. In group II (test), 30 recession defects were treated with coronally‐advanced flap along with placental membrane. Probing depth, height of the gingival recession (HGR), clinical attachment level (CAL), width of the gingival recession, and width of the keratinized tissue (WKT) were recorded at baseline and 3 and 6 months after the surgical procedures.
Results
There was a statistically‐significant reduction in the HGR, gain in the CAL, and WKT in group II compared to group I.
Conclusion
Coronally‐advanced flap with placental allograft provides a reliable technique for root coverage when compared to coronally‐advanced flap alone.
Although guidelines recommend in-person counseling before BRCA1/BRCA2 gene testing, genetic counseling is increasingly offered by telephone. As genomic testing becomes more common, evaluating ...alternative delivery approaches becomes increasingly salient. We tested whether telephone delivery of BRCA1/2 genetic counseling was noninferior to in-person delivery.
Participants (women age 21 to 85 years who did not have newly diagnosed or metastatic cancer and lived within a study site catchment area) were randomly assigned to usual care (UC; n = 334) or telephone counseling (TC; n = 335). UC participants received in-person pre- and post-test counseling; TC participants completed all counseling by telephone. Primary outcomes were knowledge, satisfaction, decision conflict, distress, and quality of life; secondary outcomes were equivalence of BRCA1/2 test uptake and costs of delivering TC versus UC.
TC was noninferior to UC on all primary outcomes. At 2 weeks after pretest counseling, knowledge (d = 0.03; lower bound of 97.5% CI, -0.61), perceived stress (d = -0.12; upper bound of 97.5% CI, 0.21), and satisfaction (d = -0.16; lower bound of 97.5% CI, -0.70) had group differences and confidence intervals that did not cross their 1-point noninferiority limits. Decision conflict (d = 1.1; upper bound of 97.5% CI, 3.3) and cancer distress (d = -1.6; upper bound of 97.5% CI, 0.27) did not cross their 4-point noninferiority limit. Results were comparable at 3 months. TC was not equivalent to UC on BRCA1/2 test uptake (UC, 90.1%; TC, 84.2%). TC yielded cost savings of $114 per patient.
Genetic counseling can be effectively and efficiently delivered via telephone to increase access and decrease costs.
People with kidney disease are disproportionately affected by atherosclerosis for unclear reasons. Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived mediator of kidney ...disease, levels of which are strongly associated with cardiovascular outcomes. We assessed suPAR's pathogenic involvement in atherosclerosis using epidemiologic, genetic, and experimental approaches. We found serum suPAR levels to be predictive of coronary artery calcification and cardiovascular events in 5,406 participants without known coronary disease. In a genome-wide association meta-analysis including over 25,000 individuals, we identified a missense variant in the plasminogen activator, urokinase receptor (PLAUR) gene (rs4760), confirmed experimentally to lead to higher suPAR levels. Mendelian randomization analysis in the UK Biobank using rs4760 indicated a causal association between genetically predicted suPAR levels and atherosclerotic phenotypes. In an experimental model of atherosclerosis, proprotein convertase subtilisin/kexin-9 (Pcsk9) transfection in mice overexpressing suPAR (suPARTg) led to substantially increased atherosclerotic plaques with necrotic cores and macrophage infiltration compared with those in WT mice, despite similar cholesterol levels. Prior to induction of atherosclerosis, aortas of suPARTg mice excreted higher levels of CCL2 and had higher monocyte counts compared with WT aortas. Aortic and circulating suPARTg monocytes exhibited a proinflammatory profile and enhanced chemotaxis. These findings characterize suPAR as a pathogenic factor for atherosclerosis acting at least partially through modulation of monocyte function.
There are over 3 million people in sub-Saharan Africa (SSA) aged 50 and over living with HIV. HIV and combined antiretroviral therapy (cART) exposure may accelerate the ageing in this population, and ...thus increase the prevalence of premature frailty. There is a paucity of data on the prevalence of frailty in an older HIV + population in SSA and screening and diagnostic tools to identify frailty in SSA. Patients aged ≥ 50 were recruited from a free Government HIV clinic in Tanzania. Frailty assessments were completed, using 3 diagnostic and screening tools: the Fried frailty phenotype (FFP), Clinical Frailty Scale (CFS) and Brief Frailty Instrument for Tanzania (B-FIT 2). The 145 patients recruited had a mean CD4 + of 494.84 cells/µL, 99.3% were receiving cART and 72.6% were virally suppressed. The prevalence of frailty by FFP was 2.758%. FFP frailty was significantly associated with female gender (
p
= 0.006), marital status (
p
= 0.007) and age (
p
= 0.038). Weight loss was the most common FFP domain failure. The prevalence of frailty using the B-FIT 2 and the CFS was 0.68%. The B-FIT 2 correlated with BMI (
r
= − 0.467,
p
= 0.0001) and CD4 count in females (
r
= − 0.244,
p
= 0.02). There is an absence of frailty in this population, as compared to other clinical studies. This may be due to the high standard of HIV care at this Government clinic. Undernutrition may be an important contributor to frailty. It is unclear which tool is most accurate for detecting the prevalence of frailty in this setting as levels of correlation are low.
To characterize changes in body composition following cytotoxic chemotherapy for germ cell carcinoma of the testis (GCT) and quantify associations between body composition metrics and ...chemotherapy-associated adverse events (AEs) and post-retroperitoneal lymph node dissection (RPLND) complications.
This retrospective multi-center study included 216 men with GCT treated with cytotoxic chemotherapy and/or RPLND (2005-2020). We measured body composition including skeletal muscle (SMI), visceral adipose (VAI,), subcutaneous adipose (SAI), and fat mass (FMI) indices on computed tomography. We quantified chemotherapy-associated changes in body composition and evaluated associations between body composition and incidence of grade 3 + AEs and post-RPLND complications on multivariable logistic regression analyses.
One hundred and eighty-two men received a median of 3 cycles of cisplatin-based chemotherapy. Following chemotherapy, median change in SMI was −6% (P = <.0001), while VAI, SAI, and FMI increased by +13% (P = <.0001), +11% (P = <.0001), and +6% (P = <.0001), respectively. Seventy-nine patients (43%) experienced at least one grade 3 + AE. A decrease in SMI following chemotherapy was associated with increased risk of grade 3 + AEs (P = .047). One hundred and 3 men with a median age of 28.5 years (IQR 23-35.5) underwent RPLND of whom 22 (21.3%) experienced at least 1 grade 3 + post-RPLND complication. No baseline body composition metrics were associated with post-RPLND complications.
In men with GCT of the testis, chemotherapy was associated with 6% loss of lean muscle mass and gains in adiposity. Lower skeletal muscle was associated with a higher incidence of chemotherapy-associated AEs. Body composition was not associated with the incidence of post-RPLND complications.
Documentation quality of patient-physician discussion, assessment, and intervention at the time of patient-directed discharges (elopement and 'against medical advice' discharges) is found to be poor ...in available studies and, importantly, may be a proxy for quality of care delivered. Less is known about the patient-physician interactions and documentation at the time a patient vocalizes the desire to leave early ('early warning interaction') prior to a patient-directed discharge. This was a cohort study comprising a retrospective chart review of patients leaving 'against medical advice' from an inpatient internal medicine-infectious disease service at a tertiary medical center from 01 July 2020 to 24 September 2021. Documentation quality was assessed using 11 extractable factors detailing patient-physician conversation elements from the assess, investigate, mitigate, explain, and document framework, plus related interventions pertinent to patient safety and care optimization. Descriptive statistics were mainly utilized with inferential statistics and regression models as appropriate. Fifty-two patients left against medical advice and 49 eloped; 11% had an early warning interaction. Aggregate documentation quality scores at early warning interaction (13%), 'against medical advice' discharge (42%), and at elopement (31%) were low. Half of the suggested documentation elements were recorded in no patients. The overall documentation quality was poor, suggesting the need for further training and interventions to facilitate more thorough documentation.
PDF
