Substance use and mental health factors associated with self-reported higher risk cannabis use among people with HIV screened in primary care.

Background: While cannabis use is prevalent among people with HIV (PWH), factors associated with higher-risk use require further study. We examined factors associated with indicators risk for cannabis use disorder (CUD) among PWH who used cannabis. Methods: Participants included adult (≥18 years old) PWH from 3 HIV primary care clinics in Kaiser Permanente Northern California who reported past three-month cannabis use through the computerized Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) screening. Primary outcome was TAPS cannabis score (range 1-3), categorized as any use (1) and higher risk for CUD (≥2). Measures included sociodemographics (age, sex, race, neighborhood deprivation index [NDI]), Charlson Comorbidity Index (CCI), HIV RNA, CD4 cell counts, higher risk tobacco use (TAPS tobacco score≥2), depression, and anxiety symptoms. Unadjusted and multivariable logistic regression examined factors associated with higher risk for CUD. Results: Of the complete sample (N=978; 94.1% Male; 58.3% White; Age Mode=51-60), 35.8% reported higher risk for CUD. Unadjusted models indicated younger age, Black race, higher CCI, depression, anxiety, and higher risk tobacco use were associated with higher risk, while only Black race (OR=1.84, 95% CI[1.29, 2.63]), anxiety (OR=1.91, 95% CI[1.22, 2.98]), and higher risk tobacco use (OR=2.27, 95% CI[1.47, 3.51]) remained significant in the multivariable model. Conclusions: Black race, anxiety and tobacco use, but not HIV clinical markers, were associated with higher risk for CUD among PWH. Clinical efforts to screen and provide interventions for preventing CUD alongside anxiety and tobacco use among PWH should be evaluated.

UK student midwives' theoretical knowledge, confidence, and experience of intermittent auscultation of the fetal heart rate during labour: An online cross-sectional survey.

AIM: This study aimed to explore student midwives' theoretical knowledge of intrapartum intermittent auscultation, their confidence in, and their experience of this mode of fetal monitoring. DESIGN AND SETTING: An online cross-section survey with closed and open questions. Descriptive statistics were used to analyse participants' intermittent auscultation knowledge, confidence, and experience. Reflexive thematic analysis was used to identify patterns within the free text about participants' experiences. PARTICIPANTS: Undergraduate midwifery students (n = 303) from Nursing and Midwifery Council-approved educational institutions within the United Kingdom. FINDINGS: Most participants demonstrated good theoretical knowledge. They had witnessed the technique being used in clinical practice, and when performed, the practice was reported to be in line with national guidance. In closed questions, participants reported feeling confident in their intermittent auscultation skills; however, these data contrasted with free-text responses. CONCLUSION: This cross-sectional survey found that student midwives possess adequate knowledge of intermittent auscultation. However, reflecting individual clinical experiences, their confidence in their ability to perform intermittent auscultation varied. A lack of opportunity to practice intermittent auscultation, organisational culture, and midwives' preferences have caused student midwives to question their capabilities with this essential clinical skill, leaving some with doubt about their competency close to registration.

Clinical and technical factors in endoscopic skull base surgery associated with reconstructive success.

BACKGROUND: In this study, we identified key discrete clinical and technical factors that may correlate with primary reconstructive success in endoscopic skull base surgery (ESBS). METHODS: ESBS cases with intraoperative cerebrospinal fluid (CSF) leaks at four tertiary academic rhinology programs were retrospectively reviewed. Logistic regression identified factors associated with surgical outcomes by defect subsite (anterior cranial fossa [ACF], suprasellar [SS], purely sellar, posterior cranial fossa [PCF]). RESULTS: Of 706 patients (50.4% female), 61.9% had pituitary adenomas, 73.4% had sellar or SS defects, and 20.5% had high-flow intraoperative CSF leaks. The postoperative CSF leak rate was 7.8%. Larger defect size predicted ACF postoperative leaks; use of rigid reconstruction and older age protected against sellar postoperative leaks; and use of dural sealants compared to fibrin glue protected against PCF postoperative leaks. SS postoperative leaks occurred less frequently with the use of dural onlay. Body-mass index, intraoperative CSF leak flow rate, and the use of lumbar drain were not significantly associated with postoperative CSF leak. Meningitis was associated with larger tumors in ACF defects, nondissolvable nasal packing in SS defects, and high-flow intraoperative leaks in PCF defects. Sinus infections were more common in sellar defects with synthetic grafts and nondissolvable nasal packing. CONCLUSIONS: Depending on defect subsite, reconstructive success following ESBS may be influenced by factors, such as age, defect size, and the use of rigid reconstruction, dural onlay, and tissue sealants.

The 2023 Orthopedic Research Society's international consensus meeting on musculoskeletal infection: Summary from the in vitro section.

Antimicrobial strategies for musculoskeletal infections are typically first developed with in vitro models. The In Vitro Section of the 2023 Orthopedic Research Society Musculoskeletal Infection international consensus meeting (ICM) probed our state of knowledge of in vitro systems with respect to bacteria and biofilm phenotype, standards, in vitro activity, and the ability to predict in vivo efficacy. A subset of ICM delegates performed systematic reviews on 15 questions and made recommendations and assessment of the level of evidence that were then voted on by 72 ICM delegates. Here, we report recommendations and rationale from the reviews and the results of the internet vote. Only two questions received a ≥90% consensus vote, emphasizing the disparate approaches and lack of established consensus for in vitro modeling and interpretation of results. Comments on knowledge gaps and the need for further research on these critical MSKI questions are included.

Oral health messages for Australia: A national consensus statement.

BACKGROUND: Oral health promotion initiatives must be evidence-based and consistent with broader health messaging. The Oral Health Messages for the Australian Public were first produced in 2009 and sought to enable a focused, and strategic approach to oral health promotion in Australia. As the evidence base and needs of the Australian population have since changed, this consensus statement was updated in 2022-2023. METHODS: The process of updating the messages consisted of 3 phases (preparatory phase, the Delphi technique, final revision phase). The preparatory phase included public and expert consultation, an umbrella review of published scientific literature and review of available recommendations, policies and guidelines. The Delphi technique used in this study was guided by Guidance on Conducting and REporting DElphi Studies (CREDES) and included 2 voting rounds. There were 70 experts in round 1 and 60 experts in round 2. Delphi participants comprised of experts from a variety of fields to ensure diversity and inclusion, balance expertise and maximize stakeholder representation. Consensus was defined as 75% agreement. RESULTS: A total of 11 messages were included in the 2022 update of Oral Health Messages for Australia. CONCLUSION: The updated oral health messages will support oral health promotion policy and activity at both individual and population level to improve the oral health of Australians.

Preoperative, technical, and postoperative considerations for skull base reconstruction: a practical review of critical concepts.

Despite widespread adoption and advances in endoscopic skull base surgery, with expanding indications and the ability to effectively treat larger and more complex pathologies, skull base reconstruction following tumor resection and prevention of cerebrospinal fluid leak remains a challenge for even the most seasoned of surgical teams. Mounting evidence in all areas have pushed our understanding of skull base reconstruction principles forward. In this narrative review, we summarize critical concepts and provide practical but comprehensive guiding principles on preoperative, intraoperative/technical, and postoperative management principles related to optimizing skull base reconstructive success. The goal is to provide an informative resource for skull base surgeons (both otolaryngologists and neurosurgeons) to reference regarding state-of-the-art evidence surrounding this ever-evolving topic.

Re-evaluation of the low-dose dexamethasone suppression test in dogs.

OBJECTIVES: This study aims to re-evaluate the low-dose dexamethasone suppression test 8-hour cortisol cut-point for the diagnosis of hypercortisolism in dogs using a solid-phase, competitive chemiluminescent enzyme immunoassay. MATERIALS AND METHODS: Twenty-seven client-owned dogs with naturally occurring hypercortisolism and 30 healthy control dogs were prospectively recruited. Performance of the low-dose dexamethasone suppression test was assessed using sensitivity, specificity and a receiver operating characteristic curve compared to a clinical diagnosis of hypercortisolism including response to treatment. RESULTS: Twenty-four dogs were diagnosed with pituitary-dependent hypercortisolism and three with adrenal-dependent hypercortisolism. In 30 healthy control dogs, 8-hour post-dexamethasone cortisol concentrations ranged from 5.5 to 39 nmol/L. A receiver operating characteristic curve curve constructed from the 8-hour post-dexamethasone cortisol concentrations of hypercortisolism and control dogs demonstrated that the most discriminatory cut-point was more than 39 nmol/L with sensitivity of 85.2% (95% confidence interval, 67.5% to 94.1%) and specificity of 100% (95% confidence interval, 88.7% to 100.0%) and an area under the curve of 0.963. CLINICAL SIGNIFICANCE: The optimal cut-point of more than 36 nmol/L proposed by this study is similar to the currently accepted 8-hour cortisol concentration cut-point for diagnosing hypercortisolism when using a solid-phase, competitive chemiluminescent enzyme immunoassay.

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer.

BACKGROUND: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. PATIENTS AND METHODS: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. RESULTS: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. CONCLUSION: With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals.

Discordance of chronic rhinosinusitis disease control between EPOS guidelines and patient perspectives identifies utility of patient-rated control assessment.

BACKGROUND: The objective of this study was to determine concordance of patient-reported chronic rhinosinusitis (CRS) disease control with CRS disease control assessed according to European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) criteria. METHODS: In 421 participants, CRS disease control was determined using EPOS criteria which include the burden of 5 symptoms measured on a binary scale, use of rescue medications in the prior 6 months and presence of diseased mucosa on nasal endoscopy. Symptom severity was also assessed using a visual analogue scale (VAS). Participants rated their CRS disease control as "controlled","partly controlled" or "uncontrolled". RESULTS: Patient-reported and EPOS-based CRS disease control ratings agreed for 49.6% of participants. Amongst cases of disagreement, EPOS guidelines assessed worse CRS disease control relative to 92.9% of patients. Facial pain/pressure and impaired sense of smell distinctly associated with patient agreement with EPOS guidelines on having "uncontrolled" CRS. Higher VAS symptom scores were associated with worse patient-reported CRS disease control (i.e., agreeing with EPOS guidelines). Removal of the nasal endoscopy criterion improved agreement between patients' and EPOS control assessments, and replacement of this criterion with patient-reported control further aligned EPOS guidelines with patient perspectives. CONCLUSIONS: EPOS guidelines regularly assess worse CRS control than assessed by patients. The lack of more gradated symptom severity criteria and inclusion of nasal endoscopy may contribute to discordance of EPOS guidelines with patient-reported CRS control. Replacement of nasal endoscopy findings with a measure of patient-reported CRS disease control better aligns EPOS CRS disease control guidelines with patients' perspectives.

High-Throughput Biofilm Assay to Investigate Bacterial Interactions with Surface Topographies.

The specific topography of biomaterials plays an important role in their biological interactions with cells and thus the safety of medical implants. Antifouling materials can be engineered with topographic features to repel microbes. Meanwhile, undesired topographies of implants can cause complications such as breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). While the cause of BIA-ALCL is not well understood, it is speculated that textured surfaces are prone to bacterial biofilm formation as a contributing factor. To guide the design of safer biomaterials and implants, quantitative screening approaches are needed to assess bacterial adhesion to different topographic surface features. Here we report the development of a high-throughput microplate biofilm assay for such screening. The assay was used to test a library of polydimethylsiloxane (PDMS) textures composed of varying sizes of recessive features and distances between features including those in the range of breast implant textures. Outliers of patterns prone to bacterial adhesion were further studied using real-time confocal fluorescence microscopy. The results from these analyses revealed that surface area itself is a poor predictor for adhesion, while the size and spacing of topographic features play an important role. This high-throughput biofilm assay can be applied to studying bacteria-material interactions and rational development of materials that inhibit bacterial colonization.

Putative mechanobiological impact of surface texture on cell activity around soft-tissue implants undergoing micromotion.

Recent reports of adverse health effects (e.g., capsular contracture, lymphoma) linked to the absence or presence of texture on soft-tissue implants (e.g., breast implants) suggest surface topography may have pathological impact(s). We propose that surface texture influences the transfer of displacements, experienced by an implant undergoing micromotion, to surrounding interfacial extracellular matrix, which in turn impacts the activity of the resident cells and is based on degree of tissue integration. We hypothesize that transfer of displacements due to micromotion promotes interstitial fluid movement that imposes hydrodynamic stresses (pressures, shear stresses) on cells residing in the interfacial tissues and impacts their activity. To address this, we developed a computer simulation to approximate hydrodynamic stresses in the interstitial environment of saturated poroelastic tissues (model soft-tissue implantation sites) generated from oscillatory implant micromotion as a function of the magnitude of translational displacement, direction of motion, degree of tissue integration, and surface roughness of the implant. Highly integrated implants were predicted to generate the highest fluid shear stresses within model tissues, with oscillatory fluid shear stresses up to 80 dyn/cm2 for a 20-µm displacement. Notably, application of oscillatory 80 dyn/cm2 shear stress to cultured human fibroblasts elicited cell death after 20 h compared to cells maintained under static conditions or exposed to 80 dyn/cm2 steady, unidirectional shear. These results indicate that oscillatory interstitial fluid stresses generated by micromotion of an integrated implant may influence the activity of the surrounding cells and play a role in the body's fibrotic response to textured soft-tissue implants.

Disease control in chronic rhinosinusitis: a qualitative study of patient perspectives.

BACKGROUND: The definition of disease control in chronic rhinosinusitis (CRS) is an active area of study. However, investigations have not engaged CRS patients in how they think about disease control. This study seeks to understand the patient perspective on CRS disease control. METHODS: Qualitative phenomenological study using constant comparative methodology was applied. The research team conducted 10, one-on-one interviews with CRS patients ranging from 22 to 55 minutes in length. The content of the interview protocol was determined through iterative discussion amongst all authors. Two authors served as coders to identify recurrent themes. Themes were analyzed for meaning and conclusions were summarized. RESULTS: Three recurring themes determined from patients were that (1) use of the terminology control adequately represents this phenomenon, (2) components of control could be classified into four main themes relating to CRS symptomatology, exacerbation of comorbid disease, quality of life and acute exacerbations of CRS, and (3) when patients deem their CRS is uncontrolled they are more willing to escalate their treatment to include escalating their daily maintenance regimen, seeking otolaryngology referral, taking rescue medication or undergoing endoscopic sinus surgery. CONCLUSIONS: CRS patients consider their daily symptoms, the severity and frequency of CRS exacerbations, impact on quality of life as well as exacerbation of comorbid disease when thinking about their disease control. Disease control is a goal of treatment for patients and uncontrolled disease motivates patients to seek further treatment. Physicians should explore all components of CRS control when considering disease status and need for further treatment.

Individual symptom visual analogue scale severity scores for determining EPOS guideline-based chronic rhinosinusitis disease control.

BACKGROUND: The goal of this study was to determine how to translate visual analogue scale (VAS) symptom scores to the binary, descriptive symptom scales used in the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) criteria for chronic rhinosinusitis (CRS) disease control. METHODS: 309 CRS patients were recruited. All patients rated their burden of 5 symptoms (nasal blockage, rhinorrhea/postnasal drip, facial pain/pressure, smell loss, sleep disturbance or fatigue) using the binary EPOS descriptive symptom scales and a VAS (on a scale of 0 to 10). In addition, participants completed a 22-item Sinonasal Outcome Test (SNOT-22) and rated their overall CRS disease control as "controlled", "partly controlled" or "uncontrolled" Results: Symptom burdens measured by VAS, binary descriptive EPOS scale and SNOT-22 were associated with worsening CRS disease control reported by participants. Each symptom had a distinct VAS score cut-off that strongly predicted the uncontrolled option on the corresponding binary descriptive EPOS symptom scale. However, the predictive ability of VAS for rhinorrhea/ postnasal drip was disparately worse than the other 4 symptoms. When considering all symptom data simultaneously, a VAS score higher than 3.5 strongly predicted the uncontrolled option on the corresponding binary descriptive EPOS symptom scale for all 5 symptoms. CONCLUSIONS: A VAS symptom score of higher than 3.5 translates to the uncontrolled option in the binary, descriptive symptom scale of the EPOS control criteria. The rhinorrhea/postnasal drip descriptive symptom scale translates disparately worse to VAS scores and may be considered for revision in future criteria.

In vitro and in vivo methods to study bacterial colonization of hydrogel dermal fillers.

Preclinical in vitro and in vivo methods to study bacterial interactions with dermal fillers and infection pathogenesis are lacking. In this work, first in vitro methods to assess protein biofouling and effective pore size of commercial dermal fillers, including degradable hyaluronic acid (HA)-based fillers and other semi-degradable or permanent fillers (non-HA), were developed. The results were then related to Staphylococcus aureus (S. aureus) adhesion rates in vitro. HA fillers had less protein sorption than non-HA fillers and overall had smaller effective pore sizes. The properties correlated with levels of bacterial adhesion, where the control glass surface had the most rapid increase in bacterial cell adhesion, with a slope of 0.29 cm-2  min-1 , three unique non-HA fillers had intermediate adhesion with slopes of 0.11 and 0.06 cm-2  min-1 , and three unique HA fillers had the least adhesion with slopes of 0.02, 0.02, and 0.01 cm-2  min-1 . S. aureus had greater motility on the HA fillers than on non-HA fillers. Next, a mouse model for dermal filler biofilm and infection was developed. Mice were inoculated with a controlled amount of bioluminescent bacteria (Xen36 S. aureus) and polyacrylamide hydrogels of different stiffness were injected. In vivo bioluminescence was monitored longitudinally for 35 days to ensure that lasting colonization was established. The inoculum was optimized to achieve adequate bioluminescent signal, and bacterial bioburden over time and inter-animal variability in bioburden were determined. These in vitro and in vivo approaches can be used for future studies of antimicrobial interventions for dermal fillers.

Patient-reported chronic rhinosinusitis disease control is a valid measure of disease burden.

BACKGROUND: Disease control is an important treatment goal for chronic uncurable conditions such as chronic rhinosinusitis (CRS). The objective of this study was to determine whether patient-reported CRS disease control is a valid reflection of disease burden. METHODS: Prospective longitudinal study of 300 CRS patients (35% CRS with nasal polyps, 65% CRS without nasal polyps). At enrollment and at a subsequent follow-up timepoint, all participants were asked to rate their CRS disease control as 'not at all', 'a little', 'somewhat', 'very', 'completely' as well as to complete a 22-item Sinonasal Outcome Test (SNOT-22) and the 5-dimension EuroQol general health questionnaire from which the visual analogue scale (EQ-5D VAS) was used. RESULTS: At enrollment and follow-up timepoints, patient-reported CRS disease control was significantly correlated with SNOT-22 and EQ-5D VAS scores. The change in patient-reported CRS disease control was significantly correlated with change in SNOT-22 and change in EQ-5D VAS scores. There was significant cross-sectional and longitudinal correlation between patient-reported control and all SNOT-22 subdomain scores. A SNOT-22 score of ≤25 points or lower, or an EQ-5D VAS score of ≥77 was predictive of having well - (i.e. 'very' or 'completely') controlled CRS. CONCLUSIONS: Patient-reported CRS disease control is a valid measure of CRS disease burden and general QOL. A patient-reported assessment of CRS disease control could be considered as a component of a more comprehensive measure of CRS disease control.

Modulation of the N13 component of the somatosensory evoked potentials in an experimental model of central sensitization in humans.

The N13 component of somatosensory evoked potential (N13 SEP) represents the segmental response of dorsal horn neurons. In this neurophysiological study, we aimed to verify whether N13 SEP might reflect excitability changes of dorsal horn neurons during central sensitization. In 22 healthy participants, we investigated how central sensitization induced by application of topical capsaicin to the ulnar nerve territory of the hand dorsum modulated N13 SEP elicited by ulnar nerve stimulation. Using a double-blind placebo-controlled crossover design, we also tested whether pregabalin, an analgesic drug with proven efficacy on the dorsal horn, influenced capsaicin-induced N13 SEP modulation. Topical application of capsaicin produced an area of secondary mechanical hyperalgesia, a sign of central sensitization, and increased the N13 SEP amplitude but not the peripheral N9 nor the cortical N20-P25 amplitude. This increase in N13 SEP amplitude paralleled the mechanical hyperalgesia and persisted for 120 min. Pregabalin prevented the N13 SEP modulation associated with capsaicin-induced central sensitization, whereas capsaicin application still increased N13 SEP amplitude in the placebo treatment session. Our neurophysiological study showed that capsaicin application specifically modulates N13 SEP and that this modulation is prevented by pregabalin, thus suggesting that N13 SEP may reflect changes in dorsal horn excitability and represent a useful biomarker of central sensitization in human studies.

Practices and perspectives of primary care physicians in Japan and the United States about diagnosing dementia: a qualitative study.

BACKGROUND: While dementia is a common problem in Japan and the US, primary care physicians' practices and perspectives about diagnosing dementia in these different healthcare systems are unknown. METHODS: Qualitative research was conducted in an ethnographic tradition using semi-structured interviews and thematic analysis in primary care settings across Japan and in the Midwest State of Michigan, US. Participants were a total of 48 primary care physicians, 24 each from Japan and the US participated. Both groups contained a mixture of geographic areas (rural/urban), gender, age, and years of experience as primary care physicians. RESULTS: Participants in Japan and the US voiced similar practices for making the diagnosis of dementia and held similar views about the desired benefits of diagnosing dementia. Differences were found in attitudes about the appropriate timing of formally diagnosing dementia. Japanese physicians tended to make a formal diagnosis when problems that would benefit from long-term care services emerged for family members. US physicians were more proactive in diagnosing dementia in the early stages by screening for dementia in health check-ups and promoting advance directives when the patients were still capable of decision-making. Views about appropriate timing of diagnostic testing for dementia in the two systems reflect what medical or nursing care services physicians can use to support dementia patients and caregivers. CONCLUSIONS: Benefits of making the diagnosis included the need to activate the long-term care services in Japan and for early intervention and authoring advance directives in the US. Testing to establish an early diagnosis of dementia by primary care physicians only partly relates to testing and treatment options available. Benefits of making the diagnosis included the need to activate the long-term care services in Japan and for early intervention and authoring advance directives in the US.