Oncologists' perceptions of tumor genomic profiling and barriers to communicating secondary hereditary risks to African American cancer patients.

BACKGROUND: Tumor genomic profiling (TGP) identifies targets for precision cancer treatments, but also secondary hereditary risks. Oncologists are poorly trained to communicate the results of TGP, especially among patients with lower health literacy, poorer genetics knowledge, and higher mistrust. African American (AA) patients are especially vulnerable to poor understanding due to significant cancer disparities and lower uptake of TGP. The goal of this research is to inform the development of an internet-based brief educational support for oncologists to prepare them to provide better decisional support related to TGP for their AA cancer patients. METHODS: This mixed-methods study used semi-structured interviews of oncologists to inform development of an online survey with a convenience sample of US-based oncologists (n = 50) to assess perceptions of the challenges of TGP and communicating results to AA patients. RESULTS: Most interviewed oncologists felt it was important to consider racial/cultural differences when communicating about hereditary risks. Cost, family dynamics, discrimination concerns, and medical mistrust were identified as particularly salient. Survey respondents' views related to AAs and perceptions of TGP were strongly associated with years since completing training, with recent graduates expressing stronger agreement with statements identifying barriers/disadvantages to TGP for AA patients. CONCLUSIONS: Oncologists who had more recently completed training expressed more negative perceptions of TGP and more perceived challenges in communicating about TGP with their AA patients. Focused training for oncologists that addresses barriers specific to AAs may be helpful in supporting improved communication about TGP and improved decisional support for AA patients with cancer considering TGP to evaluate their tumors.

Understanding perceptions of tumor genomic profile testing in Black/African American cancer patients in a qualitative study: the role of medical mistrust, provider communication, and family support.

Tumor genomic profiling (TGP) examines genes and somatic mutations specific to a patient's tumor to identify targets for cancer treatments but can also uncover secondary hereditary (germline) mutations. Most patients are unprepared to make complex decisions related to this information. Black/African American (AA) cancer patients are especially at risk because of lower health literacy, higher levels of medical mistrust, and lower awareness and knowledge of genetic testing. But little is known about their TGP attitudes or preferences. Five in-person focus groups were conducted with Black/AA cancer patients (N = 33) from an NCI-designated cancer center and an affiliated oncology unit in an urban safety-net hospital located in Philadelphia. Focus groups explored participants' understanding of TGP, cultural beliefs about genetics, medical mistrust, and how these perceptions informed decision-making. Participants were mostly female (81.8%), and one-third had some college education; mean age was 57 with a SD of 11.35. Of patients, 33.3% reported never having heard of TGP, and 48.5% were not aware of having had TGP as part of their cancer treatment. Qualitative analysis was guided by the principles of applied thematic analysis and yielded five themes: (1) mistrust of medical institutions spurring independent health-information seeking; (2) genetic testing results as both empowering and overwhelming; (3) how provider-patient communication can obviate medical mistrust; (4) how unsupportive patient-family communication undermines interest in secondary-hereditary risk communication; and (5) importance of developing centralized patient support systems outside of treatment decisions. Results improve understanding of how Black/AA patients perceive of TGP and how interventions can be developed to assist with making informed decisions about secondary hereditary results.

Understanding the delivery of substance use treatment services to transgender and gender-diverse people: Findings from a mixed-methods study of healthcare professionals.

BACKGROUND: Transgender and gender diverse (TGD) people who use drugs report barriers to accessing substance use treatment, including provider mistreatment. Little research has explored the multilevel factors that shape the capacity of substance use treatment professionals to provide gender-affirmative care (i.e., care that respects and affirms one's gender) to TGD people. METHODS: From October 2021 to March 2022, substance use treatment and harm reduction professionals in Rhode Island were surveyed (N = 101) and qualitatively interviewed (N = 19) about the provision of substance use treatment-related services to TGD people. Quantitative data were analyzed descriptively; differences were examined using Fisher exact tests (p < 0.05). Qualitative interviews were coded and analyzed using thematic analysis. RESULTS: Participants reported limited exposure to TGD people and lacked training on TGD health, which resulted in limited cultural and clinical competency and low self-efficacy in their ability to care for TGD people. Participants also highlighted structural factors (e.g., non-inclusive intake forms, limited availability of gender-inclusive ancillary community services) that restricted their ability to provide effective and affirming care to TGD people. Some participants also reported a "gender blind" ethos at their institutions- described by some as ignoring the potential impact of TGD peoples' unique experiences on their substance use and ability to benefit from treatment. While some perceived gender blindness as problematic, others believed this approach enabled substance use treatment professionals to consider all the identities and needs that patients/clients may have. Despite differences in treatment approaches, most participants agreed that their workplaces could benefit from efforts to create a safe and affirming space for people who use drugs, particularly TGD patients/clients. CONCLUSION: Results underscore how structural, interpersonal, and individual factors contributed to barriers in the provision of gender-affirmative substance use-related care for TGD people. Findings can inform efforts to increase the capacity of providers to deliver gender-affirmative substance use-related services, which is essential to supporting the recovery goals of TGD people.

Prevalence of methamphetamine use among gay, bisexual and other men who have sex with men: A systematic review and meta-analysis.

BACKGROUND: International efforts have reduced the availability of methamphetamine precursors, but its distribution and use continue to rise. Methamphetamine use can lead to short- and long-term adverse effects, including addiction, physical and psychosocial health problems, socioeconomic troubles, incarceration, overdose, and death. Gay, bisexual, and other men who have sex with men (MSM) have been shown to have an elevated prevalence of methamphetamine use. METHODS: We conducted a systematic review and meta-analysis to estimate the prevalence of methamphetamine use among MSM. We searched electronic databases, such as PubMed, for peer-reviewed literature published between 2011 and 2022. Data on methamphetamine use were extracted, including study features, location, study design, sampling method, recruitment period, specific MSM subgroups, prevalence period, and demographics. Employing a random-effects model, we computed the pooled prevalence of methamphetamine use among MSM across two prevalence periods: recent use (i.e., one month, three months, six months, one year) and lifetime use. RESULTS: The systematic review included 56 studies with a total of 25,953 MSM who use methamphetamine. Most studies were conducted in Europe, with the highest prevalence reported in the United Kingdom. The studies primarily used cross-sectional or cohort study designs with convenience sampling. The pooled prevalence rates across recent use (i.e., past month, past three months, past six months, and past year) was 15% (95% CI [11-19%]). Additionally, we pooled lifetime use, which was 23% (95% CI [9-38%]). High heterogeneity (I2 > 99%) was observed, indicating significant variation. CONCLUSION: This systematic review and meta-analysis provide a pooled prevalence of methamphetamine use among MSM. The analysis accounts for study design, prevalence period, specific MSM subgroups, and geographical areas to estimate methamphetamine use in diverse settings and populations. The review highlights the need for targeted interventions and harm reduction strategies focused on prevention, education, healthcare access, and stakeholder collaboration to address the multifaceted challenges of methamphetamine use among MSM.

The relationship of PrEP beliefs to perceived personal, interpersonal and structural benefits and barriers to PrEP use in women who inject drugs.

BACKGROUND: Women who inject drugs (WWID) have significant biological, behavioral, and gender-based barriers to accessing HIV prevention services, including Pre-Exposure Prophylaxis (PrEP) medication. Little is known about how beliefs about PrEP impact both perceived barriers and benefits of PrEP use and how they may be related to the decision-making process. METHODS: Surveys were conducted with 100 female clients of a large syringe services program in Philadelphia, Pennsylvania. The sample was categorized into three groups based on mean PrEP beliefs scores using terciles: accurate beliefs, moderately accurate beliefs, and inaccurate beliefs. Oneway ANOVA tests were used to compare groups by perceived benefits and barriers to PrEP, drug use stigma, healthcare beliefs, patient self-advocacy, and intention to use PrEP. RESULTS: Participants had a mean age of 39 years (SD 9.00), 66% reported being White, 74% finished high school, and 80% reported having been homeless within the past 6 months. Those with the most accurate PrEP beliefs reported highest intent to use PrEP and were more likely to agree that benefits of PrEP included it preventing HIV and helping them "feel in charge". Those with inaccurate beliefs were more likely to strongly agree that barriers, such as fear of reprisal from a partner, potential theft, or feeling they "might get HIV anyway", were reasons not to use PrEP. CONCLUSIONS: Results indicate perceived personal, interpersonal and structural barriers to PrEP use are associated with accuracy of beliefs is, pointing to important intervention targets to increase uptake among WWID.

"It's my frenemy": A qualitative exploration of knowledge and perceptions of fentanyl use during the COVID-19 pandemic in people who use drugs at a syringe services program in Philadelphia, PA.

Background: Exacerbated by the COVID-19 pandemic and the proliferation of fentanyl and fentanyl analogs, overdose deaths have surged in the United States, making it important to understand how individuals who use drugs experience and perceive the risks of fentanyl use and how it has changed during the COVID-19 pandemic. Methods: Twenty clients from a Philadelphia syringe services program completed a questionnaire and in-depth interview about their fentanyl experiences from January to March 2021. These interviews were transcribed and analyzed using thematic analysis methods. Results: Sixty percent of participants were female and racial/ethnic minority. Participants indicated they believed fentanyl use accounted for most Philadelphia opioid-related overdoses and understood that fentanyl was different from other opioids. Fentanyl use was characterized as "all-consuming" by taking over lives and inescapable. While most perceived their risk of fentanyl overdose as high, there was low interest in and reported use of harm reduction strategies such as fentanyl test strips. The COVID-19 pandemic was noted to have negative effects on fentanyl availability, use and overdose risk, as well as mental health effects that increase drug use. Conclusions: The divide between perceived risk and uptake of protective strategies could be driven by diminished self-efficacy as it relates to acting on and engaging with resources available at the syringe services program and represents a potential intervention target for harm reduction intervention uptake. But the COVID-19 pandemic has exacerbated risks due to fentanyl use, making an effective, accessible, and well-timed intervention important to address the disconnect between perceived overdose risk and use of preventive behaviors.

"We figured it out as we went along": Staff perspectives of COVID-19 response efforts at a large North American syringe services programme.

Syringe services programmes face operational challenges to provide life-sustaining services to people who use substances and those who have substance use disorders. COVID-19 has disrupted operations at these programmes and is a threat to people with substance use disorder because of severe poverty, de-prioritisation of COVID-19 safety and high prevalence of comorbidities. This phenomenological qualitative study describes 16 in-depth interviews with staff of one of the largest syringe services programme in North America-Prevention Point Philadelphia, located in the Kensington neighbourhood of Philadelphia, Pennsylvania. Interviews were conducted from December 2020 to February 2021, audio-recorded, transcribed and coded to develop a thematic framework. Participants were mostly white (71.4%) and female (68.8%) with a median age of 31.5. Three main and four sub-themes related to the impact of COVID-19 on the syringe services programme were identified: (1) COVID-19 altered services provision (sub-theme: select service changes should be retained); (2) unclear or absent COVID-19 response guidance which compromised mitigation (sub-themes: COVID-19 messaging was difficult to translate to practice, learn-as-we-go); and (3) staff and clients experienced elevated mental anguish during the pandemic (sub-theme: already limited resources were further strained). COVID-19 presented complex challenges to an organisation normally strained in pre-pandemic times. A staff culture of resourcefulness and resiliency aided the syringe services programme to balance client needs and staff safety. However, staff experienced a serious psychological impact, largely attributable to being unable to find reprieve from the stressors of COVID-19 and the difficulties associated with navigating and acting-on contradictory public health messaging. Staff also shared a belief that the relaxing of some pre-pandemic barriers allowed staff to link clients more readily with services. Syringe services programmes should embrace the potential for lasting changes to health services delivery brought about by wide-scale changes in service provisions because of COVID-19.

Coupled Si and O isotope measurements of meteoritic material by laser fluorination isotope ratio mass spectrometry.

We present a procedure for the determination of the isotopic ratios of silicon and oxygen from the same aliquot of anhydrous silicate material. The sample is placed in a bromine pentafluoride atmosphere as it is heated with a CO2 laser system releasing silicon tetrafluoride and oxygen gasses. The oxygen gas is then purified to remove other reaction by-products through several liquid nitrogen traps before being captured onto a molecular sieve and transferred to an isotope ratio mass spectrometer. The silicon tetrafluoride gas is then purified using a supplementary line by repeatedly freezing to -196°C with liquid nitrogen and then thawing with an ethanol slurry at -110°C through a series of metal and Pyrex traps. The purified gas is then condensed into a Pyrex sample tube before it is transferred to an isotope ratio mass spectrometer for silicon isotope ratio measurements. This system has silicon yields of greater than 90% for pure quartz, olivine, and garnet standards and has a reproducibility of ±0.1‰ (2σ) for pure quartz for both oxygen and silicon isotope measurements. Meteoritic samples were also successfully analyzed to demonstrate this system's ability to measure the isotopic ratio composition of bulk powders with precision. This unique technique allows for the fluorination of planetary material without the need for wet chemistry. Though designed to analyze small aliquots of meteoritic material (1.5 to 3 mg), this approach can also be used to investigate refractory terrestrial samples where traditional fluorination is not suitable.

Rapid assembly of the bicyclo[5.3.1]undecenone core of penostatin F: a successive Diels-Alder/Claisen reaction strategy with an efficient stereochemical relay.

The first synthesis of the tricyclic core of Penostatin F (1) using a stereocontrolled Diels-Alder reaction and a Claisen rearrangement in succession has been achieved in nine steps from commercially available methyl acetoacetate and (E)-2-decenal. Penostatin F is a metabolite isolated from a fungal strain of Penicillium sp., OUPS-79, separated from the marine alga Enteromorphia intestinalis and exhibits significant cytotoxicity against cultured P388 Leukemia cells (ED(50) = 1.4 micromol/mL). [reaction: see text]

The nuclear ribosomal DNA intergenic spacers of wild and cultivated soybean have low variation and cryptic subrepeats.

The intergenic ribosomal DNA spacers (IGSs) from cultivated soybean (Glycine max) and wild soybean (Glycine soja) were sequenced and compared with six other legumes. These IGS sequences were 1821 bp in length in G. soja and G. max cultivars Arksoy, Ransom, and Tokyo, and 1823 bp long in the G. max cultivar Columbus. These represent the smallest published plant IGS sequences to data. Two clones from each of the above five cultivars were sequenced and only 22 sites (1.2%) were polymorphic, thereby supporting previous work that showed low genetic variation in cultivated soybean. The amount of variation observed between different clones derived from the same individual was equal to the amount seen between different cultivars. The soybean IGS sequence was aligned with six other published legume sequences and two homologous regions were identified. The first spans positions 706-1017 in the soybean IGS sequence and ends at a putative promoter site that appears conserved among all legumes. The second is located within the 5' external transcribed spacer, spans positions 1251-1823 in soybean, and includes sequences first identified as subrepeats IV-1 and IV-2 in Vicia angustifolia. Sequences homologous to these two subrepeats were identified among all legume species examined and are here designated "cryptic subrepeats" (CS-1, CS-2) given the range in similarity value (79-96% for CS-1 and 60-95% for CS-2). Comparisons of CS-1 and CS-2 sequences within individual species show that divergence (substitutional mutations, insertions, and deletions) is sufficiently high to obscure recognition of the repeat nature of these sequences by routine dot plot analytical methods. The lack of subrepeats in the 5' half of the soybean IGSs raises questions regarding the role they play in transcription termination or enhancement.

Histamine release by morphine and diamorphine in man.

Intravenous morphine and diamorphine are routinely used for postoperative analgesia but the relative histamine releasing abilities of these drugs have not been compared in man. Thirty-eight patients were randomly allocated to receive morphine (0.16 mg.kg-1) or diamorphine (0.08 mg.kg-1) after abdominal surgery. Blood samples for histamine were taken before, and at timed intervals after, opioid administration and analysed by an isotopic radioenzymatic technique. Haemodynamic parameters and pain scores were recorded before and after analgesic administration, and a series of eight basophil histamine release studies was also performed. Significant histamine release (plasma concentration > 2 ng.ml-1 or rise of > 700% baseline) occurred in 23.5% of the morphine group and 21.1% of the diamorphine group. Histamine was released earlier in those receiving diamorphine, but no significant change in haemodynamic parameters occurred, and no histamine release was demonstrated in the basophil histamine release studies. These findings suggest that morphine and diamorphine release histamine from mast cells rather than basophils.

Ketorolac trometamol for postoperative analgesia after orthopaedic surgery.

We have compared the postoperative morphine requirements and analgesic efficacy of four doses of i.m. ketorolac 30 mg administered 6-hourly with placebo in a double-blind study of patients undergoing major or minor orthopaedic surgery. During the 24-h postoperative study period which began at the end of surgery, patients were prescribed i.m. morphine 10 mg as required 2-hourly and assessments were made of pain at 4 and 24 h. After major surgery, the median morphine consumption over 24 h was 10 mg in patients who received ketorolac, compared with 30 mg in those who received placebo (P = 0.008). Visual analogue pain scores and verbal pain assessments were better than placebo at 4 h (P = 0.028 and P = 0.008, respectively), but were not statistically different between the groups at 24 h. Overall assessment of pain was similar in both groups who had undergone major surgery. In the minor surgery groups, median morphine consumption was 0 mg in patients who received ketorolac, compared with 10 mg in those given placebo (ns). Visual analogue pain scores at 24 h after surgery were significantly less in patients who had received ketorolac compared with placebo (P = 0.046) and the overall assessment of pain relief was better in the ketorolac group (P = 0.0007). Mandatory administration of ketorolac appeared to be of benefit in both major and minor orthopaedic surgery, although the principal effects were reduction in requirement for supplementary morphine for major surgery and better overall analgesia for minor surgery.

A comparison of epidural diamorphine with intramuscular papaveretum following caesarean section.

Following caesarean section carried out under epidural blockade using local anaesthetic only, 40 consenting women were randomly allocated to receive either epidural diamorphine 2.5-5 mg in 10 ml physiological saline and intramuscular saline or epidural saline and intramuscular papaveretum 10-20 mg, dosage depending on weight, when the pain returned. When analgesia was next requested the alternative treatment was given. A visual analogue pain score was recorded before and 15, 30, 60, 120, 180 and 240 min after the first treatment. Respirations were counted and symptoms noted. On the following day the mother was asked whether she preferred the first or the second treatment. Both treatments produced a reduction in pain score but analgesia was significantly better with epidural diamorphine and the duration of action (8.5 +/- 5.2 h) was significantly longer than that following intramuscular papaveretum (4.1 +/- 2.3 h, P < 0.01). Two mothers who received epidural diamorphine initially required no further analgesia. No difference in respiratory rate was noted but side-effects were more frequent with epidural diamorphine. Despite this more women preferred this treatment. Because of enhanced mobility provided by good analgesia epidural diamorphine is worth offering to women following caesarean section.

Lumbar epidural diamorphine following thoracic surgery. A comparison of infusion and bolus administration.

Twenty-two patients received a single dose of diamorphine 5 mg through a lumbar epidural catheter before thoracic surgery. The patients were transferred after surgery to a high dependency unit where they were allocated randomly to receive either an infusion of epidural diamorphine at a rate of 1 mg/hour (group 1) or bolus doses of epidural diamorphine 5 mg on demand (group 2). There was no statistically significant difference between the groups in visual analogue pain scores in the first 18 postoperative hours. Arterial carbon dioxide tension was elevated in both groups and was consistently higher in group 1 than in group 2, with a statistically significant intergroup difference 12 hours after operation. Respiratory rate was not a useful index of respiratory depression. The commonest nonrespiratory side effect was urinary retention, but the incidences of this and other minor side effects were similar in the two groups.

Tracheostomy closure in restrictive respiratory insufficiency.

A retrospective study is presented of 31 patients who required ventilatory support via a tracheostomy for periods of one month to 27 years whilst in a tertiary referral centre for the care of patients with restrictive respiratory insufficiency. All patients underwent closure of a long-standing tracheostomy. Post-operative follow-up periods of up to 16 years are documented. The indications for and the complications of tracheostomy closure in patients with severe chronic restrictive respiratory insufficiency requiring long-term respiratory support are discussed. It is concluded that the benefits of operative tracheostomy closure outweigh the disadvantages in this unusual type of patient.

Peri-operative care in restrictive respiratory disease.

A total of 139 of 473 severely disabled, mainly ventilator-dependent patients required some form of surgery. Such patients require surgery more frequently than normal individuals, both because of their disability and because even minor unrelated disorders superimposed on permanent disability cause greater handicap. We report the peri-operative management and postoperative complications of 142 operations on 83 patients between 1982 and 1987. A simple inhalational anaesthetic technique was used; opioids and muscle relaxants were seldom given. Negative pressure ventilation was employed in the postoperative period when appropriate, and was combined with vigorous chest physiotherapy. There were three peri-operative deaths, but the overall death rate in the patients who underwent surgery was no greater throughout the study period than in those who did not require surgery. We believe that an aggressive surgical approach is appropriate in severely disabled, ventilator-dependent patients.

Purine nucleoside phosphorylase cleaves the C--O bond of ribose 1-phosphate. Evidence from the 18O shift in 31P NMR.

An equilibrium mixture of highly enriched [18(O)]Pi (represents the mixture of [[18(O)4]Pi, [[18(O)3]Pi, [18(O)2]Pi as represented in the figures, unless otherwise specified), alpha-D-ribose 1-[16(O)]phosphate, and hypoxanthine plus inosine was equilibrated with calf spleen purine-nucleoside phosphorylase (EC 2.4.2.1). The 31P NMR spectrum clearly indicated the formation of alpha-D-ribose 1-[18(O)4]-phosphate and of [16(O)]Pi. Incubation for the same time span in the absence of alpha-D-ribose 1-phosphate left the [18(O)4]Pi isotopic distribution unchanged. The results clearly demonstrated that the C--O bond of alpha-D-ribose 1-phosphate is cleaved in the enzymatic reaction. It is unlikely that the enzyme catalyzes the exchange of oxygen between Pi and H2O. Several possible mechanistic pathways are ruled out by the results, which demand attack by a phosphate oxygen at the anomeric C-1' atom.