"It gets you high as a kite but not unsick": Characterizations of and responses to a changing local drug supply by people who use drugs in Rhode Island.

BACKGROUND: The North American overdose crisis has continued at unprecedented rates with more than 100,000 overdose deaths occurring in the United States (US) in 2022. Overdose deaths have increasingly been polysubstance-involved, with novel substances (e.g., xylazine) complicating overdose risk and health outcomes. Understanding the effects of-and responses to-a changing drug supply among people who use drugs is critical to modifying harm reduction strategies to be more responsive to people's needs. METHODS: This qualitative study draws on data collected from May to December 2022 in Rhode Island. Data include in-depth interviews with 50 people who use drugs and observational fieldwork in spaces frequented by participants (e.g., encampments, drop-in centers). Qualitative data were analyzed thematically drawing on concepts of situated rationality. RESULTS: Participants described significant changes in the drug supply, with many attributing these transitions to COVID-19. Most participants characterized the local supply as "synthetic" with textures, color, and taste evolving. Notably, participants emphasized adverse outcomes related to available supplies, including during use (e.g., intense burning sensations) and post-consumption (e.g., heavy sedation, ongoing withdrawal, necrosis). Given the complex supply, participants highlighted the increased risk of overdose and shared how they altered their use practices to manage evolving health risks. CONCLUSION: Our results underscore how people who use drugs characterized the local drug supply, including perceived changes to supply contents. Implementing and scaling up harm reduction interventions that reduce risk and reinforce the agency of people who use drugs are urgently needed to effectively address the overdose crisis.

Perceptions of Long-Acting Injectable Antiretroviral Therapy Among People Living with HIV Who Use Drugs and Service Providers: a Qualitative Analysis in Rhode Island.

Long-acting injectable antiretroviral therapy (LAI-ART) is a novel method to deliver HIV treatment, and the first regimen was approved in the USA in 2021. LAI-ART may mitigate barriers to oral treatment adherence, but little is known about LAI-ART perceptions among people living with HIV (PLWH) who use drugs, despite these populations facing greater barriers to treatment retention and ART adherence. We assessed LAI-ART perceptions and implementation considerations among PLWH who use drugs and health and ancillary service providers in Rhode Island. Data was collected from November 2021 to September 2022, and include in-depth interviews with 15 PLWH who use drugs and two focus groups with HIV clinical providers (n = 8) and ancillary service providers (n = 5) working with PLWH who use drugs. Data were analyzed thematically, with attention paid to how levels of structural vulnerability and social-structural environments shaped participants' LAI-ART perceptions and the HIV care continuum. Willingness to consider LAI-ART was impacted by HIV outcomes (e.g., viral suppression) and previous experiences with oral regimens, with those on stable regimens reluctant to consider alternative therapies. However, LAI-ART was seen as potentially improving HIV outcomes for PLWH who use drugs and enhancing people's quality of life by reducing stress related to daily pill-taking. Recommendations for optimal implementation of LAI-ART varied across participants and included decentralized approaches to delivery. HIV care delivery must consider the needs of PLWH who use drugs. Developing patient-centered and community-based delivery approaches to LAI-ART may address adherence challenges specific to PLWH who use drugs.

Comprehensive testing and rapid dissemination of local drug supply surveillance data in Rhode Island.

BACKGROUND: The North American overdose crisis has continued at unprecedented rates with more than 100,000 overdose deaths estimated to have occurred in the United States in 2022. Regional variations in overdose rates signify differences in local drug supplies. State-level drug supply surveillance systems have been limited in their ability to document and communicate the rapidly changing drug supplies which can hinder harm reduction efforts at the community level. We sought to address by piloting a two-year, community-engaged local drug supply surveillance program in Rhode Island (RI). METHODS: The first set of samples (n = 125) were collected from May 2022 to January 2023 across RI and included used paraphernalia (e.g., cookers), refuse (e.g., baggies), and product. Samples were tested using comprehensive toxicology testing approaches via liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Results were disseminated to participants and the broader public across platforms. RESULTS: Fentanyl was detected in 67.2% of all samples tested. 39.2% (n = 49) of samples were expected to be fentanyl. Xylazine was detected in 41.6% of all samples-always in combination with fentanyl-and no samples were expected to contain xylazine. In expected stimulant samples (n = 39), 10% contained fentanyl and/or analogues as major substances and 30.8% contained trace amounts of fentanyl and/or analogues. In expected stimulant samples, 15.4% contained xylazine with fentanyl. No opioids or benzodiazepines were detected in expected hallucinogen or dissociative samples (n = 7). In expected benzodiazepine samples (n = 8), no opioids were detected. CONCLUSIONS: Our results describe part of the local drug supply in Rhode Island, including a presence of NPS and adulterants (e.g., designer benzodiazepines, xylazine). Importantly, our findings underscore the feasibility of developing a community-driven drug supply surveillance database. Expanding drug supply surveillance initiatives is imperative for improving the health and safety of people who use drugs and informing public health approaches to addressing the overdose crisis.

Characterizing ammonia emissions from horses fed different crude protein concentrations.

Evaluating impact of animal agriculture on air quality has been the focus of recent research. Ammonia (NH) volatilization occurs when undigested protein in feces and urea in urine is broken down by bacteria and enzymes. Information regarding NH emission from equine facilities is limited, and effects of CP intake on NH emissions have not been investigated. Nine mature geldings were used in a 3 × 3 replicated Latin square design study to determine effects of dietary CP on potential NH losses from feces and urine. We hypothesized feeding horses above the CP requirement would result in an increase in NH emissions from urine and feces and different bedding materials would affect NH emissions from urine. Diets were formulated using different ratios of bahiagrass () and Tifton-85 bermudagrass () hays, and a commercial vitamin mineral supplement to provide 3 different CP concentrations and labeled in relation to each other: LOW-CP, MED-CP, and HIGH-CP (10.6%, 11.5%, and 12%, respectively). Each study period consisted of an 11-d diet adaptation phase, followed by a 3-d total collection of urine and feces. To determine total nitrogen (TN) and urea-N concentrations, samples were pooled by period ( = 9). For in vitro determination of NH concentrations, urine and fecal samples were pooled within period by diet ( = 3) and mixed with either wheat straw or wood shavings. Ammonia emission of these samples was measured using a vessel system with an airflow rate (2.5 L/min) at 20°C over a 7-d period. Concentration of NH in each vessel was measured using a photoacoustic multigas analyzer. Temperature, airflow rate, and NH concentration in each vessel were used to calculate NH emission rate (ER). Data were analyzed using a mixed model ANOVA with repeated measures. Urinary TN and urea-N excretion increased as CP intake increased ( < 0.0001). Vessel urinary NH concentrations were not different across diets ( = 0.1225), ranging from 55.48 ppm (LOW-CP) to 101.14 ppm (HIGH-CP); however, they differed between bedding types ( < 0.0001), with straw higher than shavings (97 vs. 73.5 ppm, respectively). Cumulative urinary NH ER tended to be different across diets ( = 0.0550) ranging from 5.87 g/m to 9.97 g/m and bedding types ( = 0.0129), with straw being higher than shavings (11.1 vs. 6.9 g/m, respectively). Overfeeding CP to horses can lead to increased urinary TN and urea-N excretion, which could lead to greater of NH in the atmosphere.

Contrasting effects of calcium channel blockade versus converting enzyme inhibition on proteinuria in African Americans with non-insulin-dependent diabetes mellitus and nephropathy.

Hypertension is a common finding in non-insulin-dependent diabetes mellitus (NIDDM) nephropathy. African Americans have a high prevalence of NIDDM and hypertension, and are relatively resistant to the antihypertensive effects of converting enzyme inhibitors (CEI) but respond well to calcium channel blockers (CCB). In the long-term study presented here, the effects of isradipine, a dihydropyridine calcium antagonist, on the course of the nephropathy were investigated and compared with the effects of captopril in 31 African Americans with NIDDM and proteinuria (> or = 500 mg/day). The patients were stratified by levels of GFR and proteinuria, and they were randomized to receive isradipine (N = 16) or captopril (N = 15); doses were adjusted to maintain similar BP levels (< 140/90). At 6 months, mean arterial pressure was similar (102 +/- 3 and 104 +/- 3 mm Hg in the isradipine and captopril groups, respectively) and GFR was unchanged (delta = -4 +/- 3 and +1 +/- 3 ml/min/1.73 in the isradipine and captopril groups, respectively; P = NS). However, proteinuria in the isradipine group increased by approximately 50% (2.01 +/- 0.40 versus 3.04 +/- 0.70 mg/mg creatinine at baseline versus 6 months, respectively, P < 0.05), whereas captopril reduced proteinuria by 30% after 6 months (2.85 +/- 0.70 at baseline versus 2.30 +/- 0.70 mg/mg creatinine, P < 0.05). Dietary protein, sodium intake, and HbA1C levels were similar in both groups and did not differ from baseline. It was concluded that over 6 months, captopril reduces and isradipine increases proteinuria in African Americans with NIDDM and nephropathy. Whether this contrasting effect on proteinuria will result in different rates of progression is not known, but dihydropyridine CCB should be used cautiously in African Americans with diabetic nephropathy.

Safety and efficacy of low-dose subcutaneous erythropoietin in hemodialysis patients.

Anemia in hemodialysis patients is effectively treated by intravenous (IV) injections of recombinant human erythropoietin (rHuEPO) at each dialysis session. Because the hormone is effective by subcutaneous (SC) administration, it was decided that this study would evaluate low-dose weekly SC rHuEPO therapy. To determine the safety and efficacy of weekly SC rHuEPO administration to hemodialysis patients, only one third the weekly IV dose was given and the effects were compared with those from an age-, gender-, and nephrologic disease-matched control group treated in the standard fashion. Forty-four patients entered the trial and 27 completed the protocol along with 27 control subjects. During Phase 1, experimental and control subjects received standard IV rHuEPO at dialysis for 6 months. During Phase 2, experimental patients received weekly SC rHuEPO at one third the weekly IV dose for 10 months; control subjects continued to receive IV therapy. In Phase 3, both groups were treated for 6 more months with IV rHuEPO. In Phase 2, there was no significant reduction in hematocrit value, reticulocyte count, transferrin saturation, or ferritin level in the experimental group, even with only one third the weekly rHuEPO IV dose over the 10-month period. There were no significant differences between IV and SC rHuEPO administration or between experimental and control subjects in blood pressure, serum chemistries, or parameters of "dialysis adequacy." It was concluded that low-dose weekly SC rHuEPO administration is a safe and effective method for maintaining the hematocrit level of stable hemodialysis patients. This therapy could enhance the efficacy of rHuEPO and substantially reduce costs while preserving patient care outcomes.

Dialysis survival in a large inner-city facility: a comparison to national rates.

Impoverished patients may represent a high-risk population with poor survival. With 1993 U.S. Renal Data System survival tables (to adjust the risk of death for differences in age, race, and ESRD diagnosis), the mortality rates of patients over 3 yr in a large inner-city dialysis facility using high-flux technique were compared with national averages. At least 93.7% of patients were African-American, 50% had incomes below $7,000 per year, and employment was 5% or less. Observed and expected deaths (the latter derived from the U.S. Renal Data System tables) were used to calculate a standardized mortality ratio (observed deaths/expected deaths); the U.S. average is 1.0. The standardized mortality ratio at this facility for each year was < 0.600 and was significantly lower than the U.S. average in 1991, in 1992 (P < 0.05), and for all 3 yr (P < .001). Over all 3 yr, it was lower for females (0.540, P < 0.05), males (0.620, P < 0.05), patients with diabetes (0.593, P < 0.05), and glomerulonephritis (0.318, P < 0.05). For the 3 yr, a Cox regression analysis revealed independent associations between mortality and age (P = 0.004), serum albumin (P = 0.02), Kt/V (P = 0.02), and dialysis for more than 2 yr (P = 0.01). Patients with economic hardship can attain survival significantly better than the national average with the provision of adequate dialysis, nutrition, and support services.

The effects of calcium carbonate as the sole phosphate binder in combination with low calcium dialysate and calcitriol therapy in chronic hemodialysis patients.

Alternative phosphate binders, such as CaCO3, have been shown to be effective in the control of phosphate (P) retention in hemodialysis patients (HDP). Additionally, both oral (POC) and iv (IVC) calcitriol are purported to be of benefit in the control of secondary hyperparathyroidism. This investigation was undertaken to determine: (1) the effectiveness of CaCO3 as the sole P binder in combination with low (2.5 mEq/L) Ca dialysate; (2) the effects of discontinuing Al(OH)3 binders on both unstimulated and stimulated Al concentrations; and (3) the comparative parathyroid hormone (PTH) response to both POC and IVC in a large group of hemodialysis patients. One hundred ninety-four HDP completed part 1 of the study where CaCO3 was substituted for Al(OH)3 as the sole P binder for 6 months. A cohort of 49 HDP was given desferoximine (40 mg/kg) initially and 10 months after using CaCO3. In part 2, 54 HDP were given POC and 97 HDP were given IVC in dosages of 0.25 to 0.5 micrograms/day and 1.5 to 6.0 micrograms/wk, respectively, for an additional 6 months. In part 1, Ca and P were not different from baseline values observed with Al(OH)3 therapy. Ionized Ca increased (P < 0.05) and PTH decreased (P < 0.001) during CaCO3 therapy without vitamin D. In part 2, PTH declined 23% with IVC and was unchanged with POC in equivalent dosages (P < 0.05) at 3 months. By 6 months, PTH declined a total of 54% with IVC and was unchanged with POC. Ca, ionized Ca, P, and serum calcitriol were greater (P < 0.05) in the IVC group at 6 months. Serum Al concentrations for the entire 194 HDP fell 65% (P < 0.0001) over 12 months. In the 49 HDP cohort, serum Al fell 43.6% (P < 0.001) and stimulated Al concentrations decreased 68.7% (P < 0.0001) after 10 months. We conclude that: (1) CaCO3 is as effective as Al(OH)3 in controlling P, (2) a small decrease in PTH is observed with CaCO3 alone, (3) serologic evidence of Al excess is virtually eliminated, (4) PTH suppression with IVC is superior to that seen with POC in equivalent doses.

Multicenter study of change in dialysis therapy-maintenance hemodialysis to continuous ambulatory peritoneal dialysis.

Serial prospective observations were made on 40 patients with end-stage renal failure who transferred voluntarily from long-term maintenance hemodialysis (MHD) to continuous ambulatory peritoneal dialysis (CAPD). Adequate data were available through 6 months on CAPD in 26 participants, whereas 20 completed the study (1 year on CAPD). There were 12 (30%) treatment failures, including two deaths. Standard CAPD (four 2-L exchanges per day) proved to be inadequate therapy in large, young males with low total urea clearances (Ktu) on MHD. There was a large variation in Ktu within MHD and CAPD therapies that employed apparently similar or identical dialysis prescriptions; this underscores the need to quantify dialysis by a measure such as Ktu. Hematocrit, white blood cell (WBC) and platelet counts, and serum bicarbonate levels were significantly higher, whereas blood urea nitrogen (BUN) and serum potassium levels were significantly lower on CAPD than on MHD. While body weight, blood pressure, bone disease, parathyroid hormone (PTH) levels, and lipid profile did not change significantly, nutritional indices tended to decline with time on CAPD. Urea generation rate (Gu) decreased significantly after transfer to CAPD and correlated with Ktu regardless of treatment modality. Central nervous system (CNS) function reflecting uremic symptomatology and as indexed by average quantified electroencephalogram (EEG) discriminant scores did not change significantly. Hospitalization rates and stays were similar during equal time intervals on both therapies. Sufficiently diverse responses followed the MHD to CAPD therapy change to warrant more extended observations on larger numbers of patients.

Complications with permanent peritoneal dialysis catheters: experience with 154 percutaneously placed catheters.

A prospective study evaluated the complications in 154 patients in whom a permanent peritoneal dialysis catheter was inserted percutaneously from April 1982 to June 1986. Obstruction to flow and fluid leakage occurred in 9.2 and 2.6% of the catheters, respectively. Catheter survival was 64.6 and 48.6% at 1- and 2-year follow-up, respectively. The complication rates and survival of percutaneously placed catheters was comparable to those reported for surgically placed catheters. Percutaneous insertion of Tenckhoff catheters is a viable alternative to using the surgical technique.

Prolonged hypotension after initial minoxidil dose.

Severe prolonged hypotension developed in a hypertensive patient several hours after the initial doses of minoxidil therapy. Hemodynamic measurements revealed a markedly low systemic vascular resistance and a markedly high cardiac output. Other causes of hypotension were ruled out. The patient's hemodynamic abnormalities lasted three days after minoxidil therapy was discontinued, and she then reverted to hypertension. Thus, a 10-mg starting dose of minoxidil may produce profound life-threatening hypotension, which can last up to 72 hours.

Cadaveric kidneys for transplantation. A paradox of shortage in the face of plenty.

The number of cadaveric kidneys currently available for transplantation is insufficient; therefore, the Center for Disease Control (CDC) undertook a collaborative pilot project to increase the number of cadaveric kidneys available for transplantation. In phase one, a retrospective review of medical records of in-hospital deaths was done to determine the potential number of cadaveric kidney donors and to define the characteristics of potential donors. The medical records of 10,420 (43.1%) of the 24,164 patients who died in 67 acute-care hospitals in Georgia, Kansas, and Missouri were retrieved. In addition to determining suitability for donorship, criteria were developed to reflect the broadest range of criteria in use. By center-specific criteria there were 1.7 potential donors/100 in-hospital deaths, which could make available 109 kidneys/million population. By broad intercenter criteria there were 3.5 potential donors/100 in-hospital deaths, which could provide 232 kidneys/million population. During 1975, by center-specific criteria, kidneys from 19.3% of the suitable potential donors were retrieved. The small number of transplantable cadaveric kidneys retrieved was not attributable to lack of suitable organs but rather the failure to identify suitable donors, obtain consent, and retrieve the kidneys.

Increasing the supply of cadaveric kidneys for transplantation.

The number of cadaveric kidneys currently available for transplantation is insufficient. Therefore, the Center for Disease Control (CDC) undertook a collaborative project with the two transplant programs in Georgia to increase te retrieval of cadaveric kidneys. We used retrospective analysis to select productive hospitals, hospital-specific surveillance systems to identify potential donors, and procurement and retrieval evaluation to identify preventable deficiencies. During 900 hospital months of prospective surveillance, we identified a total of 555 potential donors by death record review, giving a potential donor rate of 2.3 donors/100 deaths (110 kidneys/million population/year). We observed an increase in the number of referrals, consent obtained from next of kin, and kidneys retrieved. This period of intensive activity demonstrated that additional kidneys can be retrieved by using systematic methods.

Ultrasonographic evaluation of vascular access complications.

In 24 patients, sonograms were obtained of 25 vascular accesses, 16 of which were bovine grafts, 7 arteriovenous fistulae, 1 a polytetrafluoroethylene graft, and 1 an external Silastic shunt. On the sonograms, the lumen, course, and insertions of the vascular grafts and fistulae were outlined, anterior and posterior aneurysms demonstrated, hematomas differentiated from aneurysms, and intrinsic distinguished from extrinsic lesions. The authors conclude ultrasonography is a valuable adjunct to clinical evaluation in assessing certain complications of vascular access.

Hemodialysis-associated hepatitis: report of an epidemic with further evidence on mechanisms of transmission.

In the period January-September 1974, 50 cases of hepatitis B infection occurred among a nephrology center's hemodialysis patients and staff. The in-center patient population had an attack rate of 96%. Epidemiologic analysis of risk factors for patients revealed an association between the receipt of intravenous medication and the subsequent development of hepatitis, suggesting that parenteral inoculation was a mode of spread among patients (p equals .008). Nineteen per cent of the staff contracted hepatitis, and all of these personnel had had close contact with patients (p equals .005). The prevalence of hepatitis B infection in staff was related to the failure to use gloves (p less than .01), and accidental needle puncture was associated with the development of clinical hepatitis. These data suggested that disease was transmitted to staff by contact with contaminated blood or close personal contact with patients. Additional data showed that the presence of endogenous antibody protected both patients and staff from antigenemia (p equals .002). These data support the hypothesis that contact with blood is the primary mechanism of spread of hepatitis B in dialysis units, and suggest that, as preventive measures, gloves should be used and antibody-positive staff should dialyze antigen-positive patients.