2023 Undetectable = Untransmittable global policy roundtable report: a multistakeholder perspective on Undetectable = Untransmittable research and policy priorities.

Background Launched in 2016 by Prevention Access Campaign, the 'Undetectable=Untransmittable' (U=U) campaign empowers people living with HIV to live full social, sexual and reproductive lives, dismantle stigma, promote increased treatment access, and advocate for updated HIV guidelines. Methods Key priorities for promoting improvements to community-centred, evidence-informed U=U policy and research were the focus of a half-day global roundtable held in 2023 alongside the 12th International AIDS Society Conference in Brisbane, Australia. After a series of presentations, experts in U=U research, policymaking, advocacy and HIV clinical care participated in facilitated discussions, and detailed notes were taken on issues related to advancing U=U policy and research. Results Expert participants shared that knowledge and trust in U=U remains uneven, and is largely concentrated among people living with HIV, particularly those connected to gay and bisexual networks. It was agreed that there is a need to ensure all members of priority populations are explicitly included in U=U policies that promote U=U. Participants also identified a need for policymakers, healthcare professionals, advocates and researchers to work closely with community-based organisations to ensure the U=U message is relevant, useful, and utilised in the HIV response. Adopting language, such as 'zero risk', was identified as crucial when describing undetectable viral load as an effective HIV prevention strategy. Conclusion U=U can have significant benefits for the mental and physical wellbeing of people living with HIV. There is an urgent need to address the structural barriers to HIV care and treatment access to ensure the full benefits of U=U are realised.

Correcting for methane interferences on δ2H and δ18O measurements in pore water using H2Oliquid-H2Ovapor equilibration laser spectroscopy.

Cavity ring-down spectroscopy (CRDS) is a new and evolving technology that shows great promise for isotopic δ(18)O and δ(2)H analyses of pore water from equilibrated headspace H(2)O vapor from environmental and geologic cores. We show that naturally occurring levels of CH(4) can seriously interfere with CRDS spectra, leading to erroneous δ(18)O and δ(2)H results for water. We created a new CRDS correction algorithm to account for CH(4) concentrations typically observed in subsurface and anaerobic environments, such as ground waters or lake bottom sediments. We subsequently applied the correction method to a series of geologic cores that contain CH(4). The correction overcomes the spectral interference and provides accurate pore water δ(18)O and δ(2)H values with acceptable precision levels as well as accurate concentrations of CH(4).

Balancing the circulation: theoretic optimization of pulmonary/systemic flow ratio in hypoplastic left heart syndrome.

OBJECTIVES: This study examined the effects of the pulmonary (QP)/systemic (QS) blood flow ratio (QP/QS) on systemic oxygen availability in neonates with hypoplastic left heart syndrome. BACKGROUND: The management of neonates with hypoplastic left heart syndrome is complex and controversial. Both before and after surgical palliation and before heart transplantation, a univentricle with parallel pulmonary and systemic circulations exists. It is generally assumed that balancing pulmonary and systemic blood flow is best to stabilize the circulation. METHODS: We developed a mathematical model that was based on the simple flow of oxygen uptake in the lungs and whole-body oxygen consumption to study the effect of varying the QP/QS ratio. An equation was derived that related the key variables of cardiac output, pulmonary venous oxygen saturation and the QP/QS ratio to systemic oxygen availability. RESULTS: The key findings are 1) as the QP/QS ratio increases, systemic oxygen availability increases initially, reaches a maximum and then decreases; 2) for maximal systemic oxygen availability, the optimal QP/QS ratio is < or = 1; 3) the optimal QP/QS ratio decreases as cardiac output or percent pulmonary venous oxygen saturation, or both, increase; 4) the critical range of QP/QS, where oxygen supply exceeds basal oxygen consumption, decreases as cardiac output and percent pulmonary venous oxygen saturation decrease; 5) the relation between oxygen availability and QP/QS is very steep when QP/QS approaches this critical value; and 6) the percent oxygen saturation of systemic venous blood is very low outside the critical range of QP/QS and high within the critical range. CONCLUSIONS: This analysis provides a theoretic basis for balancing both the pulmonary and systemic circulation and suggests that evaluating both systemic arterial and venous oxygen saturation may be a useful way to determine the relative pulmonary and systemic flows. When high systemic arterial and low systemic venous oxygen saturation are present, pulmonary blood flow should be decreased; conversely, when both low systemic arterial and venous oxygen saturation are present, more flow should be directed to the pulmonary circulation.

Absence of antibody to human immunodeficiency virus in long-term, socially rehabilitated methadone maintenance patients.

Human immunodeficiency virus (HIV) infection has become widespread among parenteral drug abusers. We measured antibody to HIV and hepatitis B virus markers in 58 long-term, socially rehabilitated methadone-maintained former heroin addicts. None of the 58 had antibody to HIV, but one or more markers of hepatitis B virus infection were seen in 53 (91%). The duration of methadone maintenance was 16.9 +/- 0.5 years, and the median dose of methadone was 60 mg (range, 5 to 100 mg). Before methadone treatment, the patients had abused heroin parenterally for 10.3 +/- 1.7 years, and they had engaged in additional high-risk practices for HIV infection. We conclude that successful outcomes during methadone maintenance treatment are associated with sparing of parenteral drug abusers from HIV infection.

Clinical research techniques in tardive dyskinesia.

The authors have developed standardized assessment and control techniques designed to provide objective measures of tardive dyskinesia in patients progressing through an experimental treatment program. Standardized videotaping is carried out and blind ratings on the Abnormal Involuntary Movement Scale are made by a team of psychiatrists and neurologists. Other assessments include several measurements of vocal function and a quantitative acceleration profile standardized on normal subjects. Such measures allow quantifiable determination of response to drug treatment and may provide clues to the etiology and definition of the dyskinetic syndrome.

Quality assessment and improvement in group psychotherapy.

OBJECTIVE: The authors sought a practical means of monitoring and evaluating group psychotherapy, using existing clinical resources, for purposes of quality improvement and education on a large general hospital psychiatric service. METHOD: Monitoring indicators were developed which addressed 1) the integration of group psychotherapy into treatment planning and 2) the competence and technique of group psychotherapists. The second indicator was assessed by skilled observers using a newly constructed Group Psychotherapy Rating Scale in direct observation of group psychotherapy sessions. The rating scale was examined for interrater reliability and, as a measure of construct validity, for its ability to distinguish the performance of professional staff therapists from that of trainees. RESULTS: The indicators provided useful monitors of the use and quality of group psychotherapy. The rating scale had satisfactory interrater reliability and construct validity. The immediate constructive educational critique given by the observers of the therapy groups was highly valued by group therapists. CONCLUSIONS: The monitoring and evaluation program proved to be a practical, positive, and inexpensive means of assuring and improving the quality of group psychotherapy in a clinical setting.

High-dose benzodiazepine therapy in hospitalized anxious patients.

Severely anxious hospitalized patients were treated with rapidly increasing doses of two benzodiazepine compounds to test the feasibility of rapid pharmacotherapy of the condition. Twenty-one subjects completing the study all obtained substantial relief from symptoms; in only three subjects were symptoms completely eliminated. No serious side effects were encountered.

Holmium:YAG laser transmyocardial revascularization relieves angina and improves functional status.

BACKGROUND: Transmyocardial revascularization (TMR) surgery uses laser channeling of diseased myocardium to treat ischemia and angina. Rigorous prospective randomized studies have been previously unavailable. METHODS: Forty-three patients were randomized to a medication group and 43 to a group scheduled for TMR surgery and medication. All had advanced cardiac ischemia with CCSA class 3 or 4 angina, took at least 2 cardiac medications at maximum doses, and were ineligible for angioplasty or bypass. RESULTS: Forty-two of 43 TMR group patients received surgery and were discharged after hospitalizations averaging 3.2 days. Two suffered perioperative MIs, with one death. Four others died within 12 months of surgery, 3 from cardiac events and 1 from pneumonia. Five medical group patients died from cardiac events within 12 months. Three, 6, and 12 month exams showed angina class improvement in TMR patients compared to preoperative values (3.86 +/- 0.05 vs 1.71 +/- 0.2, P < 0.0001), and to controls at 12 months (3.77 +/- 0.07 vs 1.71 +/- 0.2, P < 0.0001). Exercise tolerance improved in TMR patients over preoperative values, and was better than medication group scores after 12 months (490 +/- 17 sec. vs 294 +/- 12 sec., p = 0.0002). CONCLUSIONS: Holmium:YAG laser channeling of the myocardium improves function and reduces angina in advanced cardiac patients who lack alternative therapeutic options.

Loss of an X chromosome in aggressive angiomyxoma of female soft parts: a case report.

Cytogenetic analysis of an aggressive angiomyxoma of the vulvar region of a 16-year-old female revealed loss of one X chromosome (45,X,-X) in eight of 20 metaphase cells analyzed. Fluorescence in situ hybridization (FISH) performed on disaggregated cells from paraffin embedded lesional tissue confirmed loss of an X chromosome in 31% of cells. Cytogenetic analysis performed on peripheral blood showed a normal chromosomal complement (46,XX). Thus, loss of one X chromosome appears to be confined to the neoplasm. This anomaly has not been previously described in aggressive angiomyxoma.

The medical status of methadone maintenance patients in treatment for 11-18 years.

To assess the safety and potential health consequences of long-term methadone maintenance treatment, we identified 111 male patients admitted to methadone maintenance treatment between 1965 and 1968, still enrolled in 1980 and in continuous treatment for at least 10 years. We were able, between 1980 and 1985, to examine patients or review records of 110 patients (99%). Most medical diagnoses, symptomatic complaints, physical examination findings and laboratory test results occurred with similar frequency in the long-term methadone maintenance patients and in a group of 56 long-term heroin addicts. These data suggest that prolonged methadone maintenance treatment is safe and is not associated with unexpected adverse effects.

Surgical myocardial revascularization.

In conclusion, surgical myocardial revascularization has utilized diverse methods to increase blood flow to the starving myocardium. These methods initially used the microcirculation as the portal to reach myocytes until angiography showed that the obstructions were macrovascular. This resulted in a 30-year era of direct attack on the coronary blockages by coronary bypass. Surgical conduits unfortunately have longevity considerably less than that of native arteries and are limited in number. Alternative conduits, both biologic and prosthetic, have not yet proved to have the same clinical results as the ITA. More patients are living long enough to have the extensiveness of their disease exhaust conventional therapies. Newer therapy, restricted thus far to untreatables, revisits the microcirculation by making laser channels. These many innovative procedures have benefited hundreds of thousands of patients. They emerged from the probity and innovation of many individual surgeons.

Causes and rates of death among methadone maintenance patients before and after the onset of the HIV/AIDS epidemic.

Causes of death and the mortality rates of active methadone patients and those who had left treatment were compared. Prior to the HIV epidemic, death rates among discharged methadone patients were more than twice that of patients who continued with their methadone treatment. However, the death rate from heroin-related causes in the post-treatment period was 51 times the rate among active patients. Alcohol-related conditions were the leading causes of death in patients more than 30 years old on methadone. During the post-treatment period, alcohol-related deaths were second to those of heroin-related causes. Alcohol-related deaths were particularly pronounced among black patients. Death rates among active male and female patients were identical, but the death rate for discharged female patients was greater than for discharged males. With the onset of the HIV epidemic in the 1980s, AIDS-related causes became the major cause of death in treatment. However, other causes of death, such as alcohol and other medical conditions, identified prior to the AIDS epidemic, persisted. AIDS-related deaths peaked in the mid-1990s and have recently subsided. However, within the past two years, deaths related to HCV have increased to 9% of all patient deaths in a major methadone program. With the emergence of HCV, deaths from this cause are expected to eclipse AIDS-related deaths within the next decade.

An alternative program for methadone maintenance dropouts: description and preliminary data.

Time in drug treatment has been shown to be one of the best predictors of post-treatment success. Since as many as half of the enrollees leave methadone treatment during the first year, the project described in this article was designed to test the effectiveness of an alternative program for individuals who have recently dropped out of methadone maintenance treatment. The goals of this "Alternative Program" are to help participants re-connect with formal drug treatment and other community or medical programs, reduce their HIV risk behavior, decrease or eliminate drug use, join self-help groups, and obtain entitlements. Program components include: contacts by local outreach workers, cognitive-behavioral relapse-prevention group counseling, and individual counseling for needs assessment and referral. This paper describes the basis for development of the intervention, summarizes the methodology being used, and provides preliminary data on participation in the Alternative Program.

The converging epidemics of mood-altering-drug use, HIV, HCV, and partner violence: a conundrum for methadone maintenance treatment.

BACKGROUND: Accumulating evidence suggests that partner violence may be associated with HIV risk behavior and drug use among women in methadone maintenance treatment programs (MMTPs), yet the mechanisms linking these overlapping problems remain unclear. The main purpose of this qualitative study is to explore in detail how drug-related activities and HIV risk behavior occur in the context of a recent episode of partner violence among women in MMTPs. METHOD: We conducted and analyzed in-depth interviews with 31 women who reported having experienced physical or sexual violence by an intimate partner during the past year. Guided by existing research, feminist theory and trauma theory, we constructed a set of questions which were designed to explore multiple ways in which drug-related activities or HIV risk behavior may be linked directly or indirectly to the recent event. To examine the extent and significance of the woman sand/or her partner s drug-related activities or sexual HIV risk issues occurring immediately before, during and/or after the most recent event, we adapted a series of techniques for thematic analysis of qualitative data. RESULTS: Of the 31 women who reported recent events: 83.8 % (n=26) recalled recent events in which there was some drug-involvement; 40% (n=13) indicated that both she and her partner were involved in drug-related activities during the most recent event of partner abuse; 35% (n=11) reported that the partner was drug-involved; and only two women (6.4%) indicated that they alone had been drug-involved. One-fifth (19.3%, n=6) of the women indicated that they had used drugs immediately after the event because they were upset or in physical pain. One-fifth of the women (n=6) reported that they had coerced, unprotected sex during or after the most recent incident. CONCLUSIONS: The multiple ways in which the use of mood-altering drugs are related to partner violence and the occurrence of coerced, unprotected sex underscore the need to design specific interventions for preventing drug relapse, and HIV and HCV infection among abused women in MMTPs. Treatment and policy implications of study findings are discussed.

Methadone medical maintenance (MMM): treating chronic opioid dependence in private medical practice--a summary report (1983-1998).

BACKGROUND: Methadone Medical Maintenance (MMM) was implemented in 1983 to enable socially rehabilitated methadone patients to be treated in the offices of private physicians rather than in the traditional clinic system. Over a period of 15 years, 158 methadone patients who fulfilled specific criteria within the clinic system entered this program in New York City. Participating patients reported to their physician once a month and received a one-month supply of methadone tablets rather than a one-day liquid dose in a bottle. METHOD: Of the 158 patients who entered this program, 132 (83.5%) were compliant with the regulations and proved to be treatable within the hospital-based private practices of internists participating in the program. Compliant MMM patients found it easier to improve their employment status and business situations, finish their educations, and normalize their lives in MMM as opposed to the traditional clinic system because they had simplified reporting schedules and fewer clinical restrictions. Twelve (8%) compliant patients were able to successfully withdraw from methadone after an average of 17.7 years of treatment in both the traditional clinics and MMM. Twenty compliant patients (13%) died from a variety of causes, 40% of which were related to cigarette smoking. None of the deaths were attributable to long-term methadone treatment. Other causes of death included hepatitis C, AIDS, cancer, homicide, complications of morbid obesity and meningitis. RESULTS: The 26 noncompliant patients (16.5%) were referred back to their clinics for continued treatment or were discharged for failure to report as directed. A major cause of failure in MMM was abuse of crack/cocaine. CONCLUSIONS: Stigma concerning enrollment in methadone treatment was a major social issue that patients faced. Many refused to inform employers, members of their families, friends, and other physicians who treated them for a various of conditions that they were methadone patients. The methadone medical maintenance physician, therefore, functions as a medical ombudsman for the patient, educating other physicians who treat the patient about methadone maintenance and its applicability to the patient. Our results can serve as a model for the expansion of office-based MMM treatment.

Cerebral metabolism in opiate-dependent subjects: effects of methadone maintenance.

BACKGROUND: The long-term effects of opiate use on human brain are not known. The goal of this preliminary study was to determine whether human subjects with histories of opiate dependence have persistent differences in brain function as compared with individuals without substance use disorders, and whether methadone maintenance reverses or ameliorates the potential abnormality. METHOD: Positron emission tomographic (PET) [18F]fluorodeoxyglucose (FDG) method was used to compare the regional cerebral metabolic rate for glucose(rCMRglc) in three groups: four opiate-dependent subjects currently receiving methadone maintenance therapy (MM), four opiate-dependent subjects not receiving methadone maintenance therapy (MW), and a comparison group of five subjects without substance use disorders. RESULTS: A significant difference in rCMRglc in the anterior cingulate gyrus was found between the MW and Control groups (Mann-Whitney U=2.0, p=0.05). Generally speaking, rCMRglc's in MM subjects were intermediate between those of MW and Control groups, although the difference did not reach statistical significance. CONCLUSIONS: The results of this study suggest that neurobiological abnormalities can persist in the brain of a chronic opiate user several years after detoxification from methadone. Future research is needed to replicate these results and to determine whether the observed rCMRglc differences are related to opiate use or to neurochemical abnormalities that play a role in developing addictive behavior.

Drug use, HIV-related risk behaviors and dropout status of new admissions and re-admissions to methadone treatment.

New entrants to methadone maintenance treatment programs (MMTP) have been reported to have different drug use patterns than re-admissions. This study assesses differences between 211 re-admissions and 128 new admissions to a NYC MMTP. Those new to MMTP were found to be less likely to have ever injected drugs, have used more types of drugs, and used heroin at higher frequencies in the 30 days prior to admission. Within the first three months of treatment, new admissions dropped out at a higher rate than the re-admissions (31% vs. 20%, p < 0.05). The most frequent reasons for dropout, for both groups, included "lost to contact" and incarceration. Further research on strategies to address polydrug use of MMTP admissions is needed. Efforts to identify concerns of new admissions early in treatment, and programs to continue drug treatment services to incarcerated clients, are indicated.

Parapubic hernia: case report and review of the literature.

Parapubic hernia is considered rare, with 18 hernias described in five articles published since 1971. The hernia results from iatrogenically or traumatically detached rectus abdominis muscles at the pubic bone and presents a therapeutic challenge because there is no strong aponeurotic anchoring structure in the defect's caudal aspect. We describe a patient with a large parapubic hernia repaired by a combined preperitoneal and onlay prosthetic method. This report adds another dimension to the prosthetic repair options in parapubic hernias and illustrates the effectiveness of the tension-free repair principle in their definitive management.

Entero-colocutaneous fistula: a late consequence of polypropylene mesh abdominal wall repair: case report and review of the literature.

BACKGROUND: The underlying risk associated with visceral mesh erosion is the close opposition of adjacent intestines to the prosthetic graft. This highly morbid condition has been described with most types and techniques of abdominal wall mesh repair. PATIENT: We report the case of a 52-year-old man who presented with an entero-colocutaneous fistula 10 years after prosthetic mesh repair of an incisional hernia. The fistula was excised and the abdominal wall defect repaired with a tissue-impervious composite. CONCLUSIONS: The use of a tissue-impervious barrier avoids development of enteric fistula when a prosthesis is placed directly over the viscera.