Contextual determinants of mass drug administration performance: Modelling fourteen years of lymphatic filariasis treatments in West Africa.

BACKGROUND: Effective mass drug administration (MDA) is the cornerstone in the elimination of lymphatic filariasis (LF) and a critical component in combatting all neglected tropical diseases for which preventative chemotherapy is recommended (PC-NTDs). Despite its importance, MDA coverage, however defined, is rarely investigated systematically across time and geography. Most commonly, investigations into coverage react to unsatisfactory outcomes and tend to focus on a single year and health district. Such investigations omit more macro-level influences including sociological, environmental, and programmatic factors. The USAID NTD database contains measures of performance from thousands of district-level LF MDA campaigns across 14 years and 10 West African countries. Specifically, performance was measured as an MDA's epidemiological coverage, calculated as persons treated divided by persons at risk. This analysis aims to explain MDA coverage across time and geography in West Africa using sociological, environmental, and programmatic factors. METHODOLOGY: The analysis links epidemiological coverage data from 3,880 LF MDAs with contextual, non-NTD data via location (each MDA was specific to a health district) and time (MDA month, year). Contextual data included rainfall, temperature, violence or social unrest, COVID-19, the 2014 Ebola outbreak, road access/isolation, population density, observance of Ramadan, and the number of previously completed MDAs. PRINCIPAL FINDINGS: We fit a hierarchical linear regression model with coverage as the dependent variable and performed sensitivity analyses to confirm the selection of the explanatory factors. Above average rainfall, COVID-19, Ebola, violence and social unrest were all significantly associated with lower coverage. Years of prior experience in a district and above average temperature were significantly associated with higher coverage. CONCLUSIONS/SIGNIFICANCE: These generalized and context-focused findings supplement current literature on coverage dynamics and MDA performance. Findings may be used to quantify typically anecdotal considerations in MDA planning. The model and methodology are offered as a tool for further investigation.

Piperphentonamine (PPTA) attenuated cerebral ischemia-induced memory deficits via neuroprotection associated with anti-apoptotic activity.

The calcium sensitizers levosimendan and piperphentonamine hydrochloride (PPTA) are used as cardiovascular drugs for treatment of heart failure. Given that levosimendan has been reported to exhibit a neuroprotective profile in a model of traumatic brain injury, it was interesting to know whether PPTA, a new calcium sensitizer recently developed in China, exerts a similar effect. The objective of this study was to determine whether PPTA exhibited neuroprotective effects and whether these properties were associated with memory. Four-vessel occlusion (4-VO) was used to induce global cerebral ischemia/reperfusion injury in rats treated with or without PPTA (5, 10 mg/kg, i.p., 2 h after the onset of reperfusion and then once a day for 15 consecutive days). Memory was measured using the step-through passive avoidance test. Neurochemical changes were examined in rat PC12 cells treated with oxygen-glucose deprivation (OGD) for 4 h followed by reoxygenation (OGD-R) for 24 h, in the absence or presence of PPTA. In vehicle-treated animals, 4-VO for 10 min produced memory deficits, as demonstrated by decreased retention in step-through passive avoidance, and massive neuron loss in the hippocampal CA1 subregion. These effects were attenuated by PPTA. The results were consistent with those observed in PC12 cells. PPTA treatment increased cell viability, as indicated by MTT assay, inhibited apoptosis, and decreased extracellular lactate dehydrogenase levels in Na(2)S(2)O(4)-treated PC12 cells. These results provide novel demonstration for the ability of PPTA to attenuate cerebral ischemia-induced memory deficits via neuroprotection in the hippocampus. The neuroprotective effect of PPTA appears to be associated with its anti-apoptotic activity. PPTA has the therapeutic potential for ischemic stroke.

[Effects of piperphentonamine hydrochloride on cognitive deficits in rats induced by cerebral ischemia-reperfusion].

OBJECTIVE: To investigate the effect of piperphentonamine hydrochloride (PPTA) on cognitive deficits induced by ischemia-reperfusion and explore the possible mechanisms. METHODS: SD rats were randomly divided into sham-operated group, ischemia-reperfusion group (with saline injection), PPTA-treated groups (2.5, 5, 10 mg/kg) and edaravone-treated group (6 mg/kg). Cerebral ischemia-reperfusion injury was induced by middle cerebral artery occlusion, and the agents were administrated 1 h after ischemia. At 24 h after ischemia, step-through passive avoidance test was carried out, and 24 h later IL-1ß, TNF-α, caspase-3 and HSP-70 mRNA expressions in the ischemic brain tissues were measured with RT-PCR. RESULTS: In the step-through passive avoidance test, the rats in the ischemia-reperfusion group showed significantly shorter latency and more error times than those in the sham group, and these behavioral changes were improved significantly by treatments with PPTA and edaravone. Cerebral ischemia-reperfusion caused significantly increased expressions of IL-1ß, TNF-α, caspase-3 and HSP-70 mRNA, and these changes were obviously reversed by PPTA, but not by edaravone. CONCLUSIONS: PPTA can reverse cognitive deficits induced by cerebral ischemia-reperfusion probably by decreasing the inflammatory responses and cell apoptosis in the brain, suggesting its potential as a new therapeutic agent for improving the cognitive function following cerebral ischemia-reperfusion.

Psychedelic and entactogenic drugs in the treatment of depression.

CNS deficiency of 5-hydroxytryptamine (serotonin) has been implicated as a biochemical basis in some forms of depression. Existing drug modalities for treating depression include some with serotonergic effects. Studies suggest that psychedelic drugs are also serotonergic. This may indicate a role for psychedelics in the treatment of depression. Such treatment has already been attempted using psychedelic drugs in both the indoleamine and phenylalkylamine categories. Encouraging results seem to recommend further research, with special emphasis on drugs in the phenylisopropylamine subgroup of phenylalkylamines that are only peripherally psychedelic. Certain of these, called entactogens or empathogens, cause substantially less distortion of normative consciousness than classic psychedelics, such as LSD or mescaline. They could therefore be more easily assimilated into existing psychotherapy approaches, where their function would be to enhance the normal psychotherapeutic process rather than serving a maintenance role as chemotherapeutic agents. Their usefulness in such an application would be mainly at the start of psychotherapy in order to (1) reduce the client's "fear response" that often inhibits ability to deal with repressed traumatic material; (2) facilitate the client's interpersonal communications with the therapist, spouse or significant others; and (3) accelerate formation of a therapeutic alliance between client and therapist.

Phenomenology and sequelae of 3,4-methylenedioxymethamphetamine use.

3,4-Methylenedioxymethamphetamine (MDMA) has been at the center of a debate over its potential benefits as an adjunct to psychotherapy versus its capability for neurotoxic effects and is currently classified as a Schedule 1 drug by the Drug Enforcement Administration (DEA). However, as yet, there is very little methodological data on the subjective experience of the MDMA-induced state or its psychological and behavioral sequelae. The present study was, therefore, designed to obtain this kind of information. Twenty psychiatrists who had taken MDMA previously were evaluated using a semistructured interview. Subjective experience of the actual MDMA-induced state, as well as both short-term (less than 1 week) and relatively longer term (greater than 1 week) sequelae, were examined retrospectively. Side effects, insight gained, pleasure, and intensity of the MDMA experience were evaluated as were the influence of set and setting at the time the MDMA was taken and the dosage utilized. Finally, the authors discuss methodological problems and limitations of a study of this type.

Can drugs be used to enhance the psychotherapeutic process?

Many preindustrial cultures traditionally use certain psychedelic plants to enhance a procedure that resembles psychotherapy--an idea that was also tested in Western psychiatry in the 1950s and 1960s. LSD and related drugs were used to facilitate the production of memories, fantasies and insights and to enhance the therapeutic alliance. The results were inconclusive, and research was largely abandoned after the drugs became difficult to obtain. It may now be possible to revive this research, using new drugs that do not have some of the disadvantages of the old ones. The drug now of most interest is MDMA (3,4-methylenedioxymethamphetamine) a relatively mild and short-acting substance that is said to give a heightened capacity for introspection and intimacy without the perceptual changes, emotional unpredictability, and occasional adverse reactions associated with LSD. Therapists who have used the drug claim that it can enhance the therapeutic alliance by inviting self-disclosure and promoting trust. Whether MDMA fulfills this promise or not, other drugs may eventually prove useful in psychotherapy. Research on their potential should not be curtailed because of fear that they will be subject to illicit abuse.

Ecstacy: a review of MDMA and MDA.

The Drug Enforcement Administration classified the drug methylenedioxymethamphetamine, MDMA, also known as Ecstacy, as a Schedule I controlled substance on July 1, 1985. The controversy surrounding the classification of MDMA is related to the question of its efficacy as an adjunct to psychotherapy and the larger issue of how to regulate the production and use of designer drugs. The authors review the literature on MDMA and its predecessor, MDA, a substance that differs from MDMA by one methyl group.