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Biomedical subjects

M Morin

Publications and source records attributed to M Morin.

At least 37 records · Page 2Linked to original sources
PubMed2001

CEREC: the power of technology.

Dentistry has had a remarkable history. Technological advances have contributed immeasurably to efficient procedures, quality treatment, and patient satisfaction. CEREC, a computer-assisted design/computer-assisted manufacture (CAD/CAM) development that has been on the market for 15 years, is one such innovation. Capable of providing a durable, cosmetic, nonmetal filling in only one appointment and in less than an hour, the efficient use of the CEREC unit contributes markedly to quality care, patient satisfaction, and practice profit. CEREC, an acronym for ceramic-reconstruction, is a technology developed in 1985 by two Swiss researchers, a dentist and an electronics engineer, from the University of Zurich. With 15 years of research and development and more restorations placed than any comparable unit, the CEREC family of products has earned its role in dental history as the technology that gives patients one of the finest restorations in the world in only one visit.

Ceramics↗
PubMed2000

Low level laser therapy (classes I, II and III) for the treatment of osteoarthritis.

BACKGROUND: Osteoarthritis (OA) affects a large proportion of the population. Low Level Laser Therapy (LLLT) is a light source that generates extremely pure light, of a single wavelength. The effect is not thermal, but rather related to photochemical reactions in the cells. LLLT was introduced as an alternative non-invasive treatment for OA about 10 years ago, but its effectiveness is still controversial. OBJECTIVES: To assess the effectiveness of LLLT in the treatment of OA. SEARCH STRATEGY: We searched MEDLINE, EMBASE, the Cochrane Musculoskeletal registry, the registry of the Rehabilitation and Related Thereapies field and the Cochrane Controlled Trials Register up to January 30, 2000. SELECTION CRITERIA: Following an a priori protocol, only controlled clinical trials of LLLT for the treatment of patients with a clinical diagnosis of OA were eligible. Abstracts were excluded unless further data could be obtained from the authors. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials and abstracted data using predetermined forms. Heterogeneity was tested with Cochran's Q test. A fixed effects model was used throughout for continuous variables, except where heterogeneity existed, in which case, a random effects model was used. Results were analyzed as weighted mean differences (WMD) with 95% confidence intervals (CI), where the difference between the treated and control groups was weighted by the inverse of the variance. Standardized mean differences (SMD) were calculated by dividing the difference between treated and control by the baseline variance. SMD were used when different scales were used to measure the same concept (e.g. pain). Dichotomous outcomes were analyzed with odds ratios. MAIN RESULTS: Five trials were included, with 112 patients randomized to laser, 85 patients to placebo laser. Treatment duration ranged from 4 to 10 weeks. Pain was assessed by four trials. The pooled estimate (random effects) of three trials showed no effect on pain measured using a scale (SMD: -0.2, 95% CI: -1.0, +0.6), but there was statistically significant heterogeneity (p>0,05). Two of the trials showed no effect and one demonstrated very beneficial effects with laser. In another trial, with no scale-based pain outcome, significantly more patients reported pain relief (yes/no) with laser with an odds ratio of 0.05, (95% CI: 0.0 to 1.56). Other outcomes of joint tenderness, joint mobility and strength were not significant. REVIEWER'S CONCLUSIONS: For OA, the results are conflicting in different studies and may depend on the method of application and other features of the LLLT application. Clinicians and researchers should consistently report the characteristics of the LLLT device and the application techniques used. New trials on LLLT should make use of standardized, validated outcomes. Despite some positive findings, this meta-analysis lacked data on how LLLT effectiveness is affected by four important factors: wavelength, treatment duration of LLLT, dosage and site of application over nerves instead of joints. There is clearly a need to investigate the effects of these factors on LLLT effectiveness for OA in randomized controlled clinical trials.

Humans↗
PubMed2000

Low level laser therapy (classes I, II and III) in the treatment of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) affects a large proportion of the population. Low Level Laser Therapy (LLLT) was introduced as an alternative non-invasive treatment for RA about 10 years ago. LLLT is a light source that generates extremely pure light, of a single wavelength. The effect is not thermal, but rather related to photochemical reactions in the cells. The effectiveness of LLLT for rheumatoid arthritis is still controversial. OBJECTIVES: To assess the effectiveness of LLLT in the treatment of RA. SEARCH STRATEGY: We searched MEDLINE, EMBASE, the registries of the Cochrane Musculoskeletal group and the field of Rehabilitation and Related Therapies as well as the Cochrane Controlled Trials Register up to January 30, 2000. SELECTION CRITERIA: Following an a priori protocol, we selected only randomized controlled trials of LLLT for the treatment of patients with a clinical diagnosis of RA were eligible. Abstracts were excluded unless further data could be obtained from the authors. DATA COLLECTION AND ANALYSIS: Two reviewers independently select trials for inclusion, then extracted data and assessed quality using predetermined forms. Heterogeneity was tested with Cochran's Q test. A fixed effects model was used throughout for continuous variables, except where heterogeneity existed, in which case, a random effects model was used. Results were analyzed as weighted mean differences (WMD) with 95% confidence intervals (CI), where the difference between the treated and control groups was weighted by the inverse of the variance. Standardized mean differences (SMD) were calculated by dividing the difference between treated and control by the baseline variance. SMD were used when different scales were used to measure the same concept (e.g. pain). Dichotomous outcomes were analyzed with odds ratios. MAIN RESULTS: A total of 204 patients were included in the five placebo-controlled trials, with 112 randomized to laser therapy. Relative to a separate control group, LLLT reduced pain by 70% relative to placebo and reduced morning stiffness duration by 27.5 minutes (95%CI: 2.9 to 52 minutes) and increased tip to palm flexibility by 1.3 cm (95% CI: 0. 8 to 1.7 cm). Other outcomes such as functional assessment, range of motion and local swelling did not differ between groups. There were no significant differences between subgroups based on LLLT dosage, wavelength, site of application or treatment length. For RA, relative to a control group using the opposite hand, there was no difference between the control and treatment hand, but all hands improved in terms of pain relief and disease activity. REVIEWER'S CONCLUSIONS: In summary, LLLT for RA is beneficial as a minimum of a four-week treatment with reductions in pain and morning stiffness. On the one hand, this meta-analysis found that pooled data gave some evidence of a clinical effect, but the outcomes were in conflict, and it must therefore be concluded that firm documentation of the application of LLLT in RA is not possible. Clinicians and researchers should consistently report the characteristics of the LLLT device and the application techniques used. New trials on LLLT should make use of standardized, validated outcomes. Despite some positive findings, this meta-analysis lacked data on how LLLT effectiveness is affected by four important factors: wavelength, treatment duration of LLLT, dosage and site of application over nerves instead of joints.

Arthritis, Rheumatoid↗
PubMed2000

Analysis of lung tumour risk in radon-exposed rats: an intercomparison of multi-step modelling.

Three carcinogenesis modelling groups have both jointly and separately applied a multi-step carcinogenesis model with clonal expansion to one data set of lung tumours in rats exposed to radon (CEA, France). This study was designed to investigate the differences in modelling approach and fitting procedures used by the three groups in detail, and to explore possible discrepancies in the results. Using the same model assumptions and a (linear) radiation dependence on the first model step only, the three groups arrived at identical best fits, proving that the mathematical formalisms and fitting procedures do not lead to different results. However, when each group was allowed to find its own preferred fit for this data set, all three found a significantly better, but different fit to the data. All solutions indicated radiation to be an initiating agent and found additional radiation action necessary. The character of this additional radiation dependence, however, could not be unambiguously pinpointed. Tumour incidence data were described equally well when radiation dependence was taken into account in clonal expansion ("promotion") or in the second mutational step ("transformation"); extension to three model stages also resulted in an adequate description. The study showed that, although the three groups used one carcinogenesis model in principle, different model assumptions and/or different methods of finding the "best fit" could result in different descriptions of experimental data. This implies that on statistical grounds, different interpretations can be given for the action that radiation had in this data set. Different data, i.e. other data sets with age-dependent tumour data and/or information from cellular radiobiology experiments, are needed to specifically pin down the radiation dependence in the multi-step carcinogenesis process.

Age Factors↗
PubMed2000

Adherence to HIV combination therapy.

The emergence of drug-resistant strains of HIV virus and treatment failure can result from non-adherence to antiretroviral therapy. While non-adherence to therapy is not a new issue or specific to HIV/AIDS, it has received renewed attention because of the complicated combination treatment regimens being prescribed. This paper reviews the relevant background literature on the contributions of social and behavioural science to non-adherence to HIV medications. Data indicating problems with adherence prior to combination therapy are reported. Despite limitations, even self-report assessments have already succeeded in showing that adherence to combination therapy is significantly related to HIV viral load. Recent research data are discussed. Implications of findings for counselling patients to increase their adherence are presented.

Anti-HIV Agents↗
PubMed2000

Injecting drug users' adherence to HIV antiretroviral treatments: physicians' beliefs.

This paper investigates physicians' judgements about adherence to antiretroviral treatment (ART) among patients who have been HIV-infected through injecting drug use (IDU). Comparisons were made between data collected from physicians at enrollment (January 1996 to January 1998) of a prospective cohort study (MANIF 2000) and self-declarations of 196 HIV-infected injecting drug users (IDUs) who have been prescribed ART. The likelihood of being perceived as 'adherent' by physicians was higher for women, patients of 30 years of age or older, with biological markers indicative of a healthier status, and who were perceived as 'free of injecting behaviour' and not in drug maintenance treatment. Although the proportion of non-adherent patients was similar in physicians' assessment (26.0%) and patients' self-declarations (27.0%), a strong discordance occurred: 60.4% of patients self-reporting non-adherence to ART (80.0% for those receiving a protease inhibitor) were classified as adherent by their prescribing physicians. The study suggests that a priori judgements based on clinical experience but also on social stereotypes interfere with physicians' assessment, and that physicians' decisions to initiate complex treatment regimens may further induce optimistic biases and an underestimation of the problems faced by IDU patients to adequately adhere to them.

Adolescent↗
PubMed2000

Transformation by radiation of rat foetal glial cells.

PURPOSE: To establish and characterize an in vitro model of radiation-induced transformation of normal glial cells. MATERIALS AND METHODS: During the last week of gestation, pregnant Sprague-Dawley rats were either irradiated at 3.5 Gy (0.022 Gy h(-1)) with a 60Co source or sham irradiated. On day 21 of gestation, cortical nerve cells from foetuses were isolated, and then maintained in culture for about 100 passages, in presence of 10(-9) g/ml of tetradecanoyl phorbol acetate (TPA). To follow transformation, various parameters: cell type, proliferation, clonogenicity, karyotypes and tumorigenicity, were studied at different passages. RESULTS: As the number of passages increased, control cells lost their glial morphology and were immortalized. They kept on expressing specific markers of type 2 astrocytes (glial fibrillary acid protein (GFAP) and A2B5). Karyotypes remained near diploid. At all passages tested, they were not tumorigenic in nude mice. Irradiated cells expressed the 2A progenitor cell specific markers: GFAP, vimentin and A2B5. Karyotypes evolved toward polyploidy and cells displayed an iso 7 and a marker. These changes were synchronous with modifications in tumorigenicity. Metastases were even observed in nude mice. CONCLUSIONS: Cells from irradiated animals were fully transformed, while cells from sham irradiated animals were only immortalized.

Animals↗
PubMed2000

The RNA-binding protein HuD is required for GAP-43 mRNA stability, GAP-43 gene expression, and PKC-dependent neurite outgrowth in PC12 cells.

The RNA-binding protein HuD binds to a regulatory element in the 3' untranslated region (3' UTR) of the GAP-43 mRNA. To investigate the functional significance of this interaction, we generated PC12 cell lines in which HuD levels were controlled by transfection with either antisense (pDuH) or sense (pcHuD) constructs. pDuH-transfected cells contained reduced amounts of GAP-43 protein and mRNA, and these levels remained low even after nerve growth factor (NGF) stimulation, a treatment that is normally associated with protein kinase C (PKC)-dependent stabilization of the GAP-43 mRNA and neuronal differentiation. Analysis of GAP-43 mRNA stability demonstrated that the mRNA had a shorter half-life in these cells. In agreement with their deficient GAP-43 expression, pDuH cells failed to grow neurites in the presence of NGF or phorbol esters. These cells, however, exhibited normal neurite outgrowth when exposed to dibutyryl-cAMP, an agent that induces outgrowth independently from GAP-43. We observed opposite effects in pcHuD-transfected cells. The GAP-43 mRNA was stabilized in these cells, leading to an increase in the levels of the GAP-43 mRNA and protein. pcHuD cells were also found to grow short spontaneous neurites, a process that required the presence of GAP-43. In conclusion, our results suggest that HuD plays a critical role in PKC-mediated neurite outgrowth in PC12 cells and that this protein does so primarily by promoting the stabilization of the GAP-43 mRNA.

Animals↗
PubMed2000

Neutron RBE for induction of tumors with high lethality in Sprague-Dawley rats.

The effectiveness of fission neutrons is compared to that of gamma rays and X rays with regard to the induction of malignancies in male Sprague-Dawley rats. The analysis is based on autopsy results. It is focused on tumors that tend to be present in animals dying early, which is indicative of a high degree of lethality. The relative biological effectiveness (RBE) is deduced from a comparison of the cumulative hazard functions. Different nonparametric models-the constant relative risk model, a time shift model, and an acceleration model-are employed in the comparison, and the resulting values of RBE are seen to be substantially independent of the choice of model. The results are in good agreement with earlier studies of nonlethal lung tumors in the same series of experiments. At neutron doses of 20 to 60 mGy, the RBE of fission neutrons is about 50.

Animals↗
PubMed2000

Low level laser therapy for osteoarthritis and rheumatoid arthritis: a metaanalysis.

OBJECTIVE: Osteoarthritis (OA) and rheumatoid arthritis (RA) affect a large proportion of the population. Low level laser therapy (LLLT) was introduced as an alternative noninvasive treatment for RA and OA about 10 years ago, but its effectiveness is still controversial. We assessed the effectiveness of LLLT in the treatment of RA and OA. METHODS: A systematic review was conducted, following an a priori protocol, according to the methods recommended by the Cochrane Collaboration. Trials were identified by a literature search of Medline, Embase, and the Cochrane Controlled Trials Register. Only randomized controlled trials of LLLT for the treatment of patients with a clinical diagnosis of RA or OA were eligible. Thirteen trials were included, with 212 patients randomized to laser and 174 patients to placebo laser, and 68 patients received active laser on one hand and placebo on the opposite hand. Treatment duration ranged from 4 to 10 weeks. Followup was reported by only 2 trials for up to 3 months. RESULTS: In patients with RA, relative to a separate control group, LLLT reduced pain by 70% relative to placebo and reduced morning stiffness by 27.5 min (95% CI -52.0 to -2.9), and increased tip to palm flexibility by 1.3 cm (95% CI -1.7 to -0.8). Other outcomes such as functional assessment, range of motion, and local swelling were not different between groups. There were no significant differences between subgroups based on LLLT dosage, wavelength, site of application, or treatment length. In RA, relative to a control group using the opposite hand, there was no difference between control and treatment hand, but all hands were improved in terms of pain relief and disease activity. For OA, a total of 197 patients were randomized. Pain was assessed by 3 trials. The pooled estimate (random effects) showed no effect on pain (standardized mean difference -0.2, 95% CI -1.0 to +0.6), but there was statistically significant heterogeneity (p > 0.05). Other outcomes of joint tenderness, joint mobility, and strength were not significant. CONCLUSION: LLLT should be considered for short term relief of pain and morning stiffness in RA, particularly since it has few side effects. For OA, the results are conflicting in different studies and may depend on the method of application and other features of the LLLT. Clinicians and researchers should consistently report the characteristics of the LLLT device and the application techniques. New trials on LLLT should make use of standardized, validated outcomes. Despite some positive findings, this metaanalysis lacked data on how effectiveness of LLLT is affected by 4 factors: wavelength, treatment duration of LLLT, dosage, and site of application over nerves instead of joints. There is a need to investigate the effects of these factors on effectiveness of LLLT for RA and OA in randomized controlled clinical trials.

Aged↗
PubMed1999

Typing of porcine circovirus in clinical specimens by multiplex PCR.

A multiplex PCR assay was developed to detect and differentiate between the porcine circovirus (PCV) infecting persistently the PK 15 cell line (PCV type I) and the PCV associated with postweaning multisystemic wasting syndrome (PMWS) (PCV type II). DNA products with unique sizes characteristic of each type of PCV were obtained. Sequencing of these products demonstrated that the nucleotide sequences were type-specific. Tissue samples from a total of 42 field cases from Québec were studied, among which 41 were collected in 1997-1998 and one which had been previously collected in 1994. These 42 cases found previously to be PCV-positive by PCR were tested in the present study by a multiplex PCR assay to determine the type of PCV in each case. From these 42 field cases, 40 cases were PCV type II-positive, one case was PCV type I-positive and one case was positive for both PCV types I and II. PCV type II was identified in typical PMWS field cases, but also in field cases submitted for various clinical histories, some of which were not suggestive of PMWS. In the field case where PCV type I was detected, there was no clinical evidence nor histological lesions suggestive of PMWS. The demonstration of PCV type II in a total of 41/42 field cases in the present study suggests that PCV type II may be the main type of PCV circulating in pigs. Furthermore the detection of PCV type II in a field case dating back to 1994 indicates that this PCV type was circulating in pigs in Québec several years before the report of clinical PMWS in this province.

Animals↗
PubMed1999

French general practitioners' attitudes toward therapeutic advances in HIV care: results of a national survey.

We aimed to assess attitudes to French primary care providers towards recent advances in HIV care. Telephone surveys in a random sample of French general practitioners (GPs) were carried out in April 1996 (response rate=70.3%; n=1186). Only 40.5% of the sample had participated in the regular medical follow-up of HIV-infected patients during the previous year. Among these 480 respondents, only a few (13.3%) declared that they would take care of an asymptomatic patient with a high (>500 cells/mm3) CD4 count as the unique provider. A majority (66.2%) had referred at least one HIV-infected patient to a hospital specialist in the previous year. A total of 31.4% declared that they considered it appropriate for an antiretroviral treatment to be initiated to an asymptomatic patient with 300 CD4 cells/mm3, and only 23.5% were already in favour of combination therapies rather than zidovudine monotherapy as treatment of choice. GPs with the most experience with HIV care tended to be the most reluctant to modify their attitude in favour of earlier initiation of antiretroviral therapies and of the switch from monotherapy to combination therapies. The survey suggests there is a gap between attitudes of GPs and those of AIDS specialists toward preliminary reports of therapeutic advances in HIV care. Whether or not such a gap may create problems for an appropriate diffusion of new antiretroviral therapies should be carefully monitored, in the context of current reforms emphasizing the key role of primary providers in most health-care systems.

Anti-HIV Agents↗
PubMed1999

Influence of exposure rate on lung cancer induction in rats exposed to radon progeny.

Animal studies were used in addition to epidemiological studies to investigate the effects of exposure, exposure rate and other factors in predicting risks resulting from exposures to radon progeny. A trend toward increasing tumor risk with decreasing exposure rate was observed in rats exposed at a cumulative exposure varying from about 0.72 J h m(-3) (200 WLM) up to 10.8 J h m(-3) (3,000 WLM) and high exposure rates varying from 25 WLM per week to 500 WLM per week. In contrast, at low cumulative exposure, comparable to lifetime domestic indoor exposures or lifetime occupational exposure in uranium mines, no evidence of an inverse exposure-rate effect was found. Chronic radon exposure at 0.09 J h m(-3) (25 WLM), protracted over 18 months, at a potential alpha-particle energy concentration (PAEC) of 0.042 mJ m(-3) (2 WL), resulted in fewer lung carcinomas in rats than a similar cumulative exposure protracted over 4 to 6 months at a PAEC of 2.1 mJ m(-3) (100 WL). The preliminary results of a new series of experiments carried out at relatively low cumulative exposures of 0.36 J h m(-3) (100 WLM) and PAEC varying from 0.21 mJ m(-3) (10 WL) to 3.15 mJ m(-3) (150 WL) indicate that at cumulative exposures comparable to lifetime indoor or occupational exposures, the risk of lung cancer in rats decreases with decreasing PAEC, i.e. exposure rate. These data suggest that the risk of radon-induced lung cancer results from a complex interplay between cumulative exposure and exposure rate at a given exposure level.

Animals↗
PubMed1998

Interaction of insulin receptor substrate-1 with the sigma3A subunit of the adaptor protein complex-3 in cultured adipocytes.

Signaling through the insulin receptor tyrosine kinase involves its autophosphorylation in response to insulin and the subsequent tyrosine phosphorylation of substrate proteins such as insulin receptor substrate-1 (IRS-1). In basal 3T3-L1 adipocytes, IRS-1 is predominantly membrane-bound, and this localization may be important in targeting downstream signaling elements that mediate insulin action. Since IRS-1 localization to membranes may occur through its association with specific membrane proteins, a 3T3-F442A adipocyte cDNA expression library was screened with non-tyrosine-phosphorylated, baculovirus-expressed IRS-1 in order to identify potential IRS-1 receptors. A cDNA clone that encodes sigma3A, a small subunit of the AP-3 adaptor protein complex, was demonstrated to bind IRS-1 utilizing this cloning strategy. The specific interaction between IRS-1 and sigma3A was further verified by in vitro binding studies employing baculovirus-expressed IRS-1 and a glutathione S-transferase (GST)-sigma3A fusion protein. IRS-1 and sigma3A were found to co-fractionate in a detergent-resistant population of low density membranes isolated from basal 3T3-L1 adipocytes. Importantly, the addition of exogenous purified GST-sigma3A to low density membranes caused the release of virtually all of the IRS-1 bound to these membranes, while GST alone had no effect. These results are consistent with the hypothesis that sigma3A serves as an IRS-1 receptor that may dictate the subcellular localization and the signaling functions of IRS-1.

3T3 Cells↗
PubMed1998

French pharmacovigilance survey evaluating the hepatic toxicity of coumarin.

Synthetic coumarin (benzopyrone) was launched in France in 1988 for the adjuvant therapy of lymphoedema of the upper limb following radiosurgical treatment of breast cancer. Further to the reporting of hepatic reactions, a national survey has been carried out. The survey dealt with 22 cases reported to the pharmacovigilance regional centres and 20 to Knoll France company (five duplicate cases) up to June 1996. Thirty-four cases corresponding to an elevation of ALT over 2N and/or alkaline phosphatase over 1.5N (criteria chosen for selection in this survey) had been taken into account. Among these cases, a causal relationship was considered likely or probable for 15 of them. Two positive rechallenges were reported. The hepatic reactions observed between 2 to 6 months of treatment in two-thirds of the cases (average dose: 90 mg/day; i.e. recommended dose) was essentially cytolytic in 85% of the cases, with jaundice in 14 cases and hyperbilirubinaemia reported in five other cases. In 23 cases (68%), the increase of ALT exceeded 10N. Of the patients 41% were hospitalized. Severe liver failure with encephalopathy justified liver transplantation once and likely led to encephalopathy and fatal evolution in two other cases. The evolution was favourable in the other cases. The drug was prescribed for other uses than the registered indication in more than 50% of these cases. No risk factors could be identified in the survey. This survey provides a strong signal for potential hepatotoxicity of coumarin (likely due to the production of a reactive metabolite in some patients exhibiting a coumarin 7-hydroxylation deficiency).

Journal Article↗
PubMed1997

[Observance during clinical trials in HIV infection. A discontinuity between patient history and trial logic].

OBJECTIVES: Describe and analyze the processes which lead to patient compliance or non-compliance in HIV treatment trials and to develop a model for strategies aimed at improving compliance and facilitating inclusion (adherence) of these patients. METHOD: First, 12 members of the health care teams at two day care clinics (Internal medicine unit, Sainte-Marguerite Hospital, Marseille and Hematology unit, Cimiez Hospital, Nice) were interviewed. In addition, 40 patients involved in the Delta trial (known compliance in 22, non compliance in 7, trial refusal in 7 and eligibility in 5 who were not invited to participate) responded in semi-directive discussions. RESULTS: The physicians found that the responses were a priori in agreement with patient compliance for those who had participated. Physicians tended to introduce "unofficial" criteria to select patients on the basis of "psychosociological" patterns. Patient agreement to begin the trial or to refuse inclusion and their compliance to medical prescriptions depended in part on their personal opinion concerning AIDS treatment. Patients who presevered in following medical prescriptions in the long-term trial adapted their lifestyle to the new care system (participation in the trial) and discussed their "adaptation" with the physician. The importance of the patient-physician relationship is of prime importance in the behavior of compliant patients. CONCLUSION: A communication strategy, reinforcing patient adherence at inclusion and favoring compliance during the trial should be part of the "basic rules" for controlled regulation of compliance in clinical trials.

Clinical Trials, Phase III as Topic↗