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Biomedical subjects

James E Frampton

Publications and source records attributed to James E Frampton.

At least 19 recordsLinked to original sources
PubMed2006

Topical brimonidine 0.2%/timolol 0.5% ophthalmic solution: in glaucoma and ocular hypertension.

A fixed combination of brimonidine (a highly selective alpha(2)-adrenergic agonist) and timolol (a non-selective beta-blocker) [brimonidine 0.2%/timolol 0.5% ophthalmic solution; brimonidine/timolol] is available for the topical treatment of glaucoma and ocular hypertension (OH). Brimonidine and timolol decrease elevated intraocular pressure (IOP) by complementary mechanisms of action and have an additive effect when coadministered to healthy volunteers and patients with glaucoma or OH. When assessed over a 3- or 12-month period in large, well designed clinical studies, brimonidine/timolol instilled twice daily (one drop in each eye) was superior to monotherapy with the individual components instilled two (brimonidine) or three (timolol) times daily, and noninferior to concomitant therapy with the individual components instilled twice daily, in lowering raised IOP in patients with glaucoma or OH. In small, randomised, comparative studies of 1 or 3 months' duration, the IOP-lowering effect of brimonidine/timolol twice daily was similar or superior to that of fixed combination dorzolamide 2%/timolol 0.5% ophthalmic solution (dorzolamide/timolol) twice daily (preliminary data). Brimonidine/timolol is generally well tolerated with a predictable local and systemic adverse event profile based on that of the individual components used alone and concomitantly. No unexpected or serious adverse events associated with the fixed combination were reported in key clinical trials. Brimonidine/timolol may be advantageous over dorzolamide/timolol with respect to ocular tolerability and comfort (preliminary data).

Antihypertensive Agents↗
PubMed2006

Topical dorzolamide 2%/timolol 0.5% ophthalmic solution: a review of its use in the treatment of glaucoma and ocular hypertension.

Topically administered dorzolamide 2%/timolol 0.5% (dorzolamide/timolol ophthalmic solution; Cosopt) is a fixed combination of two ocular hypotensive drugs (the carbonic anhydrase inhibitor dorzolamide and the beta-adrenoceptor antagonist timolol) that have an additive effect on lowering intraocular pressure (IOP) when administered together. This product is indicated for the treatment of elevated IOP in patients with open-angle glaucoma or ocular hypertension (OH) who are insufficiently responsive to topical beta-adrenoceptor antagonist monotherapy. As such, it can be considered for use in individuals who, as a consequence of failing to achieve target IOP with beta-adrenoceptor antagonist monotherapy, require the addition or substitution of another class of topical antiglaucoma medication. Clinical trials have demonstrated that dorzolamide/timolol (1 drop per eye twice daily) is an effective and generally well tolerated fixed combination for lowering IOP in patients with open angle glaucoma or OH, including individuals uncontrolled on beta-adrenoceptor antagonist monotherapy. Compared with concomitant therapy with the individual components, the primary advantage of fixed combination dorzolamide/timolol is convenience.

Drug Combinations↗
PubMed2006

Hexyl aminolevulinate: in the detection of bladder cancer.

Hexyl aminolevulinate, the hexyl ester of 5-aminolevulinic acid, is a photosensitising agent designed to enhance the detection of bladder cancer tumours, in particular highly malignant carcinoma in situ (CIS). After cellular uptake, hexyl aminolevulinate and/or hydrolysed 5-aminolevulinic acid enter the haem biosynthetic pathway and induce accumulation of the photoactive compound protoporphyrin IX (PpIX) in malignant as opposed to nonmalignant cells. PpIX emits red fluorescence when illuminated under blue light. Blue-light fluorescence cystoscopy with hexyl aminolevulinate (hexyl aminolevulinate cystoscopy) was more effective than standard (white-light) cystoscopy for detecting non-muscle-invasive ('superficial') disease in two European, multicentre, phase III trials, which evaluated hexyl aminolevulinate cystoscopy as an adjunct to standard cystoscopy in patients with known or suspected bladder cancer. In one trial, hexyl aminolevulinate cystoscopy detected 96% of the patients with CIS; it identified 28% more patients with CIS than standard cystoscopy. In the other trial, 17% of patients were selected to receive more complete treatment following hexyl aminolevulinate cystoscopy than standard cystoscopy, because of the improved tumour detection rate. Hexyl aminolevulinate cystoscopy is well tolerated as an adjunct to standard cystoscopy; adverse events were those typically associated with standard cystoscopy/biopsy (e.g. postoperative pain).

Aminolevulinic Acid↗
PubMed2006

Efavirenz/emtricitabine/tenofovir disoproxil fumarate: triple combination tablet.

A new formulation combining fixed doses of the nucleoside reverse transcriptase inhibitors emtricitabine (200mg) and tenofovir disoproxil fumarate (tenofovir DF; 300 mg) with the non-nucleoside reverse transcriptase inhibitor efavirenz (600 mg) represents the first once-daily, one-tablet antiretroviral regimen. Co-formulated efavirenz/emtricitabine/tenofovir DF demonstrated bioequivalence to concomitant administration of the individual agents in a pharmacokinetic trial in healthy volunteers (n = 48). Co-formulated efavirenz/emtricitabine/tenofovir DF has not been evaluated in clinical trials. However, a once-daily regimen of efavirenz, emtricitabine and tenofovir DF (administered as individual agents) was superior to once-daily efavirenz plus twice-daily co-formulated lamivudine/zidovudine in terms of virological suppression, immunological recovery and adverse events resulting in discontinuation of the study medications in a randomised, multicentre, noninferiority study in treatment-naive patients with HIV infection (n = 517). Both regimens are currently recommended as initial antiretroviral therapy. Preliminary data suggest that co-formulated efavirenz/emtricitabine/tenofovir DF, like the individual agents in combination with other antiretroviral drugs, is generally well tolerated. CNS adverse events, primarily headache and dizziness, were the most common treatment-emergent, drug-related adverse events in the pharmacokinetic study involving the co-formulation.

Adenine↗
PubMed2006

Pregabalin: in the treatment of generalised anxiety disorder.

Pregabalin, the pharmacologically active S-enantiomer of 3-aminomethyl-5-methyl-hexanoic acid, is a structural analogue of GABA, although it is not active at GABA receptors, nor does it acutely alter GABA uptake or degradation.black triangle Pregabalin binds with high affinity to the alpha2-delta subunit protein of voltage-gated calcium channels in CNS tissues and acts as a presynaptic modulator of the excessive release, in hyperexcited neurons, of various excitatory neurotransmitters. Binding of pregabalin to the alpha2-delta subunit appears necessary for its demonstrable anxiolytic, analgesic and anticonvulsant activities in animal models.black triangle Oral pregabalin, typically at dosages of 300-600 mg/day, was superior to placebo and similar to lorazepam 6 mg/day, alprazolam 1.5 mg/day and venlafaxine 75 mg/day in improving anxiety and depressive symptoms in patients with moderate-to-severe generalised anxiety disorder (GAD). Pregabalin had a rapid onset of anxiolytic activity relative to alprazolam and venlafaxine, which was evident after 1 week. Additionally, pregabalin (initial dosage 450 mg/day) was effective for the prevention of relapse of GAD over 34 weeks. Pregabalin was well tolerated during dosage escalation to fixed dosages (maximum 600 mg/day) over 7 days. Dizziness and somnolence, usually of mild to moderate severity, were the most common adverse events.black triangle The drug was not associated with a clinically significant medication withdrawal syndrome during a 1-week taper following 4 or 6 weeks' double-blind treatment.

Anticonvulsants↗
PubMed2006

Reduced-antigen, combined diphtheria, tetanus, and acellular pertussis vaccine (Boostrix): a review of its use as a single-dose booster immunization.

Reduced-antigen, combined diphtheria, tetanus, and acellular pertactin-containing pertussis vaccine (dTpa; Boostrix) contains reduced quantities of the same toxoids/antigens found in a diphtheria, tetanus, and acellular pertussis vaccine (DTPa; Infanrix) used for the primary immunization series in children. A single dose of dTpa (Boostrix) is indicated for booster vaccination against diphtheria, tetanus, and pertussis in individuals aged >or=4 years in Europe and Canada, in individuals aged >or=10 years in Australia, and in adolescents aged 10-18 years in the US.A single booster dose of dTpa (Boostrix) was safe and highly immunogenic for all its component toxoids/antigens when administered to adults, adolescents (including those previously unvaccinated), and children aged >or=4 years in clinical trials conducted in various countries worldwide. It was also well tolerated, as was a second (repeat) dose administered to a small number of adolescents who had previously received the vaccine as a preschool booster. Vaccinees generally reported a low incidence of severe/grade 3, solicited, local and general adverse events during the 1-month postvaccination period.Current recommendations for dTpa usage vary from country to country; they include one dose only in adolescence or adulthood (e.g. Australia, Canada, France, Switzerland, and the US), one dose at preschool age and one in adolescence (Germany), and one dose in adolescence followed by regular (10-year) doses during adulthood (Austria). Available data support the use of dTpa (Boostrix) in place of the combined diphtheria, tetanus, whole-cell pertussis vaccine (DTwP) or DTPa booster dose in preschool children and/or the reduced-antigen, combined diphtheria, tetanus vaccine (Td) booster dose in adolescents, as well as in place of a regular Td booster dose in adults who have not previously received the vaccine.

Antigens, Bacterial↗
PubMed2006

Reduced-antigen, combined diphtheria-tetanus-acellular pertussis vaccine, adsorbed (Boostrix) US formulation): use as a single-dose booster immunization in adolescents aged 10-18 years.

black triangle Boostrix US formulation (hereafter referred to as Tdap) is a formulation of reduced-antigen, combined diphtheria-tetanus-acellular pertussis vaccine, adsorbed onto aluminium approved in the US for use as a single-dose booster immunization in adolescents aged 10-18 years. The diphtheria and tetanus toxoid components of Tdap elicited serologic immune responses comparable to those induced by an approved diphtheria-tetanus (Td) booster vaccine in a large (n = 4114), randomized, observer-blind, multicenter, pivotal trial in US adolescents aged 10-18 years. In addition, antibody levels against pertussis antigens (pertussis toxoid, filamentous hemagglutinin, and pertactin) induced by Tdap were non-inferior to, and numerically higher than, those induced in infants who completed a three-dose primary immunization course with combined diphtheria-tetanus-acellular pertussis vaccine (Infanrix), which conferred 89% protection against pertussis. Tdap had a similar reactogenicity profile, including solicited local reactions and general symptoms, to that of the approved Td vaccine in the pivotal US study. In particular, Tdap was similar (non-inferior) to Td with respect to the primary safety endpoint, namely the incidence of grade 3 pain at the injection site within the 15-day post-vaccination period. No serious adverse events of potential autoimmune origin or of a new-onset, chronic nature were reported during the 6-month post-vaccination period in the pivotal US study and a smaller (n = 319) German-based trial that also evaluated Tdap.

Adolescent↗
PubMed2005

Pregabalin: in the treatment of postherpetic neuralgia.

Pregabalin, the pharmacologically active S-enantiomer of 3-aminomethyl-5-methyl-hexanoic acid, has a similar pharmacological profile to that of its developmental predecessor gabapentin, but showed greater analgesic activity in rodent models of neuropathic pain. The exact mechanism of action of pregabalin is unclear, although it may reduce excitatory neurotransmitter release by binding to the alpha2-delta protein subunit of voltage-gated calcium channels. Oral pregabalin 150-600 mg/day, administered twice or three times daily, was superior to placebo in relieving pain and improving pain-related sleep interference in three randomised, double-blind, placebo-controlled, multicentre studies of 8-13 weeks' duration in a total of 776 evaluable patients with postherpetic neuralgia (PHN). Weekly mean pain scores (primary endpoint; assessed in all three studies) and weekly mean sleep interference scores (assessed in two studies) were significantly improved at 1 week. In two studies, significant improvements in daily mean pain scores were apparent on the first or second day of treatment with pregabalin administered three times daily. Pregabalin was generally well tolerated when force-titrated over 1 week to fixed dosages (maximum 600 mg/day) in clinical trials that enrolled most elderly PHN patients. Dizziness, somnolence and peripheral oedema of mild-to-moderate intensity were the most common adverse events.

Herpes Zoster↗
PubMed2005

Emtricitabine: a review of its use in the management of HIV infection.

Emtricitabine (Emtriva) is an orally administered nucleoside reverse transcriptase inhibitor (NRTI) that is indicated in combination with other antiretroviral agents in the treatment of HIV infection in adults. As a component of antiretroviral therapy (ART), emtricitabine effectively reduces and/or maintains suppression of viral load in ART-naive adults or ART-experienced adults switching from stable combination regimens, and is generally well tolerated. Emtricitabine is a component of preferred initial HIV combination therapy regimens; it can be used in place of lamivudine as part of the dual NRTI backbone in non-nucleoside reverse transcriptase inhibitor (NNRTI)- and protease inhibitor (PI)-based regimens. Moreover, preliminary data from a randomised, open-label study suggest that emtricitabine plus tenofovir DF, a preferred dual-NRTI combination, is better tolerated than co-formulated lamivudine/zidovudine, another preferred dual-NRTI combination, resulting in a higher persistent virological response rate, as analysed using the US FDA time to loss of virological response (TLOVR) algorithm. With the convenience of once-daily (single pill) administration, no dietary restrictions and a favourable drug interaction and tolerability profile, emtricitabine should facilitate patient adherence to treatment, which, in turn, is central to the success of antiretroviral therapy. Similarly, emtricitabine is attractive as an option for ART-experienced stable adults requiring regimen simplification.

Adult↗
PubMed2005

Nelfinavir: a review of its use in the management of HIV infection.

Nelfinavir (Viracept) is an orally administered protease inhibitor. In combination with other antiretroviral drugs (usually nucleoside reverse transcriptase inhibitors [NRTIs]), nelfinavir produces substantial and sustained reductions in viral load in patients with HIV infection. Nelfinavir may be used in the treatment of adults, adolescents and children aged >or=2 years with HIV infection. It can also be used in pregnancy. Resistance to nelfinavir may develop, but the most common mutation (D30N, appearing mainly in HIV-1 subtype B) does not confer resistance to other protease inhibitors, thereby conserving these agents for later use. Although less effective than lopinavir/ritonavir, the preferred first-line treatment in US guidelines, nelfinavir is positioned as an alternative agent for the treatment of adults and adolescents with HIV infection and is an option for those unable to tolerate other protease inhibitors. Nelfinavir also has a role in the management of pregnant patients as well as paediatric patients with HIV infection.

Anti-Retroviral Agents↗
PubMed2005

Tigecycline.

Tigecycline is the first member of a new class of broad-spectrum antibacterials, the glycylcyclines, that has been specifically developed to overcome the two major mechanisms of tetracycline resistance (ribosomal protection and efflux). In vitro, tigecycline was active against a wide range of Gram-positive and -negative aerobic and anaerobic bacteria implicated in complicated skin and skin structure infections (cSSSIs) and complicated intra-abdominal infections (cIAIs). Intravenously administered tigecycline (recommended dosage regimen 100 mg initially, followed by 50 mg every 12 hours for 5-14 days) has been approved by the US FDA for the treatment of cSSSIs and cIAIs. In well designed, pivotal phase III studies, tigecycline monotherapy was noninferior to combination therapy with vancomycin 1 g plus aztreonam 2 g every 12 hours in hospitalised adult patients with cSSSIs (two trials; pooled clinical cure rates, 86.5% vs 88.6%) or broad-spectrum therapy with imipenem/cilastatin 200-500 mg/200-500 mg every 6 hours in hospitalised adult patients with cIAIs (two trials; pooled clinical cure rates, 86.1% vs 86.2%). Tigecycline was generally well tolerated in phase III studies; nausea, vomiting and diarrhoea were the most frequent adverse events in patients treated with tigecycline or an active comparator (vancomycin plus aztreonam or imipenem/cilastatin).

Anti-Bacterial Agents↗
PubMed2005

Zonisamide: a review of its use in the management of partial seizures in epilepsy.

Zonisamide (Zonegran, Excegran) is a new-generation, broad-spectrum antiepileptic drug (AED) currently approved as adjunctive therapy for the treatment of medically refractory partial seizures in adults in the US and as adjunctive therapy or monotherapy in the control of partial and generalised seizures in adults and children in Japan and Korea. Either as adjunctive therapy or monotherapy, zonisamide effectively reduces the frequency of partial seizures, with or without secondary generalisation to tonic-clonic seizures, in adults and children with epilepsy. The drug is generally well tolerated and, additionally, has a favourable pharmacokinetic profile permitting once- or twice-daily administration. Direct head-to-head comparisons with other AEDs would be beneficial in fully defining the place of zonisamide in therapy. In the meantime, adjunctive therapy or monotherapy with zonisamide is a convenient, useful option for the management of partial seizures, including those refractory to other AEDs.

Anticonvulsants↗
PubMed2005

Spotlight on pegfilgrastim in chemotherapy-induced neutropenia.

Pegfilgrastim (Neulasta), the sustained-duration form of filgrastim (recombinant human granulocyte colony-stimulating factor [G-CSF]), is created by the addition of a polyethylene glycol (PEG) moiety to filgrastim. Its approved indication in the US is to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy.A single subcutaneous injection of pegfilgrastim once per chemotherapy cycle was more effective than placebo as an adjunct to moderately myelosuppressive chemotherapy for breast cancer, no less effective than daily injections of filgrastim as an adjunct to highly myelosuppressive chemotherapy for breast cancer, and as effective as daily filgrastim as an adjunct to chemotherapy for lymphoma (predominantly non-Hodgkin lymphoma [NHL]) and acute myeloid leukemia. Pegfilgrastim has also successfully supported delivery of dose-dense chemotherapy, stem cell mobilization, and stem cell transplantation after high-dose chemotherapy in patients with non-myeloid or myeloid malignancies. By offering a convenient alternative to daily filgrastim, once-per-cycle administration of pegfilgrastim has the potential to simplify the management of chemotherapy-induced neutropenia, further improve patient health-related quality of life, and reduce total treatment costs in breast cancer and NHL, and possibly other cancer settings. Pegfilgrastim should, likewise, permit simplification of G-CSF-based stem cell mobilization and transplantation procedures.

Antineoplastic Agents↗
PubMed2005

Spotlight on gefitinib in non-small-cell lung cancer.

Gefitinib (Iressa), the first commercially available epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor, is indicated in the management of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). However, approved uses differ between countries; in most markets, gefitinib is approved for third-line use only (e.g. the US, Canada and Switzerland), although in some it is approved for both second- and third-line use (e.g. Japan and Australia) and, additionally, in patients considered unsuitable for chemotherapy (e.g. Indonesia and the Philippines). Few third-line treatment options exist for patients with inoperable advanced NSCLC who have failed both docetaxel and platinum-based chemotherapy regimens. Gefitinib represents a significant advance in the treatment of this population; a once-daily oral dosage of 250 mg/day was well tolerated, produced objective tumour responses and disease stabilization, and improved disease-related symptoms and quality of life. It also produced overall survival outcomes that compared favorably with historical outcomes in a similar group of patients treated with three or four different chemotherapy regimens. These findings have been supported by observations from a global compassionate-use program. Ongoing or planned clinical trials are designed to confirm and/or further define the role of the drug in the above and other clinical settings. Preliminary data demonstrate the presence of activating mutations in EGFR-TK among patients whose disease was highly responsive to treatment with gefitinib, although such mutations have not been correlated to all patients who benefit from the drug. Further studies are needed to fully elucidate the clinical implications of EGFR mutations and to identify patients likely to benefit from EGFR-targeted therapy.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Gefitinib: a review of its use in the management of advanced non-small-cell lung cancer.

Gefitinib (Iressa), the first commercially available epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor, is indicated in the management of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). However, approved uses differ between countries; in most markets, gefitinib is approved for third-line use only (e.g. the US, Canada and Switzerland), although in some it is approved for both second- and third-line use (e.g. Japan and Australia) and, additionally, in patients considered unsuitable for chemotherapy (e.g. Indonesia and the Philippines). Few third-line treatment options exist for patients with inoperable advanced NSCLC who have failed both platinum-based and docetaxel chemotherapies. Gefitinib represents a significant advance in the treatment of this population; a once-daily, oral dosage of 250 mg/day was well tolerated, produced objective tumour responses and disease stabilisation, and improved disease-related symptoms and quality of life. It also produced overall survival outcomes that compared favourably with historical outcomes in a similar group of patients treated with three or four different chemotherapy regimens. These findings have been supported by observations from a global compassionate-use programme. Ongoing or planned clinical trials are designed to confirm and/or further define the role of the drug in the above and other clinical settings.

Aged↗
PubMed2004

Pregabalin: in the treatment of painful diabetic peripheral neuropathy.

Pregabalin, the pharmacologically active S-enantiomer of 3-aminomethyl-5-methyl-hexanoic acid, has a similar pharmacological profile to that of its developmental predecessor gabapentin, but showed greater analgesic activity in rodent models of neuropathic pain. The exact mechanism of action of pregabalin is unclear, although it may reduce excitatory neurotransmitter release by binding to the alpha2-delta protein subunit of voltage-gated calcium channels. Oral pregabalin at fixed dosages of 300 and 600 mg/day, administered three times daily, was superior to placebo in relieving pain and improving pain-related sleep interference in three randomised, double-blind, multicentre studies of 5-8 weeks' duration in a total of 724 evaluable patients with painful diabetic peripheral neuropathy (DPN). Significant reductions in weekly mean pain scores (primary endpoint) and sleep interference scores were observed at 1 week and sustained thereafter. A significant reduction in pain was apparent on the first day of treatment with pregabalin 300 mg/day. Twice daily fixed (600 mg/day) or flexible (150-600 mg/day) pregabalin was also effective in reducing pain and sleep interference in two 12-week placebo-controlled trials in a total of 733 randomised DPN patients. Pregabalin was well tolerated in DPN patients; mild-to-moderate dizziness, somnolence and peripheral oedema were the most common adverse events.

Analgesics, Non-Narcotic↗
PubMed2004

Drotrecogin alfa (activated): a pharmacoeconomic review of its use in severe sepsis.

Drotrecogin alfa (activated) [Xigris] (DAA), the recombinant form of human activated protein C, is approved as an adjunctive therapy for patients with severe sepsis (sepsis associated with > or = 1 organ system failure [OSF]). In the international, randomised, double-blind, placebo-controlled PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) study, the absolute reduction in 28-day all-cause mortality with intravenous DAA 24 micro g/kg/h for 96 hours plus conventional care versus conventional care alone was 6.1%. Although lacking statistical power, a prospectively planned subgroup analysis of this study suggested that the absolute reduction in mortality increased in patients with a baseline APACHE (Acute Physiology and Chronic Health Evaluation) II score of > or = 25 or > or = 2 OSFs, with no clear treatment effect in patients with an APACHE II score of < or = 24 or 1 OSF. Three fully published cost-effectiveness/cost-utility models of DAA plus conventional care relative to conventional care alone adopted a national healthcare payer's and/or societal perspective in North America. The base-case (baseline) discounted incremental cost per life-year gained (LYG) with DAA for all patients with severe sepsis was $US15,801-33,300 (year of costing 2000-2002). The results were more favourable for patients with an APACHE II score of > or = 25 ($US10,833-19,723 per LYG), but considerably worse for patients with an APACHE II score of < or = 24 based on a post hoc reanalysis by the US FDA. Among several fully or partly published cost-effectiveness/cost-utility models that adopted a national healthcare payer's perspective in continental Western European countries, the base-case (baseline) undiscounted incremental cost per LYG was broadly similar and more favourable for patients with > or = 2 OSFs (9660-11,300 euros; year of costing/publication 1998/1999, 2000, 2002 or 2003) than for all patients with severe sepsis (13,436-15,071 euros) in those studies that reported both analyses. The DAA acquisition cost accounts for up to 95% of the additional cost of using the drug. In conclusion, DAA is a major advance in the treatment of severe sepsis, based on the significant mortality reduction observed in the PROWESS study. From a hospital/hospital pharmacy perspective, the drug is associated with a high acquisition cost and a small increase in other short-term costs. From a societal or national healthcare payer's perspective, however, its administration to patients who meet the PROWESS study inclusion criteria, especially individuals with more severe disease (e.g APACHE II score of > or =25 and/or > or = 2 OSFs), has a lifetime cost-effectiveness profile that compares well to that of many widely accepted therapies.

Anti-Infective Agents↗