Analgesic efficacy of naproxen sodium versus hydrocodone/acetaminophen in acute postsurgical dental pain: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Opioid/acetaminophen combinations may be overly prescribed in many post-surgical situations where a non-steroidal anti-inflammatory drug with equal or greater efficacy, fewer central nervous system side effects, and no risk for opioid abuse could be substituted. We compared a single, non-prescription dose of naproxen sodium 440 mg (NapS) against hydrocodone plus acetaminophen 10/650 mg (HYD+APAP) in post-impaction surgery pain. METHODS: Single-center, randomized, double-blind, placebo-controlled study in moderate-severe pain after surgical removal of impacted third molars (ClinicalTrials.gov: NCT04307940). Patients (n = 212) received NapS, HYD+APAP, or placebo and were assessed over 12 hours. Primary endpoint: summed pain intensity difference from 0 to 12 hours (SPID0-12). Secondary endpoints: pain intensity, pain relief, time to rescue medication, duration of pain at least half gone. Others: onset of pain relief, global assessment of treatment, adverse events. RESULTS: All 221 randomized patients formed the safety population and were included in the intention-to-treat sensitivity analysis. Nine patients discontinued treatment or had protocol violations, and 212 patients were included in the per-protocol, primary efficacy population. Both active treatments were significantly more effective than placebo. NapS was significantly more effective than HYD+APAP regarding SPID0-12 (p = 0.01; primary endpoint), total pain relief (0-6 and 0-12 hours; p < 0.05), time to rescue medication (p < 0.001), and duration of pain at least half gone (p < 0.001). HYD+APAP was not statistically superior to NapS for any endpoint. More adverse events were reported with HYD+APAP (n = 63) than NapS (n = 2) and placebo (n = 20), including nausea, vomiting, and dizziness. CONCLUSION: In moderate-to-severe postsurgical dental pain, a single dose of NapS was at least as effective as HYD+APAP in the early hours, significantly more effective at reducing pain intensity and providing greater pain relief over 12 hours, and was better tolerated. When not contraindicated, NapS should be considered a preferred alternative to opioid combinations for acute pain. (ClinicalTrials.gov, Identifier: NCT04307940; https://clinicaltrials.gov/ct2/show/NCT04307940).

Pharmacokinetic linearity of naproxen and efficacy of naproxen sodium at various doses
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OBJECTIVE: Naproxen sodium (NAPSO) is commonly used in a variety of pain conditions. There are several strengths of NAPSO available over the counter (OTC). Most published data are based on single or multiple doses using 220 mg, hence there is a need to assess the analgesic efficacy of other strengths of NAPSO used in the OTC setting. MATERIALS AND METHODS: We reviewed published and unpublished studies of naproxen (NAP) and NAPSO to establish the pharmacokinetic relationship between dosage, plasma concentration, and efficacy, and to compare the analgesic efficacy of NAPSO 220, 440, and 550 mg or NAP 500 mg versus placebo and active comparators. RESULTS: Increasing OTC doses of NAP are associated with linear pharmacokinetics, i.e., plasma levels of NAP increase proportionately with dosage. Accordingly, the therapeutic efficacy of higher doses of NAP or NAPSO is greater than lower doses. All OTC doses of NAP and NAPSO are significantly more effective than placebo. Higher strengths are as effective or more effective than lower strengths, and at least comparable to other active treatments. CONCLUSION: The pharmacokinetic linearity associated with NAP means that data on efficacy for the lower OTC doses of NAPSO can be extrapolated to the higher OTC doses. Thus, it is given that NAPSO 275 and 550 mg will be at least as effective as or superior to the lower doses of 220 and 440 mg.

Efficacy and safety of naproxen sodium 440 mg versus acetaminophen 600 mg/codeine phosphate 60 mg in the treatment of postoperative dental pain.

PURPOSE: Two studies evaluated the efficacy and safety of a single dose of naproxen sodium 440 mg (NS) compared to the combination of acetaminophen 600 mg and codeine phosphate 60 mg (AC) in subjects with postoperative dental pain. METHODS: The two studies were single center, randomized, double-blind and double-dummy trials. In both studies, subjects were randomized into one of the following three treatments in a 2:2:1 ratio, respectively: NS, AC, or placebo (PBO). Subjects were administered study medication when they had at least moderate pain following the surgical removal of three or four impacted molars, at least one of which was a mandibular partial or complete bony impaction. Efficacy assessments were completed over an 8-hour evaluation period. The co-primary efficacy assessments in both studies were time-weighted sum of categorical pain intensity differences over 4 hours (SPID4) and time-weighted sum of pain relief scores over 4 hours (TOTPAR4). Other efficacy assessments such as summed scores over 8 hours, time to onset of relief, time to rescue medication and global rating of medication were also assessed. RESULTS: In Study 1, there were 225 subjects evaluated for efficacy, and 228 evaluated for safety. In Study 2, there were 230 subjects evaluated for efficacy and safety. In both studies, NS and AC were significantly better than placebo for almost all efficacy measures. In Study 1, NS was significantly superior to AC for all summed efficacy scores over 4 and 8 hours except for SPID4. NS was also superior to AC for most individual time point scores from 3 through 8 hours, as well as for the time to taking rescue medication. Both actives had a similar onset of effect. The incidence of adverse events (AEs) was significantly higher in the AC group compared to NS and PBO. The most frequently reported AEs with AC were gastrointestinal (GI) and nervous system events. In Study 2, there were no statistically significant differences between the two active treatments for any summed efficacy score, except for TOTPAR8, where NS was significantly better than AC. NS was significantly better than AC for individual pain relief time point scores from 3 through 8 hours and significantly better for individual pain intensity difference scores from 5 through 8 hours. AC had a significantly faster onset of effect compared to NS, but NS had a significantly longer time to rescue compared to AC. Nervous system AEs (dizziness and somnolence) were reported significantly more frequently with AC compared to NS. In conclusion, Both NS and AC are effective in the relief of postoperative dental pain. NS provided comparable to superior relief vs. AC and its analgesic effects lasted significantly longer. NS was well tolerated and resulted in a lower rate of AEs than AC. CLINICAL SIGNIFICANCE: In 2017, the US Department of Human Health Services declared a public health emergency to address the national opioid crisis. Since dentists are among the most common specialty groups prescribing opioids, these studies show that NSAIDs (such as naproxen sodium) are effective analgesics for relieving postoperative pain.

Longer analgesic effect with naproxen sodium than ibuprofen in post-surgical dental pain: a randomized, double-blind, placebo-controlled, single-dose trial.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line medications in mild-to-moderate acute pain. However, comparative data regarding the duration of analgesia for commonly-used NSAIDs at non-prescription doses is lacking. This study evaluated the time to rescue medication following a single dose of naproxen sodium (NAPSO) vs ibuprofen (IBU) and placebo in subjects with moderate-to-severe post-surgical dental pain.Methods: This single-center, randomized, double-blind, parallel group, placebo-controlled study included healthy subjects with moderate-to-severe baseline pain (Categorical Pain Intensity Scale) who also rated their pain ≥ 5 on a 0-10 pain intensity Numerical Rating Scale following extraction of two impacted mandibular third molars. A single oral dose of NAPSO (440 mg), IBU (400 mg), or placebo was administered. The primary efficacy endpoint was the time to first rescue medication, while secondary endpoints included the sum of pain intensity difference (SPID) and total pain relief (TOTPAR) over 24 h. ClinicalTrials.gov trial registration number: NCT03404206 (EudraCT 2017-005049-67).Results: In the per protocol population (n = 385; mean age = 19 years), the time to rescue medication was significantly (p < .001) longer with NAPSO than IBU and placebo. After treatment, the greatest separation of NAPSO from IBU occurred at 9-14 h and from placebo at 1-6 h. Fewer NAPSO subjects required rescue medication (58/166, 34.9%) compared with IBU (137/165, 83.0%) and placebo (44/54, 81.5%). SPID 0-24 h and TOTPAR 0-24 h were both greater with NAPSO than IBU or placebo.Conclusions: The duration of pain relief after a single dose of NAPSO was significantly longer than after IBU, and significantly fewer NAPSO-treated subjects required rescue medication over a 24-h period.

Safety of naproxen compared with placebo, ibuprofen and acetaminophen: a pooled analysis of eight multiple-dose, short-term, randomized controlled studies.

Objective: To quantify the rate of adverse events reported with naproxen compared with placebo, ibuprofen and acetaminophen at non-prescription doses in multiple-dose, multi-day (7-10 days) duration clinical trials and further contribute towards current knowledge regarding the safety profile of naproxen. Methods: Safety data were retrospectively collected from eight randomized, controlled trials that included subjects exposed to a fixed dosing regimen of 220-750 mg naproxen per day over 7-10 days. All data on adverse events and their duration, severity and possible relationship to the study drug were taken from the clinical study reports. The data were used in a post-hoc pooled analysis of participants exposed to naproxen 220-750 mg/day (N = 1494) and grouped according to age (<65 and ≥65 years), daily dose, race and gender. Results: The safety profile of naproxen closely resembled that of placebo, with similar rates of adverse events across treatment groups as the active comparators. There was no dose effect of naproxen, and there were no differences in older versus younger participants. Most events were mild to moderate. The most frequently reported adverse events in all groups were related to the gastrointestinal system (most commonly dyspepsia with naproxen), with no differences between groups. Conclusions: Our pooled analysis did not find an increased risk of adverse events with short-term use of non-prescription doses of naproxen compared with placebo, or compared to other common analgesics.

Analgesic efficacy and safety of non-prescription doses of naproxen sodium in the management of moderate osteoarthritis of the knee or hip.

OBJECTIVES: Current osteoarthritis therapies aim to alleviate pain and maintain joint function. Non-prescription oral non-steroidal anti-inflammatory drugs are frequently used alone for pain relief in osteoarthritis. This post-hoc pooled analysis evaluated the analgesic efficacy and safety of two non-prescription doses of naproxen sodium for short-term use in patients with osteoarthritis of the knee or hip. A separate sub-group analysis of older patients who were administered a lower dose of naproxen sodium was performed. METHODS: In four multi-center, multi-dose, randomized, parallel, double-blind, placebo-controlled studies, oral naproxen sodium (age-based dosing regimen: <65 years, 660 mg/day; ≥65 years, 440 mg/day) or placebo was administered over 7 days. Data at baseline and after 7 days in 818 patients who received naproxen sodium or placebo (n = 409 in each group) was pooled and analyzed. Five-point rating scales were used to assess knee or hip joint pain, stiffness after rest, day and night pain, and patient and investigator assessment of treatment, while function was evaluated using a timed 50-foot walk test. RESULTS: Compared with placebo, there were significant improvements in pain and physical function with naproxen sodium (p < .05), and treatment was rated "good" to "excellent" significantly more often (p < .001) by investigators and patients. Efficacy results were similar among younger and older patients. There were no significant differences in adverse events between groups, regardless of age. CONCLUSIONS: For the acute management of underlying pain in patients with moderate osteoarthritis of the hip or knee, non-prescription naproxen sodium is effective and well tolerated in patients of all ages.

Over-the-counter ibuprofen and risk of gastrointestinal bleeding complications: a systematic literature review.

BACKGROUND: Exposure to over-the-counter (OTC) ibuprofen and other OTC non-steroidal anti-inflammatory drugs (NSAIDs) is substantial. Although the literature on gastrointestinal (GI) safety of NSAID therapy is extensive, the risk profiles of OTC and prescription dosing are seldom separated, and few studies provide risks specific to OTC ibuprofen. OBJECTIVE: To conduct a literature review to evaluate the risk of GI bleeding events related to OTC ibuprofen use. METHODS: Published clinical trials, observational studies, and meta-analyses of OTC ibuprofen use, defined as up to 1200 mg/day or stated as 'over the counter,' reporting endpoints of incidence rates and proportions of GI bleeding events (e.g., GI bleeding-related hospitalizations and deaths) were identified via MEDLINE through 2010. Data from these studies were summarized. RESULTS: Twenty studies (nine observational, ten clinical trials, one meta-analysis) reporting incidence rates and proportions of a GI bleeding-related event associated with OTC or OTC-specific doses of ibuprofen were included. The frequency of a GI-related hospitalization was <0.2% for patients on OTC-comparable doses. Incidence rates among those using OTC-comparable doses ranged from 0 to 3.19 per 1000 patient-years. The incidence of a GI bleeding-related event increased with age and the use of concomitant medications, and there was a general, though not always statistically significant, ibuprofen dose-response relationship. The relative risk of any GI bleeding-related event ranged from 1.1 to 2.4 for users of OTC-specific doses of ibuprofen compared to non-users. CONCLUSIONS: Studies reported low incidence of GI bleeding events with use of OTC ibuprofen. Few published studies that specifically investigated OTC ibuprofen use were identified. Varying methodologies and definitions of exposure and outcomes prevented direct comparison of many results. Only studies that used the methods herein described were identified. Further research evaluating the risk of GI bleeding events in patients taking OTC-specific ibuprofen use may be useful.

Manejo de la pareja esteril en Quito: un año de experiencia / Management of the sterile couple in Quito: 1-year experience

Entre Marzo de 1984 a Febrero de 1985, en el Instituto de Reproducción Humana de Quito, se estudiaron bajo un protocolo definido a 20 parejas estériles y 4 infértiles. En las estériles los factores etiológicos fueron anovulación crónica 7 casos (35%), tubo-peritoneal-uterino 7 casos (35%), masculino 5 (25%); imunológico 5 casos (25%), psicológico 2 casos (10%) y coital 1 caso (5%). El porcentaje de éxito en esta serie, entendido por embarazo con recién nacido vivo, fue del 30% (6 casos) en parejas estériles y del 75% (3 casos) en infértiles. En las 6 parejas estériles en las que se obtuvo éxito, dos fueron tratadas con clomifeno, con Psicoterapia 2 parejas, con Inseminación Artificial Heteróloga una paciente y con hormona específica para hipotiroidismo la restante. Las parejas infértiles representaron un esquema especial de estudio y tratamiento, de los 3 casos exitosos, uno fue con hormona tiroidea, otro con 17 alfa hidroxiprogesterona y el tercero con ceclaje cervical

Fertilidad masculina I / Male fertility I

En esta revisión sobre el factor masculino en la infertilidad conyugal, se destaca la importancia de una historia clínica completa. Se discute acerca de los exámenes complementarios a solicitarse, el método de colección del semen y su análisis macro y microscópico. Se relaciona las características del semen con la fertilidad. Finalmente se discute la participación del eje hipófisis-testículo en la génesis de la infertilidad masculina