Outcomes of a Postoperative Data-Extraction Questionnaire After Adenotonsillectomy in Children.

OBJECTIVES/HYPOTHESIS: To evaluate outcomes of a postoperative telephone questionnaire for children who underwent adenotonsillectomy (T&A). To determine whether episodes of postoperative hemorrhage were not captured until the call, and whether this impacted knowledge of physician rates of hemorrhage. STUDY DESIGN: Retrospective database analysis. METHODS: Retrospective analysis of outcomes of an 11-question data extraction tool utilized at a tertiary care children's hospital for follow-up in T&A patients <18 years of age over a 2-year period. Sub-analysis of positive responses to the question asking about incidence of postoperative hemorrhage. RESULTS: During the study period, 1,068/3,142 (34.0%) parents responded to the phone call. Median age was 6.0 years (interquartile range [IQR] 4.0-8.2), and 566 (53.0%) were male. Ninety (8.4%) noted that the child was still snoring, but only 9 (0.84%) reported signs of obstructed breathing. A total of 402 (37.6%) reported a voice change after surgery. Most children (n = 885, 82.9%) did not receive opioid analgesics, and 252 (23.6%) received acetaminophen/ibuprofen 7 days postoperatively. Return visits to the emergency department were reported in 149 patients; primarily for hemorrhage in 46 (30.8%). In 7 (15.2%) patients, the hemorrhage event was not recorded until the call. The majority-of respondents (n = 1,031, 96.5%) were satisfied with the outcome of the procedure. CONCLUSIONS: The postoperative T&A tool provided a means of gathering information on success and satisfaction with surgical outcomes. Children were able to be managed primarily with acetaminophen and ibuprofen. Most complications were captured in the electronic record, although some episodes of hemorrhage were not noted until the call, emphasizing the importance of follow-up. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2821-E2826, 2021.

Ibuprofen Better than Acetaminophen for Reducing Fever, Pain in Young Children.

According to this study: In children younger than age two, treatment with ibuprofen was associated with reduced fever and less pain within the first 24 hours compared with acetaminophen.The incidence of adverse events was low with both treatments.

Analgesic efficacy of morphine sulfate immediate release vs. oxycodone/acetaminophen for acute pain in the emergency department.

OBJECTIVE: Previous research demonstrated that administration of Morphine Sulfate Immediate Release (MSIR) results in similar analgesic efficacy to Oxycodone but with significantly lesser degrees of euphoria and reward. The purpose of this study sit to investigate if MSIR combined with Acetaminophen can serve as an opioid analgesic alternative to Oxycodone combined with acetaminophen (Percocet) for acute pain in the Emergency Department (ED). METHODS: A prospective, randomized, double-blind trial of ED patients aged 18 to 64 years presenting with moderate to severe acute pain as defined by an 11-point numeric rating scale (NRS) with an initial score of ≥5 (0 = no pain and 10 = very severe pain). Patients were randomized to receive either 15 mg MSIR combined with 650 mg of Acetaminophen or 10 mg Oxycodone combined with 650 mg Acetaminophen. Patients were assessed at baseline, 30, 45 and 60 min. The primary outcome was reduction in pain at 60 min. Secondary outcomes include drug likeability and adverse events. RESULTS: 80 patients were enrolled in the study (40 per group). Demographic characteristics were similar between the groups (P > 0.05). Mean NRS pain scores at baseline were 8.44 for the MSIR group and 8.53 for the Percocet group (P = 0.788). Mean pain scores decreased over time but remained similar between the groups: 30 min (6.03 vs. 6.43; P = 0.453), 45 min (5.31 vs. 5.48; P = 0.779), and 60 min (4.22 vs. 4.87; P = 0.346). Reduction in mean NRS pain scores were statistically significant from baseline to 30, 45 and 60 min within each group (P < 0.0001 at each time point for both groups). The largest NRS mean difference was from baseline to 60 min: 4.2 (95% CI: 3.43 to 5.01) for MSIR group and 3.61 (95% CI: 2.79 to 4.43) for Percocet group. No clinically significant changes or any serious adverse events were observed in either group. CONCLUSION: MSIR provides similar analgesic efficacy as Percocet for short-term pain relief in the ED, similar rates of nausea/vomiting, and lower rates of likeability of the drug.

Comparison of Acetaminophen (Paracetamol) With Ibuprofen for Treatment of Fever or Pain in Children Younger Than 2 Years: A Systematic Review and Meta-analysis.

Importance: Acetaminophen (paracetamol) and ibuprofen are the most widely prescribed and available over-the-counter medications for management of fever and pain in children. Despite the common use of these medications, treatment recommendations for young children remain divergent. Objective: To compare acetaminophen with ibuprofen for the short-term treatment of fever or pain in children younger than 2 years. Data Sources: Systematic search of the databases MEDLINE, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials and the trial registers ClinicalTrials.gov and the Australian New Zealand Clinical Trials Registry from inception to March 2019, with no language limits. Study Selection: Studies of any design that included children younger than 2 years and directly compared acetaminophen with ibuprofen, reporting antipyretic, analgesic, and/or safety outcomes were considered. There were no limits on length of follow-up. Data Extraction and Synthesis: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline, 2 authors independently extracted data and assessed quality. Data were pooled using a fixed-effects method if I2 was less than 50% and using a random-effects method if I2 was 50% or greater. Main Outcomes and Measures: The primary outcomes were fever or pain within 4 hours of treatment onset. Safety outcomes included serious adverse events, kidney impairment, gastrointestinal bleeding, hepatotoxicity, severe soft tissue infection, empyema, and asthma and/or wheeze. Results: Overall, 19 studies (11 randomized; 8 nonrandomized) of 241 138 participants from 7 countries and various health care settings (hospital-based and community-based) were included. Compared with acetaminophen, ibuprofen resulted in reduced temperature at less than 4 hours (4 studies with 435 participants; standardized mean difference [SMD], 0.38; 95% CI, 0.08-0.67; P = .01; I2 = 49%; moderate quality evidence) and at 4 to 24 hours (5 studies with 879 participants; SMD, 0.24; 95% CI, 0.03-0.45; P = .03; I2 = 57%; moderate-quality evidence) and less pain at 4 to 24 hours (2 studies with 535 participants; SMD, 0.20; 95% CI, 0.03-0.37; P = .02; I2 = 25%; moderate-quality evidence). Adverse events were uncommon. Acetaminophen and ibuprofen appeared to have similar serious adverse event profiles (7 studies with 27 932 participants; ibuprofen vs aceteminophen: odds ratio, 1.08; 95% CI, 0.87-1.33; P = .50, I2 = 0%; moderate-quality evidence). Conclusions and Relevance: In this study, use of ibuprofen vs acetaminophen for the treatment of fever or pain in children younger than 2 years was associated with reduced temperature and less pain within the first 24 hours of treatment, with equivalent safety.

Deriving harmonised permitted daily exposures (PDEs) for paracetamol (acetaminophen) CAS #: 103-90-2.

In the pharmaceutical industry, cleaning criteria are required for multipurpose manufacturing facilities. These Health Based Exposure Limits (HBELs), also called permitted daily exposures (PDEs) values, are derived from toxicological and pharmacological evaluation of the active pharmaceutical ingredients (APIs). The purpose of this publication is to show an example of how authors from different companies evaluate a generic drug, paracetamol, and discuss different approaches and relevance of the nonclinical studies for deriving PDEs. PDE limits of 25 mg/day for the oral route, and 20 mg/day for the intravenous (i.v.) and inhalation (inhal.) routes, respectively, were established herein. However, it has been already recognised that there are acceptable differences in the PDE calculations, which may be based on data accessibility, company-specific science-policy decisions or expert judgments. These differences can cause up to a 3-fold lower or higher values. If unnecessarily high factors are applied, this would result in a very conservative PDE value and unneeded additional cleaning and higher manufacturing costs. The PDE values presented are considered to be protective against adverse and pharmacological effects observed in clinical trials and in this case, a very long postmarketing period of paracetamol.

A Meta-Analysis of the Utility of Preoperative Intravenous Paracetamol for Post-Caesarean Analgesia.

Background and objectives: Worldwide, the number of caesarean sections performed has increased exponentially. Some studies have reported better pain control and lower postoperative requirements for opioids when intravenous (IV) paracetamol was administered preoperatively. This meta-analysis thus aimed to investigate the utility of preoperative IV paracetamol for post-caesarean analgesia. Materials and Methods: By using the keywords (paracetamol OR acetaminophen) AND [cesarea* OR caesarea* OR cesaria* OR caesaria*], a systematic literature search was conducted using PubMed, Medline, Embase, Google Scholar and ClinicalTrials.gov databases for papers published in English between January 1, 1960 and March 1, 2019. Grey literature was searched as well. Results: Seven clinical trials were reviewed, while five randomized, placebo-controlled, double-blind studies were included in the final meta-analysis. Applying per-protocol analysis and a random-effects model, there was a significant reduction in postoperative opioid consumption and pain score in the group that received preoperative IV paracetamol, compared to placebo, as the standardized mean difference (SMD) were -0.460 (95% CI -0.828 to -0.092, p = 0.014) and -0.719 (95% CI: -1.31 to -0.13, p = 0.018), respectively. However, there was significant heterogeneity amongst the different studies included in the meta-analysis (I2 = 70.66%), perhaps owing to their diverse protocols. Some studies administered IV paracetamol 15 min before induction while others gave it before surgical incision. Conclusion: This is the first review on the topic. Overall, preoperative IV paracetamol has convincingly demonstrated useful opioid-sparing effects and it also appears safe for use at the time of delivery. It should be considered as a component of an effective multimodal analgesic regimen. Future studies could be conducted on other patient groups, e.g., those with multiple comorbidities or chronic pain disorders, and further delineate the optimal timing to administer the drug preoperatively.

Multimodal oral analgesia for non-severe trauma patients: evaluation of a triage-nurse directed protocol combining methoxyflurane, paracetamol and oxycodone.

Insufficient analgesia affects around 50% of emergency department patients. The use of a protocol helps to reduce the risk of oligoanalgesia in this context. Our objective was to describe the feasibility and efficacy of a multimodal analgesia protocol (combining paracetamol, oxycodone, and inhaled methoxyflurane) initiated by triage nurse. We performed a prospective, observational study in an emergency department (Grenoble Alpes University Hospital, France) between December 2017 and April 2018. Adult non-severe trauma patients with a numerical pain rating scale (NRS) score ≥ 4 were included. The primary efficacy criterion was the proportion of patients with an NRS score ≤ 3 at 15 min. Pain intensity was measured for 60 min and during radiography. Data on adverse events and satisfaction were recorded. A total of 200 adult patients were included (median [interquartile range (IQR)] age: 32 [23-49] years; 126 men (63%)). Sixty-six patients (33%) reported an NRS score ≤ 3 at 15 min. The time required to achieve a decrease of at least 2 points in the NRS score was 10 (5-20) min. The median [IQR] pain intensity was 4 [2-5] before radiography and 4 [2-6] during radiography. Adverse events were frequent (n = 128, 64%). No serious adverse events were reported. The patients and caregivers reported good levels of satisfaction. The administration of a nurse-driven multimodal analgesia protocol (combining paracetamol, oxycodone, and methoxyflurane) was feasible on admission to the emergency department. It rapidly produced long-lasting analgesia in adult trauma patients.Trial registration: NCT03380247.

Paracetamol versus other analgesia in adult patients with minor musculoskeletal injuries: a systematic review.

OBJECTIVES: Pain treatment in acute musculoskeletal injuries usually consists of paracetamol, non-steroidal antiinflammatory drugs (NSAIDs) or opioids. It would be beneficial to determine whether paracetamol is as effective as other analgesics. The objective of this study was to evaluate available evidence regarding efficacy of paracetamol in these patients. METHODS: Embase, MEDLINE, Cochrane and relevant trial registers were searched from inception to 14 February 2018 by two independent reviewers to detect all randomised studies with adult patients with acute minor musculoskeletal injuries treated with paracetamol as compared with other analgesics. There were no language or date restrictions. Two independent reviewers evaluated risk of bias and quality of evidence. Primary outcome was decrease in pain scores during the first 24 hours, and secondary outcomes included pain decrease beyond 24 hours, need for additional analgesia and occurrence of adverse events. RESULTS: Seven trials were included, evaluating 2100 patients who were treated with paracetamol or NSAIDs or the combination of both as comparisons, of which only four studies addressed the primary outcome. No studies were found comparing paracetamol with opioids. There were no differences in analgesic effectiveness within and beyond 24 hours, nor in need for additional analgesia and occurrence of adverse events. Overall, quality of evidence was low. Because of methodological inconsistencies, a meta-analysis was not possible. CONCLUSIONS: Based on available evidence, paracetamol is as effective as NSAIDs or the combination of both in treating pain in adult patients with minor musculoskeletal injuries in the acute setting. The quality of evidence is low.

Drug Quality in South Africa: A Field Test.

To assess drug quality and pharmaceutical care in South Africa, "mystery" (i.e., anonymous) customers collected 316 samples from July to September 2016. Solid dosage forms containing amoxicillin alone or in combination with clavulanic acid as well as analgesics containing paracetamol alone or in combination with other drugs were sampled in a randomized fashion from the formal market (pharmacies) and by convenient sampling from the informal market. Visual inspection, uniformity of dosage units, and dissolution testing were performed to evaluate adherence to pharmacopoeial quality standards and to identify counterfeit, degraded, or substandard drugs. Although no counterfeited products were identified, only 55.4% (173/312) of samples were able to fulfill all pharmacopeial requirements for quality. Most of the 139 samples that failed were unable to pass the visual inspection due to inappropriate labeling and packaging. In addition, several substandard products were identified: 17 (5.4%) samples failed dissolution testing and 15 (4.8%) failed the content uniformity test. To improve drug quality and the quality of pharmaceutical care, better education of pharmaceutical professionals and monitoring of the pharmaceutical supply chain in South Africa are needed. Further field studies are necessary to evaluate risks and quality issues for other drug classes and distribution channels.

Long-term adverse effects of paracetamol - a review.

Paracetamol (acetaminophen) is the most commonly used drug in the world, with a long record of use in acute and chronic pain. In recent years, the benefits of paracetamol use in chronic conditions has been questioned, notably in the areas of osteoarthritis and lower back pain. Over the same period, concerns over the long-term adverse effects of paracetamol use have increased, initially in the field of hypertension, but more recently in other areas as well. The evidence base for the adverse effects of chronic paracetamol use consists of many cohort and observational studies, with few randomized controlled trials, many of which contradict each other, so these studies must be interpreted with caution. Nevertheless, there are some areas where the evidence for harm is more robust, and if a clinician is starting paracetamol with the expectation of chronic use it might be advisable to discuss these side effects with patients beforehand. In particular, an increased risk of gastrointestinal bleeding and a small (~4 mmHg) increase in systolic blood pressure are adverse effects for which the evidence is particularly strong, and which show a degree of dose dependence. As our estimation of the benefits decreases, an accurate assessment of the harms is ever more important. The present review summarizes the current evidence on the harms associated with chronic paracetamol use, focusing on cardiovascular disease, asthma and renal injury, and the effects of in utero exposure.

The Quality of Medicines Used in Children and Supplied by Private Pharmaceutical Wholesalers in Kinshasa, Democratic Republic of Congo: A Prospective Survey.

Poor-quality medicines are a threat to public health in many low- and middle-income countries, and prospective surveys are needed to inform corrective actions. Therefore, we conducted a cross-sectional survey on a sample of products used for children and available in the private market in Kinshasa, Democratic Republic Congo: amoxicillin (AX) and artemether/lumefantrine (AL), powders for suspension, and paracetamol (PC) tablets 500 mg. Overall, 417 products were covertly purchased from 61 wholesalers. To obtain a representative sample, the products were weighted on their market shares and a subset of 239 samples was randomly extracted to undergo in-depth visual inspection locally, and they were chemically assessed at two accredited laboratories in Belgium. Samples were defined of "poor-quality" if they failed to comply with at least one specification of the International Pharmacopoeia (for AL) or United States Pharmacopoeia 37 (for AX and PC). Results are reported according to the Medicine Quality Assessment Reporting Guideline. The visual inspection detected nonconformities in the aspects of antimalarial powders for suspension, and poor-quality labels across all medicine types. According to chemical analysis, 27.2% samples were of poor quality and 59.5% of AL samples were underdosed in artemether. Poor quality was more frequent for locally manufactured antimalarials (83.3%, P = 0.021; 86.4%, P = 0.022) and PC (4.8%, P = 0.000). The poor quality of the surveyed products may decrease the treatment's efficacy and favor the development of resistances to antimalarials. It is hoped that these findings may guide the corrective actions of the Democratic Republic of Congo Regulatory Authority, which was the main partner in the research.

Downstream processing from melt granulation towards tablets: In-depth analysis of a continuous twin-screw melt granulation process using polymeric binders.

The concept of twin-screw melt granulation (TSMG) has steadily (re)-gained interest in pharmaceutical formulation development as an intermediate step during tablet manufacturing. However, to be considered as a viable processing option for solid oral dosage forms there is a need to understand all critical sources of variability which could affect this granulation technique. The purpose of this study was to provide an in-depth analysis of the continuous TSMG process in order to expose the critical process parameters (CPP) and elucidate the impact of process and formulation parameters on the critical quality attributes (CQA) of granules and tablets during continuous TSMG. A first part of the study dealt with the screening of various amorphous polymers as binder for producing high-dosed melt granules of two model drug (i.e. acetaminophen and hydrochlorothiazide). The second part of this study described a quality-by-design (QbD) approach for melt granulation of hydrochlorothiazide in order to thoroughly evaluate TSMG, milling and tableting stage of the continuous TSMG line. Using amorphous polymeric binders resulted in melt granules with high milling efficiency due to their brittle behaviour without producing excessive amounts of fines, providing high granule yields with low friability. Therefore, it makes them extremely suitable for further downstream processing. One of the most important CPP during TSMG with polymeric binders was the granulation-torque, which - in case of polymers with high Tg - increased during longer granulation runs to critical levels endangering the continuous process flow. However, by optimizing both screw speed and throughput or changing to polymeric binders with lower Tg it was possible to significantly reduce this risk. This research paper highlighted that TSMG must be considered as a viable option during formulation development of solid oral dosage forms based on the robustness of the CQA of both melt granules and tablets.

Prediction of color changes in acetaminophen solution using the time-temperature superposition principle.

A prediction method for color changes based on the time-temperature superposition principle (TTSP) was developed for acetaminophen solution. Color changes of acetaminophen solution are caused by the degradation of acetaminophen, such as hydrolysis and oxidation. In principle, the TTSP can be applied to only thermal aging. Therefore, the impact of oxidation on the color changes of acetaminophen solution was verified. The results of our experiment suggested that the oxidation products enhanced the color changes in acetaminophen solution. Next, the color changes of acetaminophen solution samples of the same head space volume after accelerated aging at various temperatures were investigated using the Commission Internationale de l'Eclairage (CIE) LAB color space (a*, b*, L* and ΔE*ab), following which the TTSP was adopted to kinetic analysis of the color changes. The apparent activation energies using the time-temperature shift factor of a*, b*, L* and ΔE*ab were calculated as 72.4, 69.2, 72.3 and 70.9 (kJ/mol), respectively, which are similar to the values for acetaminophen hydrolysis reported in the literature. The predicted values of a*, b*, L* and ΔE*ab at 40 °C were obtained by calculation using Arrhenius plots. A comparison between the experimental and predicted values for each color parameter revealed sufficiently high R(2) values (>0.98), suggesting the high reliability of the prediction. The kinetic analysis using TTSP was successfully applied to predicting the color changes under the controlled oxygen amount at any temperature and for any length of time.

High-visibility warning labels on paracetamol-containing products do not prevent supratherapeutic ingestion in a simulated scenario.

CONTEXT: In Australia, legislation requires medication containing paracetamol display warning of co-administration with other paracetamol products, and safe maximum daily dosing (4 g). Labelling style, size and visibility differ, potentially leading possible supratherapeutic misadventure. OBJECTIVE: We studied the likelihood of participants exceeding the recommended dose of paracetamol using products with standard packaging versus products labelled with one of two additional warning labels. METHODS: This was a pilot prospective, observational study, conducted from May 2013 to July 2014. Participants undertook a structured interview to create a simulated 24-h scenario in which they chose from a range of labelled lone paracetamol- and compound paracetamol-containing medications to treat dental pain on six occasions. Participants were randomized to choose from one of three groups of analgesic medications with different package labelling: (1) standard packaging alone, (2) standard packaging + a pre-existing warning label and (3) standard packaging + large customized warning label. The primary outcome was to determine if participants would administer >4 g in 24 h, exceeding the recommended daily dose. RESULTS: One hundred eighteen surveys were completed (response rate 100%, 56% females). Forty-one (35% of total) participants took >4 g within the 24-h scenario period. About 24% (10/42) of the standard packaging group, 37% (13/35) of the standard packaging + pre-existing warning label group and 48% (19/40) of the SP + large customized warning label group ingested >4 g of paracetamol. There were no significant differences between the three groups (p > 0.05). CONCLUSION: In this small, simulated dental pain scenario, use of customized warning labels did not reduce the likelihood of supratherapeutic misadventure.

In-vitro evaluation of the quality of paracetamol and co-trimoxazole tablets used in Malawi based on pharmacopoeial standards.

OBJECTIVES: This study was an in-vitro evaluation of different brands of paracetamol and cotrimoxazole tablets, used or found in Malawi, based on Pharmacopoeia standards, in order to ascertain the existence and extent of substandard medicines in Malawi and to give an overview of their distribution in the public and private sectors. METHODOLOGY: A cross-sectional analytical study was conducted using 11 samples each of paracetamol and cotrimoxazole tablets. Stratified random sampling was used to collect samples. Samples were analyzed using HPLC and Spectrophometric methods as outlined in the BP-2007 and USP-32 at the National Drug Quality Control Laboratory (NDQCL)-Lilongwe (under Pharmacy Medicines and Poisons Board-PMPB) and Orient Pharma Co. Ltd of Taiwan. The results were analyzed using Epi Info. RESULTS AND DISCUSSION: Fifty percent of samples (n=22) were not registered in the country by the PMPB as required by the PMP Act with the majority of those coming from public health facilities. All paracetamol and cotrimoxazole samples complied with identification tests using spectrophotometric and HPLC method. Overall, 27.3% of samples failed to meet the BP-2007 standards for Active Ingredient content, while 22.7% of the samples failed the Friability test. The results from Malawi are similar in magnitude to those within surrounding countries in Africa. CONCLUSION: This pilot study provides objective evidence to show that substandard and unregistered paracetamol and cotrimoxazole are present and being used in Malawi, and thus posing a considerable hazard to public health in Malawi. PMPB, together with the Ministry of Health, must continue to develop a quality assurance system to ensure that medicines are randomly and routinely checked.

Development of a quantitative approach using surface-enhanced Raman chemical imaging: first step for the determination of an impurity in a pharmaceutical model.

This publication reports, for the first time, the development of a quantitative approach using surface-enhanced Raman chemical imaging (SER-CI). A pharmaceutical model presented as tablets based on paracetamol, which is the most sold drug around the world, was used to develop this approach. 4-Aminophenol is the main impurity of paracetamol and is actively researched in pharmaceutical formulations because of its toxicity. As its concentration is generally very low (<0.1%, w/w), conventional Raman chemical imaging cannot be used. In this context, a SER-CI method was developed to quantify 4-aminophenol assessing a limit of quantification below its limit of specification of 1000 ppm. Citrate-reduced silver nanoparticles were used as SERS substrate and these nanoparticles were functionalized using 1-butanethiol. Different ways to cover the tablets surface by butanethiol-functionalized silver nanoparticles were tested and a homogeneity study of the silver nanoparticles covering was realized. This homogeneity study was performed in order to choose the best way to cover the surface of tablets by silver colloid. Afterwards, the optimization of the SER-CI approach was necessary and different spectral intensity normalizations were tested. Finally, a quantitative approach using SER-CI was developed enabling to quantify 4-aminophenol from 0.025% to 0.2% in paracetamol tablets. This quantitative approach was tested on two different series of tablets using different batches of silver nanoparticles.

Prenatal and perinatal analgesic exposure and autism: an ecological link.

BACKGROUND: Autism and Autism Spectrum Disorder (ASD) are complex neurodevelopmental disorders. Susceptibility is believed to be the interaction of genetic heritability and environmental factors. The synchronous rises in autism/ASD prevalence and paracetamol (acetaminophen) use, as well as biologic plausibility have led to the hypothesis that paracetamol exposure may increase autism/ASD risk. METHODS: To explore the relationship of antenatal paracetamol exposure to ASD, population weighted average autism prevalence rates and paracetamol usage rates were compared. To explore the relationship of early neonatal paracetamol exposure to autism/ASD, population weighted average male autism prevalence rates for all available countries and U.S. states were compared to male circumcision rates - a procedure for which paracetamol has been widely prescribed since the mid-1990s. Prevalence studies were extracted from the U.S. Centers for Disease Control and Prevention Summary of Autism/ASD Prevalence Studies database. Maternal paracetamol usage and circumcision rates were identified by searches on Pub Med. RESULTS: Using all available country-level data (n = 8) for the period 1984 to 2005, prenatal use of paracetamol was correlated with autism/ASD prevalence (r = 0.80). For studies including boys born after 1995, there was a strong correlation between country-level (n = 9) autism/ASD prevalence in males and a country's circumcision rate (r = 0.98). A very similar pattern was seen among U.S. states and when comparing the 3 main racial/ethnic groups in the U.S. The country-level correlation between autism/ASD prevalence in males and paracetamol was considerably weaker before 1995 when the drug became widely used during circumcision. CONCLUSIONS: This ecological analysis identified country-level correlations between indicators of prenatal and perinatal paracetamol exposure and autism/ASD. State level correlation was also identified for the indicator of perinatal paracetamol exposure and autism/ASD. Like all ecological analyses, these data cannot provide strong evidence of causality. However, biologic plausibility is provided by a growing body of experimental and clinical evidence linking paracetamol metabolism to pathways shown to be important in autism and related developmental abnormalities. Taken together, these ecological findings and mechanistic evidence suggest the need for formal study of the role of paracetamol in autism.

NIR imaging spectroscopy for quantification of constituents in polymers thin films loaded with paracetamol.

Thin films loaded with the drug paracetamol were produced from polymer blends formed by hydroxypropylmethylcellulose (HPMC), polyvinylpyrrolidone (PVP) and polyethyleneglycol (PEG), at various mass ratios of polymers and drug defined by a D-optimal experimental design. NIR hyperspectral images were obtained from each thin film formulation and the pixel-to-pixel quantification of the constituents were carried out by partial least square (PLS) and multivariate curve resolution-alternating least square (MCR-ALS) with three different calibration/validation strategies. These strategies differ in the way to construct the calibration and validation matrices and they had to be carried out to suppress the bias on the quantification of the constituents in the polymer blend. The errors of prediction in the models from MCR-ALS were influenced by the calibration/validation strategy employed, but they were similar to the ones from PLS model. Concentration distribution maps were built after pixel-to-pixel predictions and their characteristics were analyzed.

Interchangeability between paracetamol tablets marketed in Palestine. Is there a quality reason for a higher price?

The objective of this study was to evaluate the quality of 10 commercial paracetamol products available on the Palestinian market. We carried out a survey on the price of all paracetamol tablet products and assessed their quality. To assess quality, all products were examined visually for their organoleptic properties, tested for weight uniformity, friability, disintegration, and dissolution profile, and assayed for paracetamol content. All imported products were 2 to 3 times more expensive than the locally produced generic products. Based on our testing procedure, all paracetamol products were equivalent to the innovator product except for 1 imported product which fell below the approved specifications developed for the innovator product. Although the majority of generic products met the dissolution specification requirement that 80% of the drug must dissolve in 30 minutes, 1 generic product failed. These results demonstrate that generic paracetamol tablets produced by local manufacturers are often comparable in vitro to the innovator product and have lower costs.