Investigating the risk of reintubation by cough force assessment using cough peak expiratory flow: a single-center observational pilot study.

BACKGROUND: No objective indicator exists for evaluating cough strength during extubation of tracheally intubated patients. This study aimed to determine whether cough peak expiratory flow (CPEF) can predict the risk of reintubation due to decreased cough strength. METHODS: This was a retrospective cohort study of patients who were admitted to our Emergency Intensive Care Unit between September 1, 2020 and August 31, 2021 and were under artificial ventilation management for ≥ 24 h. The patients were divided into two groups: successful extubation and reintubation groups, and the relationship between CPEF immediately before extubation and reintubation was investigated. RESULTS: Seventy-six patients were analyzed. In the univariate analysis, CPEF was significantly different between the successful extubation (90.7 ± 25.9 L/min) and reintubation (57.2 ± 6.4 L/min) groups (p < 0.001). In the multivariate analysis with age and duration of artificial ventilation as covariates, CPEF was significantly lower in the reintubation group (p < 0.01). The cutoff value of CPEF for reintubation according to the receiver operating characteristic curve was 60 L/min (area under the curve, 0.897; sensitivity, 78.5%; specificity, 90.9%; p < 0.01). CONCLUSION: CPEF in tracheally intubated patients may be a useful indicator for predicting the risk of reintubation associated with decreased cough strength. The cutoff CPEF value for reintubation due to decreased cough strength was 60 L/min.

Subclinical tuberculosis: a meta-analysis of prevalence and scoping review of definitions, prevalence and clinical characteristics.

BACKGROUND: This scoping review aimed to characterise definitions used to describe subclinical tuberculosis (TB), estimate the prevalence in different populations and describe the clinical characteristics and treatment outcomes in the scientific literature. METHODS: A systematic literature search was conducted using PubMed. We included studies published in English between January 1990 and August 2022 that defined "subclinical" or "asymptomatic" pulmonary TB disease, regardless of age, HIV status and comorbidities. We estimated the weighted pooled proportions of subclinical TB using a random-effects model by World Health Organization reported TB incidence, populations and settings. We also pooled the proportion of subclinical TB according to definitions described in published prevalence surveys. RESULTS: We identified 29 prevalence surveys and 71 other studies. Prevalence survey data (2002-2022) using "absence of cough of any duration" criteria reported higher subclinical TB prevalence than those using the stricter "completely asymptomatic" threshold. Prevalence estimates overlap in studies using other symptoms and cough duration. Subclinical TB in studies was commonly defined as asymptomatic TB disease. Higher prevalence was reported in high TB burden areas, community settings and immunocompetent populations. People with subclinical TB showed less extensive radiographic abnormalities, higher treatment success rates and lower mortality, although studies were few. CONCLUSION: A substantial proportion of TB is subclinical. However, prevalence estimates were highly heterogeneous between settings. Most published studies incompletely characterised the phenotype of people with subclinical TB. Standardised definitions and diagnostic criteria are needed to characterise this phenotype. Further research is required to enhance case finding, screening, diagnostics and treatment options for subclinical TB.

Chronic Cough and Obstructive Sleep Apnea.

Chronic cough, defined as a cough lasting more than 8 weeks, is a common medical condition occurring in 5% to 10% of the population. Its overlap with another highly prevalent disorder, obstructive sleep apnea (OSA), is therefore not surprising. The relationship between chronic cough and OSA extends beyond this overlap with higher prevalence of OSA in patients with chronic cough than in the general population. The use of continuous positive airway pressure can result in improvement in chronic cough although further studies are needed to understand which patients will experience benefit in their cough from the treatment of comorbid OSA.

[Effect of transcutaneous electrical acupoint stimulation on postoperative cough in lung cancer patients undergoing video-assisted thoracoscopic surgery].

OBJECTIVE: To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) for alleviating postoperative cough in lung cancer patients undergoing video-assisted thoracoscopic surgery. METHODS: A total of 110 patients with lung cancer undergoing video-assisted thoracoscopic surgery were randomly divided into a TEAS group (55 cases, 2 cases dropped out) and a sham-TEAS group (55 cases, 4 cases dropped out). In the TEAS group, TEAS was delivered 30 min before anesthesia and on day 1 to day 4 after operation separately, with disperse-dense wave, in frequence of 2 Hz/100 Hz. The acupoints included Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Hegu (LI 4), Lieque (LU 7) and Taixi (KI 3) on the both sides. In the sham-TEAS group, at the same time points and same acupoints as the TEAS group, the electrode pads were attached to the acupoints, but without electric stimulation. The interventions were given 30 min each time, once daily in the two groups. The incidence of cough and the scores of visual analogue scale (VAS) for cough on the first day (T1), the third day (T2), the fifth day (T3), 1 month (T4) and 3 months (T5) after operation, as well as the scores of the Leicester cough questionnaire (LCQ) on T4 and T5 were compared between the two groups; the contents of serum C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were detected before surgery (T0) and at T1, T2 and T3. The first flatus time, the first defecation time, the first ambulation time, the postoperative hospital day and the incidence of postoperative nausea and vomiting were compared between the two groups. RESULTS: Compared with the sham-TEAS group, the cough incidence at T3 and cough VAS scores at T1 to T5 were lower in the TEAS group (P<0.05, P<0.01), and the LCQ scores at T4 and T5 were higher (P<0.05). The serum contents of CRP, IL-6 and TNF-αat T1 to T3 in the TEAS group were lower than those of the sham-TEAS group (P<0.01). The first flatus time, the first defecation time and the first ambulation time were earlier (P<0.05, P<0.01); and the postoperative hospital day was shorter (P<0.05) and the incidence of postoperative nausea and vomiting was lower (P<0.05) in the TEAS group when compared with those of the sham-TEAS group. CONCLUSION: TEAS relieves cough in lung cancer patients undergoing video-assisted thoracoscopic surgery, improves quality of life and promotes the early postoperative recovery.

Pulmonary Rehabilitation Exercises Effectively Improve Chronic Cough After Surgery for Non-small Cell Lung Cancer.

INTRODUCTION: Cough is a major complication after lung cancer surgery, potentially impacting lung function and quality of life. However, effective treatments for managing long-term persistent postoperative cough remain elusive. In this study, we investigated the potential of a pulmonary rehabilitation training program to effectively address this issue. METHODS: Between January 2019 and December 2022, a retrospective review was conducted on patients with non-small cell lung cancer (NSCLC) who underwent lobectomy and lymph node dissection via video-assisted thoracoscopic surgery (VATS) at Daping hospital. Based on their postoperative rehabilitation methods, the patients were categorized into 2 groups: the traditional rehabilitation group and the pulmonary rehabilitation group. All patients underwent assessment using the Leicester cough questionnaire (LCQ) on the third postoperative day. Additionally, at the 6-month follow-up, patients' LCQ scores and lung function were re-evaluated to assess the long-term effects of the pulmonary rehabilitation training programs. RESULTS: Among the 276 patients meeting the inclusion criteria, 195 (70.7%) were in the traditional rehabilitation group, while 81 (29.3%) participated in the pulmonary rehabilitation group. The pulmonary rehabilitation group showed a significantly lower incidence of cough on the third postoperative day (16.0% vs 29.7%, P = .018) and higher LCQ scores in the somatic dimension (5.09 ± .81 vs 4.15 ± 1.22, P = .007) as well as in the total score (16.44 ± 2.86 vs 15.11 ± 2.51, P = .018, whereas there were no significant differences in psychiatric and sociological dimensions. At the 6-month follow-up, the pulmonary rehabilitation group continued to have a lower cough incidence (3.7% vs 12.8%, P = .022) and higher LCQ scores across all dimensions: somatic (6.19 ± .11 vs 5.75 ± 1.20, P = .035), mental (6.37 ± 1.19 vs 5.85 ± 1.22, P = .002), sociological (6.76 ± 1.22 vs 5.62 ± 1.08, P < .001), and total (18.22 ± 2.37 vs 16.21 ± 2.53, P < .001). Additionally, lung function parameters including FVC, FVC%, FEV1, FEV1%, MVV, MVV%, DLCO SB, and DLCO% were all significantly higher in the pulmonary rehabilitation group compared to the traditional group. CONCLUSION: Pulmonary rehabilitation exercises significantly reduced the incidence of postoperative cough and improved cough-related quality of life in patients undergoing lobectomy, with sustained benefits observed at the 6-month follow-up. Additionally, these exercises demonstrated superior lung function outcomes compared to traditional rehabilitation methods.

Pulmonary rehabilitation exercises significantly reduced the incidence of postoperative cough and improved cough-related quality of life in patients undergoing lobectomy, with sustained benefits observed at the 6-month follow-up. Additionally, these exercises demonstrated superior lung function outcomes compared to traditional rehabilitation methods.

Effects of C-reactive protein rapid testing and communication skills training on antibiotic prescribing for acute cough. A cluster factorial randomised controlled trial.

This cluster randomised clinical trial carried out in 20 primary care centres in Barcelona was aimed at assessing the effect of a continuous intervention focused on C-reactive protein (CRP) rapid testing and training in enhanced communication skills (ECS) on antibiotic consumption for adults with acute cough due to lower respiratory tract infection (LRTI). The interventions consisted of general practitioners and nurses' use of CRP point-of-care and training in ECS separately and combined, and usual care. The primary outcomes were antibiotic consumption and variation of the quality-adjusted life years during a 6-week follow-up. The difference in the overall antibiotic prescribing between the winter seasons before and after the intervention was calculated. The sample size calculated could not be reached due to the COVID-19 outbreak. A total of 233 patients were recruited. Compared to the usual care group (56.7%) antibiotic consumption among patients assigned to professionals in the ECS group was significantly lower (33.9%, adjusted odds ratio [aOR] 0.38, 95% CI 0.15-0.94, p = 0.037), whereas patients assigned to CRP consumed 43.8% of antibiotics (aOR 0.70, 95% CI 0.29-1.68, p = 0.429) and 38.4% in the combined intervention group (aOR 0.45, 95% CI, 0.17-1.21; p = 0.112). The overall antibiotic prescribing rates in the centres receiving training were lower after the intervention compared to those assigned to usual care, with significant reductions in ß-lactam rates. Patient recovery was similar in all groups. Despite the limited power due to the low number of patients included, we observed that continuous training achieved reductions in antibiotic consumption.

Successful bilateral lung transplantation in pulmonary alveolar microlithiasis: A case report and review of literature.

BACKGROUND: Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive genetic disorder with approximately 1000 known cases worldwide, in which calcium phosphate microliths deposit in the alveolar air spaces. As of writing this report, no definitive conventional therapy exists, and many PAM cases may progress to severe respiratory failure and potential death. Bilateral lung transplantation (BLx) seems to be the most optimal solution; however, this procedure is challenging along with limited reports regarding the outcome in PAM. We report a case of PAM successfully treated with BLx for the first time in Iran. METHOD: We present the case of a 42-year-old female with a longstanding history of cough, not responding to conventional antitussive medication, who was diagnosed as a case of PAM following a hospitalization due to coughing, dyspnea on exertion, and hemoptysis. Despite treatment with corticosteroid and medical treatment, no improvement was achieved and she subsequently developed respiratory and right ventricular failure, with oxygen ventilation dependence. Eventually, she was scheduled for BLx. The operation was successful and during her 2-year follow-up, no recurrence or significant postoperative complications has been reported. CONCLUSION: This case presentation and literature review confirm the effectiveness of BLx as a promising treatment for PAM-diagnosed patients, improving both life expectancy and quality of life.

Low-Dose Alfentanil Inhibits Sufentanil-Induced Cough During Anesthesia Induction: A Prospective, Randomized, Double-Blind Study.

Background: Cough is one of the most common complications following intravenous administration of sufentanil during anesthesia induction. The study aimed to investigate the protective effect of alfentanil, afentanyl derivative with short onset time and short duration, in reducing sufentanil-induced cough. Patients and methods: Eighty patients that scheduled for thyroid surgery under general anesthesia were randomly divided into the alfentanil group and normal saline group, with 40 cases per group. Patients in the alfentanil group received intravenous administration of 2 µg/kg alfentanil prior to sufentanil injection during general anesthesia induction, while the same dose of normal saline was administered in the normal saline group. The outcomes measures included the incidence and severity of cough and common side effects of opioids following the administration of sufentanil during the induction of general anesthesia, intraoperative hemodynamics parameters and major adverse events during anesthesia recovery period. Results: The incidence of cough within one minute after the injection of sufentanil during anesthesia induction was 40% in the normal saline group, and the pretreatment of alfentanil significantly reduced the incidence of sufentanil-induced cough to 5% (p < 0.05). Correspondingly, the patients in the alfentanil group had decreased severity of sufentanil-induced cough compared with the normal saline group (p < 0.05). No significant differences in the incidences of common side effects of opioids (dizziness, nausea and vomiting, chest tightness and respiratory depression) within one minute after sufentanil injection were found (p > 0.05). Furthermore, there were no significant differences between the two groups in intraoperative hemodynamic parameters, extubation time, or the incidences of emergence agitation, respiratory depression, delayed recovery from anesthesia and postoperative nausea and vomiting during Postanesthesia Care Unit stay (p > 0.05). Conclusion: Pretreatment with low-dose alfentanil (2 µg/kg) effectively and safely reduced both the incidence and severity of sufentanil-induced cough during anesthesia induction. Clinical Trial Registration Number: Chinese Clinical Trial Registry (identifier: ChiCTR2300069286).

Assessing the reproducibility and predictive value of objective cough measurement for successful withdrawal of invasive ventilatory support in adult patients.

BACKGROUND: Utilizing clinical tests, such as objective cough measurement, can assist in predicting the success of the weaning process in critically ill patients. METHODS: A multicenter observational analytical study was conducted within a prospective cohort of patients recruited to participate in COBRE-US. We assessed the capability of objective cough measurement to predict the success of the spontaneous breathing trial (SBT) and extubation. Intra- and inter-observer reproducibility of the cough test and was evaluated using the intraclass correlation coefficient (ICC) and Cohen's weighted kappa. We used receiver operating characteristic curves (ROC-curve) to evaluate the predictive ability of objective cough measurement. RESULTS: We recruited 367 subjects who were receiving invasive mechanical ventilation. A total of 451 objective cough measurements and 456 SBTs were conducted. A significant association was found between objective cough measurement and successful SBT (OR: 1.68; 95% CI 1.48-1.90; p = 0.001). The predictive capability of the objective cough test for SBT success had a ROC-curve of 0.58 (95% CI: 0.56-0.61). Objective cough measurement to predict successful extubation had a ROC-curve of 0.61 (95% CI: 0.56-0.66). The intraobserver reproducibility exhibited an ICC of 0.94 (95% CI: 0.89-0.96; p < 0.001), while the interobserver reproducibility demonstrated an ICC of 0.72 (95% CI: 0.51-0.85; p < 0.001). The intraobserver agreement, assessed using Cohen's weighted kappa was 0.94 (95% CI: 0.93-0.99; p < 0.001), whereas the interobserver agreement was 0.84 (95% CI: 0.67 - 0.10; p < 0.001). CONCLUSIONS: The objective measurement of cough using the method employed in our study demonstrates nearly perfect intra-observer reproducibility and agreement. However, its ability to predict success or failure in the weaning process is limited.

[The role of spectral analysis of cough sounds in the diagnosis of COVID-19].

AIM: To evaluate the possibility of using spectral analysis of cough sounds in the diagnosis of a new coronavirus infection COVID-19. MATERIALS AND METHODS: Spectral toussophonobarography was performed in 218 patients with COVID-19 [48.56% men, 51.44% women, average age 40.2 (32.4; 51.0)], in 60 healthy individuals [50% men, 50% women, average age 41.7 (32.2; 53.0)] with induced cough (by inhalation of citric acid solution at a concentration of 20 g/l through a nebulizer). The recording was made using a contact microphone located on a special tripod at a distance of 15-20 cm from the face of the subject. The resulting recordings were processed in a computer program, after which spectral analysis of cough sounds was performed using Fourier transform algorithms. The following parameters of cough sounds were evaluated: the duration of the cough act (ms), the ratio of the energy of low frequencies (60-600 Hz) to the energy of high frequencies (600-6000 Hz), the frequency of the maximum energy of the cough sound (Hz). RESULTS: After statistical processing, it was found out that the parameters of the cough sound of COVID-19 patients differ from the cough of healthy individuals. The obtained data were substituted into the developed regression equation. Rounded to integers, the resulting number had the following interpretation: "0" - there is no COVID-19, "1" - there is COVID-19. CONCLUSION: The technique showed high levels of sensitivity and specificity. In addition, the method is characterized by sufficient ease of use and does not require expensive equipment, therefore it can be used in practice for timely diagnosis of COVID-19.

Impulse oscillometry in the diagnosis of cough variant asthma in children.

BACKGROUND: Cough variant asthma (CVA) is one of the most common causes of chronic cough in children worldwide. The diagnosis of CVA in children remains challenging. This study aimed to assess the diagnostic utility of impulse oscillometry (IOS) pulmonary function in children with CVA. METHODS: This study included children aged 4 to 12 years diagnosed with CVA who underwent IOS pulmonary function and bronchodilation (BD) tests. A control group of healthy children was matched. Pre- and post-BD IOS parameters were recorded and presented as mean ± standard deviation or median. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated to evaluate the discriminatory potential of the IOS parameters for diagnosing CVA. RESULTS: A total of 180 patients with CVA and 65 control subjects were included. The baseline IOS parameters in the CVA group, except X5%pred, were significantly greater compared to the control group. After inhalation of salbutamol sulfate, all IOS parameters improved significantly in the CVA group. However, Z5%pred, R5%pred, and R20%pred remained greater in the CVA group compared to the control group. The improvement rates of IOS parameters in the CVA group significantly surpassed those in the control group. The ROC curve results for pre-BD IOS parameters and the improvement rate during the BD test showed that the combinations of pre-Z5%pred+△Z5% and pre-R5%pred+△R5% achieved the highest AUC value of 0.920 and 0.898, respectively. The AUC values of these combined parameters surpassed those of individual ones. CONCLUSIONS: This study highlights that children with CVA exhibit greater IOS parameters compared to healthy children. The changes in IOS parameters during the BD test provided valuable diagnostic information for CVA, and the combination of various parameters can help pediatricians accurately identify CVA in children.

Feature fusion method for pulmonary tuberculosis patient detection based on cough sound.

Since the COVID-19, cough sounds have been widely used for screening purposes. Intelligent analysis techniques have proven to be effective in detecting respiratory diseases. In 2021, there were up to 10 million TB-infected patients worldwide, with an annual growth rate of 4.5%. Most of the patients were from economically underdeveloped regions and countries. The PPD test, a common screening method in the community, has a sensitivity of as low as 77%. Although IGRA and Xpert MTB/RIF offer high specificity and sensitivity, their cost makes them less accessible. In this study, we proposed a feature fusion model-based cough sound classification method for primary TB screening in communities. Data were collected from hospitals using smart phones, including 230 cough sounds from 70 patients with TB and 226 cough sounds from 74 healthy subjects. We employed Bi-LSTM and Bi-GRU recurrent neural networks to analyze five traditional feature sets including the Mel frequency cepstrum coefficient (MFCC), zero-crossing rate (ZCR), short-time energy, root mean square, and chroma_cens. The incorporation of features extracted from the speech spectrogram by 2D convolution training into the Bi-LSTM model enhanced the classification results. With traditional futures, the best TB patient detection result was achieved with the Bi-LSTM model, with 93.99% accuracy, 93.93% specificity, and 92.39% sensitivity. When combined with a speech spectrogram, the classification results showed 96.33% accuracy, 94.99% specificity, and 98.13% sensitivity. Our findings underscore that traditional features and deep features have good complementarity when fused using Bi LSTM modelling, which outperforms existing PPD detection methods in terms of both efficiency and accuracy.

Cervical percutaneous interferential current stimulation improves citric acid cough tests in patients with Parkinson's disease on medication.

Aspiration pneumonia is the leading cause of death in patients with Parkinson's disease. The incidence of silent aspiration is high in such patients owing to decreased pharyngeal and laryngeal sensation; thus, interventions for this condition may help prevent pneumonia. In this single-arm, open-label study, we used a cervical percutaneous interferential current stimulation device to activate pharyngeal and laryngeal sensory nerves. We evaluated its effectiveness in patients with Hoehn-Yahr stages 2-4 Parkinson's disease. The primary endpoint was the proportion of patients with a normal cough reflex after consuming 1% citric acid at the end of the intervention compared with baseline measurements. In total, 25 patients received neck percutaneous interferential current stimulation for 20 min twice weekly for 8 weeks. Afterward, the proportion of patients with a normal cough reflex after 1% citric acid consumption increased significantly (p = 0.001), whereas other indicators, such as tongue pressure, peak expiratory flow, and penetration or aspiration during videofluoroscopic examination, remained unchanged. A longer duration of illness, higher Unified Parkinson's Disease Rating Scale total scores, and higher levodopa equivalent daily doses were significantly associated with improved cough test outcomes. Hence, cervical percutaneous interferential current stimulation significantly improved cough reflexes and may improve silent aspiration. Trial Registration: Japan Registry of Clinical Trials, jRCTs062220013, first registered 09/05/2022.

Evaluation of disease severity and prediction of severe cases in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era: a multicenter retrospective study.

BACKGROUND: The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. METHODS: A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. RESULTS: After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P < 0.05), compared to the pre-COVID-19 group. Moreover, age, BMI, fever duration, leucocyte count, lymphocyte proportion, proportion of CD3+ T cells, tumor necrosis factor α (TNF-α), and IL-10 were confirmed to be independently associated with severe H1N1 infection in post-COVID-19 era. A prediction model integrating these above eight variables was established, and this model had good discrimination, accuracy, and clinical practicability. CONCLUSIONS: Pediatric H1N1 infection during post-COVID-19 era showed a higher overall disease severity than the classical H1N1 infection in pre-COVID-19 period. Meanwhile, cough and seizures were more prominent in children with H1N1 infection during post-COVID-19 era. Clinicians should be aware of these changes in such patients in clinical work. Furthermore, a simple and practical prediction model was constructed and internally validated here, which showed a good performance for predicting severe H1N1 infection in post-COVID-19 era.

How Should Regulators and Manufacturers Prevent Avoidable Deaths of Children From Contaminated Cough Syrup?

This commentary responds to a case about diethylene glycol-contaminated glycerin in cough syrup. Glycerin is a commonly used excipient in medicines to improve texture and taste. Excipients are typically pharmacologically inactive ingredients contained in prescription and over-the-counter drugs that play a critical role in the delivery, effectiveness, and stability of active drug substances. The commentary first canvasses how contaminants enter the excipient supply chains. One way is by misleading labeling or intentional adulteration by manufacturers or suppliers. Another way is by human or systemic error. This commentary then discusses quality control testing and suggests the ethical and clinical importance of increased transparency in excipient supply chains.