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Abstract Background Hypoxia associated with bronchiolitis is not always easy to assess on clinical grounds alone. The aim of this study was to determine the value of food intake during the previous 24 hours (bottle and spoon feeding), as a percentage of usual intake (24h FI), as a marker of hypoxia, and to compare its diagnostic value with that of usual clinical signs. Methods In this observational, prospective, multicenter study, 18 community pediatricians, enrolled 171 infants, aged from 0 to 6 months, with bronchiolitis (rhinorrhea + dyspnea + cough + expiratory sounds). Infants with risk factors (history of prematurity, chronic heart or lung disorders), breast-fed infants, and infants having previously been treated for bronchial disorders were excluded. The 24h FI, subcostal, intercostal, supracostal retractions, nasal flaring, respiratory rate, pauses, cyanosis, rectal temperature and respiratory syncytial virus test results were noted. The highest stable value of transcutaneous oxygen saturation (SpO2) was recorded. Hypoxia was noted if SpO2 was below 95% and verified. Results 24h FI ≥ 50% was associated with a 96% likelihood of SpO2 ≥ 95% [95% CI, 91–99]. In univariate analysis, 24h FI Conclusion In practice, the measure of 24 h FI may be useful in identifying hypoxia and deserves further study.

Haemophilus influenzae (Hi) is one of the leading bacteria implicated in childhood acute otitis media (AOM). Recent concerns have been raised about the emergence of Hi-resistant strains. We aimed to analyze the evolution of β-lactam resistance to Hi among strains isolated from nasopharyngeal carriage in children with AOM and in mild ear fluid (MEF) after the spontaneous perforation of the tympanic membrane (SPTM) in France. In this national ambulatory-based cohort study over 16 years, we analyzed the rate of Hi nasopharyngeal carriage and the proportion of β-lactam-resistant Hi strains over time using a segmented linear regression model. Among the 13,865 children (median [IQR] age, 12.7 [9.3-17.3] months; 7400 [53.4%] male) with AOM included from November 2006 to July 2022, Hi was isolated in 7311 (52.7%) children by nasopharyngeal sampling. The proportion of β-lactamase-producing and β-lactamase-negative, ampicillin-resistant (BLNAR) Hi strains in nasopharyngeal carriage remained stable during the study period. Among the 783 children (median [IQR] age, 20 [12.3-37.8] months; 409 [52.2%] male) with SPTM included from October 2015 to July 2022, Hi was isolated in 177 (22.6%) cases by MEF sampling. The proportions of β-lactamase-producing and BLNAR Hi strains did not significantly differ between nasopharyngeal (17.6% and 8.8%, respectively) and MEF (12.6% and 7.4%) samples. Accordingly, amoxicillin remains a valid recommendation as the first-line drug for AOM in France.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Febrile seizures (FS) are usually self-limiting and cause no morbidity. Nevertheless they represent very traumatic events for families. There is a need to identify key messages that reassure carers and help to prevent inappropriate, anxiety-driven behaviors associated with "fever phobia." No recommendations have been proposed to date regarding the content of such messages. Using a Delphi process, we have established a consensus regarding the information to be shared with families following a FS. Twenty physicians (child neurologists and pediatricians) from five European countries participated in a three-step Delphi process between May 2018 and October 2019. In the first step, each expert was asked to give 10 to 15 free statements about FS. In the second and third steps, statements were scored and selected according to the expert ranking of importance. A list of key messages for families has emerged from this process, which offer reassurance about FS based on epidemiology, underlying mechanisms, and the emergency management of FS should they recur. Interestingly, there was a high level of agreement between child neurologists and general pediatricians.Conclusion: We propose key messages to be communicated with families in the post-FS clinic setting. What is Known: • Febrile seizures (FS) are traumatic events for families. • No guidelines exist on what information to share with parents following a FS. What is New: • A Delphi process involving child neurologists and pediatricians provides consensual statement about information to deliver after a febrile seizure. • We propose key messages to be communicated with families in the post-FS clinic setting., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Several studies indicated that children seem to be less frequently infected with SARS-CoV-2 and are potentially less contagious than adults. To examine the spread of SARS-CoV-2, we combined both Reverse transcription-PCR testing and serology in children in the most affected region in France, Paris, during the COVID-19 epidemic., Methods: From 14 April 2020 to 12 May 2020, we conducted a cross-sectional, prospective, multicentre study. Healthy controls and pauci-symptomatic children from birth to age 15 years were enrolled by 27 ambulatory paediatricians. A nasopharyngeal swab was taken for detection of SARS-CoV-2 by Reverse transcription-PCR and a microsample of blood for micromethod serology., Results: Among the 605 children, 322 (53.2%) were asymptomatic and 283 (46.8%) were symptomatic. Reverse transcription-PCR and serology results were positive for 11 (1.8%) and 65 (10.7%) children, respectively, with no significant difference between asymptomatic and pauci-symptomatic children. Only three children were Reverse transcription-PCR-positive without any antibody response detected. The frequency of Reverse transcription-PCR SARS-CoV-2 positivity was significantly higher for children with positive than negative serology results (12.3% vs 0.6%, p<0.001). Contact with a person with confirmed COVID-19 increased the odds of Reverse transcription-PCR positivity (OR 7.8, 95% CI 1.5 to 40.7) and serology positivity (OR 15.1, 95% CI 6.6 to 34.6)., Conclusion: In an area heavily affected by COVID-19, after the peak of the first epidemic wave and during the lockdown, the rate of children with Reverse transcription-PCR SARS-CoV-2 positivity was very low (1.8%), but that of serology positivity was higher (10.7%). Most children with positive Reverse transcription-PCR results also had positive serology results., Trial Registration Number: NCT04318431., Competing Interests: Competing interests: RC, CL and EV received personal fees and non-financial support from Pfizer. RC reports personal fees from Merck, GSK, Sanofi and AstraZeneca outside the submitted work. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pneumococcal conjugate vaccine (PCV) implementations led to major changes in serotype distribution and antibiotic resistance in carriage, accompanied by changes in antibiotic consumption., Objectives: To assess the dynamic patterns of antimicrobial non-susceptibility across non-PCV13 serotypes following PCV implementations., Methods: We conducted a quasi-experimental interrupted time series analysis based on a 17 year French nationwide prospective cohort. From 2001 to 2018, 121 paediatricians obtained nasopharyngeal swabs from children with acute otitis media who were aged 6 months to 2 years. The main outcome was the rate of penicillin-non-susceptible pneumococci (PNSP), analysed by segmented regression., Results: We enrolled 10 204 children. After PCV13 implementation, the PNSP rate decreased (-0.5% per month; 95% CI -0.9 to -0.1), then, after 2014, the rate slightly increased (+0.7% per month; 95% CI +0.2 to +1.2). Global antibiotic use within the previous 3 months decreased over the study period (-22.2%; 95% CI -33.0 to -11.3), but aminopenicillin use remained high. Among the main non-PCV13 serotypes, four dynamic patterns of penicillin susceptibility evolution were observed, including unexpected patterns of serotypes emerging while remaining or even becoming penicillin susceptible. In contrast to PNSP strains, for these latter patterns, the rate of co-colonization with Haemophilus influenzae increased concomitant with their emergence., Conclusions: In a context of continuing high antibiotic selective pressure, a progressive increase in PNSP rate was observed after 2014. However, we highlighted an unexpected variability in dynamic patterns of penicillin susceptibility among emerging non-PCV13 serotypes. Antibiotic resistance may not be the only adaptive mechanism to antimicrobial selective pressure, and co-colonization with H. influenzae may be involved., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

After pneumococcal conjugate vaccine (PCV) implementation, the number of acute otitis media (AOM) episodes has decreased, but AOM still remains among the most common diagnoses in childhood. From 2% to 17% of cases of AOM feature spontaneous perforation of the tympanic membrane (SPTM). The aim of this study was to describe the bacteriological causes of SPTM 5 to 8 years years after PCV13 implementation, in 2010. From 2015 to 2018, children with SPTM were prospectively enrolled by 41 pediatricians. Middle ear fluid was obtained by sampling spontaneous discharge. Among the 470 children with SPTM (median age 20.8 months), no otopathogen was isolated for 251 (53.4% [95% CI 48.8%;58.0%]): 47.1% of infants and toddlers, 68.3% older children (p<0.001). Among children with isolated bacterial otopathogens (n = 219), non-typable Haemophilus influenzae (NTHi) was the most frequent otopathogen isolated (n = 106, 48.4% [95% CI 41.6%;55.2%]), followed by Streptoccocus pyogenes (group A streptococcus [GAS]) (n = 76, 34.7% [95% CI 28.4%;41.4%]) and Streptococcus pneumoniae (Sp) (n = 61, 27.9% [95% Ci 22.0%;34.3%]). NTHi was frequently isolated in infants and toddlers (53.1%), whereas the main otopathogen in older children was GAS (52.3%). In cases of co-infection with at least two otopathogens (16.9%, n = 37/219), NTHi was frequently involved (78.4%, n = 29/37). When Sp was isolated, PCV13 serotypes accounted for 32.1% of cases, with serotype 3 the main serotype (16.1%). Among Sp strains, 29.5% were penicillin-intermediate and among NTHi strains, 16.0% were β-lactamase-producers. More than 5 years after PCV13 implementation, the leading bacterial species recovered from AOM with SPTM was NTHi for infants and toddlers and GAS for older children. In both age groups, Sp was the third most frequent pathogen and vaccine serotypes still played an important role. No resistant Sp strains were isolated, and the frequency of β-lactamase-producing NTHi did not exceed 16%., Competing Interests: The authors have declared that no competing interests exist.

Background: Biofilm production by Haemophilus influenzae and Streptococcus pneumoniae has been implicated in the pathogenesis of otitis media, mainly in chronic and recurrent cases. We studied the "in vitro" biofilm production by these 2 species isolated alone or together from the nasopharynx of children with acute otitis media., Methods: The studied strains were from 3 pneumococcal conjugate vaccine (PCV) periods: pre-PCV7, post-PCV7/pre-PCV13 and post-PCV13. A modified microtiter plate assay with crystal violet stain was used to study the biofilm production of 182 H. influenzae and 191 S. pneumoniae strains., Results: Overall, 117/181 (64.6%) H. influenzae and 128/191 (66.8%) S. pneumoniae strains produced biofilm. The proportion of biofilm-producing H. influenzae strains was greater with than without the isolation of S. pneumoniae in the same sample (75.5% vs 52.3%, p = 0.001). Conversely, the proportion of biofilm-producing S. pneumoniae strains was not affected by the presence or not of H. influenzae (66.3% vs 67.4%). S. pneumoniae serotypes 6B, 15B/C, 19A, 35F and 35B were the better biofilm producers (80%). Serotypes 11A, 14, 15A, 19F and 19A were more associated with H. influenzae biofilm-producing strains. Overall, 89/94 (94.6%) of cases with combined isolation showed biofilm production by S. pneumoniae or H. influenzae., Conclusion: This study emphasizes the high proportion of biofilm production by H. influenzae and S. pneumoniae strains isolated from the nasopharynx of children with acute otitis media, which reinforces the results of studies suggesting the importance of biofilm in the pathogenesis of acute otitis media.

Febrile seizures (FS) are the most common seizures seen in the paediatric population in the out-of-hospital and emergency department settings, and they account for the majority of seizures seen in children younger than 5 years old. An FS is a seizure accompanied by fever, without central nervous system infection, occurring in children between 6 months and 5 years old. Five criteria have been used and taught to classify any FS as simple or complex FS. These factors do not bear the same significance for clinical practice, in particular, the decision to perform a lumbar puncture for cerebrospinal fluid analysis to rule out an intracranial infection. Moreover, epidemiological studies have illustrated that some factors are predictive of febrile seizure recurrence while others are predictive of epilepsy occurrence. On this basis, a workshop was organized to provide an answer to three clinical practice questions: when should a lumbar puncture be performed in a child who has experienced a seizure during a fever episode, is the prescription of a rescue drug required with a risk of a prolonged febrile seizure recurrence, when should a neurological consultation be requested (risk of later epilepsy)? Based on a review of the literature and on a 1-day workshop, we report here the conclusion of the working group. A lumbar puncture is required in any child with meningitis symptoms or septic signs or behaviour disturbance. A lumbar puncture should be discussed based on the clinical symptoms and their progression over time when a child has experienced a focal FS or repetitive FSs without signs of meningitis or sepsis or behaviour disturbance. The lumbar puncture is not necessary in case of simple FS without signs of meningitis, including in infants between 6 and 12 months old. An early clinical evaluation (at least 4 h after the first clinical assessment) could be helpful, in particular in infants younger than 12 months of age. A rescue drug might be prescribed when there is a high risk of prolonged FS (i.e., risk higher than 20%): age at FS<12months OR a history of a previous febrile status epilepticus OR if the first FS was a focal seizure OR abnormal development/neurological exam/MRI OR a family history of nonfebrile seizure. A neurological consultation should be requested for any child who has experienced a prolonged FS before the age of 1 year, for children who have experienced prolonged and focal FS or repetitive (within 24h) focal FS, for children who have experienced multiple complex (focal or prolonged or repetitive) FS, for children with an abnormal neurological exam or abnormal development experiencing a FS. Although childhood febrile seizures in most cases are benign, witnessing such seizures is always a terrifying experience for the child's parents. Most parents feel that their child is dying or could have severe brain injury related to the episode. Therefore, the group also suggests a post-FS visit with the primary care physician., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background. Objectives: Behavioral changes in a febrile child are usually considered to stem from the fever. We studied sickness behavior (SB) in terms of its clinical components and its relation to fever., Methods: This observational, multicenter study included children aged 6 months to 3 years who were either febrile (fever ≥12 hours, ≥ 39°C and ≥38°C at inclusion) or non-febrile and well. The child had to have been awake for the 2 hours preceding the consultation and cared for by the parent who brought him/her to the doctor. SB was evaluated according to 6 parameters over this 2-hour period: time spent playing, distance covered, time spent seeking comfort, time spent whining or crying, time spent in a state of irritation or of anger, most distorted facial expression. Two parameters were assessed for the 24-hour period preceding the consultation: time spent sleeping and appetite. The parent reported the degree of change in these parameters compared with the usual situation, using rating scales., Results: 200 febrile children (most with nonspecific upper respiratory infections) and 200 non-febrile children were included. The mean values of the 8 parameters differed significantly (p<0.001) between the 2 groups and were independent of the height of fever at inclusion in the febrile children. In the study conditions, paracetamol failed to improve SB when the child was still feverish., Conclusion: The 8 parameters suggested that SB and fever are two independent manifestations that are activated simultaneously during an infection. This independence is in harmony with recommendations to treat the discomfort of SB and not the fever.

A substantial proportion of subjects exposed to a contagious tuberculosis case display lack of tuberculin skin test (TST) reactivity. We previously mapped a major locus (TST1) controlling lack of TST reactivity in families from an area in South Africa where tuberculosis is hyperendemic. Here, we conducted a household tuberculosis contact study in a French area where the endemicity of tuberculosis is low. A genome-wide analysis of TST negativity identified a significant linkage signal (P < 3 × 10(-5)) in close vicinity of TST1. Combined analysis of the 2 samples increased evidence of linkage (P = 2.4 × 10(-6)), further implicating genetic factors located on 11p14-15. This region overlaps the TNF1 locus controlling mycobacteria-driven tumor necrosis factor α production., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Background: Hypoxia associated with bronchiolitis is not always easy to assess on clinical grounds alone. The aim of this study was to determine the value of food intake during the previous 24h (bottle and spoon feeding), as a percentage of usual intake (24h FI), as a marker of hypoxia, and to compare its diagnostic value with that of usual clinical signs., Methods: In this observational, prospective, multicenter study, 18 community pediatricians, enrolled 171 infants, aged from 0 to 6 months, with bronchiolitis (rhinorrhea+dyspnea+cough+expiratory sounds). Infants with risk factors (history of prematurity, chronic heart or lung disorders), breast-fed infants, and infants having previously been treated for bronchial disorders were excluded. The 24h FI, subcostal, intercostal, supracostal retractions, nasal flaring, respiratory rate, pauses, cyanosis, rectal temperature and respiratory syncytial virus test results were noted. The highest stable value of transcutaneous oxygen saturation (SpO2) was recorded. Hypoxia was noted if SpO2 was below 95% and verified., Results: 24h FI greater or equal to 50% was associated with a 96% likelihood of SpO2 greater or equal to 95% [95% CI, 91-99%]. In univariate analysis, 24h FI less than 50% had the highest odds ratio (13.8) for SpO2 less than 95%, compared to other 24h FI values and other clinical signs, as well as providing one of the best compromises between specificity (90%) and sensitivity (60%) for identifying infants with hypoxia. In multivariate analysis with adjustment for age, SpO2 less than 95% was related to the presence of intercostal retractions (OR=9.1 [95% CI, 2.4-33.8%]) and 24h FI less than 50% (OR=10.9 [95% CI, 3.0-39.1%]). Hospitalization (17 infants) was strongly related to younger age, 24h FI and intercostal retractions., Conclusion: In practice, the measure of 24h FI may be useful in identifying hypoxia and deserves further study., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

We investigated mechanisms of the false-positive test results on rapid-antigen detection test (RADT) for group A Streptococcal (GAS) pharyngitis. Most RADT false-positives (76%) were associated with polymerase chain reaction-positive GAS results, suggesting that RADT specificity could be considered close to 100%. Finding that 61% of GAS culture-negative but RADT-positive cases were positive on both GAS polymerase chain reaction and Staphylococcus aureus testing, we posit bacterial inhibition as causative., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: To assess the acceptability of a vaccine against meningococcus B by pediatricians and GP and to analyze how the vaccine could be implemented in France, InfoVac-France has set up a national survey., Methods: An email explained the purpose of this study and the practitioners of InfoVac-France network answered an online questionnaire (e-CRF)., Results: Of the 6905 pediatricians and GP who saw the mail sent by InfoVac-France between 11 and 24 January, 2012, 1351 (13.5 %) completed the e-CERF : 361 GP (26.7%), 797 pediatricians (59%) and 193 other doctors (14.3%). The majority of practitioners (96.1%) believe that is important to implement a vaccine against meningococcus B in the French immunization schedule. In 80.5% of cases, practitioners do not want to vaccine three times routinely during a single consultation and more than half (53.5%) would prefer to use this vaccine alone. The best schedule of primary vaccination (80.6%) is the injection at 3, 5 and 6 months. The arguments considered likely to encourage parents to accept the vaccination would be the incidence of the disease, severity of meningitis (82.1%) and the rapid mortality (82.8%)., Conclusion: This survey by InfoVac-France shows that the practitioners know the epidemiology of meningococcal B invasive disease in children. They would support the implementation of this vaccine for children under 2 years with a primary vaccination at 3, 5 and 6 months., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: In US, pneumococcal conjugate vaccine (PCV7) had reduced the burden of AOM and changed the profile of the disease. Prior to PCV7 implementation in France, AOM represented 8% of pediatricians visits and failure rate was 12%. The aim of this study is to describe the epidemiologic characteristics of AOM after PCV7 implementation., Methods: From 2007 to 2008, 30 pediatricians enrolled 3141 patients 3 to 36 months old with AOM. Standardized history and physical examination findings were recorded. Factors related to AOM failures were identified by multivariate logistic regression., Results: AOM accounted for 5.8% of the 43 433 visits or 6.2 cases/week per pediatrician. Among 3141 evaluable AOM cases (mean age 16.7±8 months, peak incidence at 10 months), 99% had been vaccinated with PCV7 and 42.1% attended day care (DCC). Recurrent AOM comprised 24.5% of cases and 51% of children had received ATB in the last 3 months. At the time of diagnosis, 47.1% had fever≥38,5°C, 74.5% otalgia and 4.7% otorrhea. Febrile and painful AOM accounted for 29.5% of cases and cunjunctivitis-otitis syndrome for 18.2%. ATB was prescribed in 98.7% of cases (cefpodoxime proxetil, 59% and amoxicillin/clavulanate, 37%). The failure rate was 6.4% and failure risk was greater in children in DCC (OR=1.50, [1.10;2.05]), young age<18 months (OR=1.47, [1.06;2.04]) and history of recurrent AOM (OR=1.45, [1.02;2.06])., Conclusion: Despite PCV7 implementation, AOM remains a very frequent childhood infection and a major reason for ATB prescriptions., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: Compliance with antibiotics is essential to ensure treatment efficacy and to prevent the emergence of bacterial resistant stains. In children who take oral form, the palatability and the frequency of administration seem to be factors important to good compliance., Patients and Methods: This observational study was designed to assess the acceptability of oral antibiotics (including generics) commonly prescribed to children by primary care physicians in France. It was given to 50 pediatricians and 50 GPs in private practice. For each patient, the physician and parents completed a questionnaire, and parents filled out a log for each drug intake., Results: Between September 2006 and September 2007, 91 physicians enrolled 2400 children and 1482 patient records are fully assessable. The two factors that improve significantly compliance are administration in two doses by day (OR 2.2 [95% CI 1 6-3]) and acceptability ≥80% (OR 2.6, [95% CI 1.9-3.7]). The acceptability was better for amoxicillin-clavulanic acid 65.4% (95% CI [57.6 to 72.4]) than for cefpodoxime 47.1% (95% CI [43.8-50.4]) or cefuroxime axetil 26% (95% [CI 15.9-39.6]). Conversely, cefpodoxime proxetil obtained a better score for compliance 91.8% (95% CI [89.8 to 93.4) as amoxicillin-clavulanic acid 84.6% (95%CI 80.8 to 87.8) because of its mode of administration in two doses per day. There is no difference between the amoxicillin clavulanic acid reference product and its generics as a whole, however a large variability exists between generics. If, for antibiotics prescribed in two doses per day, the two administrations by day are roughly equidistant, it is not the same for those prescribed three times a day: indeed, while the doses taken are identical, only four hours separate the first intake of the morning from the second intake in mid-day and more than 12 hours between the evening dose from the next morning intake., Conclusions: This study confirms the disparity in terms of acceptability among the different antibiotics prescribed for children even for the same drug, warranting evaluation for marketing of future generic drugs pediatric oral suspension. The disparity ranges for drugs three times daily asking consequences pharmacokinetics and dosage adjustment for a transition to two doses per day., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Tepid sponge bathing to reduce temperature may be an aggression against the febrile child organism leading to reactions that will limit the cooling. During the bath, the decrease of the skin temperature induces not only peripheral vasoconstriction, shivering, and metabolic heat production, but also a discomfort. This discomfort occurs when there is a difference between the thermal informations coming from the body and the central thermoregulator set point. It triggers crying when the child has no way to escape. Considering the little effectiveness (0.3 degree C on average) of the association bath cooling and antipyretic treatment versus antipyretic treatment, and the preservation of the child comfort, bathing in tepid water is not useful in current care of children fever.

The brain is especially sensitive to heat stress. To limit the increase of intracranial heat in case of hyperthermia or fever, a system of selective cooling is put on. It includes two heat-exchangers. The first one, in the face and scalp skin, disperses calories through sweat evaporation. The second one is intracranial, close to the arteries which irrigate the brain. They are connected by a vascular network. In these conditions, the arterial blood temperature, of which cerebral temperature depends upon, is reduced by the cooled venous blood which comes from subcutaneous tissues through the skull wall. On feverish children, increasing such a selective cooling by face fanning can limit cerebral thermal stress.

Thermic comfort is the affective perception of temperature (to be or not comfortable). It depends on the difference between thermoregulatory central set point and body temperature. Any measures which help to reduce this difference is felt as pleasant, and vice-versa. This must be taken into consideration in the prescriptions and advices for feverish children. Thus antipyretic therapy, and face fanning are always felt as pleasant, while undressing and tepid baths may be felt as unpleasant.