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Evaluation of the disease severity of acute urticaria (AU) is essential for adequate treatment of patients. However, there are no reliable biomarkers for such an evaluation. In our department, we observed patients with severe AU having elevated plasma D-dimer levels. Thus, the objective of this study was to investigate the elevated D-dimer levels in patients with severe AU in more detail. One hundred and thirty-nine hospital patients diagnosed with severe AU were enrolled. Clinical laboratory data were collected from electronic medical records. One hundred and seventeen of the patients presented with elevated plasma D-dimer levels. Compared to the normal group, the elevated group had a significantly higher proportion of patients who were female, younger, febrile, and had a shorter prehospital time (P < 0.05). Univariate regression analysis showed that neutrophil percentage, C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels increased as D-dimer levels increased, while prehospital time showed the opposite trend. Multiple regression analysis was used to estimate the simultaneous effects of CRP and LDH on D-dimer levels. Patients who responded to additional antibiotic treatment had higher levels of D-dimer. The group with highly elevated D-dimer levels required a higher maximum dose of daily glucocorticoids (GCs) to control the symptoms of AU. In conclusion, patients with severe AU might have elevated plasma D-dimer levels, which are positively correlated with CRP and LDH levels. Patients with severe AU with dramatically elevated D-dimer levels might need a higher dose of daily GCs and antibiotics to relieve symptoms. D-dimer may be a reasonable marker to evaluate the severity of AU and guide treatment.

BACKGROUND: During the Coronavirus disease 2019 (COVID-19) pandemic, a protocol was adopted by our department on antibiotics treatment for Acute Uncomplicated Appendicitis (AUA). Our study aimed to determine the feasibility and safety of non-operative treatment (NOT), compared to upfront laparoscopic appendectomy (LA), for AUA in children during the pandemic.
METHODS: Our prospective comparative study was conducted from May 1, 2020 to January 31, 2021. Patient selection criteria included: age ≥5 years, abdominal pain duration ≤48 h, ultrasound (US)/Computered Tomography scan confirmation of AUA, US appendiceal diameter 6-11 mm with no features of perforation/abscess collection and no faecolith. For NOT patients, intravenous antibiotics were administered for 24-48 h followed by oral for 10-day course. Comparison was performed between patients whose parents preferred NOT to those who opted for up-front appendectomy. Primary outcomes were NOT success at index admission, early and late NOT failure rates till 27 months. Secondary outcomes were differences in complication rate, hospital length of stay (LOS) and cost between groups.
RESULTS: 77 patients were recruited: 43 (55.8%) underwent NOT while 34 (44.2%) patients opted for LA. Success of NOT at index admission was 90.7% (39/43). Overall, NOT failure rate at 27 months\' follow-up was 37.2% (16/43). Of the NOT failures, 1 appendix was normal on histology while only 1 was perforated. There were no significant differences in secondary outcomes between both groups except for LOS of late NOT failure. Cost for upfront LA was nearly thrice that of NOT.
CONCLUSIONS: Our stringent COVID protocol together with shared decision-making with parents is a safe and feasible treatment option during a crisis situation.
METHODS: Treatment study, Level II.

BACKGROUND: The syndromic approach is a simple and affordable strategy for the management of sexually transmitted infections in countries with low-resource settings. However, because of the lack of specificity and accuracy, the risk of overuse and misuse of antibiotics is very high. Here, we proposed a more specific and accurate algorithm compared with the current algorithm used for syndromic case management of 3 common sexually transmitted pathogens and compared its precision with laboratory-based tests.
OBJECTIVE: This study aimed to report a comparative account of the accuracy of existing syndromic case management guidelines followed in mainstream hospitals, for taking care of patients with nonviral sexually transmitted infections, concerning an approach involving an alternative algorithm formulated in our laboratory followed by polymerase chain reaction testing.
METHODS: This was an observational study that compared the data between 2 categories based on diagnostics accuracy and treatment. In category I, symptoms of infection were scored on the basis of the existing National AIDS Control Organization and National AIDS Control Programme guidelines, and patients were treated before testing by polymerase chain reaction. In category II, patients were recruited on the basis of the National AIDS Control Organization and National AIDS Control Programme guidelines with additional alternative syndromic case management parameters. All samples were tested by polymerase chain reaction for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis and clinically correlated before giving the treatment.
RESULTS: In category I, among 646 women with symptomatic infection, only 46 (7.82%) tested positive by polymerase chain reaction assay for at least 1 of the pathogens, and 600 (92.87%) tested negative for infection by any of the 3 pathogens. The total estimated percentages of the overuse and misuse of antibiotics were 92.87% and 8.69%, respectively. Correct and complete treatment based on laboratory outcome compared with National AIDS Control Programme guidelines was 42 of 46 (91.30%). The estimated overuse of azithromycin and cefixime (Gray Kit) was 29.69%, the estimated overuse of a combination of doxycycline, cefixime, and metronidazole (Yellow Kit) was 29.87%, and the estimated overuse of a combination of doxycycline, cefixime, metronidazole, and azithromycin (Gray with Yellow Kit) was 11.45%. In category II, wherein patients were treated using an alternative syndromic approach and polymerase chain reaction diagnostics, 243 of 319 patients (76.15%) were infected with either of the pathogens (Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis), whereas 76 of 319 patients (23.82%) were negative for any of the 3 pathogens. Among 243 patients with infection, 99 of 243 (40.74%) were infected with a single pathogen, whereas 144 of 243 (59.20%) were coinfected. Of 144 coinfected patients, the percentage of Chlamydia trachomatis + Neisseria gonorrhoeae infection was the highest (51.38%), followed by coinfection with all 3 pathogens (30%). Coinfection with Chlamydia trachomatis + Trichomonas vaginalis was 9.72%, and coinfection with Neisseria gonorrhoeae + Trichomonas vaginalis was 9.03%. The estimated overuse of antibiotics was found to be 23.82% only.
CONCLUSIONS: The proposed alternative strategies of syndromic case management can reduce the percentage of misuse and overuse of antibiotics from 92.87% to 23.82%. Moreover, syndromic case management alone was insufficient for disease management.

OBJECTIVE: Escherichia coli and Bacteroides species are the most frequently detected species in ascites in perforated appendicitis and are generally sensitive to non-empiric cephalosporins like cefazolin or cefmetazole. However, monotherapy with such antibiotics is mostly insufficient for perforated appendicitis. To investigate this issue, this study aimed to compare bacterial floras in ascites culture between perforated and non-perforated appendicitis.
METHODS: Ascites culture results in perforated and non-perforated appendicitis cases were analyzed using a departmental database. The duration of symptoms before surgery, pre-surgical white blood cell count, C-reactive protein value, postsurgical length of stay, length of antibiotic treatment, and the rate of using second-line antibiotics or complications were also compared.
RESULTS: A total of 608 and 72 cases of non-perforated and perforated appendicitis were included. Escherichia coli and Bacteroides species were the dominant bacteria in both conditions. However, the total proportions of Pseudomonas aeruginosa, Streptococcus anginosus group, and Enterococcus group were significantly higher in perforated appendicitis than in non-perforated appendicitis.
CONCLUSIONS: Pseudomonas aeruginosa, Streptococcus anginosus group, and Enterococcus group have better susceptibility to penicillin-based empiric antibiotics than cephalosporins. The abundance of these bacteria might explain why non-empiric cephalosporins are not effective in perforated appendicitis and the superiority of penicillin-based empiric antibiotics.

UNASSIGNED: Since the beginning of the COVID-19 pandemic, many patients with clinically acute presentations have been approached differently. The fear of viral transmission along with the short period of study made patients delay their hospital visits and doctors reassess the approach of certain acute situations. This study aimed to assess the changes in the management of patients with acute cholecystitis before and during COVID-19.
UNASSIGNED: A systematic review of the literature using PubMed (MEDLINE), Scopus, and ScienceDirect databases was performed until 01 September 2021. Totally, two kinds of studies were included, those assessing the management of acute cholecystitis during COVID-19 and those comparing the periods before and during the pandemic. The outcomes recorded include management approaches, complications, and mean length of stay.
UNASSIGNED: A number of 15 eligible articles were included in the study. During the pandemic, six studies revealed a shift toward conservative management of acute cholecystitis and five of them reported that conservative management was opted in 73% of the patients. On the contrary, data from all studies revealed that the surgical approach was preferred in only 29.2% of patients. Furthermore, when comparing the periods before vs. during COVID-19, the conservative approach was reported in 36.3 and 43.2% before vs. during COVID-19, respectively, whereas surgical intervention was performed in 62.5% of patients before COVID-19 and 55.3% during the pandemic. The length of stay was delayed when a non-surgical approach was selected in most studies. Complications, mainly classified by the Clavien-Dindo scale, were higher in the pandemic period.
UNASSIGNED: A tendency toward more conservative approaches was observed in most studies, reversing the previously used surgical approach in most cases of acute cholecystitis. In most of the examined cases during the COVID-19 pandemic, antibiotic treatment and percutaneous cholecystostomy were much more considered and even preferred.

OBJECTIVE: Expectancies about symptom improvement or deterioration are reliable predictors of symptom progression and treatment outcomes (symptom resolution or symptomatic improvement) in many (non-)pharmacological studies and treatments. This study examined predictors of symptom improvement after antimicrobial therapy for persistent symptoms attributed to Lyme disease, hypothesizing particularly pre-treatment expectancies regarding symptom improvement to be predictive.
METHODS: A predictive study was performed on pre-treatment and post-treatment individual characteristics, including expectancies, and physical and mental health-related quality of life (HRQoL) from the PLEASE-trial comparing randomized 12-weeks of doxycycline, clarithromycin-hydroxychloroquine, or placebo following 2 weeks of intravenous ceftriaxone. At end-of-treatment (14 weeks after trial start) and follow-up (52 weeks), complete data of 231 and 170 (of initial 280) patients with persistent symptoms temporally related to a history of erythema migrans or otherwise confirmed symptomatic Lyme disease, or accompanied by B. burgdorferi IgG or IgM antibodies, were examined through hierarchical regression analyses.
RESULTS: In addition to pre-treatment HRQoL, pre-treatment expectancies regarding symptom improvement were consistently associated with stronger physical and mental HRQoL improvements at both end-of-treatment and follow-up (95% CI range: .09;.54, p < .01 to .27;.92, p < .001). Post-treatment expectancies regarding having received antibiotics vs. placebo was associated with more HRQoL improvement at end-of-treatment, but not at follow-up (95% CI-range 1.00;4.75, p = .003 to -7.34; -2.22, p < .001).
CONCLUSIONS: The present study shows that, next to pre-treatment functioning, patients\' pre-treatment and post-treatment expectancies regarding improvement of persistent symptoms attributed to Lyme disease relate to a more beneficial symptom course. Expectancies of patients may be relevant to explain and potentially improve patient outcomes (e.g., by optimized communication about treatment success).
BACKGROUND: ClinicalTrials.gov, NCT01207739 (Registration date: 23-09-2010) Key Points • As there is currently no sufficient symptom resolution or symptomatic improvement for many patients with persistent symptoms attributed to Lyme disease, it is relevant to know which factors determine symptom progression and predict heterogeneity in treatment response. • Next to pre-treatment functioning, expectancies regarding symptom improvement and having received antimicrobial study medication are associated with a more beneficial symptom course after both shorter-term and longer-term antimicrobial treatment. • Expectancies are relevant to consider in treatment studies and may be useful in clinical settings to improve symptom course and treatment outcome (e.g., by optimized communication about treatment success).

Individuals may respond differently to the same treatment, and there is a need to understand such heterogeneity of causal individual treatment effects. We propose and evaluate a modelling approach to better understand this heterogeneity from observational studies by identifying patient subgroups with a markedly deviating response to treatment. We illustrate this approach in a primary care case-study of antibiotic (AB) prescription on recovery from acute rhino-sinusitis (ARS).
Our approach consists of four stages and is applied to a large dataset in primary care dataset of 24,392 patients suspected of suffering from ARS. We first identify pre-treatment variables that either confound the relationship between treatment and outcome or are risk factors of the outcome. Second, based on the pre-treatment variables we create Synthetic Random Forest (SRF) models to compute the potential outcomes and subsequently the causal individual treatment effect (ITE) estimates. Third, we perform subgroup discovery using the ITE estimates as outcomes to identify positive and negative responders. Fourth, we evaluate the predictive performance of the identified subgroups for predicting the outcome in two ways: the likelihood ratio test, and whether the subgroups are selected via the Akaike Information Criterion (AIC) using backward stepwise variable selection. We validate the whole modelling strategy by means of 10-fold-cross-validation.
Based on 20 pre-treatment variables, four subgroups (three for positive responders and one for negative responders) were identified. The log likelihood ratio tests showed that the subgroups were significant. Variable selection using the AIC kept two of the four subgroups, one for positive responders and one for negative responders. As for the validation of the whole modelling strategy, all reported measures (the number of pre-treatment variables associated with the outcome, number of subgroups, number of subgroups surviving variable selection and coverage) showed little variation.
With the proposed approach, we identified subgroups of positive and negative responders to treatment that markedly deviate from the mean response. The subgroups showed additive predictive value of the outcome. The modelling approach strategy was shown to be robust on this dataset. Our approach was thus able to discover understandable subgroups from observational data that have predictive value and which may be considered by the clinical users to get insight into who responds positively or negatively to a proposed treatment.

The intestinal pH can greatly influence the stability and absorption of oral drugs. Therefore, knowledge of intestinal pH is necessary to understand the conditions for drug delivery. This has previously been measured in humans and rats. However, information on intestinal pH in mice is insufficient despite these animals being used often in preclinical testing. In this study, 72 female ICR mice housed in SPF (specific pathogen-free) conditions were separated into nine groups to determine the intestinal pH under conditions that might cause pH fluctuations, including high-protein diet, ageing, proton pump inhibitor (PPI) treatment, several antibiotic treatment regimens and germ-free mice. pH was measured in samples collected from the ileum, cecum and colon, and compared to control animals. An electrode, 3 mm in diameter, enabled accurate pH measurements with a small amount of gastrointestinal content. Consequently, the pH values in the cecum and colon were increased by high-protein diet, and the pH in the ileum was decreased by PPI. Drastic alkalization was induced by antibiotics, especially in the cecum and colon. The alkalized pH values in germ-free mice suggested that the reduction in the intestinal bacteria caused by antibiotics led to alkalization. Alkalization of the intestinal pH caused by antibiotic treatment was verified in mice. We need further investigations in clinical settings to check whether the same phenomena occur in patients.

Management of tubo-ovarian abscesses (TOA) is often complex and may include antibiotics, image-guided drainage via interventional radiology (IR) or surgery. We aim to (i) identify clinical factors that prognosticate primary drainage and (ii) compare outcomes of each treatment regimen.
This is a retrospective analysis on patients with TOA, admitted to KK Hospital, a tertiary women\'s hospital in Singapore from June 2016 to June 2017. Pregnant patients or patients who were discharged against medical advice were excluded. 102 patients were included in this study.
85.3% patients received antibiotics only, while 14.7% patients received antibiotics with IR drainage or surgery (primary drainage) as initial treatment. Subsequently, 20.7% failed antibiotic treatment and required IR drainage or surgery (secondary drainage). Patients aged above 40 years, TOA diameter of larger than 7 cm and presence of fever were found to be predictive of antibiotic failure, requiring secondary drainage. However, patients with primary drainage had a longer length of stay by 2.69 days (95% CI 1.44-3.94, p value < 0.001), compared to patients successfully managed conservatively.
Patients who are above 40 years, febrile and have a larger TOA are at a higher risk of medical treatment failure, and should, therefore, be recommended for primary drainage at presentation. Further prospective studies should be conducted with a larger sample size to compare the outcomes of conservative management versus drainage of TOA.