Clinical outcomes from ART in predicted hyperresponders: in vitro maturation of oocytes versus conventional ovarian stimulation for IVF/ICSI.

STUDY QUESTION: Do ongoing pregnancy rates (OPRs) differ in predicted hyperresponders undergoing ART after IVM of oocytes compared with conventional ovarian stimulation (OS) for IVF/ICSI? SUMMARY ANSWER: One cycle of IVM is non-inferior to one cycle of OS in women with serum anti-Müllerian hormone (AMH) levels ≥10 ng/ml. WHAT IS KNOWN ALREADY: Women with high antral follicle count and elevated serum AMH levels, indicating an increased functional ovarian reserve, are prone to hyperresponse during ART treatment. To avoid iatrogenic complications of OS, IVM has been proposed as a mild-approach alternative treatment in predicted hyperresponders, including women with polycystic ovary syndrome (PCOS) who are eligible for ART. To date, inferior pregnancy rates from IVM compared to OS have hampered the uptake of IVM by ART clinics. However, it is unclear whether the efficiency gap between IVM and OS may differ depending on the extent of AMH elevation. STUDY DESIGN, SIZE, DURATION: This study is a retrospective cohort analysis of clinical and laboratory data from the first completed highly purified hMG (HP-hMG) primed, non-hCG-triggered IVM or OS (FSH or HP-hMG stimulation in a GnRH antagonist protocol) cycle with ICSI in predicted hyperresponders ≤36 years of age at a tertiary referral university hospital. A total of 1707 cycles were included between January 2016 and June 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Predicted hyperresponse was defined as a serum AMH level ≥3.25 ng/ml (Elecsys® AMH, Roche Diagnostics). The primary outcome was cumulative ongoing pregnancy rate assessed 10-11 weeks after embryo transfer (ET). The predefined non-inferiority limit was -10.0%. The analysis was adjusted for AMH strata. Time-to-pregnancy, defined as the number of ET cycles until ongoing pregnancy was achieved, was a secondary outcome. Statistical analysis was performed using a multivariable regression model controlling for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Data from 463 IVM cycles were compared with those from 1244 OS cycles. Women in the IVM group more often had a diagnosis of Rotterdam PCOS (434/463, 93.7%) compared to those undergoing OS (522/1193, 43.8%), were significantly younger (29.5 years versus 30.5 years, P ≤ 0.001), had a higher BMI (25.7 kg/m2 versus 25.1 kg/m2, P ≤ 0.01) and higher AMH (11.6 ng/ml versus 5.3 ng/ml, P ≤ 0.001). Although IVM cycles yielded more cumulus-oocyte complexes (COCs) (24.5 versus 15.0 COC, P ≤ 0.001), both groups had similar numbers of mature oocytes (metaphase II (MII)) (11.9 MII versus 10.6 MII, P = 0.9). In the entire cohort, non-adjusted cumulative OPR from IVM was significantly lower (198/463, 42.8%) compared to OS (794/1244, 63.8%), P ≤ 0.001. When analysing OPR across different serum AMH strata, cumulative OPR in both groups converged with increasing serum AMH, and OPR from IVM was non-inferior compared to OS from serum AMH levels >10 ng/ml onwards (113/221, 51.1% (IVM); 29/48, 60.4% (OS)). The number of ETs needed to reach an ongoing pregnancy was comparable in both the IVM and the OS group (1.6 versus 1.5 ET's, P = 0.44). Multivariable regression analysis adjusting for ART type, age, BMI, oocyte number, and PCOS phenotype showed that the number of COCs was the only parameter associated with OPR in predicted hyperresponders with a serum AMH >10 ng/ml. LIMITATIONS, REASONS FOR CAUTION: These data should be interpreted with caution as the retrospective nature of the study holds the possibility of unmeasured confounding factors. WIDER IMPLICATIONS OF THE FINDINGS: Among subfertile women who are eligible for ART, IVM, and OS resulted in comparable reproductive outcomes in a subset of women with a serum AMH ≥10 ng/ml. These findings should be corroborated by a randomised controlled trial (RCT) comparing both treatments in selected patients with elevated AMH. STUDY FUNDING/COMPETING INTEREST(S): There was no external funding for this study. P.D. has been consultant to Merck Healthcare KGaA (Darmstadt, Germany) from April 2021 till June 2023 and is a Merck employee (Medical Director, Global Medical Affairs Fertility) with Merck Healthcare KGAaA (Darmstadt, Germany) since July 2023. He declares honoraria for lecturing from Merck KGaA, MSD, Organon, and Ferring. The remaining authors declared no conflict of interest pertaining to this study. TRIAL REGISTRATION NUMBER: N/A.

Predicting the number of oocytes retrieved from controlled ovarian hyperstimulation with machine learning.

STUDY QUESTION: Can machine learning predict the number of oocytes retrieved from controlled ovarian hyperstimulation (COH)? SUMMARY ANSWER: Three machine-learning models were successfully trained to predict the number of oocytes retrieved from COH. WHAT IS KNOWN ALREADY: A number of previous studies have identified and built predictive models on factors that influence the number of oocytes retrieved during COH. Many of these studies are, however, limited in the fact that they only consider a small number of variables in isolation. STUDY DESIGN, SIZE, DURATION: This study was a retrospective analysis of a dataset of 11,286 cycles performed at a single centre in France between 2009 and 2020 with the aim of building a predictive model for the number of oocytes retrieved from ovarian stimulation. The analysis was carried out by a data analysis team external to the centre using the Substra framework. The Substra framework enabled the data analysis team to send computer code to run securely on the centre's on-premises server. In this way, a high level of data security was achieved as the data analysis team did not have direct access to the data, nor did the data leave the centre at any point during the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: The Light Gradient Boosting Machine algorithm was used to produce three predictive models: one that directly predicted the number of oocytes retrieved and two that predicted which of a set of bins provided by two clinicians the number of oocytes retrieved fell into. The resulting models were evaluated on a held-out test set and compared to linear and logistic regression baselines. In addition, the models themselves were analysed to identify the parameters that had the biggest impact on their predictions. MAIN RESULTS AND THE ROLE OF CHANCE: On average, the model that directly predicted the number of oocytes retrieved deviated from the ground truth by 4.21 oocytes. The model that predicted the first clinician's bins deviated by 0.73 bins whereas the model for the second clinician deviated by 0.62 bins. For all models, performance was best within the first and third quartiles of the target variable, with the model underpredicting extreme values of the target variable (no oocytes and large numbers of oocytes retrieved). Nevertheless, the erroneous predictions made for these extreme cases were still within the vicinity of the true value. Overall, all three models agreed on the importance of each feature which was estimated using Shapley Additive Explanation (SHAP) values. The feature with the highest mean absolute SHAP value (and thus the highest importance) was the antral follicle count, followed by basal AMH and FSH. Of the other hormonal features, basal TSH, LH, and testosterone levels were similarly important and baseline LH was the least important. The treatment characteristic with the highest SHAP value was the initial dose of gonadotropins. LIMITATIONS, REASONS FOR CAUTION: The models produced in this study were trained on a cohort from a single centre. They should thus not be used in clinical practice until trained and evaluated on a larger cohort more representative of the general population. WIDER IMPLICATIONS OF FINDINGS: These predictive models for the number of oocytes retrieved from COH may be useful in clinical practice, assisting clinicians in optimizing COH protocols for individual patients. Our work also demonstrates the promise of using the Substra framework for allowing external researchers to provide clinically relevant insights on sensitive fertility data in a fully secure, trustworthy manner and opens a number of exciting avenues for accelerating future research. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the French Public Bank of Investment as part of the Healthchain Consortium. T.Fe., C.He., J.C., C.J., C.-A.P., and C.Hi. are employed by Apricity. C.Hi. has received consulting fees and honoraria from Vitrolife, Merck Serono, Ferring, Cooper Surgical, Dibimed, Apricity, and Fairtility and travel support from Fairtility and Vitrolife, participates on an advisory board for Merck Serono, was the founder and organizer of the AI Fertility conference, has stock in Aria Fertility, TMRW, Fairtility, Apricity, and IVF Professionals, and received free equipment from Planar in exchange for first user feedback. C.J. has received a grant from BPI. J.C. has also received a grant from BPI, is a member of the Merck AI advisory board, and is a board member of Labelia Labs. C.He has a contract for medical writing of this manuscript by CHU Nantes and has received travel support from Apricity. A.R. haș received honoraria from Ferring and Organon. T.Fe. has received a grant from BPI. TRIAL REGISTRATION NUMBER: N/A.

Season at the time of oocyte collection and frozen embryo transfer outcomes.

STUDY QUESTION: Does the meteorological season at the time of oocyte retrieval affect live birth rates in subsequent frozen embryo transfers? SUMMARY ANSWER: Frozen embryo transfers resulting from oocytes retrieved in summer have 30% increased odds of live birth compared to frozen embryo transfers resulting from oocytes retrieved in autumn, regardless of the season at the time of embryo transfer. WHAT IS KNOWN ALREADY: Season at the time of frozen embryo transfer does not appear to be associated with live birth rate. One study in the northern hemisphere found increased odds of live birth with frozen embryo transfer resulting from oocytes collected in summer when compared to those collected in winter. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study including all frozen embryo transfers performed by a single clinic over eight years, from January 2013 to December 2021. There were 3659 frozen embryo transfers with embryos generated from 2155 IVF cycles in 1835 patients. Outcome data were missing for two embryo transfers, which were excluded from analysis. Outcomes were analysed by the season, temperatures, and measured duration of sunshine at the time of oocyte collection and at the time of frozen embryo transfer. PARTICIPANTS/MATERIALS, SETTING, METHODS: There were no significant differences between patients with oocyte collection or embryo transfers in different seasons. Meteorological conditions on the day of oocyte collection and the day of frozen embryo transfer, and in the preceding 14- and 28-day periods, were collected including mean, minimum, and maximum temperatures, and recorded duration of sunshine hours. Clinical and embryological outcomes were analysed for their association with seasons, temperatures, and duration of sunshine with correction for repeated cycles per participant, age at the time of oocyte retrieval, and quadratic age. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to frozen embryo transfers with oocyte retrieval dates in autumn, transfers with oocyte retrieval dates in summer had 30% increased odds of live birth (odds ratio (OR): 1.30, 95% CI: 1.04-1.62) which remained consistent after adjustment for season at the time of embryo transfer. A high duration of sunshine hours (in the top tertile) on the day of oocyte retrieval was associated with a 28% increase in odds of live birth compared to duration of sunshine hours in the lowest tertile (OR 1.28, 95% CI: 1.06-1.53). Temperature on the day of oocyte retrieval did not independently affect the odds of live birth. The odds of live birth were decreased by 18% when the minimum temperature on the day of embryo transfer was high, compared with low (OR: 0.82, 95% CI: 0.69-0.99), which was consistent after correction for the conditions at the time of oocyte retrieval. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective cohort study, however, all patients during the study period were included and data was missing for only two patients. Given the retrospective nature, causation is not proven and there are other factors that may affect live birth rates and for which we did not have data and were unable to adjust, including pollutants and behavioural factors. We were also not able to stratify results based on specific patient populations (such as poor- or hyper-responders) nor report the cumulative live birth rate per commenced cycle. WIDER IMPLICATIONS OF THE FINDINGS: These findings may be particularly relevant for patients planning oocyte or embryo cryopreservation. Given the increasing utilization of cryopreservation, identification of factors that influence outcomes in subsequent frozen embryo transfers has implications for future therapeutic and management options. Further studies to clarify the physiology underlying the influence of sunshine hours or season on subsequent frozen embryo transfer outcomes are required, including identification of specific populations that may benefit from these factors. STUDY FUNDING/COMPETING INTERESTS: No funding was provided for this study. S.L. has received educational travel assistance from Besins, Merck and Organon outside the submitted work. R.H. is National Medical Director of City Fertility and Medical Director of Fertility Specialists of Western Australia, has received honoraria from MSD, Merck Serono, Origio and Ferring outside the submitted work, and has equity interests in CHA SMG. C.R., M.W., and E.N. declare that they have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Homeopathic Medicines in Second Wave of COVID-19: Prognostic Factor Research.

BACKGROUND: The clinical profile and course of COVID-19 evolved perilously in a second wave, leading to the use of various treatment modalities that included homeopathy. This prognostic factor research (PFR) study aimed to identify clinically useful homeopathic medicines in this second wave. METHODS: This was a retrospective, multi-centred observational study performed from March 2021 to May 2021 on confirmed COVID-19 cases who were either in home isolation or at COVID Care Centres in Delhi, India. The data were collected from integrated COVID Care Centres where homeopathic medicines were prescribed along with conventional treatment. Only those cases that met a set of selection criteria were considered for analysis. The likelihood ratio (LR) was calculated for the frequently occurring symptoms of the prescribed medicines. An LR of 1.3 or greater was considered meaningful. RESULTS: Out of 769 confirmed COVID-19 cases reported, 514 cases were selected for analysis, including 467 in home isolation. The most common complaints were cough, fever, myalgia, sore throat, loss of taste and/or smell, and anxiety. Most cases improved and there was no adverse reaction. Certain new symptoms, e.g., headache, dryness of mouth and conjunctivitis, were also seen. Thirty-nine medicines were prescribed, the most frequent being Bryonia alba followed by Arsenicum album, Pulsatilla nigricans, Belladonna, Gelsemium sempervirens, Hepar sulphuris, Phosphorus, Rhus toxicodendron and Mercurius solubilis. By calculating LR, the prescribing indications of these nine medicines were ascertained. CONCLUSION: Add-on use of homeopathic medicines has shown encouraging results in the second wave of COVID-19 in integrated care facilities. Further COVID-related research is required to be undertaken on the most commonly prescribed medicines.

Comparison of blastocyst euploidy rates following luteal versus follicular phase stimulation in a GnRH antagonist protocol: a prospective study with repeated ovarian stimulation cycles.

STUDY QUESTION: Is there any difference in the mean number of euploid embryos following luteal phase start (LS) and follicular phase start (FS) of ovarian stimulation? SUMMARY ANSWER: The mean number of euploid blastocysts is equivalent independent of whether the inseminated oocytes are derived from FS or LS. WHAT IS KNOWN ALREADY: Starting ovarian stimulation at any time of the cycle ('random-start') is commonly used for emergency fertility preservation in cancer patients. A few retrospective studies have been published evaluating LS in women undergoing ovarian stimulation in the context of IVF, but there is a lack of robust data on the comparative efficacy of LS versus FS.Although 'random start' is commonly used in cancer survivors, few retrospective and uncontrolled studies have been published evaluating luteal phase stimulation in women undergoing ovarian stimulation in the context of IVF. Owing to this evident lack of robust data on the efficacy of LS, guidelines typically recommend the LS approach only for medical reasons and not in the context of IVF. STUDY DESIGN, SIZE, DURATION: This is a prospective, equivalence study, with repeated stimulation cycles, conducted between May 2018 and December 2021. Overall, 44 oocyte donors underwent two identical consecutive ovarian stimulation cycles, one initiated in the FS and the other in the LS. The primary outcome of the study was to evaluate whether FS and LS in the same patient would result in equivalent numbers of euploid embryos following fertilization of oocytes with the same sperm sample. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 44 oocyte donors underwent two consecutive ovarian stimulation protocols with 150 µg corifollitropin alpha followed by 200 IU recombinant FSH (rFSH) in a fixed GnRH antagonist protocol. The only difference between the two cycles was the day of initiation of ovarian stimulation, which was in the early follicular phase (FS) in one cycle, and in the luteal phase (LS) in the other. Forty-four oocyte recipients participated in the study receiving a mean of six metaphase II (MII) oocytes from each stimulation cycle (FS and LS). All MIIs were inseminated with the corresponding recipient's partner sperm (which had been previously frozen) or donor sperm, in order to safeguard the use of the same sample for either the FS or LS. Following fertilization and blastocyst culture, all generated embryos underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuploidy). MAIN RESULTS AND THE ROLE OF CHANCE: FS resulted in a significantly shorter duration of ovarian stimulation (difference between means (DBM) -1.05 (95% CI -1.89; -0.20)) and a lower total additional dose of daily rFSH was needed (DBM -196.02 (95% CI -319.92; -72.12)) compared with LS. The donors' hormonal profile on the day of trigger was comparable between the two stimulation cycles, as well as the mean number of oocytes (23.70 ± 10.79 versus 23.70 ± 8.81) (DBM 0.00 (95% CI -3.03; 3.03)) and MII oocytes (20.27 ± 9.60 versus 20.73 ± 8.65) (DBM -0.45 (95% CI -2.82; 1.91)) between FS and LS cycles, respectively. Following fertilization, the overall blastocyst formation rate was 60.70% with a euploid rate of 57.1%. Comparisons between the two stimulation cycles did not reveal any significance differences in terms of fertilization rates (71.9% versus 71.4%), blastocyst formation rates (59.4% versus 62%) and embryo euploidy rates (56.9 versus 57.3%) for the comparison of FS versus LS, respectively. The mean number of euploid blastocysts was equivalent between the FS (1.59 ± 1.30) and the LS (1.61 ± 1.17), (DBM -0.02 (90%CI -0.48; 0.44)). LIMITATIONS, REASONS FOR CAUTION: The study was performed in young, potentially fertile oocyte donors who are patients with high blastocyst euploidy rates. Although results may be extrapolated to young infertile women with good ovarian reserve, caution is needed prior to generalizing the results to infertile women of older age. WIDER IMPLICATIONS OF THE FINDINGS: The current study provides evidence that initiation of ovarian stimulation in the luteal phase in young potentially fertile women may result in a comparable number of oocytes and comparable blastocyst euploidy rates compared with follicular phase stimulation. This may imply that in case of a freeze-all protocol in young patients with good ovarian reserve, clinicians may safely consider initiation of ovarian stimulation during the luteal phase. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by an unrestricted grant from MSD/Organon. N.P.P. has received Research grants and honoraria for lectures from: Merck Serono, MSD/Organon, Ferring Pharmaceuticals, Besins Intenational, Roche Diagnostics, IBSA, Theramex, Gedeon Richter. F.M., E.C., M.R. and S.G. declared no conflict of interests. TRIAL REGISTRATION NUMBER: The study was registered at Clinical Trials Gov (NCT03555942).

Homoeopathic Medicine Arsenicum album 30 C for Covid-19 in 2020: A Retrospective Analysis from Mass-level Data.

Background and Objective: Homoeopathy has played a notable role in managing epidemics in the past. The Ministry of Ayush, Government of India, declared Arsenicum album 30 C as a prophylactic for Covid-19, which was followed by the distribution of the medicine across India. The Central Council for Research in Homoeopathy (CCRH) collected post-prophylactic consumption data of individuals from various colleges over months, which created a data pool. Considering the importance of these mass-level data and their possible impact on public healthcare decisions, the information gathered from this heterogeneous population cohort was subjected to a retrospective data analysis to observe the incidence of Covid-19 in the community. Methods: Data from 50 colleges from February-August 2020 showed that 10.6 million people in 13 states of India received prophylactic medicine during the study period. The data was collected from individuals three weeks following prophylactic consumption for a retrospective analysis. The incidence of Covid-19 was assessed. Results: The data of 584 980 individuals who met the study criteria were included in the analysis. The incidence of Covid-19 in the population cohort was 13.58 per 10 000-person weeks (95% CI, 13.04 to 14.14), which remained near-constant over time despite the increasing disease burden in the country (12.87 to 14.52 per 10 000-person weeks). Consumption of the prophylactic significantly reduced the risk of contracting Covid-19 in high-risk groups as compared to their counterparts. Conclusion: The study concludes that Arsenicum album 30 C has a potential prophylactic effect against Covid-19. Further controlled studies are recommended to establish a causal relation.

Homeopathic Treatment of Subclinical Hypothyroidism-A Series of 19 Cases.

BACKGROUND: Subclinical hypothyroidism (SCH) is a common clinical problem. Controversy surrounds the definition, clinical importance, and need for prompt diagnosis and treatment of the mild form of SCH. AIM: The aim of the study was to analyze the evolution of serum thyroid stimulating hormone (TSH) levels after a therapeutic homeopathic intervention in women older than 40 years with SCH. METHODS: This study is a retrospective series of 19 cases of SCH, with serum TSH levels between 5 and 10 mIU/L, treated exclusively with homeopathic medicines prescribed on an individualized basis. RESULTS: Nineteen patients were included according to the inclusion and exclusion criteria. Their mean age was 56 years, they were followed for a mean duration of 69 months, the mean number of serum TSH level measurements was 18, and the intervention was successful for 13 patients. CONCLUSION: The homeopathic therapeutic intervention was successful in 68% of the patients, with serum TSH levels back within the normal range (0.5-5.0 mIU/L).

Homeopathy for COVID-19 Prevention: Report of an Intervention at a Brazilian Service Sector Company.

BACKGROUND: COVID-19 quickly became a serious public health problem worldwide, with serious economic and social repercussions. Homeopaths around the world have been studying to find a genus epidemicus (GE) medicine that might help in the prevention and treatment of this disease. OBJECTIVE: To compare the incidence of COVID-19 between employees who received or did not receive a homeopathic GE medicine for disease prevention. METHODS: Retrospective cohort analysis. The study population comprised all employees of a service sector company in São Paulo, Brazil, and followed up by the corporate Occupational Health department. Intervention consisted of administering Arsenicum album 30cH in a one-weekly dose. Primary outcome was incidence of COVID-19 during 3-months' follow-up (April to July, 2020). RESULTS: We analyzed 1,642 of 1,703 employees without previous diagnosis of COVID-19 at onset of the study period: 53.34% of employees were referred to telework at home and did not receive intervention (Group 1, G1); 24.66% remained working on-premises in the state of São Paulo and received the intervention (Group 2, G2); 21.98% remained working on company premises in other states and did not receive intervention (Group 3, G3). Incidence rate of COVID-19 was respectively 13.35%, 0.74%, and 67.87% (p < 0.001). The odds ratio of being infected in (1) G3 versus G1 was 13.70 (95% confidence interval [CI], 10.21 to 18.39), (2) G3 versus G2 was 283.02 (95% CI, 88.98 to 900.18), and (3) G1 versus G2 was 20.66 (95% CI, 6.53 to 65.39). LIMITATIONS: The present is a retrospective analysis of a real-world experience. We could not ensure direct observed treatment, and neither could we control adherence to general prevention measures outside company premises. CONCLUSION: The incidence of COVID-19 was significantly lower amongst on-premises employees who received the GE medication in comparison to workers who did not receive the intervention (those either at other company premises or teleworking at home).

Trajectory of Patients Treated With Classical Homeopathy: A Retrospective Analysis.

CONTEXT: Controversy over the efficacy of homeopathic medicine is rooted in the view that its methodology is implausible. OBJECTIVE: The study intended to explore the postintervention results for a randomly selected group of patients in an actual practice. DESIGN: The study was a retrospective review of the charts of patients receiving homeopathy, performed as a pilot study. SETTING: The study took place at a part-time, urban practice in the Mid-Atlantic USA with an area population of about 600 000. PARTICIPANTS: The charts of 53 patients were randomly sampled for later abstraction and were included in the study. They were admitted between August 2010 and June 2014 for first-time visits and took part in at least one follow-up visit during the six months after the intervention. OUTCOME MEASURES: A standardized tool was used to abstract the data from patients' charts. After exclusions and losses to follow-up, data from 40 charts were analyzed. The actual number of visits after the initial visit that was included in the analysis varied from one to five. The current status of up to five diagnoses or problems were tracked for each patient and each visit as was the number of allopathic medications in use and the overall trajectory based on classical homeopathic analysis, evaluating whether the patient was better, worse, or unchanged overall. RESULTS: The charts of 27 patients demonstrated overall improvement; the charts of 12 patients demonstrated no overall change or a worsening of problems or symptoms. The difference between the improved and the nonimproved groups of participants postintervention were significant (P = .0026). Data also demonstrated a significant reduction in the use of allopathic medication and an increase in the number of improved individual conditions or diagnoses (P < .05). CONCLUSIONS: The current study of the treatment experience of 40 persons with a variety of medical conditions found that a majority of patients, when their charts were analyzed according to specific criteria, experienced improvements while undergoing classical homeopathic treatment. The reasons for these improvements can't be determined from available data, but the results do pose important questions about how humans heal. While other factors might account for this result, it's difficult to fully dismiss the idea that homeopathic medicine may have had some impact on observed results.

Clinical Characteristics and Remedy Profiles of Patients with COVID-19: A Retrospective Cohort Study.

OBJECTIVE: The aim of the study was to identify indicated homeopathic remedies based on the clinical characteristics of coronavirus disease 2019 (COVID-19) patients in India. METHODS: In this retrospective, cohort study, confirmed COVID-19 patients admitted at a COVID Health Centre in New Delhi between April 29 and June 17, 2020 were given conventional and homeopathic treatment. Patients were grouped into mild, moderate or severe categories of disease. Their symptomatologic profiles were analyzed to identify indicated homeopathic medicines. RESULTS: A total of 196 COVID-19 patients were admitted. One hundred and seventy-eight patients had mild symptoms; eighteen patients had moderate symptoms; no patients with severe symptoms were included as they were referred to tertiary care centers with ventilatory support. The mean age of patients with mild symptoms was significantly lower (38.6 years; standard deviation or SD ± 15.8) compared with patients in the moderate category (66.0 years; SD ± 9.09). The most important symptoms identified were fever (43.4%), cough (47.4%), sore throat (29.6%), headache (18.4%), myalgia (17.9%), fatigue (16.8%), chest discomfort (13.8%), chills (12.6%), shortness of breath (11.2%) and loss of taste (10.2%). Twenty-eight homeopathic medicines were prescribed, the most frequently indicated being Bryonia alba (33.3%), Arsenicum album (18.1%), Pulsatilla nigricans (13.8%), Nux vomica (8%), Rhus toxicodendron (7.2%) and Gelsemium sempervirens (5.8%), in 30C potency. CONCLUSION: Data from the current study reveal that Arsenicum album, Bryonia alba, Pulsatilla nigricans, Nux vomica, Rhus toxicodendron and Gelsemium sempervirens are the most frequently indicated homeopathic medicines. A randomized controlled clinical trial based on this finding is the next step.

A novel, nonopiod-based treatment approach to men with urologic chronic pelvic pain syndrome using ultrasound-guided nerve hydrodissection and pelvic floor musculature trigger point injections.

INTRODUCTION: Urological chronic pelvic pain syndrome (UCPPS) represents a group of pain symptoms relating to patients with pelvic pain for which treatment is largely unsatisfactory. The objective of this study is to analyze the effects of a novel treatment strategy in males suffering from UCPPS. METHODS: This retrospective, institutional review board-approved study analyzed eight male patients aged 24 to 61 with UCPPS. All the patients had a trial of antibiotic therapy, NSAIDs, and pelvic floor physical therapy before the study. The Visual Analog scale (VAS) and Functional Pelvic Pain scale (FPPS) were collected pretreatment. While continuing physical therapy, patients underwent weekly ultrasound-guided pelvic floor trigger point injections to the iliococcygeus, pubococcygeus, and puborectalis with lidocaine 1%. Concomitantly, patients received peripheral nerve hydrodissection performed on the pudendal nerve and the posterior femoral cutaneous nerve. The first two injections combined 1% lidocaine with dexamethasone, while the next four injections consisted of 1% lidocaine with traumeel (a homeopathic, plant-derived anti-inflammatory medication). At the 6-week follow-up, each patient retook the VAS and FPPS. RESULTS: The mean age of our patients was 31.8 years and the average duration of symptoms of the UCPPS was 21 months. Pretreatment, the mean VAS was 3.3 (STD 1.7) and the mean VAS posttreatment was 1.8 (STD 1.4); P < .05; 95% CI, 0.73 to 2.27. The mean FPPS pretreatment was 11.0 (STD 8.0) and the mean FPPS posttreatment was 6.3 (STD 5.3); P < .05; 95% CI, 0.03 to 9.22. CONCLUSION: Our results show promise for a novel, nonopioid-based treatment for UCPPS.

The use of home remedies and complementary health approaches in endometriosis.

RESEARCH QUESTION: Conventional treatments are often associated with adverse effects and endometriosis pain symptoms may reoccur despite treatment. Consequently, many women use complementary health approaches (CHA) and home remedies (HR) to relieve their pain. The aim of this study was to examine the frequency and the subjectively perceived efficacy of CHA/HR use by women affected by endometriosis. DESIGN: Retrospective evaluation using medical charts and a questionnaire. Women recruited in hospitals and in self-help groups were asked about the use of 'topical heat', 'repose/relaxation', 'movement/massages', 'homeopathy/phytotherapy', 'acupuncture/traditional Chinese medicine (TCM)' and 'kinesiology/physiotherapy'. RESULTS: From a total of 574 women with a confirmed diagnosis of endometriosis, 359 (62.5%) applied some form of CHA/HR. Women suffering from fatiguing disease symptoms more often selected alternative therapies (odds ratio [OR] 3.14, 95% confidence interval [CI] 1.39-7.11, P = 0.006) compared with women without these characteristics. Furthermore, women dissatisfied with healthcare provided by their treating physician, more frequently (OR 2.30, 95% CI 1.19-4.45, P = 0.013) chose the aforementioned alternative strategies. CONCLUSION: As conventional therapies may not be sufficiently effective, women's needs should be closely examined, and individual treatment options should be discussed and initiated by clinicians to provide the best comprehensive treatment possible for endometriosis.

Opioid Prescribing Can Be Reduced in Oral and Maxillofacial Surgery Practice.

PURPOSE: Pain management is one of the most critical aspects of practice in oral and maxillofacial surgery. The purpose of this study was to measure the change in strong (stronger than codeine 30 mg) opioid use after introducing the standardized protocol ("office protocol") designed for opioid-free postoperative pain management. MATERIALS AND METHODS: This is a retrospective cohort study of patients who had surgical procedures performed at the NorthShore Center for Oral and Facial Surgery (Gurnee, IL). Data of patients who underwent qualified surgical procedures and filled prescriptions for strong opioids before and after introduction of the office protocol were analyzed. The primary predictor variable was introduction of the office protocol. The primary outcome variable was filling of a strong opioid prescription that was correlated to pain control as assessed by patients. Age and gender distributions also were analyzed. Proportions and associated 95% confidence intervals were used to compare the number of hydrocodone or oxycodone (strong) prescriptions filled by patients during a 3-year interval. RESULTS: In March 2016, the office protocol for pain management, designed to decrease opioid use, was introduced. In 2015 (before introduction of the office protocol), 2,016 adult patients (15 to 85 yr old) underwent qualified surgical procedures at the author's practice, 1,184 (59%) of whom required and filled strong opioid prescriptions. In 2017 (2 yr after introduction of the office procedure) that number decreased to 19%, whereas the number of qualified surgical procedures performed remained relatively the same between the years. Postoperative pain control was not qualitatively measured but was assumed adequate and correlated with the filling of a strong opioid prescription or requiring a refill, which would be recorded as part of total prescriptions filled. CONCLUSION: A 3-fold decrease in hydrocodone or oxycodone prescription fill was seen at the 2-year interval. As alternatives, nonsteroidal anti-inflammatory drugs, acetaminophen, and a homeopathic recovery kit (Vega Recovery Kit, StellaLife, Glenview, IL) were used for pain management for patients undergoing various oral surgery procedures.

Polycystic ovarian morphology and the diagnosis of polycystic ovary syndrome: redefining threshold levels for follicle count and serum anti-Müllerian hormone using cluster analysis.

STUDY QUESTION: Can cluster analysis be used to differentiate between normo-ovulatory women with normal ovaries and normo-ovulatory women with polycystic ovarian morphology (PCOM) in a non-subjective manner? SUMMARY ANSWER: Cluster analysis can be used to accurately and non-subjectively differentiate between normo-ovulatory women with normal ovaries and normo-ovulatory women with PCOM. WHAT IS KNOWN ALREADY: Currently, PCOM is diagnosed using a fixed threshold level, i.e. 12 or more follicles per ovary, and is one of the diagnostic criteria of polycystic ovary syndrome (PCOS). However, PCOM is also encountered in normo-ovulatory women, suggesting that it could just represent a normal variant. On the other hand, recent studies have shown subtle endocrine abnormalities in women with isolated PCOM that resemble those found in women with PCOS. Because of the strong correlation between anti-Müllerian hormone (AMH) and follicle number, a high serum AMH level has been proposed as a surrogate marker for PCOM and could, therefore, be integrated in the diagnostic classifications for PCOS. STUDY DESIGN, SIZE, DURATION: This was a retrospective observational cohort study. Original cohorts had been recruited for previous studies between 1998 and 2010. Two hundred ninety-seven regularly cycling women and 700 women with PCOS were eligible for inclusion. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cluster analysis was performed in 297 regularly cycling women. After exclusion of 'PCOM' clusters, each 'non-PCOM' cluster (young, n = 118 and old, n = 100) was included in the construction of a receiver operating characteristics curve to test the diagnostic performance of follicle number per ovary (FNPO) and serum AMH in discriminating similarly aged full-blown PCOS patients (n = 411 and 237, respectively) from normal regularly cycling non-PCOM women. MAIN RESULTS AND ROLE OF CHANCE: The optimal number of clusters was four; age was the most important classifying variable, followed by the FNPO and serum AMH. Two distinct clusters of normo-ovulatory women with PCOM were isolated and differed solely by age, i.e. 'young' and 'old'. Both 'PCOM' clusters had their similarly aged counterpart of 'non-PCOM' clusters. Likewise, two clusters comprised women younger than 30 years, with (n = 28, 'PCOM regularly cycling women') or without (n = 118, 'normal regularly cycling women') features of PCOM (increased FNPO and/or serum AMH). The two other clusters in older women could be labelled 'normal regularly cycling women' or 'PCOM regularly cycling women' (n = 100 and 51, respectively). The prevalence of PCOM was significantly greater in old than in young regularly cycling women controls. In the young population, after exclusion of the 'PCOM regularly cycling women', the diagnostic performance of AMH, expressed by area under the curve (AUC) (AUC = 0.903; CI (0.876-0.930)) to differentiate PCOS women from normal regularly cycling women was similar to that using the FNPO (AUC = 0.915, CI (0.891-0.940)) (P = 0.25), confirming results from earlier studies. In the old population, the diagnostic performance of AMH was greater than that of FNPO (AUCs = 0.948 (0.927-0.970) vs 0.874 (0.836-0.912), respectively, P = 0.00035). Cut-off levels of AMH and antral follicle count distinguishing regularly cycling non-PCOM women from PCOS women were higher in young women than in older women. LIMITATIONS, REASONS FOR CAUTION: Data of normal women were obtained from earlier studies, aiming to measure normal endocrine values. Apparently, the strong effect of age in cluster analysis revealed a dichotomy in the age distribution among the cohort of regularly cycling women included. This was involuntary since in none of the original studies, eligibility was limited by age and there was considerable overlap in age ranges of the cohorts. Transvaginal ultrasound was performed using a 6.5-8 mHz probe and our data confirm that this threshold level for FNPO is still valid if using such probe frequencies, although the use of devices with a maximum frequency lower than 8 mHz has become obsolete. Obviously, newer ultrasound scanner using higher transducer frequency will facilitate the detection of more follicles. WIDER IMPLICATIONS OF THE FINDINGS: Our data support the use of AMH as a surrogate for ultrasound to define PCOM, which is one of the three items of the Rotterdam classification. They also show that age should be taken into account to define the optimal threshold. The fact that the prevalence of PCOM was increased in the older regularly cycling women, may be due to 'attenuated' PCOS, a phenomenon that has been described in ageing women with PCOS. These women might have had anovulatory cycles in the past and have become ovulatory with increasing age, and were, therefore, eligible for this study. However, since most women included at older age have had spontaneous pregnancies in the past, PCOM at older age may be associated with a subclinical form of PCOS, which may also be present in young regularly cycling women. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. J.S.E.L. has received grants and support from Ferring, MSD, Organon, Merck-Serono, Schering Plough and Serono during recruitment and analysis of data for this study. S.L.F., A.D. and D.D. do not have any conflict of interest.

Salve and Burdock: A Safe, Effective Amish Remedy for Treatment of Traumatic Wounds?

BACKGROUND: Amish patients show a demonstrated preference for traditional, herbal remedies over modern medical interventions such as skin grafting. One such remedy is a mixture of Burn & Wound Ointment (B & W Ointment; Holistic Acres, LLC; Newcomerstown, Ohio) and steeped burdock leaves. Although both have demonstrated some antimicrobial and wound healing properties, burdock and/or the combination of B & W Ointment and burdock has never been studied to determine its purported ability to reduce pain, prevent infection, and accelerate wound healing. METHODS: A retrospective chart review was performed on 6 Amish patients treated with salve and burdock leaves instead of skin grafting following complex traumatic wounds to determine whether the traditional treatment incurred any patient harm. RESULTS: The time of wound epithelialization and healing complications were noted, among other data points. Time to full epithelialization ranged from 1 to 7 months. Time to full wound healing was proportional to wound size. CONCLUSIONS: Although the treatment presented here is unconventional, it did not cause harm to the patients studied.

Individualized homeopathic treatment in addition to conventional treatment in type II diabetic patients in Hong Kong - a retrospective cohort study.

OBJECTIVE: Glycaemic goals are not achieved in most patients with type II diabetes mellitus (T2DM), especially in those with long disease duration and taking multiple oral antidiabetic drugs (OAD). We aimed to investigate the effectiveness of individualized homeopathic treatment in glycaemic control. DESIGN: Retrospective cohort study. SETTING: At least 6 months of individualized homeopathic treatment at a private homeopathic centre in Hong Kong. PARTICIPANTS: Twenty-seven adults aged 37-84 years were treated with individualized homeopathic remedies between 2012 and 2015. Published data on 40 T2DM patients under standard conventional treatment in Hong Kong were used as a control. MAIN OUTCOME MEASURE: Change in fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) at 12-month or the last follow-up, whichever is earlier. RESULTS: Compared with the conventional treatment only group, the homeopathy group had higher baseline FPG (p = 0.044), and more patients had a long (>20 years) duration of diabetes (p = 0.006), and a history of cardiac events (p = 0.022). The mean difference in FPG in the homeopathy group was significantly greater than in the control after 12 months: -2.24 mmol/L (95% confidence interval [CI]: -3.47 to -1.01) vs 0.16 mmol/L (95% CI: -1.72 to 2.04), p = 0.001. The mean difference in glycated haemoglobin (HbA1c) was also significantly greater, -1.11% (95% CI: -2.17 to -0.05) vs 0.08% (95% CI: -1.37 to 1.53), p = 0.046. Poorer baseline glycaemic control was associated with better outcome (r = -0.750, p < 0.001), but not the duration of diabetes (r = 0.058, p = 0.772). The improvement was robust to sensitivity analyses. CONCLUSION: Individualized homeopathic treatment was associated with better glycaemic control compared with standard conventional treatment alone.

[Effectiveness of preventive treatment by Influenzinum in the winter period against the onset of influenza-like illnesses]. / Efficacité d'un traitement préventif par Influenzinum en période hivernale contre la survenue d'un syndrome grippal.

AIM: In vitro Influenzinum induce a cellular change. We present the results of the first study examining the effectiveness of Influenzinum against influenza-like illnesses. METHOD: Retrospective cohort study during winter 2014-2015. After influenza epidemic, a self-assessment questionnaire was offered to patients presenting for a consultation. The primary endpoint was the declaration of an influenza-like illness. The exposed patients (treated by Influenzinum) were matched to two non-exposed patients (untreated) with a propensity score. A conditional logistic model expressed influenza-like illness risk reduction provided by the Influenzinum. RESULTS: The cohort included 3514 patients recruited from 46 general practitioners. After matching, the treated group (n=2041) and the untreated group (n=482) did not differ on variables collected. Influenzinum preventive therapy does not significantly alter the likelihood of influenza-like illness (adjusted odds ratio=0,91 [0,62 to 1,35], p=0,64). CONCLUSION: Influenzinum preventive therapy did not appear effective in preventing influenza-like illness.

Homeopathic therapy in pediatric atopic diseases: short- and long-term results.

AIM: To study the outcomes of atopic diseases in children treated with homeopathy at the Homeopathic Clinic of Lucca (Italy) and related long-term results after approximately an 8-year period. MATERIALS AND METHODS: Our data derive from an observational longitudinal study carried out on 857 pediatric patients who consecutive visited from 1998 to 2014. Children with atopic diseases were 325 (37.9%), 126 (39%) suffered from atopic dermatitis, 72 (22%) from allergic rhinitis, and 127 (39%) from asthma. Moreover, a long-term study was conducted on a subset of 107/165 patients, consecutively visited from 1998 to 2006, and with ≥5 years follow-up. The study also investigated the evolution of overall symptoms in those patients with a complex atopic symptomatology. RESULTS: 75.8% of atopic children had moderate or major improvement (67.1% with asthma as the primary disease; 84.2% rhinitis; 84.2% dermatitis). At re-evaluation after 5-10 years, complete remission of atopic symptoms was obtained in 70.1% of the children: 84.2% in dermatitis; 48.1% in allergic rhinitis; 71.4% in asthma. Children with two or three atopic diseases at the first visit were completely cured in 40% of cases. CONCLUSION: The results seem to confirm that homeopathic medicine produces positive therapeutic response in atopic children.

Prevalence and likelihood ratio of symptoms in patients with good therapeutic response to Lycopodium clavatum. A retrospective study.

BACKGROUND: Assessment of the likelihood ratio (LR) of symptoms has been proposed as a rational means for detecting indicators to homeopathic medicines. AIMS: To investigate the prevalence and LR of symptoms commonly attributed to the homeopathic medicine Lycopodium clavatum (Lyc). Secondarily, to answer the question if experienced homeopaths could intuitively infer which the main symptoms of this medicine are. METHODS: The presence of 35 selected symptoms, prescribed medicines and therapeutic response were assessed retrospectively. The symptoms' prevalence in the Lyc responding population and the LR of the symptoms compared to their prevalence in the remainder of the population were calculated. RESULTS: Two hundred and two Lyc and 550 non Lyc cases (total 752) were included for analysis. Twenty-two symptoms were confirmed as pertaining to Lyc's semiology (prevalence %; LR): contemptuous (3.3; 6.7), urinary stones history (2.7; 5.4), egotism (5.6; 3.6), dictatorial (33.3; 3.4), haughty (8.7; 3.3), sleeps on abdomen (3.3; 3.3), intolerance to clothing in abdomen (12.0; 3.1), reproaches (4.0; 3.0), helplessness (24.0; 2.7), fear of failure (10.7; 2.6), irritability on waking in the morning (16.7; 2.5), constipation alternating with diarrhea (8.7; 2.5), intolerant to contradiction (59.3; 2.3), want of self confidence (30.0; 2.4), abdominal distension after eating (23.3; 2.1); ailments from anticipation (32.0; 1.9), irritability before menses (23.3; 1.8), conscientious (26.0; 1.6), desire of sweets (52.0; 1.6), desire of chocolate (16.7; 1.6), lack of vital heat (41.3; 1.3), and flatterer (1.3; ∞). Surveyed homeopaths' intuitive inferences correlated well with symptoms' prevalence but not with their LR. CONCLUSIONS: Lycopodium's main symptoms are well known by homeopaths, but their knowledge correlates well with the symptoms' prevalence and not with their LR. Retrospective assessment of prevalence and LR of symptoms in good responders might be a means for better selection of symptoms for prospective studies.

Buerger's disease in the northeast of Iran: Epidemiology and clinical features.

BACKGROUND: The aim of this study is to present our long-term clinical experience in describing a clinical picture of Buerger's disease in our region. MATERIALS AND METHODS: In a retrospective study, files of 225 patients who were admitted to the hospital with diagnosis of thromboangiitis obliterans in a 10 year period from 2000 to 2010 were reviewed. All data including demographic, signs and symptoms, history of previous illness, history of smoking, medications, laboratory tests, angiography, and details of surgical operation were obtained. RESULTS: A total of 222 (98.7%) and 3 (1.3%) of patients were male and female, respectively. Average age of hospitalized patients was 40.7 ± 8.5 (20-62) years. A total of 200 patients (88.9%) were active cigarette smokers while 168 (74.7%) of them were opium addicts. The most prevalent symptoms were chronic ulcers (80%) and claudication (63.6%). Minor and major amputation was required in 113 (50.2%) and 41 (18.4%) patients, respectively. Amputation was carried out on the lower limb (80%), upper limb (4.1%), or on both (15.1%). Also, four patients underwent revascularization through surgical bypass procedures. CONCLUSIONS: The diagnosis and treatment of Buerger's Disease is still a challenge in those communities where the disease is endemic. Therefore, identifying the natural course of the disease can play a pivotal role in the diagnosis and treatment of these patients.