Tumor-Induced Osteomalacia in a Patient with Crohn's Disease: A Case Report and Approach to Investigating Hypophosphatemia.

Introduction: Hypophosphatemia occurs commonly in inflammatory bowel disease (IBD) patients and can cause considerable morbidity. The differential diagnoses in IBD include nutritional causes and hypophosphatemia induced by some formulations of intravenous iron infusions. Case Presentation: We present the case of a 37-year-old man with active Crohn's disease, presenting with difficulty walking and fractures of the vertebrae and calcaneus. He had long-standing hypophosphatemia. Nutritional causes for hypophosphatemia were considered in the first instance given the presence of chronic diarrhea and vitamin D deficiency; however, there was minimal response to appropriate supplementation with oral phosphorous and vitamin D. Iron infusion-induced hypophosphatemia was then considered, but the nadir phosphate level preceded any iron infusion. Therefore, work-up was undertaken for less common causes. He was ultimately diagnosed with tumor-induced osteomalacia, caused by excess fibroblast growth factor 23 (FGF23) secretion from a phosphaturic mesenchymal tumor about the knee. He had complete resolution of symptoms and biochemical abnormalities following successful resection of the tumor. Conclusion: This case illustrates the approach to investigation of hypophosphatemia in IBD patients. If the time course and response to phosphate supplementation are not as expected for nutritional or iron infusion-induced hypophosphatemia, less common causes should be considered.

Homeopathic medicinal products for preventing and treating acute respiratory tract infections in children.

BACKGROUND: Acute respiratory tract infections (ARTIs) are common and may lead to complications. Most children experience between three and six ARTIs annually. Although most infections are self-limiting, symptoms can be distressing. Many treatments are used to control symptoms and shorten illness duration. Most treatments have minimal benefit and may lead to adverse events. Oral homeopathic medicinal products could play a role in childhood ARTI management if evidence for their effectiveness is established. This is an update of a review first published in 2018. OBJECTIVES: To assess the effectiveness and safety of oral homeopathic medicinal products compared with placebo or conventional therapy to prevent and treat ARTIs in children. SEARCH METHODS: We searched CENTRAL (2022, Issue 3), including the Cochrane Acute Respiratory Infections Specialised Register, MEDLINE (1946 to 16 March 2022), Embase (2010 to 16 March 2022), CINAHL (1981 to 16 March 2022), AMED (1985 to 16 March 2022), CAMbase (searched 16 March 2022), and British Homeopathic Library (searched 26 June 2013 - no longer operating). We also searched the WHO ICTRP and ClinicalTrials.gov (16 March 2022), checked references, and contacted study authors to identify additional studies. SELECTION CRITERIA: We included double-blind randomised controlled trials (RCTs) or double-blind cluster-RCTs comparing oral homeopathy medicinal products with identical placebo or self-selected conventional treatments to prevent or treat ARTIs in children aged 0 to 16 years. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: In this 2022 update, we identified three new RCTs involving 251 children, for a total of 11 included RCTs with 1813 children receiving oral homeopathic medicinal products or a control treatment (placebo or conventional treatment) for ARTIs. All studies focused on upper respiratory tract infections (URTIs), with only one study including some lower respiratory tract infections (LRTIs). Six treatment studies examined the effect on URTI recovery, and five studies investigated the effect on preventing URTIs after one to four months of treatment. Two treatment and three prevention studies involved homeopaths individualising treatment. The other studies used predetermined, non-individualised treatments. All studies involved highly diluted homeopathic medicinal products, with dilutions ranging from 1 x 10-4 to 1 x 10-200. We identified several limitations to the included studies, in particular methodological inconsistencies and high attrition rates, failure to conduct intention-to-treat analysis, selective reporting, and apparent protocol deviations. We assessed three studies as at high risk of bias in at least one domain, and many studies had additional domains with unclear risk of bias. Four studies received funding from homeopathy manufacturers; one study support from a non-government organisation; two studies government support; one study was co-sponsored by a university; and three studies did not report funding support. Methodological inconsistencies and significant clinical and statistical heterogeneity precluded robust quantitative meta-analysis. Only four outcomes were common to more than one study and could be combined for analysis. Odds ratios (OR) were generally small with wide confidence intervals (CI), and the contributing studies found conflicting effects, so there was little certainty that the efficacy of the intervention could be ascertained. All studies assessed as at low risk of bias showed no benefit from oral homeopathic medicinal products, whilst trials at unclear or high risk of bias reported beneficial effects. For the comparison of individualised homeopathy versus placebo or usual care for the prevention of ARTIs, two trials reported on disease severity; due to heterogeneity the data were not combined, but neither study demonstrated a clinically significant difference. We combined data from two trials for the outcome need for antibiotics (OR 0.79, 95% CI 0.35 to 1.76; low-certainty evidence). For the comparison of non-individualised homeopathy versus placebo or usual care for the prevention of ARTIs, only the outcome recurrence of ARTI was reported by more than one trial; data from three studies were combined for this outcome (OR 0.60, 95% CI 0.21 to 1.72; low-certainty evidence). For the comparison of both individualised and non-individualised homeopathy versus placebo or usual care for the treatment of ARTIs, two studies provided data on short-term cure (OR 1.31, 95% CI 0.09 to 19.54) and long-term cure (OR 1.01, 95% CI 0.10 to 9.96; very low-certainty evidence). The studies demonstrated an opposite direction of effect for both outcomes. Six studies reported on disease severity but were not combined as they used different scoring systems and scales. Three studies reported adverse events (OR 0.79, 95% CI 0.16 to 4.03; low-certainty evidence). AUTHORS' CONCLUSIONS: Pooling of five prevention and six treatment studies did not show any consistent benefit of homeopathic medicinal products compared to placebo on ARTI recurrence or cure rates in children. We assessed the certainty of the evidence as low to very low for the majority of outcomes. We found no evidence to support the efficacy of homeopathic medicinal products for ARTIs in children. Adverse events were poorly reported, and we could not draw conclusions regarding safety.

Homeopathic Preparations for Preventing and Treating Acute Upper Respiratory Tract Infections in Children: A Systematic Review and Meta-Analysis.

BACKGROUND: Acute upper respiratory tract infections (ARTIs) are common and mostly self-limiting. A range of treatments are used with the aim to cure or treat symptoms, including widespread use of homeopathic treatments. OBJECTIVE: To undertake a systematic review and meta-analysis of trials with the highest level of evidence, to establish the benefits and risks for oral homeopathic remedies used to treat and prevent ARTIs in children. DATA SOURCES: MEDLINE, Embase, CINAHL, AMED, CAMbase, British Homeopathic Library, CENTRAL, WHO ICTRP and ClinicalTrials.gov registers to March 2018. STUDY ELIGIBILITY, PARTICIPANTS, AND INTERVENTIONS: Double-blinded randomized trials in children, treated with oral homeopathic remedies versus placebo or conventional treatments for ARTI. APPRAISAL AND SYNTHESIS METHODS: Studies were reviewed in duplicate for inclusion, data extraction, and risk of bias. Meta-analysis was performed on only 4 outcomes. Other outcomes were reported narratively. RESULTS: Eight studies (1562 children) were included. Four studies examined treatment and 4 prevention of ARTIs. Four studies involved homeopaths individualizing treatment versus four with non-individualized treatments. Three studies had high risk of bias in at least 1 domain. All studies with low risk of bias showed no benefit from homeopathy; trials at uncertain and high risk of bias reported beneficial effects. Two individualized treatment studies (N = 155) did not show benefit on short-term or long-term cure. Prevention trials showed no significant outcomes: recurrence of ARTIs. No serious events were reported. LIMITATIONS: Methodological inconsistencies and heterogeneity. CONCLUSIONS: The effectiveness for homeopathic remedies for childhood ARTIs is not supported in higher quality trials.

Homeopathic medicinal products for preventing and treating acute respiratory tract infections in children.

BACKGROUND: Acute respiratory tract infections (ARTIs) are common and may lead to complications. Most children experience between three and six ARTIs annually. Although these infections are self-limiting, symptoms can be distressing. Many treatments are used to control symptoms and shorten illness duration. Most have minimal benefit and may lead to adverse effects. Oral homeopathic medicinal products could play a role in childhood ARTI management if evidence for effectiveness is established. OBJECTIVES: To assess the effectiveness and safety of oral homeopathic medicinal products compared with placebo or conventional therapy to prevent and treat acute respiratory tract infections in children. SEARCH METHODS: We searched CENTRAL (2017, Issue 11) including the Cochrane Acute Respiratory Infections Specialised Register, MEDLINE (1946 to 27 November 2017), Embase (2010 to 27 November 2017), CINAHL (1981 to 27 November 2017), AMED (1985 to December 2014), CAMbase (searched 29 March 2018), British Homeopathic Library (searched 26 June 2013 - no longer operating). We also searched the WHO ICTRP and ClinicalTrials.gov trials registers (29 March 2018), checked references, and contacted study authors to identify additional studies. SELECTION CRITERIA: Double-blind, randomised controlled trials (RCTs) or double-blind cluster-RCTs comparing oral homeopathy medicinal products with identical placebo or self-selected conventional treatments to prevent or treat ARTIs in children aged 0 to 16 years. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included eight RCTs of 1562 children receiving oral homeopathic medicinal products or a control treatment (placebo or conventional treatment) for upper respiratory tract infections (URTIs). Four treatment studies examined the effect on URTI recovery, and four studies investigated the effect on preventing URTIs after one to three months of treatment, followed up for the remainder of the year. Two treatment and two prevention studies involved homeopaths individualising treatment. The other studies used predetermined, non-individualised treatments. All studies involved highly diluted homeopathic medicinal products.We found several limitations to the included studies, in particular methodological inconsistencies and high attrition rates, failure to conduct intention-to-treat analysis, selective reporting, and apparent protocol deviations. We assessed three studies as at high risk of bias in at least one domain, and many had additional domains with unclear risk of bias. Three studies received funding from homeopathy manufacturers; one support from a non-government organisation; two government support; one was cosponsored by a university; and one did not report funding support.Methodological inconsistencies and significant clinical and statistical heterogeneity precluded robust quantitative meta-analysis. Only four outcomes were common to more than one study and could be combined for analysis. Odds ratios (OR) were generally small with wide confidence intervals (CI), and the contributing studies found conflicting effects, so there was little certainty that the efficacy of the intervention could be ascertained. All studies assessed as at low risk of bias showed no benefit from oral homeopathic medicinal products; trials at uncertain and high risk of bias reported beneficial effects.We found low-quality evidence that non-individualised homeopathic medicinal products confer little preventive effect on ARTIs (OR 1.14, 95% CI 0.83 to 1.57). We found low-quality evidence from two individualised prevention studies that homeopathy has little impact on the need for antibiotic usage (N = 369) (OR 0.79, 95% CI 0.35 to 1.76). We also assessed adverse events, hospitalisation rates and length of stay, days off school (or work for parents), and quality of life, but were not able to pool data from any of these secondary outcomes.There is insufficient evidence from two pooled individualised treatment studies (N = 155) to determine the effect of homeopathy on short-term cure (OR 1.31 favouring placebo, 95% CI 0.09 to 19.54; very low-quality evidence) and long-term cure rates (OR 0.99, 95% CI 0.10 to 9.67; very low-quality evidence). Adverse events were reported inconsistently; however, serious events were not reported. One study found an increase in the occurrence of non-severe adverse events in the treatment group. AUTHORS' CONCLUSIONS: Pooling of two prevention and two treatment studies did not show any benefit of homeopathic medicinal products compared to placebo on ARTI recurrence or cure rates in children. We found no evidence to support the efficacy of homeopathic medicinal products for ARTIs in children. Adverse events were poorly reported, so conclusions about safety could not be drawn.

Homeopathic medicinal products for preventing and treating acute respiratory tract infections in children.

BACKGROUND: Acute respiratory tract infections (ARTIs) are common and may lead to complications. Most children experience between three and six ARTIs each year. Although these infections are self limiting, the symptoms can be distressing. Many treatments are used to control symptoms and shorten the duration of illness. They often have minimal benefit and may lead to adverse effects. Oral homeopathic medicinal products could play a role in the treatment of ARTIs for children if evidence for effectiveness is established. OBJECTIVES: To assess the effectiveness and safety of oral homeopathic medicinal products compared with placebo or conventional therapy to prevent and treat acute respiratory tract infections in children. SEARCH METHODS: We searched CENTRAL (2017, Issue 11), which contains the Cochrane Acute Respiratory Infections Specialised Register, MEDLINE (1946 to 27 November 2017), Embase (2010 to 27 November 2017), CINAHL (1981 to 27 November 2017), AMED (1985 to December 2014), CAMbase (searched 29 March 2018), British Homeopathic Library (searched 26 June 2013 - no longer operating). We also searched the WHO ICTRP and ClinicalTrials.gov trials registers (29 March 2018), checked references, and contacted study authors to identify additional studies. SELECTION CRITERIA: Double-blind, randomised controlled trials (RCTs) or double-blind cluster-RCTs comparing oral homeopathy medicinal products with identical placebo or self selected conventional treatments to prevent or treat ARTIs in children aged 0 to 16 years. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included eight RCTs of 1562 children receiving oral homeopathic medicinal products or a control treatment (placebo or conventional treatment) for upper respiratory tract infections (URTIs). Four treatment studies examined the effect on recovery from URTIs, and four studies investigated the effect on preventing URTIs after one to three months of treatment and followed up for the remainder of the year. Two treatment and two prevention studies involved homeopaths individualising treatment for children. The other studies used predetermined, non-individualised treatments. All studies involved highly diluted homeopathic medicinal products.We found several key limitations to the included studies, in particular methodological inconsistencies and high attrition rates, failure to conduct intention-to-treat analysis, selective reporting, and apparent protocol deviations. We assessed three studies as at high risk of bias in at least one domain, and many had additional domains with unclear risk of bias. Three studies received funding from homeopathy manufacturers; one reported support from a non-government organisation; two received government support; one was cosponsored by a university; and one did not report funding support.Methodological inconsistencies and significant clinical and statistical heterogeneity precluded robust quantitative meta-analysis. Only four outcomes were common to more than one study and could be combined for analysis. Odds ratios (OR) were generally small with wide confidence intervals (CI), and the contributing studies found conflicting effects, so there was little certainty that the efficacy of the intervention could be ascertained. All studies assessed as at low risk of bias showed no benefit from oral homeopathic medicinal products; trials at uncertain and high risk of bias reported beneficial effects.We found low-quality evidence that non-individualised homeopathic medicinal products confer little preventive effect on ARTIs (OR 1.14, 95% CI 0.83 to 1.57). We found low-quality evidence from two individualised prevention studies that homeopathy has little impact on the need for antibiotic usage (N = 369) (OR 0.79, 95% CI 0.35 to 1.76). We also assessed adverse events, hospitalisation rates and length of stay, days off school (or work for parents), and quality of life, but were not able to pool data from any of these secondary outcomes.There is insufficient evidence from two pooled individualised treatment studies (N = 155) to determine the effect of homeopathy on short-term cure (OR 1.31, 95% CI 0.09 to 19.54; very low-quality evidence) and long-term cure rates (OR 1.01, 95% CI 0.10 to 9.96; very low-quality evidence). Adverse events were reported inconsistently; however, serious events were not reported. One study found an increase in the occurrence of non-severe adverse events in the treatment group. AUTHORS' CONCLUSIONS: Pooling of two prevention and two treatment studies did not show any benefit of homeopathic medicinal products compared to placebo on recurrence of ARTI or cure rates in children. We found no evidence to support the efficacy of homeopathic medicinal products for ARTIs in children. Adverse events were poorly reported, so conclusions about safety could not be drawn.