[Chronic cough in adult patients-evidence-based approach]. / Chronischer Husten bei erwachsenen Patienten ­ evidenzbasiertes Vorgehen.

Approximately 10% of the population suffer from a cough lasting longer than 8 weeks. Compared to acute cough, which usually occurs in the context of banal respiratory tract infections, the differential diagnoses of chronic cough require an increased use of diagnostic tests and thus a structured, evidence-based approach according to current international guidelines. A targeted history (smoking status, medication, previous diseases) and ENT status are always followed by chest x­ray and pulmonary function tests before extended diagnostics. In the case of angiotensin-converting enzyme (ACE) inhibitor use and unremarkable physical examination, a drug discontinuation test can be carried out first. In case of inconspicuous findings, a disease entity that can be treated empirically such as upper airway cough syndrome is most likely. If the cough remains unexplained, cough suppression techniques, physiotherapy or speech therapy should be sought before off-label-use of medication.

Automatic anatomical foot and ankle coordinate toolbox.

Accurate analysis of bone position and orientation in foot and ankle studies relies on anatomical coordinate systems (ACS). Reliable ACSs are necessary for many biomechanical and clinical studies, especially those including weightbearing computed tomography and biplane fluoroscopy. Existing ACS approaches suffer from limitations such as manual input, oversimplifications, or non-physiological methods. To address these shortcomings, we introduce the Automatic Anatomical Foot and Ankle Coordinate Toolbox (AAFACT), a MATLAB-based toolbox that automates the calculation of ACSs for the major fourteen foot and ankle bones. In this manuscript, we present the development and evaluation of AAFACT, aiming to provide a standardized coordinate system toolbox for foot and ankle studies. The AAFACT was evaluated using a dataset of fifty-six models from seven pathological groups: asymptomatic, osteoarthritis, pilon fracture, progressive collapsing foot deformity, clubfoot, Charcot Marie Tooth, and cavovarus. Three analyses were conducted to assess the reliability of AAFACT. Firstly, ACSs were compared between automatically and manually segmented bone models to assess consistency. Secondly, ACSs were compared between individual bones and group mean bones to assess within-population precision. Lastly, ACSs were compared between the overall mean bone and group mean bones to assess the overall accuracy of anatomical representation. Statistical analyses, including statistical shape modeling, were performed to evaluate the reliability, accuracy, and precision of AAFACT. The comparison between automatically and manually segmented bone models showed consistency between the calculated ACSs. Additionally, the comparison between individual bones and group mean bones, as well as the comparison between the overall mean bone and group mean bones, revealed accurate and precise ACSs calculations. The AAFACT offers a practical and reliable solution for foot and ankle studies in clinical and engineering settings. It accommodates various foot and ankle pathologies while accounting for bone morphology and orientation. The automated calculation of ACSs eliminates the limitations associated with manual input and non-physiological methods. The evaluation results demonstrate the robustness and consistency of AAFACT, making it a valuable tool for researchers and clinicians. The standardized coordinate system provided by AAFACT enhances comparability between studies and facilitates advancements in foot and ankle research.

Comparing genomes recovered from time-series metagenomes using long- and short-read sequencing technologies.

BACKGROUND: Over the past years, sequencing technologies have expanded our ability to examine novel microbial metabolisms and diversity previously obscured by isolation approaches. Long-read sequencing promises to revolutionize the metagenomic field and recover less fragmented genomes from environmental samples. Nonetheless, how to best benefit from long-read sequencing and whether long-read sequencing can provide recovered genomes of similar characteristics as short-read approaches remains unclear. RESULTS: We recovered metagenome-assembled genomes (MAGs) from the free-living fraction at four-time points during a spring bloom in the North Sea. The taxonomic composition of all MAGs recovered was comparable between technologies. However, differences consisted of higher sequencing depth for contigs and higher genome population diversity in short-read compared to long-read metagenomes. When pairing population genomes recovered from both sequencing approaches that shared ≥ 99% average nucleotide identity, long-read MAGs were composed of fewer contigs, a higher N50, and a higher number of predicted genes when compared to short-read MAGs. Moreover, 88% of the total long-read MAGs carried a 16S rRNA gene compared to only 23% of MAGs recovered from short-read metagenomes. Relative abundances for population genomes recovered using both technologies were similar, although disagreements were observed for high and low GC content MAGs. CONCLUSIONS: Our results highlight that short-read technologies recovered more MAGs and a higher number of species than long-read due to an overall higher sequencing depth. Long-read samples produced higher quality MAGs and similar species composition compared to short-read sequencing. Differences in the GC content recovered by each sequencing technology resulted in divergences in the diversity recovered and relative abundance of MAGs within the GC content boundaries.

Biomechanical Implications of Congenital Conditions of the Foot/Ankle.

Segmental foot and ankle models are often used as part of instrumented gait analysis when planning interventions for complex congenital foot conditions. More than 40 models have been used for clinical analysis, and it is important to understand the technical differences among models. These models have been used to improve clinical planning of pediatric foot conditions including clubfoot, planovalgus, and equinovarus. They have also been used to identify clinically relevant subgroups among pediatric populations, quantify postoperative outcomes, and explain variability in healthy populations.

A multicenter study to evaluate pain characteristics in osteogenesis imperfecta.

The objective was to describe pain characteristics and treatments used in individuals with varying severity of osteogenesis imperfecta (OI) and investigate pain-associated variables. This work was derived from a multicenter, longitudinal, observational, natural history study of OI conducted at 12 clinical sites of the NIH Rare Diseases Clinical Research Network's Brittle Bone Disorders Consortium. Children and adults with a clinical, biochemical, or molecular diagnosis of OI were enrolled in the study. We did a cross-sectional analysis of chronic pain prevalence, characteristics, and treatments used for pain relief and longitudinal analysis to find the predictors of chronic pain. We included 861 individuals with OI, in 41.8% chronic pain was present, with similar frequency across OI types. Back pain was the most frequent location. Nonsteroidal anti-inflammatory drugs followed by bisphosphonates were the most common treatment used. Participants with chronic pain missed more days from school or work/year and performed worse in all mobility metrics than participants without chronic pain. The variables more significantly associated with chronic pain were age, sex, positive history of rodding surgery, scoliosis, other medical problems, assistive devices, lower standardized height, and higher body mass index. The predictors of chronic pain for all OI types were age, use of a wheelchair, and the number of fractures/year. Chronic pain is prevalent in OI across all OI types, affects mobility, and interferes with participation. Multiple covariates were associated with chronic pain.

Social Prescribing: Systematic Review of the Effectiveness of Psychosocial Community Referral Interventions in Primary Care.

Introduction: Social prescribing (SP) aims to provide targeted psychosocial support and close the gap between medical and non-medical services. This review assesses the effectiveness of community-based SP interventions. Methods: We performed a systematic review and qualitative synthesis of interventional studies of community referral interventions focused on facilitating psychosocial support. We considered health-related endpoints, other patient reported outcomes, or health care utilization. Six databases, grey literature, and additional trials registers were searched. Results were screened in a two-step process, followed by data extraction, each by two independent reviewers. If data permitted such, effect sizes were calculated. Risk of bias was assessed with the EPHPP and the Cochrane RoB2 tools. Results: We identified 68 reports from 53 different projects, three were controlled studies. Uncontrolled studies with shorter time frames frequently reported positive effects. This could largely not be seen in controlled settings and for longer follow-up periods. Designs, populations, and outcomes evaluated were heterogeneous with high risk of bias for most studies. Discussion and conclusion: Current evidence suggests positive effects of SP on a variety of relevant endpoints. Due to quality deficits in the available studies, scope for conclusions concerning clinical relevance and sustainability is limited. Further methodologically rigorous controlled trials are needed.

[Acute and chronic cough - differential diagnosis and treatment]. / Akuter und chronischer Husten ­ Differenzialdiagnose und Behandlung.

Cough is a frequent reason for consultation in the general practitioner's office. Most of the time, the symptom is harmless and self-limiting, as in the case of a banal cold cough, for example - however, serious diseases such as malignancies can also be the cause. Evaluation is therefore not always easy. This article presents a targeted and appropriate approach and discusses which treatments are recommended and effective.Acute and chronic cough are differentiated according to the duration of symptoms (up to 8 weeks/longer than 8 weeks). The most common cause of acute cough is a self-limiting viral infection of the upper respiratory tract; the most important differential diagnosis is community-acquired pneumonia. If there are no defined warning signs (red flags), the history and clinical examination are sufficient to establish the diagnosis in the case of an acute cough; medication is not necessary. In the case of a chronic cough, a chest X-ray is usually ordered and then further investigations are carried out in accordance with the most probable suspected diagnosis; probationary therapies are an important part of the workup. Coughs that are refractory to treatment or unexplained require individualised treatment (pharmacological, including off-label, non-pharmacological) and regular re-evaluation.

Glycoside hydrolase from the GH76 family indicates that marine Salegentibacter sp. Hel_I_6 consumes alpha-mannan from fungi.

Microbial glycan degradation is essential to global carbon cycling. The marine bacterium Salegentibacter sp. Hel_I_6 (Bacteroidota) isolated from seawater off Helgoland island (North Sea) contains an α-mannan inducible gene cluster with a GH76 family endo-α-1,6-mannanase (ShGH76). This cluster is related to genetic loci employed by human gut bacteria to digest fungal α-mannan. Metagenomes from the Hel_I_6 isolation site revealed increasing GH76 gene frequencies in free-living bacteria during microalgae blooms, suggesting degradation of α-1,6-mannans from fungi. Recombinant ShGH76 protein activity assays with yeast α-mannan and synthetic oligomannans showed endo-α-1,6-mannanase activity. Resolved structures of apo-ShGH76 (2.0 Å) and of mutants co-crystalized with fungal mannan-mimicking α-1,6-mannotetrose (1.90 Å) and α-1,6-mannotriose (1.47 Å) retained the canonical (α/α)6 fold, despite low identities with sequences of known GH76 structures (GH76s from gut bacteria: <27%). The apo-form active site differed from those known from gut bacteria, and co-crystallizations revealed a kinked oligomannan conformation. Co-crystallizations also revealed precise molecular-scale interactions of ShGH76 with fungal mannan-mimicking oligomannans, indicating adaptation to this particular type of substrate. Our data hence suggest presence of yet unknown fungal α-1,6-mannans in marine ecosystems, in particular during microalgal blooms.

[Sore Throat - Guideline-based Diagnostics and Therapy]. / Halsschmerzen ­ leitlinienbasierte Diagnostik und Therapie.

Background: Sore throat is a common reason for consultation of family physicians. Acute sore throat (< 14 days) is usually triggered by infections of the pharynx. Less than 35 % of cases are caused by bacterial infections; nevertheless, antibiotics are prescribed far more often. Evidence-based guideline recommendations are available to reduce non-indicated administration of antibiotics in the treatment of sore throat. Search Methods: Update of the clinical guideline "sore throat" of the German College of General Practitioners and Family Physicians (DEGAM) by means of a systematic search of the literature for international guidelines and systematic reviews. Main Messages: After excluding red flags such as immunosuppression and severe systemic infections, acute sore throat is usually self-limiting with a mean duration of 7 days. Patients should be encouraged in self-management; ibuprofen and naproxen are recommended for symptomatic treatment. If antibiotics are considered, clinical scores (Centor, McIsaac, FeverPAIN) should be used to assess the risk of bacterial pharyngitis. At low risk (< 3 points), antibiotics are not indicated; if at least moderate (3 points), delayed prescription is an option; if high (> 3 points), antibiotics can be taken immediately. Even if scores suggestive a bacterial cause, the evidence suggests that antibiotic treatment only shortens the duration of symptoms modestly. Penicillin is the first choice (clarithromycin as an alternative). The antibiotic should be taken for 5-7 days. Conclusions: In the absence of red flags, a regular use of symptomatic treatment will help to control discomfort. If administration of antibiotics is still considered a risk-adapted approach, using clinical scores is recommended.

[Acute Cough in Adult Patients]. / Akuter Husten bei erwachsenen Patient*innen.

Background: Acute cough (< 8 weeks) is a frequent complaint in family practice consultations. The most common cause are respiratory infections. The Guideline "Acute and chronic cough" of the German College of General Practitioners and Family Physicians (DEGAM) was updated in 2021 and contains recommendations for an evidence-based approach for the management of acute cough in primary care. Methods: The guideline has been updated in accordance with the findings of a systematic search of the literature for international guidelines and systematic reviews. All recommendations were developed by an interdisciplinary guideline committee and agreed by formal consensus. Results: History-taking, exclusion of red flags and a physical examination are the basis of diagnostic evaluation. If an acute, uncomplicated bronchitis is likely, no laboratory tests, sputum diagnostics, or chest x-rays should be performed, and antibiotics should not be administered. Evidence based strategies to avoid antibiotic therapy (delayed prescribing, shared decision making, point-of-care-tests) can be used. There is inadequate evidence for the efficacy of antitussive or expectorant drugs against acute cough. The state of the evidence for phytotherapeutic agents is heterogeneous; clinical importance is minimal. COVID-19 should currently be considered in cases of acute respiratory symptoms. If specific symptoms or red flags occur, further diagnoses in the context of acute cough such as community-acquired pneumonia, influenza disease and exacerbations of chronic respiratory diseases (bronchial asthma, COPD) should be taken into consideration. Conclusions: These evidence-based recommendations are intended to reduce the use of antibiotics to treat colds and acute bronchitis, for which they are not indicated. Further clinical trials of symptomatic treatments for cough should be performed in order to extend the evidence base.

What are the long-term outcomes of lateral column lengthening for pes planovalgus in cerebral palsy?

BACKGROUND: Lateral column lengthening (LCL) is commonly performed on children and adolescents with cerebral palsy (CP) for correction of pes planovalgus (PPV). There are limited reports of the long-term outcomes of this procedure. The purpose of this study was to examine the long-term results of LCL for correction of PPV in individuals with CP by evaluating subjects when they had transitioned to adulthood and were entering the workforce. METHODS: Clinical assessments, quantitative gait analysis including the Milwaukee Foot Model (MFM) for segmental foot kinematics, and patient reported outcomes were collected from 13 participants with CP treated with LCL for PPV in childhood (average age 24.4 ± 5.7 years, average 15.3 ± 8.5 years since LCL). Additionally, 27 healthy adults average age 24.5 ± 3.6 years functioned as controls. RESULTS: Strength and joint range of motion were reduced in the PPV group (p < 0.05). Sixty nine percent showed operative correction of PPV based on radiologic criteria. Gait analysis showed reduced walking speed and stride length, as well as midfoot break and residual forefoot abduction. Patient reported outcomes indicated that foot pain was not the only factor that caused limited activity and participation. LCL surgery for PPV in childhood resulted in long-term operative correction. Decreased ankle passive range of motion and strength, subtalar joint arthritic changes, inefficient and less stable ambulation, and problems with participation (difficulties in physical function, education, and employment) were observed in the long-term. CONCLUSION: This study identified postoperative impairments and limitations to guide future clinical decision-making. These results provide clinicians and researchers the common residual and recurrent issues for these individuals as they age. The inclusion of contextual factors that influence the disease and impairments can equip these individuals with enhanced skills they need as they transition into adulthood.

Chronic Cough.

BACKGROUND: Chronic cough, i.e., cough lasting longer than eight weeks, affects approximately 10% of the population and is a common reason for outpatient medical consultation. Its differential diagnosis is extensive, and it is generally evaluated in poorly structured fashion with a variety of diagnostic techniques. The German Clinical Practice Guideline on Acute and Chronic Cough was updated in 2021 and contains a description of the recommended stepwise, patient-centered, and evidencebased procedure for the management of chronic cough. METHODS: The guideline has been updated in accordance with the findings of a systematic search of the literature for international guidelines and systematic reviews. All recommendations were developed in an interdisciplinary manner and agreed upon by formal consensus. The target group consists of adult patients with cough. RESULTS: History-taking, after the exclusion of red flags, should include questioning about smoking status, medications, and relevant present and past illnesses (COPD, asthma). Subsequent diagnostic testing should include a chest x-ray and pulmonary function tests. If the patient is taking an ACE inhibitor, a test of drug discontinuation can be carried out first. Radiologically detected pulmonary masses or evidence of rare diseases (interstitial lung diseases, bronchiectasis) are an indication for chest CT or for direct referral to an appropriate specialist. If the imaging studies and pulmonary function tests are normal, the patient is most likely suffering from a disease entity that can be treated empirically, such as upper airway cough syndrome or cough variant asthma. Any patient with an unexplained or refractory cough must receive proper patient education; individual therapeutic trials of physiotherapeutic or speech-therapeutic methods are possible, as is the off-label use of gabapentin or morphine. CONCLUSION: Chronic cough should be evaluated according to an established diagnostic algorithm in collaboration with specialists. Treatments such as inhaled corticosteroids should be tested exhaustively in accordance with the guidelines, and the possibility of multiple causes as well as the role of patient compliance should be kept in mind before a diagnosis of unexplained or intractable cough is assigned.

Multi-segment foot kinematics during gait following ankle arthroplasty.

Ankle arthritis is a debilitating disease marked by pain and limited function. Total ankle arthroplasty improves pain while preserving motion and offers an alternative to the traditional treatment of ankle fusion. Gait analysis and functional outcomes tools can provide an objective balanced analysis of ankle replacement for the treatment of ankle arthritis. Twenty-nine patients with end-stage ankle arthritis were evaluated before and after ankle arthroplasty. Multi-segment foot and ankle kinematics were assessed annually following surgery (average 3.5 years, range 1-6 years) using the Milwaukee Foot Model and a Vicon video motion analysis system. Functional outcomes (American Orthopedic Foot and Ankle Society [AOFAS] ankle/hindfoot scale, short form 36 [SF-36] questionnaire) and temporal-spatial parameters were also assessed. Kinematic results were compared to findings from a previously collected group of healthy ambulators. AOFAS and SF-36 mean scores improved postoperatively. Walking speed and stride length increased after surgery. There were significant improvements in tibial sagittal range of motion in terminal stance and hindfoot sagittal range of motion in preswing. Decreased external rotation of the tibia and increased external rotation of the hindfoot were noted throughout the gait cycle. Pain and function improved after ankle replacement as supported by better outcomes scores, increased temporal-spatial parameters, and significant improvement in tibial sagittal range of motion during terminal stance and hindfoot sagittal range of motion during preswing. While multi-segment foot kinematics were improved, they were not restored to control values. Statement of clinical significance: Total ankle arthroplasty does not fully normalize mutli-segment gait kinematics despite improved patient-reported outcomes and gait mechanics.

Gait Characteristics in Youth With Transverse Myelitis.

BACKGROUND: Transverse myelitis (TM) in childhood is a rare disorder characterized by the presence of spinal cord inflammation. Gait difficulty in children with TM is common; however, there is a paucity of literature regarding quantitative assessment of gait in children and adolescents with TM. OBJECTIVES: To characterize gait patterns in a cohort of ambulatory children with TM and age-matched, typically developing peers in order to better understand the functional mobility of patients diagnosed with childhood TM. METHODS: This was a retrospective study of 26 ambulatory pediatric patients with a confirmed diagnosis of TM who had undergone three-dimensional, instrumented gait analysis (3D-IGA) at 3 years of age or older. A group of 38 typically developing children served as a control group. RESULTS: Gait in children with TM was characterized by moderate kinematic deviations as measured by the Gait Deviation Index (GDI) and a crouched gait pattern (p < .001), increased anterior pelvic tilt (p < .001), decreased motion at the knees (p < .001), and a wider base of support (foot progression angle, p < .001). The TM group had a slower walking speed (p < .001), shorter strides (p < .001), and an increased stance phase compared to controls. CONCLUSION: Our study results showed moderate kinematic deviations quantified by the GDI. Overall, the gait pattern in the TM population tested had greater hip and knee flexion with wider foot progression angle. Identification of gait characteristics in children with TM is the first step in predicting changes in gait pattern as they mature over time, which may ultimately allow for targeted intervention to maintain their ambulatory function.

Assignment of local coordinate systems and methods to calculate tibiotalar and subtalar kinematics: A systematic review.

The introduction of biplane fluoroscopy has created the ability to evaluate in vivo motion, enabling six degree-of-freedom measurement of the tibiotalar and subtalar joints. Although the International Society of Biomechanics defines a standard method of assigning local coordinate systems for the ankle joint complex, standards for the tibiotalar and subtalar joints are lacking. The objective of this systematic review was to summarize and appraise the existing literature that (1) defined coordinate systems for the tibia, talus, and/or calcaneus or (2) assigned kinematic definitions for the tibiotalar and/or subtalar joints. A systematic literature search was developed with search results limited to English Language from 2006 through 2020. Articles were screened by two independent reviewers based on title and abstract. Methodological quality was evaluated using a modified assessment tool. Following screening, 52 articles were identified as having met inclusion criteria. Methodological assessment of these articles varied in quality from 61 to 97. Included articles adopted primary methods for defining coordinate systems that included: (1) anatomical coordinate system (ACS) based on individual bone landmarks and/or geometric shapes, (2) orthogonal principal axes, and (3) interactive closest point (ICP) registration. Common methods for calculating kinematics included: (1) joint coordinate system (JCS) to calculate rotation and translation, (2) Cardan/Euler sequences, and (3) inclination and deviation angles for helical angles. The methods each have strengths and weaknesses. This summarized knowledge should provide the basis for the foot and ankle biomechanics community to create an accepted standard for calculating and reporting tibiotalar and subtalar kinematics.

Clinical Practice Guideline: Sore Throat.

BACKGROUND: Sore throat is a common reason for consultation of primary care physicians, pediatricians, and ENT specialists. The updated German clinical practice guideline on sore throat provides evidence-based recommendations for treatment in the German healthcare system. METHODS: Guideline revision by means of a systematic search of the literature for international guidelines and systematic reviews. All recommendations resulted from interdisciplinary cooperation and were agreed by formal consensus. The updated guideline applies to patients aged 3 years and over. RESULTS: In the absence of red flags such as immunosuppression, severe comorbidity, or severe systemic infection, acute sore throat is predominantly self-limiting. The mean duration is 7 days. Chronic sore throat usually has noninfectious causes. Laboratory tests are not routinely necessary. Apart from non-pharmacological self-management, ibuprofen and naproxen are recommended for symptomatic treatment. Scores can be used to assess the risk of bacterial pharyngitis: one point each is assigned for tonsil lesions, palpable cervical lymph nodes, patient age, disease course, and elevated temperature. If the risk is low (<3 points), antibiotics are not indicated; if at least moderate (3 points), delayed prescribing is recommended; if high (>3 points), antibiotics can be taken immediately. Penicillin remains the first choice, with clarithromycin as an alternative for those who do not tolerate penicillin. The antibiotic should be taken for 5-7 days. CONCLUSION: After the exclusion of red flags, antibiotic treatment is unnecessary in many cases of acute sore throat. If administration of antibiotics is still considered in spite of consultation on the usual course of tonsillopharyngitis and the low risk of complications, a risk-adapted approach using clinical scores is recommended.

In situ visualization of glycoside hydrolase family 92 genes in marine flavobacteria.

Gene clusters rich in carbohydrate-active enzymes within Flavobacteriia genera provide a competitiveness for their hosts to degrade diatom-derived polysaccharides. One such widely distributed polysaccharide is glucuronomannan, a main cell wall component of diatoms. A conserved gene cluster putatively degrading glucuronomannan was found previously among various flavobacterial taxa in marine metagenomes. Here, we aimed to visualize two glycoside hydrolase family 92 genes coding for α-mannosidases with fluorescently-labeled polynucleotide probes using direct-geneFISH. Reliable in situ localization of single-copy genes was achieved with an efficiency up to 74% not only in the flavobacterial strains Polaribacter Hel1_33_49 and Formosa Hel1_33_131 but also in planktonic samples from the North Sea. In combination with high-resolution microscopy, direct-geneFISH gave visual evidence of the contrasting lifestyles of closely related Polaribacter species in those samples and allowed for the determination of gene distribution among attached and free-living cells. We also detected highly similar GH92 genes in yet unidentified taxa by broadening probe specificities, enabling a visualization of the functional trait in subpopulations across the borders of species and genera. Such a quantitative insight into the niche separation of flavobacterial taxa complements our understanding of the ecology of polysaccharide-degrading bacteria beyond omics-based techniques on a single-cell level.

Do Bisphosphonates Alleviate Pain in Children? A Systematic Review.

PURPOSE OF REVIEW: The goal of this systematic review is to analyze the effectiveness of bisphosphonates (BPs) to treat bone pain in children and adolescents who have diseases with skeletal involvement. RECENT FINDINGS: We included 24 studies (2 randomized controlled trials, 3 non-randomized controlled trials, 10 non-randomized open-label uncontrolled studies, 8 retrospective studies, and 1 study with design not specified). The majority of included studies assessed pain from a unidimensional approach, with pain intensity the most frequently evaluated dimension. Only 38% of studies used validated tools; visual analogue scale was the most frequently employed. BPs were used to alleviate bone pain in a wide variety of pediatrics conditions such as osteogenesis imperfecta, secondary osteoporosis, osteonecrosis related to chemotherapy, chronic non-bacterial osteitis, idiopathic juvenile osteoporosis, unresectable benign bone tumor, and cancer-related pain. Twenty of the 24 studies reported a positive effect of BPs for alleviating pain in different pathologies, but 58% of the studies were categorized as having high risk of bias. Intravenous BPs are helpful in alleviating bone pain in children and adolescents. It is advised that our results be interpreted with caution due to the heterogeneity of the doses used, duration of treatments, and types of pathologies included. In addition, this review shows the paucity of high-quality evidence in the available literature and further research is needed. TRIAL REGISTRATION: Before the completion of this review, the protocol was registered to PROSPERO (International prospective register of systematic reviews), PROSPERO 2020 ID # CRD42020158316. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020158316.