Side Effects of sevelamer: A Synthesis of Findings from 28 Studies

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Original Abstract of the Article

Main Research Findings

Sevelamer is a phosphate binder widely used to treat hyperphosphatemia, a common complication of end-stage renal disease. While effective, sevelamer can cause various side effects, with some being potentially serious. 7 One major concern is sevelamer carbonate crystal-induced colitis, a condition causing inflammation and ulceration of the colon. 7 This side effect can be manifested as recurrent abdominal pain and nausea, and can even lead to near-obstruction of the colon. 7 Another important finding is that sevelamer hydrochloride can worsen metabolic acidosis and increase potassium levels in hemodialysis patients. 4 These studies highlight the importance of considering the potential side effects of sevelamer and monitoring patients closely for gastrointestinal issues and metabolic changes.

Reasons for Side Effects

The side effects of sevelamer are attributed to the accumulation of sevelamer crystals in the gastrointestinal tract. 7 These crystals can cause inflammation and ulcers in the intestinal lining, leading to symptoms like abdominal pain, nausea, and even gastrointestinal bleeding. 5 19 28 The accumulation of crystals can also affect bowel movement, leading to constipation or diarrhea. 4 Additionally, sevelamer can interfere with iron absorption, potentially causing anemia. 17

Common Side Effects

Nausea

Nausea is a common side effect of sevelamer, potentially caused by the irritation of the gastrointestinal lining due to the accumulation of crystals. 7 5 19 28

Vomiting

Vomiting can also occur due to the irritation caused by sevelamer crystals in the intestines. 7 5 19 28

Diarrhea

Diarrhea can be a side effect of sevelamer, potentially due to the crystals affecting bowel movements. 7 5 19 28

Constipation

Sevelamer can slow down bowel movements, leading to constipation. 7 5 19 28

Abdominal Pain

Abdominal pain is a potential side effect of sevelamer, often linked to the inflammation and ulcers caused by crystal accumulation. 7 5 19 28

Bloating

Bloating can be caused by sevelamer, potentially due to the accumulation of crystals affecting gas production. 7 5 19 28

Malabsorption

Malabsorption can occur as a side effect of sevelamer, possibly due to the crystals hindering nutrient absorption. 7 5 19 28

Gastrointestinal Bleeding

Gastrointestinal bleeding is a potentially serious side effect of sevelamer, often associated with ulceration caused by the crystals. 7 5 19 28

Metabolic Acidosis

Sevelamer hydrochloride can worsen metabolic acidosis in hemodialysis patients. 4

Hyperkalemia

Sevelamer hydrochloride can increase potassium levels in hemodialysis patients. 4

Countermeasures for Side Effects

Constipation

Staying hydrated by drinking plenty of fluids is crucial to prevent constipation associated with sevelamer. 4 Increasing fiber intake through diet can also be helpful. If constipation persists, consult a doctor who might recommend laxatives. 17

Gastrointestinal Bleeding

If you experience symptoms of gastrointestinal bleeding, seek immediate medical attention. 7 5 19 28

Comparison between Studies

Common Points in Studies

These studies demonstrate that sevelamer is effective in lowering phosphate levels in patients with kidney disease. They also highlight that sevelamer can cause various side effects, including gastrointestinal issues, metabolic acidosis, and hyperkalemia.

Differences in Studies

There are some discrepancies in the frequency and severity of side effects reported. For example, some studies emphasize gastrointestinal issues like colitis and bleeding, 7 5 19 28 while others focus on metabolic disturbances. 4 These variations may be due to differences in study design, patient populations, and sevelamer formulations.

Notes on Application to Real Life

While sevelamer is a valuable treatment option for hyperphosphatemia, it's crucial to be aware of its potential side effects. It's essential to discuss these concerns with your doctor and follow their instructions carefully. This is especially important for elderly patients and those with compromised kidney function, as they might be at higher risk for complications. Furthermore, remember to inform your doctor about all medications you are taking, as sevelamer can interact with other drugs.

Limitations of Current Research

There is a need for more comprehensive research on the side effects of sevelamer, particularly concerning its long-term impact. Additionally, the current research lacks consistency in terms of the frequency and severity of side effects reported, potentially due to variations in study design and populations.

Future Research Directions

Future research should focus on understanding the long-term effects of sevelamer use, the exact mechanisms behind its side effects, and the potential development of strategies to minimize these issues. It's also important to conduct more rigorous research to establish a clear picture of the frequency and severity of sevelamer side effects across different patient populations.

Conclusion

Sevelamer is an important treatment option for hyperphosphatemia, but its use requires careful consideration of its potential side effects. While generally well-tolerated, sevelamer can cause gastrointestinal issues, particularly colitis, as well as metabolic disturbances. It's crucial to stay informed, discuss any concerns with your doctor, and follow their guidance carefully. Further research is crucial to better understand the long-term effects and potential strategies to minimize the risk of side effects associated with sevelamer use.

Keywords
Benefit Keywords
Better tolerability
Higher compliance
Hyperphosphatemia treatment
1
Definitive identification
Differential diagnosis
2
Bind phosphorus
3
Phosphate control
4
Phosphorous management
6
Hyperphosphatemia treatment
8
Lower serum phosphorus
Reduced pill burden
9
Lower serum phosphate
Minimal iron absorption
Reduced pill burden
10
Hyperphosphatemia treatment
11
Control of dietary phosphate absorption
12
Bind phosphorus
13
Improved growth
Tumor reduction
16
Reduced GI symptoms
17
Hyperphosphatemia treatment
18
End-stage renal disease treatment
19
CKD
Hyperphosphatemia
Phosphate Binders
20
Cost saving
Hyperphosphatemia treatment
21
Phosphate binder
22
Lower serum phosphorus
23
Hyperphosphataemia treatment
Reduced bone toxicity
Reduced cardiovascular calcification
24
Control phosphorous level
25
Hyperkalemia treatment
Metabolic acidosis treatment
26
High phosphate binding capacity
Hyperphosphatemia treatment
Low iron release
27
Phosphate Reduction
28
Risk Keywords
High dropout rate
Side effects
1
Vascular calcification
3
Hyperkalemia
Metabolic acidosis
Secondary hyperparathyroidism
4
Gastrointestinal bleeding
5
Colitis
Gastrointestinal side effects
7
Diarrhea
Discolored feces
9
Calcifications
Gastrointestinal symptoms
Hypercalcemia
Tissue accumulation
10
Phosphate binder side effects
11
Absorption of aluminium
Absorption of calcium
12
Extra-osseous calcifications
13
Peritonitis
14
Cardiovascular mortality
Hypercalcemia
Vascular calcification
15
Metabolic acidosis
16
Sevelamer side effects
19
Aluminum Toxicity
Calcium Overload
Gastrointestinal Bleeding
20
Safety concerns
22
High 2PY levels
Poor patient tolerance
23
Side effects
24
Gastrointestinal side effects
26
Bowel Ischemia
Necrosis
28
Literature analysis of 28 papers
Positive Content
25
Neutral Content
0
Negative Content
3
Article Type
3
0
0
9
24
1.

Prospective randomized multicenter trial of sevelamer hydrochloride and calcium carbonate for the treatment of hyperphosphatemia in hemodialysis patients in Japan.

Author: KoiwaFumihiko, OnodaNoritaka, KatoHitoshi, TokumotoAkihide, OkadaTomoyuki, FukagawaMasashi, ShigematsuTakashi,

Better tolerability
Higher compliance
Hyperphosphatemia treatment
High dropout rate
Side effects

This study examined the effectiveness and safety of sevelamer hydrochloride, a phosphate binder, in combination with calcium carbonate (CC) for treating hyperphosphatemia in hemodialysis patients. The study found that sevelamer had an additive effect when combined with CC, resulting in better control of serum phosphorus levels. The combination therapy was also better tolerated than either medication alone, leading to higher patient compliance.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

2.

Diagnosis of Ion-Exchange Resin Depositions in Paraffin Sections Using Corrective Light and Electron Microscopy-NanoSuit Method.

Author: OoishiMako, YamadaSatoshi, ItohToshiya, MeguroShiori, YagiHaruna, KosugiIsao, IwashitaToshihide, ShinmuraKazuya, MisawaKiyoshi, HariyamaTakahiko, KawasakiHideya

Definitive identification
Differential diagnosis

This study investigates the definitive identification of ion-exchange resins using correlative light and electron microscopy (CLEM)-energy-dispersive X-ray spectroscopy and the NanoSuit method (CENM). It shows that CENM can be used for the differential pathological diagnosis of ion-exchange resins in paraffin sections.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

3.

Phosphate binder usage in kidney failure patients.

Author: BleyerAnthony J

Bind phosphorus
Vascular calcification

This article discusses the use of phosphorus binders in patients with kidney failure. It highlights the evolution of phosphorus binder therapy, from aluminium-based binders to calcium-containing binders, and then to newer alternatives such as sevelamer.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

4.

Metabolic acidosis aggravation and hyperkaliemia in hemodialysis patients treated by sevelamer hydrochloride.

Author: SonikianMacroui A, PaniIoanna T, IliopoulosAnastasios N, KoutalaKaliopi G, MarioliStamatia I, VlassopoulosDimosthenis A

Phosphate control
Hyperkalemia
Metabolic acidosis
Secondary hyperparathyroidism

Long-term use of sevelamer hydrochloride (SH) was associated with acidosis aggravation and hyperkaliemia, while also potentially contributing to worsening of secondary hyperparathyroidism.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

5.

Colonic Mucosal Ulceration and Gastrointestinal Bleeding Associated with Sevelamer Crystal Deposition in a Patient with End Stage Renal Disease.

Author: NambiarSudheer, PillaiUnnikrishnan Kunjan, DevasahayamJoe, OliverTony, KarippotAsha

Gastrointestinal bleeding

People with end-stage kidney disease often experience gastrointestinal bleeding. This case report describes a patient who had gastrointestinal bleeding after taking sevelamer, a medication to lower phosphate levels. Physicians should be aware of this potential side effect of sevelamer.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

6.

Management of hyperphosphataemia of chronic kidney disease: lessons from the past and future directions.

Author: MallucheHartmut H, MawadHanna

Phosphorous management

Phosphate binders have evolved significantly over the past 40 years, with new agents showing better efficacy and fewer side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

8.

Safety and efficacy of sevelamer in the treatment of uncontrolled hyperphosphataemia of haemodialysis patients.

Author: AlmirallJaume, LopezThaïs, VallveMontserrat, RuizAna, LlibreJoan, BetriuAngels

Hyperphosphatemia treatment

This study investigates the potential benefits of sevelamer hydrochloride, a non-absorbable phosphate-binding polymer, in managing uncontrolled hyperphosphataemia in dialysis patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

10.

Phosphate binders for the treatment of chronic kidney disease: role of iron oxyhydroxide.

Author: CernaroValeria, SantoroDomenico, LacquanitiAntonio, CostantinoGiuseppe, ViscontiLuca, BuemiAntoine, BuemiMichele

Lower serum phosphate
Minimal iron absorption
Reduced pill burden
Calcifications
Gastrointestinal symptoms
Hypercalcemia
Tissue accumulation

This review discusses the use of sucroferric oxyhydroxide for treating hyperphosphatemia in patients with chronic kidney disease. Sucroferric oxyhydroxide has a similar efficacy and safety profile as sevelamer with a lower pill burden.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

11.

Emerging drugs for hyperphosphatemia.

Author: BellinghieriGuido, SantoroDomenico, SavicaVincenzo

Hyperphosphatemia treatment
Phosphate binder side effects

Hyperphosphatemia is a major risk factor for cardiovascular mortality in dialysis patients. While aluminum-based phosphate binders have side effects, calcium-based binders can worsen calcification. New non-aluminum and non-calcium binders like sevelamer and lanthanum carbonate show promise, but long-term studies are needed. The possibility of salivary phosphate binders is being explored to reduce phosphate absorption.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

12.

Effect of RenaGel, a non-absorbed, calcium- and aluminium-free phosphate binder, on serum phosphorus, calcium, and intact parathyroid hormone in end-stage renal disease patients.

Author: GoldbergD I, DillonM A, SlatopolskyE A, GarrettB, GrayJ R, MarburyT, WeinbergM, WomboltD, BurkeS K

Control of dietary phosphate absorption
Absorption of aluminium
Absorption of calcium

This study examined the efficacy of RenaGel, a calcium- and aluminium-free polymeric phosphate binder, in end-stage renal disease patients as a potential alternative to calcium- and aluminium-containing binders, which have associated side effects.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

[Management of hyperphosphoremia].

Author: AmorJ, PalmaA

Bind phosphorus
Extra-osseous calcifications

This article discusses the importance of phosphorus control in patients with chronic renal failure (CRF) and provides an overview of phosphorus binders. It highlights the limitations of calcium-based binders and the potential benefits of newer calcium-free binders like sevelamer.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : Spanish

14.

Sevelamer use and incidence of peritonitis in peritoneal dialysis.

Author: KerschbaumJulia, KönigPaul, HausdorferJohann, MayerGert, RudnickiMichael

Peritonitis

Treatment with Sevelamer is not associated with a higher risk for peritonitis. The mean peritonitis incidence rate was to 0.50/patient year. An identified risk factor for peritonitis was time on PD. Neither Sevelamer use in general nor the mean daily intake was associated with the risk for peritonitis even after adjustment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

Oral phosphate binders for the management of serum phosphate levels in dialysis patients.

Author: MohammedIsmail, HutchisonAlastair J

Cardiovascular mortality
Hypercalcemia
Vascular calcification

Hyperphosphatemia is a common consequence of end-stage chronic kidney disease and affects the majority of dialysis patients. It is statistically linked to increased cardiovascular mortality in this population. Dietary restriction and current dialysis modalities are not sufficiently effective to maintain serum phosphate levels within the recommended range, leading most dialysis patients to require oral phosphate binders. However, the benefits of achieving the recommended range have not been demonstrated prospectively. Traditional phosphate binders have limitations and side effects. Aluminium-containing agents, while highly efficient, are no longer widely used due to established toxicity. Calcium-based salts are inexpensive, effective, and most widely used but are now associated with hypercalcemia and vascular calcification. Sevelamer hydrochloride and lanthanum carbonate, non-aluminum, calcium-free phosphate binders, are effective and generally well-tolerated but do not control phosphate levels in all patients. Patient education programs have been shown to be effective in improving serum phosphate target achievement.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

16.

Hyperphosphatemic familial tumoral calcinosis: response to acetazolamide and postulated mechanisms.

Author: FinerGal, PriceHeather E, ShoreRichard M, WhiteKenneth E, LangmanCraig B

Improved growth
Tumor reduction
Metabolic acidosis

Acetazolamide, a carbonic anhydrase inhibitor, effectively controlled severe hyperphosphatemic familial tumoral calcinosis (HFTC) in a 7-year-old boy despite no change in serum phosphate. This suggests that acetazolamide may improve calcium-phosphate complex solubility and increase FGF23 locally to control HFTC.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Treatment of hyperphosphatemia with bixalomer in Japanese patients on long-term hemodialysis with gastrointestinal symptoms.

Author: ItoKae, TakeshimaAkiko, ShishidoKanji, WakasaMikio, KumataChiaki, MatsuzakaKantaro, NakajimaYutaka, OgataHiroaki

Reduced GI symptoms

Switching from sevelamer hydrochloride to bixalomer in hemodialysis patients significantly reduced gastrointestinal symptoms without affecting serum phosphorus levels or overall health parameters.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Observational StudyResearch that observes and collects data on participants' behavior and outcomes in their natural state, without intervention.

Language : English

18.

A review of sucroferric oxyhydroxide for the treatment of hyperphosphatemia in patients receiving dialysis.

Author: BousherAva, Al-MakkiAkram, SuttonJames, SheplerBrian

Hyperphosphatemia treatment

Sucroferric oxyhydroxide, a new phosphate binder, shows promise in managing hyperphosphatemia in patients with chronic kidney disease, but more research is needed to determine its optimal role.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

19.

[Colonic Mass Secondary to Sevelamer-associated Rectal Ulcer].

Author: LeeJin Hee, ParkSang Hyoung, ShinJin Ho, HongSeung-Mo, ParkJin Hwa, HwangSung Wook, YangDong-Hoon, ByeonJeong-Sik, MyungSeung-Jae, YeByong Duk, YangSuk-Kyun

End-stage renal disease treatment
Sevelamer side effects

This case report describes a 29-year-old male with end-stage renal disease who developed a sevelamer-induced rectal ulcer.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : Korean

20.

The Rising Risk of Chronic Kidney Disease (CKD) and How it is Dealt with: A Review of Current and Potential Phosphate Binders (PB).

Author: GosikRobert, DanelKrzysztof

CKD
Hyperphosphatemia
Phosphate Binders
Aluminum Toxicity
Calcium Overload
Gastrointestinal Bleeding

This review discusses different phosphate binders (PBs) used for treating hyperphosphatemia, a risk factor for chronic kidney disease (CKD). The review explores the pros and cons of current PBs, highlighting the need for new PBs that can also function as protection modifiers.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

22.

Preclinical studies of VS-505: a non-absorbable highly effective phosphate binder.

Author: Wu-WongJ Ruth, ChenYung-Wu, WongJonathan T, WessaleJerry L

Phosphate binder
Safety concerns

VS-505 is a novel, non-absorbable phosphate binder derived from plants. Preclinical studies showed promising results, suggesting its potential for treating phosphate imbalance in chronic kidney disease (CKD) patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

23.

Efficacy and safety of nicotinamide in haemodialysis patients: the NICOREN study.

Author: LengletAurélie, LiabeufSophie, El EsperNajeh, BrissetSandrine, MansourJanette, Lemaire-HurtelAnne-Sophie, MaryAurelien, BrazierMichel, KamelSaid, MentaverriRomuald, ChoukrounGabriel, FournierAlbert, MassyZiad A

Lower serum phosphorus
High 2PY levels
Poor patient tolerance

Nicotinamide and sevelamer were equally effective in lowering serum phosphorus in patients with chronic kidney disease, but nicotinamide was less well tolerated.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

24.

Improving phosphate-binder therapy as a way forward.

Author: HutchisonAlastair J

Hyperphosphataemia treatment
Reduced bone toxicity
Reduced cardiovascular calcification
Side effects

This study reviews the use of phosphate binders to treat hyperphosphatemia in patients with end-stage renal disease. It focuses on the need for safe and effective non-calcium, non-aluminium-based alternative treatments. The study discusses sevelamer hydrochloride and lanthanum carbonate, with lanthanum carbonate emerging as a promising new agent.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

26.

Lanthanum carbonate versus sevelamer hydrochloride: improvement of metabolic acidosis and hyperkalemia in hemodialysis patients.

Author: FiliopoulosVassilis, KoutisIoannis, TrompoukiSofia, HadjiyannakosDimitrios, LazarouDimitrios, VlassopoulosDimosthenis

Hyperkalemia treatment
Metabolic acidosis treatment
Gastrointestinal side effects

This study compared the effects of sevelamer hydrochloride (SH) and lanthanum carbonate (LC) on acid-base status and serum potassium in hemodialysis patients. LC improved metabolic acidosis and hyperkalemia compared to SH. However, LC had more gastrointestinal side effects and difficulties in chewing the tablet, potentially leading to decreased compliance.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

27.

Novel oral phosphate binder with nanocrystalline maghemite-phosphate binding capacity and pH effect.

Author: NguyenT M-H, MüllerR H, TaupitzM, SchnorrJ, HammB, WagnerS

High phosphate binding capacity
Hyperphosphatemia treatment
Low iron release

C-PAM-10, a novel iron-based phosphate binder, demonstrated high phosphate binding capacity over the entire gastrointestinal pH range with low iron release, making it a promising candidate for hyperphosphatemia treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

28.

Ischemic Colitis in Association with Sevelamer Crystals.

Author: KeriK C, VeitlaV, SamjiN S

Phosphate Reduction
Bowel Ischemia
Necrosis

Sevelamer is a drug used to lower serum phosphate levels in kidney disease. This case report describes a rare adverse effect: colonic hemorrhage and perforation due to bowel ischemia and sevelamer crystal deposition.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

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